Selective reminding of prospective memory in Multiple Sclerosis.

PubMed

McKeever, Joshua D; Schultheis, Maria T; Sim, Tiffanie; Goykhman, Jessica; Patrick, Kristina; Ehde, Dawn M; Woods, Steven Paul

2017-04-19

Multiple sclerosis (MS) is associated with prospective memory (PM) deficits, which may increase the risk of poor functional/health outcomes such as medication non-adherence. This study examined the potential benefits of selective reminding to enhance PM functioning in persons with MS. Twenty-one participants with MS and 22 healthy adults (HA) underwent a neuropsychological battery including a Selective Reminding PM (SRPM) experimental procedure. Participants were randomly assigned to either: (1) a selective reminding condition in which participants learn (to criterion) eight prospective memory tasks in a Selective Reminding format; or (2) a single trial encoding condition (1T). A significant interaction was demonstrated, with MS participants receiving greater benefit than HAs from the SR procedure in terms of PM performance. Across diagnostic groups, participants in the SR conditions (vs. 1T conditions) demonstrated significantly better PM performance. Individuals with MS were impaired relative to HAs in the 1T condition, but performance was statistically comparable in the SR condition. This preliminary study suggests that selective reminding can be used to enhance PM cue detection and retrieval in MS. The extent to which selective reminding of PM is effective in naturalistic settings and for health-related behaviours in MS remains to be determined.

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

PubMed

Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

Prospective memory impairment in multiple sclerosis: a review.

PubMed

Rouleau, Isabelle; Dagenais, Emmanuelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

2017-08-04

Multiple sclerosis (MS) is a progressive disease of the central nervous system affecting information processing speed, episodic memory, attention, and executive functions. MS patients also often report prospective memory (PM) failures that directly impact their functional autonomy, including professional and social life. The purpose of this paper was to review the literature concerning the assessment and remediation of PM deficits in MS. The literature pertaining to PM impairment in MS was carefully reviewed using PubMed, PsyINFO, and Google Scholar, as well as cross-references from the articles published on this topic. Since PM rehabilitation in MS patients is still in its infancy, this review mainly focuses on studies that have directly assessed PM through various measures including questionnaires, standardized clinical tests, and experimental procedures. This literature review confirms the presence of PM deficits in MS patients, even in the early stages of the disease. A further need for controlled studies on PM assessment and PM interventions in patients with MS is stressed.

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

PubMed

Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

2018-01-01

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.

Adherence to subcutaneous interferon beta-1a treatment using an electronic injection device: a prospective open-label Scandinavian noninterventional study (the ScanSmart study)

PubMed Central

Pedersen, Elena Didenko; Stenager, Egon; Vadgaard, JL; Jensen, MB; Schmid, R; Meland, N; Magnussen, G; Frederiksen, Jette L

2018-01-01

Background Disease modifying drugs help control the course of relapsing remitting multiple sclerosis (RRMS); however, good adherence is needed for long-term outcomes. Objective To evaluate patient adherence to treatment with subcutaneous interferon beta-1a using RebiSmart® and assess injection-site reactions and treatment satisfaction. Methods This prospective, single-arm, open-label, noninterventional multicenter Phase IV trial included disease modifying drug-experienced mobile patients with RRMS. Adherence was measured over 12 weeks. Items 13–23, 35, 37, and 38 of the Multiple Sclerosis Treatment Concerns Questionnaire (injection-site reactions and treatment satisfaction) were recorded at 12 weeks. Results Sixty patients were recruited (mean age 43.7 [±SD 7.9] years; 83% female; mean years since multiple sclerosis diagnosis 6.7 [SD 4.5]). Adherence data were obtained in 54 patients only due to technical problems with six devices. Over 12 weeks, 89% (n=48) of patients had ≥90% adherence to treatment. Most patients experienced mild influenza-like symptoms and injection-site reactions, and global side effects were minimal. Most patients (78%) rated the convenience as the most important aspect of the device, and most experienced no or mild pain. Conclusion RRMS patients treated with subcutaneous interferon beta-1a, administered with RebiSmart, demonstrated generally good adherence, and the treatment was generally well tolerated. PMID:29720872

Adherence to subcutaneous interferon beta-1a treatment using an electronic injection device: a prospective open-label Scandinavian noninterventional study (the ScanSmart study).

PubMed

Pedersen, Elena Didenko; Stenager, Egon; Vadgaard, J L; Jensen, M B; Schmid, R; Meland, N; Magnussen, G; Frederiksen, Jette L

2018-01-01

Disease modifying drugs help control the course of relapsing remitting multiple sclerosis (RRMS); however, good adherence is needed for long-term outcomes. To evaluate patient adherence to treatment with subcutaneous interferon beta-1a using RebiSmart ® and assess injection-site reactions and treatment satisfaction. This prospective, single-arm, open-label, noninterventional multicenter Phase IV trial included disease modifying drug-experienced mobile patients with RRMS. Adherence was measured over 12 weeks. Items 13-23, 35, 37, and 38 of the Multiple Sclerosis Treatment Concerns Questionnaire (injection-site reactions and treatment satisfaction) were recorded at 12 weeks. Sixty patients were recruited (mean age 43.7 [±SD 7.9] years; 83% female; mean years since multiple sclerosis diagnosis 6.7 [SD 4.5]). Adherence data were obtained in 54 patients only due to technical problems with six devices. Over 12 weeks, 89% (n=48) of patients had ≥90% adherence to treatment. Most patients experienced mild influenza-like symptoms and injection-site reactions, and global side effects were minimal. Most patients (78%) rated the convenience as the most important aspect of the device, and most experienced no or mild pain. RRMS patients treated with subcutaneous interferon beta-1a, administered with RebiSmart, demonstrated generally good adherence, and the treatment was generally well tolerated.

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

PubMed Central

Kasperavičiūtė, Dalia; Catarino, Claudia B.; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Bárbara; Hessel, Ellen V. S.; Hallmann, Kerstin; Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P.; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J.; Zumsteg, Dominik; Duncan, Susan; Kälviäinen, Reetta K.; Eriksson, Kai J.; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M.; Stogmann, Elisabeth; Zimprich, Fritz; Théâtre, Emilie; Smith, Colin; O’Brien, Terence J.; Meng Tan, K.; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R.; Buono, Russell J.; Hakonarson, Hakon; Chaves, João; Costa, Paulo P.; Silva, Berta M.; da Silva, António M.; de Graan, Pierre N. E.; Koeleman, Bobby P. C.; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S.; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo M.; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E.; Berkovic, Samuel F.; Weale, Michael E.; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L.; Kunz, Wolfram S.

2013-01-01

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26–1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures. PMID:24014518

Pre-diagnostic plasma urate and the risk of amyotrophic lateral sclerosis.

PubMed

O'Reilly, Éilis J; Bjornevik, Kjetil; Schwarzschild, Michael A; McCullough, Marjorie L; Kolonel, Laurence N; Le Marchand, Loic; Manson, Joann E; Ascherio, Alberto

2018-05-01

To prospectively examine for the first time the association between plasma urate levels measured in healthy participants and future amyotrophic lateral sclerosis (ALS) risk. A pooled case-control study nested in five US prospective cohorts comprising 319,617 participants who provided blood, of which 275 had ALS during follow-up. Pre-diagnostic plasma urate was determined for all participants using a clinical colorimetric enzyme assay. Gender-specific multivariable-adjusted rate ratios (RR) of ALS incidence or death estimated by conditional logistic regression and pooled using inverse-variance weighting. In age- and matching factor-adjusted analyses, a 1 mg/dL increase in urate concentration was associated with RR = 0.88 (95% CI: [0.78, 0.997] p = 0.044). After adjustment for BMI, a strong predictor of ALS and urate levels, and other potential covariates, the RR = 0.89 (95% CI: [0.78, 1.02]; p = 0.08 for 1mg/dL increase in urate). Elevation of plasma urate was modestly inversely associated with the risk of ALS and warrants further study for a potential role in this disease.

A unique retinal epitheliopathy is associated with amyotrophic lateral sclerosis/Parkinsonism-Dementia complex of Guam.

PubMed

Steele, John C; Wresch, Robert; Hanlon, Samuel D; Keystone, Jay; Ben-Shlomo, Yoav

2015-08-01

The aim of this work was to examine whether a linear retinal pigment epitheliopathy is associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. A total of 918 Guamanian Chamorros, with and without amyotrophic lateral sclerosis/parkinsonism-dementia complex, were examined cross-sectionally for linear retinal pigment epitheliopathy (LRPE). Overall, 239 Guamanians, who were neurologically asymptomatic, were followed for up to 20 years to determine the risk of developing amyotrophic lateral sclerosis/parkinsonism-dementia complex. The epitheliopathy was present in 59.7% (117 of 196) patients with amyotrophic lateral sclerosis/parkinsonism-dementia complex, but in only 24.7% (178 of 722) of subjects who were neurologically asymptomatic (age- and sex-adjusted risk difference: 35.0%; 95% confidence interval [CI]: 27.5-42.6; p < 0.0001). Prospectively, 15 of 50 cases with epitheliopathy developed amyotrophic lateral sclerosis/parkinsonism-dementia complex, compared to 4 of 189 cases without epitheliopathy (age- and sex-adjusted hazard ratio: 13.1; 95% CI: 4.0-43.1; P < 0.0001). Amyotrophic lateral sclerosis/parkinsonism-dementia complex is associated with an LRPE and predicts future neurological disease. Identifying the cause of this retinopathy could provide an understanding about the pathogenesis of amyotrophic lateral sclerosis/parkinsonism-dementia complex and related diseases. © 2015 International Parkinson and Movement Disorder Society.

A prospective study of quality of life in amyotrophic lateral sclerosis patients.

PubMed

Jakobsson Larsson, B; Ozanne, A G; Nordin, K; Nygren, I

2017-12-01

The aim of this prospective and longitudinal study was to describe individual quality of life in patients with amyotrophic lateral sclerosis (ALS) and its correlations with physical function and emotional well-being from diagnosis and over time. Thirty-six patients were included in the study. Individual quality of life was measured with the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), illness severity was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS FRS-R), and emotional distress was measured using the Hospital Anxiety and Depression Scale (HADS). Data were collected from diagnosis and thereafter, every six months for a period of two years. Twelve patients completed the 24-month follow-up. Family, friends and own physical health were important for overall quality of life, from diagnosis and during the disease progression. Most patients had good quality of life, which remained stable, despite changed physical functions. Several patients scored above the cut-off score for doubtful and clinical anxiety and depression early on after diagnosis, and there was a significant decrease in anxiety over time. Soon after diagnosis, there was a correlation between depression and quality of life. The family, social relations and own physical health are important for overall quality of life in patients with ALS. Thus, supporting the family and facilitating so that patients can continue to stay in contact with friends are important aspects during the disease. Conducting an early screening for depression can be important for preventing decreased quality of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effects of prolonged wear of textured shoe insoles on gait, foot sensation and proprioception in people with multiple sclerosis: study protocol for a randomised controlled trial.

PubMed

Hatton, Anna L; Dixon, John; Rome, Keith; Brauer, Sandra G; Williams, Katrina; Kerr, Graham

2016-04-21

Many people with multiple sclerosis experience problems with walking, which can make daily activities difficult and often leads to falls. Foot sensation plays an important role in keeping the body balanced whilst walking; however, people with multiple sclerosis often have poor sensation on the soles of their feet. Wearing a specially designed shoe insole, which enhances plantar sensory information, could help people with multiple sclerosis to walk better. This study will explore whether long-term wear of a textured insole can improve walking in people with multiple sclerosis. A prospective randomised controlled trial with two parallel groups will be conducted aiming to recruit 176 people with multiple sclerosis living in the community (Brisbane, Australia). Adults with a clinical diagnosis of multiple sclerosis, Disease Steps score 1-4, who are ambulant over 100 m and who meet specific inclusion criteria will be recruited. Participants will be randomised to a smooth control insole (n = 88) or textured insole (n = 88) group. The allocated insole will be worn for 12-weeks within participants' own footwear, with self-report wear diaries and falls calendars being completed over this period. Blinded assessors will conduct two baseline assessments and one post-intervention assessment. Gait tasks will be completed barefoot, wearing standardised footwear only, and wearing standardised footwear with smooth and textured insoles. The primary outcome measure will be mediolateral base of support when walking over even and uneven surfaces. Secondary measures include spatiotemporal gait parameters (stride length, stride time variability, double-limb support time, velocity), gait kinematics (hip, knee, and ankle joint angles, toe clearance, trunk inclination, arm swing, mediolateral pelvis/head displacement), foot sensation (light touch-pressure, vibration, two-point discrimination) and proprioception (ankle joint position sense). Group allocation will be concealed and all analyses will be based on an intention-to-treat principle. This study will explore the effects of wearing textured insoles over 12-weeks on gait, foot sensation and proprioception in people with multiple sclerosis. The study has the potential to identify a new, evidence-based footwear intervention which has the capacity to enhance mobility and independent living in people with multiple sclerosis. Australian New Zealand Clinical Trials Registry ACTRN12615000421538 . Registered 4 May 2015.

Somatosensory impairment and its association with balance limitation in people with multiple sclerosis.

PubMed

Jamali, Akram; Sadeghi-Demneh, Ebrahim; Fereshtenajad, Niloufar; Hillier, Susan

2017-09-01

Somatosensory impairments are common in multiple sclerosis. However, little data are available to characterize the nature and frequency of these problems in people with multiple sclerosis. To investigate the frequency of somatosensory impairments and identify any association with balance limitations in people with multiple sclerosis. The design was a prospective cross-sectional study, involving 82 people with multiple sclerosis and 30 healthy controls. Tactile and proprioceptive sensory acuity were measured using the Rivermead Assessment of Somatosensory Performance. Vibration duration was assessed using a tuning fork. Duration for the Timed Up and Go Test and reaching distance of the Functional Reach Test were measured to assess balance limitations. The normative range of sensory modalities was defined using cut-off points in the healthy participants. The multivariate linear regression was used to identify the significant predictors of balance in people with multiple sclerosis. Proprioceptive impairments (66.7%) were more common than tactile (60.8%) and vibration impairments (44.9%). Somatosensory impairments were more frequent in the lower limb (78.2%) than the upper limb (64.1%). All sensory modalities were significantly associated with the Timed Up and Go and Functional Reach tests (p<0.05). The Timed Up and Go test was independently predicted by the severity of the neurological lesion, Body Mass Index, ataxia, and tactile sensation (R2=0.58), whereas the Functional Reach test was predicted by the severity of the neurological lesion, lower limb strength, and vibration sense (R2=0.49). Somatosensory impairments are very common in people with multiple sclerosis. These impairments are independent predictors of balance limitation. Copyright © 2017 Elsevier B.V. All rights reserved.

Temporal resolution in individuals with neurological disorders

PubMed Central

Rabelo, Camila Maia; Weihing, Jeffrey A; Schochat, Eliane

2015-01-01

OBJECTIVE: Temporal processing refers to the ability of the central auditory nervous system to encode and detect subtle changes in acoustic signals. This study aims to investigate the temporal resolution ability of individuals with mesial temporal sclerosis and to determine the sensitivity and specificity of the gaps-in-noise test in identifying this type of lesion. METHOD: This prospective study investigated differences in temporal resolution between 30 individuals with normal hearing and without neurological lesions (G1) and 16 individuals with both normal hearing and mesial temporal sclerosis (G2). Test performances were compared, and the sensitivity and specificity were calculated. RESULTS: There was no difference in gap detection thresholds between the two groups, although G1 revealed better average thresholds than G2 did. The sensitivity and specificity of the gaps-in-noise test for neurological lesions were 68% and 98%, respectively. CONCLUSIONS: Temporal resolution ability is compromised in individuals with neurological lesions caused by mesial temporal sclerosis. The gaps-in-noise test was shown to be a sensitive and specific measure of central auditory dysfunction in these patients. PMID:26375561

The significance of HLA DRB1*1501 and oligoclonal bands in multiple sclerosis: clinical features and disability.

PubMed

Balnytė, Renata; Rastenytė, Daiva; Ulozienė, Ingrida; Mickevičienė, Dalia; Skordenienė, Erika; Vitkauskienė, Astra

2011-01-01

The aim of the present study was to determine the value of immunogenetic risk factors and to estimate their relationship with the clinical features and disability status of patients with multiple sclerosis in a Lithuanian population. This was a prospective study of 80 patients with multiple sclerosis. The diagnosis of multiple sclerosis was based on the revised McDonald criteria. Oligoclonal bands (OCBs) of immunoglobulin G (IgG) were tested using isoelectric focusing and IgG specific immunofixation. HLA DRB1 alleles were genotyped using polymerase chain reaction. Of all patients, 55% were positive for OCBs and 56% for HLA DRB1*1501. OCB-positive patients with multiple sclerosis had higher EDSS scores than their OCB-negative counterparts at onset of the disease (3.93±1.21 and 3.36±0.96 points, respectively; P=0.02) and during the last visit (4.31±2.06 and 3.09±1.98 points, respectively; P=0.009). The mean relapse rate was higher in the OCB-positive group compared with OCB-negative group (1.45±0.69 and 0.58±0.64, respectively; P=0.001). OCB-positive patients had higher IgG index compared with OCB-negative patients (P=0.0001). No relationship was found between HLA DRB1*1501 antigen status and the clinical features or EDSS score, and presence or absence of OCB in the present subset of patients with multiple sclerosis. The presence of oligoclonal bands in the cerebrospinal fluid of the patients with multiple sclerosis was associated with the greater number of exacerbations, higher degree of disability, and higher IgG index. There were no significant associations between the presence of HLA DRB1*1501 allele and the clinical symptoms, course of disease, or disability score.

Stem cells for the treatment of neurodegenerative diseases

PubMed Central

2010-01-01

Stem cells offer an enormous pool of resources for the understanding of the human body. One proposed use of stem cells has been as an autologous therapy. The use of stem cells for neurodegenerative diseases has become of interest. Clinical applications of stem cells for Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis will increase in the coming years, and although great care will need to be taken when moving forward with prospective treatments, the application of stem cells is highly promising. PMID:21144012

Value of 18fluorodeoxyglucose-positron-emission tomography in amyotrophic lateral sclerosis: a prospective study.

PubMed

Van Laere, Koen; Vanhee, Annelies; Verschueren, Jolien; De Coster, Liesbeth; Driesen, An; Dupont, Patrick; Robberecht, Wim; Van Damme, Philip

2014-05-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting the motor system, with extramotor involvement to a variable extent. Biomarkers for early differential diagnosis and prognosis are needed. An autosomal dominant hexanucleotide (GGGGCC) expansion in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent genetic cause of ALS, but its metabolic pattern has not been studied systematically. To evaluate the use of 18fluorodeoxyglucose-positron-emission tomography as a marker of ALS pathology and investigate whether a specific metabolic signature is present in patients with C9orf72 mutations. In total, 81 patients with a suspected diagnosis of ALS at University Hospital Leuven were prospectively investigated. All underwent detailed neurological examination and electrodiagnostic and genetic testing for the major known genetic causes of ALS (C9orf72, SOD1, TARDBP, and FUS). A diagnosis of ALS was made in 70 of 81 patients. Of these, 11 were C9orf72 positive and 59 were C9orf72 negative. In 7 patients, the diagnosis of primary lateral sclerosis was made; 4 patients had progressive muscular atrophy. A screened healthy control population was used for comparison. Positron-emission tomographic data were spatially normalized and analyzed using a predefined volume of interest and a voxel-based analysis (SPM8). Discriminant analysis was done both volume of interest based and voxel based using a support vector machine approach. Compared with control participants, 18fluorodeoxyglucose-positron-emission tomography showed perirolandic and variable prefrontal hypometabolism in most patients. Patients with primary lateral sclerosis showed a similar pattern. Patients with C9orf72-positive ALS had discrete relative hypometabolism in the thalamus and posterior cingulate compared with those with C9orf72-negative ALS. A posteriori-corrected discriminant analysis was able to correctly classify 95% of ALS cases and 71% of primary lateral sclerosis cases. Prefrontal hypometabolism was associated with reduced clinical functioning (ALS Functional Rating Scale). Extensive hypometabolism in the prefrontal or anterior temporal areas was present in 10% of patients and associated with significantly shorter survival as an independent factor (n = 63, P < .001). Patients who were C9orf72 positive did not differ in survival compared with those who were C9orf72 negative. 18Fluorodeoxyglucose-positron-emission tomography is a useful early diagnostic and prognostic marker for ALS. Amyotrophic lateral sclerosis that is positive for C9orf72 is characterized by only mild cerebral metabolic differences that show no prognostic difference.

Neuropsychological, balance, and mobility risk factors for falls in people with multiple sclerosis: a prospective cohort study.

PubMed

Hoang, Phu D; Cameron, Michelle H; Gandevia, Simon C; Lord, Stephen R

2014-03-01

To determine whether impaired performance in a range of vision, proprioception, neuropsychological, balance, and mobility tests and pain and fatigue are associated with falls in people with multiple sclerosis (PwMS). Prospective cohort study with 6-month follow-up. A multiple sclerosis (MS) physiotherapy clinic. Community-dwelling people (N=210; age range, 21-74y) with MS (Disease Steps 0-5). Not applicable. Incidence of falls during 6 months' follow-up. In the 6-month follow-up period, 83 participants (39.7%) experienced no falls, 57 (27.3%) fell once or twice, and 69 (33.0%) fell 3 or more times. Frequent falling (≥3) was associated with increased postural sway (eyes open and closed), poor leaning balance (as assessed with the coordinated stability task), slow choice stepping reaction time, reduced walking speed, reduced executive functioning (as assessed with the difference between Trail Making Test Part B and Trail Making Test Part A), reduced fine motor control (performance on the 9-Hole Peg Test [9-HPT]), and reported leg pain. Increased sway with the eyes closed, poor coordinated stability, and reduced performance in the 9-HPT were identified as variables that significantly and independently discriminated between frequent fallers and nonfrequent fallers (model χ(2)3=30.1, P<.001). The area under the receiver operating characteristic curve for this model was .712 (95% confidence interval, .638-.785). The study reveals important balance, coordination, and cognitive determinants of falls in PwMS. These should assist the development of effective strategies for prevention of falls in this high-risk group. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Different clinical response to interferon beta and glatiramer acetate related to the presence of oligoclonal IgM bands in CSF in multiple sclerosis patients.

PubMed

Casanova, Bonaventura; Lacruz, Laura; Villar, María Luisa; Domínguez, José Andrés; Gadea, María Carcelén; Gascón, Francisco; Mallada, Javier; Hervás, David; Simó-Castelló, María; Álvarez-Cermeño, José Carlos; Calles, Carmen; Olascoaga, Javier; Ramió-Torrentà, Lluís; Alcalá, Carmen; Cervelló, Angeles; Boscá, Isabel; Pérez-Mirallles, Francisco Carlos; Coret, Francisco

2018-06-07

To study the efficacy of interferon beta (IFNβ) and glatiramer acetate (GA) related to the presence of oligoclonal M bands (OCMB) in the cerebrospinal fluid in relapsing-remitting multiple sclerosis (RRMS). This is an observational, multicenter and retrospective study with prospectively collected data of patients that started treatment with IFNβ or GA. Treatment decision was made blinded to the OCMB status. Time to first attack after starting therapy was compared by using Kaplan-Meier curves, and adjustment by Cox regression analysis was performed. Two hundred and fifty-six patients entered in the study (141-55% received IFNβ; 115-45% received GA). After a mean follow-up of 41 and 65 months, 54.7% of patients remained free from further attacks (RF). The proportion of RF patients was higher in the GA group than in the IFNβ group (72.2 vs. 40.4%, p < 0.001). The IFNβ patients with OCMB+ presented the poorest response, 31.3% RF vs. 48.1% in IFNβ without OCMB, p = 0.03. OCMB in CSF could be a biomarker of treatment response in multiple sclerosis.

Absence of airway secretion accumulation predicts tolerance of noninvasive ventilation in subjects with amyotrophic lateral sclerosis.

PubMed

Vandenberghe, Nadia; Vallet, Anne-Evelyne; Petitjean, Thierry; Le Cam, Pierre; Peysson, Stéphane; Guérin, Claude; Dailler, Frédéric; Jay, Sylvie; Cadiergue, Vincent; Bouhour, Françoise; Court-Fortune, Isabelle; Camdessanche, Jean-Philippe; Antoine, Jean-Christophe; Philit, François; Beuret, Pascal; Bin-Dorel, Sylvie; Vial, Christophe; Broussolle, Emmanuel

2013-09-01

To assess factors that predict good tolerance of noninvasive ventilation (NIV), in order to improve survival and quality of life in subjects with amyotrophic lateral sclerosis. We conducted a prospective study in subjects with amyotrophic lateral sclerosis and requiring NIV. The primary end point was NIV tolerance at 1 month. Subjects, several of whom failed to complete the study, were classified as "tolerant" or "poorly tolerant," according to the number of hours of NIV use (more or less than 4 h per night, respectively). Eighty-one subjects, 73 of whom also attended the 1-month follow-up visit, participated over 34 months. NIV tolerance after the first day of utilization predicted tolerance at 1 month (77.6% and 75.3% of subjects, respectively). Multivariate analysis disclosed 3 factors predicting good NIV tolerance: absence of airway secretions accumulation prior to NIV onset (odds ratio 11.5); normal bulbar function at initiation of NIV (odds ratio 8.5); and older age (weakly significant, odds ratio 1.1). Our study reveals 3 factors that are predictive of good NIV tolerance, in particular the absence of airway secretion accumulation, which should prompt NIV initiation before its appearance.

Do patient and proxy agree? Long-term changes in multiple sclerosis physical impact and walking ability on patient-reported outcome scales.

PubMed

Sonder, Judith M; Balk, Lisanne J; Bosma, Libertje V A E; Polman, Chris H; Uitdehaag, Bernard M J

2014-10-01

Patient-reported outcome scales (PROs) are useful in monitoring changes in multiple sclerosis (MS) over time. Although these scales are reliable and valid measures in longitudinal studies in MS patients, it is unknown what the impact is when obtaining longitudinal data from proxies. The objective of this paper is to compare longitudinal changes in patient and proxy responses on PROs assessing physical impact of MS and walking ability. In a prospective observational study, data on the Multiple Sclerosis Impact Scale (MSIS-29 physical) and Multiple Sclerosis Walking Scale (MSWS-12) were obtained from 137 patient-proxy couples at baseline and at two-year follow-up. Demographic and disease-related variables explaining agreement or disagreement between patients and proxies were investigated using linear regression analyses. Full agreement was found in 56% (MSIS) and 62% (MSWS) of the patient-proxy couples. Complete disagreement was very rare for both scales (2% MSIS, 5% MSWS). When patients were more positive than proxies, a higher age, longer disease duration, longer patient-proxy relationship and increased levels of depression, anxiety and caregiver burden in proxies were observed. In the majority of the patient-proxy couples there was agreement. Proxies can serve as a valuable source of information, but caution remains essential when using scores from proxies. © The Author(s), 2014.

Cross-cultural adaptation and validation of als Functional Rating Scale-Revised in Portuguese language.

PubMed

Guedes, Keyte; Pereira, Cecília; Pavan, Karina; Valério, Berenice Cataldo Oliveira

2010-02-01

The aim of this study is the cross-cultural, as well as to validate in Portuguese language the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). We performed a prospective study of individuals with amyotrophic lateral sclerosis (ALS) clinically defined. The scale, after obtaining the final version in Portuguese, was administered in 22 individuals and three weeks after re-applied. There were no significant differences between the application and reapplication of the scale (p=0.069). The linear regression and internal consistency measured by Pearson correlation and alpha Conbrach were significant with r=0.975 e alpha=0.934. The reliability test-retest demonstrated by intraclass correlation coefficient was strong with ICC=0.975. Therefore, this version proved to be applicable, reliable and easy to be conducted in clinical practice and research.

Walking Distance as a Predictor of Falls in People With Multiple Sclerosis.

PubMed

Nilsagård, Ylva; Westerdahl, Elisabeth; Wittrin, Anna; Gunnarsson, Martin

2016-06-01

People with multiple sclerosis (PwMS) experience falls, usually when walking and transferring. The aim was to investigate if walking distance and patient overestimate of walking distance are predictors of falls in PwMS. A prospective study was conducted, with a single test occasion followed by prospective registration of falls for 3 months. All PwMS in Region Örebro County with a previously registered Expanded Disability Status Scale score between 3.0 and 7.0 in the Swedish MS Registry were invited to participate (n = 149). Altogether, data from 49 PwMS being relapse free for at least 3 months and with a confirmed Expanded Disability Status Scale between 1.5 and 7.0 upon study entry were analysed. Twenty-two PwMS (45%) fell during the study period, providing information of 66 falls. Walking distance or overestimate of one's walking distance, as compared with test results, did not predict falls in this MS sample. Walking and standing activities are associated with numerous falls in PwMS. Our data do not clearly support routine measurements of walking distance in assessing individual fall risk. © 2015 The Authors. Physiotherapy Research International published by John Wiley & Sons, Ltd. © 2015 The Authors. Physiotherapy Research International published by John Wiley & Sons, Ltd.

Lexical access changes in patients with multiple sclerosis: a two-year follow-up study.

PubMed

Sepulcre, Jorge; Peraita, Herminia; Goni, Joaquin; Arrondo, Gonzalo; Martincorena, Inigo; Duque, Beatriz; Velez de Mendizabal, Nieves; Masdeu, Joseph C; Villoslada, Pablo

2011-02-01

The aim of the study was to analyze lexical access strategies in patients with multiple sclerosis (MS) and their changes over time. We studied lexical access strategies during semantic and phonemic verbal fluency tests and also confrontation naming in a 2-year prospective cohort of 45 MS patients and 20 healthy controls. At baseline, switching lexical access strategy (both in semantic and in phonemic verbal fluency tests) and confrontation naming were significantly impaired in MS patients compared with controls. After 2 years follow-up, switching score decreased, and cluster size increased over time in semantic verbal fluency tasks, suggesting a failure in the retrieval of lexical information rather than an impairment of the lexical pool. In conclusion, these findings underline the significant presence of lexical access problems in patients with MS and could point out their key role in the alterations of high-level communications abilities in MS.

Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study.

PubMed

Martínez-Payá, Jacinto J; Ríos-Díaz, José; Medina-Mirapeix, Francesc; Vázquez-Costa, Juan F; Del Baño-Aledo, María Elena

2018-01-01

The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Structural correlates of subjective and objective memory performance in multiple sclerosis.

PubMed

Pardini, Matteo; Bergamino, Maurizio; Bommarito, Giulia; Bonzano, Laura; Luigi Mancardi, Gian; Roccatagliata, Luca

2014-04-01

Subjective and objective memory deficits represent a frequent and ill-understood aspect of multiple sclerosis (MS), and a significant cause of disability and quality of life reduction. The aim of the study is to verify the role of hippocampal and temporal associative fibers' damage in MS-related memory complaints. To reach this aim, 25 patients with low disability relapsing-remitting MS and 19 healthy controls were included in the study. All subjects underwent 3D T1 structural imaging and Diffusion Tensor Imaging. Additionally, MS patients underwent neuropsychological evaluation of objective (Selective Reminding Test and Spatial Recall Test) and of subjective (Perceived Deficit Questionnaire, Retrospective and Prospective Memory Subscales) memory deficits. Normalized hippocampal volume (NHV) and mean Fractional Anisotropy (FA) for the uncinate fasciculus (UF) and for the ventral division of the cingulum bundle (VCB) were calculated for all subjects. We showed that, compared to controls, MS subjects presented with reduced right NHV and with reduced mean FA bilaterally in the UF and the VCB. In the MS group, verbal memory scores correlated with left NHV, spatial memory scores correlated with right NHV, while perceived retrospective and prospective memory deficits correlated with left VCB and left UF mean FA respectively. Our data confirm an early involvement of memory-related brain structures in MS patients. Our data suggest that verbal and nonverbal memory as well as perceived retrospective and prospective memory deficits are related to alterations of discrete anatomical structures in the low-disability phase of MS. Copyright © 2013 Wiley Periodicals, Inc.

Diagnosis of multiple sclerosis through the lens of ultra-high-field MRI

NASA Astrophysics Data System (ADS)

Sati, Pascal

2018-06-01

The long-standing relationship between ultra-high-field (7 T) MRI and multiple sclerosis (MS) has brought new insights to our understanding of lesion evolution and its associated pathology. With the recent FDA approval of a commercially available scanner, 7 T MRI is finally entering the clinic with great expectations about its potential added value. By looking through the prism of MS diagnosis, this perspective article discusses current limitations and prospects of 7 T MRI techniques relevant to helping clinicians diagnose patients encountered in daily practice.

Internal jugular and vertebral vein volume flow in patients with clinically isolated syndrome or mild multiple sclerosis and healthy controls: results from a prospective sonographer-blinded study.

PubMed

Chambers, Brian; Chambers, Jayne; Churilov, Leonid; Cameron, Heather; Macdonell, Richard

2014-09-01

We evaluated internal jugular vein and vertebral vein volume flow using ultrasound, in patients with clinically isolated syndrome or mild multiple sclerosis and controls, to determine whether volume flow was different between the two groups. In patients and controls, internal jugular vein volume flow increased from superior to inferior segments, consistent with recruitment from collateral veins. Internal jugular vein and vertebral vein volume flow were greater on the right in supine and sitting positions. Internal jugular vein volume flow was higher in the supine posture. Vertebral vein volume flow was higher in the sitting posture. Regression analyses of cube root transformed volume flow data, adjusted for supine/sitting, right/left and internal jugular vein/vertebral vein, revealed no significant difference in volume flow in patients compared to controls. Our findings further refute the concept of venous obstruction as a causal factor in the pathogenesis of multiple sclerosis. Control volume flow data may provide useful normative reference values. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Impaired ambulation and steroid therapy impact negatively on bone health in multiple sclerosis.

PubMed

Tyblova, M; Kalincik, T; Zikan, V; Havrdova, E

2015-04-01

The prevalence of osteopenia and osteoporosis is higher amongst patients with multiple sclerosis in comparison with the general population. In addition to the general determinants of bone health, two factors may contribute to reduced bone mineral density in multiple sclerosis: physical disability and corticosteroid therapy. The aim of this study was to examine the effect of physical disability and steroid exposure on bone health in weight-bearing bones and spine and on the incidence of low-trauma fractures in multiple sclerosis. In this retrospective analysis of prospectively collected data, associations between bone mineral density (at the femoral neck, total femur and the lumbar spine) and its change with disability or cumulative steroid dose were evaluated with random-effect models adjusted for demographic and clinical determinants of bone health. The incidence of low-trauma fractures during the study follow-up was evaluated with Andersen-Gill models. Overall, 474 and 438 patients were included in cross-sectional and longitudinal analyses (follow-up 2347 patient-years), respectively. The effect of severely impaired gait was more apparent in weight-bearing bones (P ≤ 10(-15) ) than in spine (P = 0.007). The effect of cumulative steroid dose was relatively less pronounced but diffuse (P ≤ 10(-4) ). Risk of low-trauma fractures was associated with disability (P = 0.02) but not with cumulative steroid exposure and was greater amongst patients with severely impaired gait (annual risk 3.5% vs. 3.0%). Synergistic effects were found only between cumulative steroid dose in patients ambulatory without support (P = 0.02). Bone health and the incidence of low-trauma fractures in multiple sclerosis are more related to impaired gait than to extended corticosteroid therapy. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

[Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

PubMed

Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

Euthanasia and physician-assisted suicide in amyotrophic lateral sclerosis: a prospective study.

PubMed

Maessen, Maud; Veldink, Jan H; Onwuteaka-Philipsen, Bregje D; Hendricks, Henk T; Schelhaas, Helenius J; Grupstra, Hepke F; van der Wal, Gerrit; van den Berg, Leonard H

2014-10-01

The objective of this study is to determine if quality of care, symptoms of depression, disease characteristics and quality of life of patients with amyotrophic lateral sclerosis (ALS) are related to requesting euthanasia or physician-assisted suicide (EAS) and dying due to EAS. Therefore, 102 ALS patients filled out structured questionnaires every 3 months until death and the results were correlated with EAS. Thirty-one percent of the patients requested EAS, 69% of whom eventually died as a result of EAS (22% of all patients). Ten percent died during continuous deep sedation; only one of them had explicitly requested death to be hastened. Of the patients who requested EAS, 86% considered the health care to be good or excellent, 16% felt depressed, 45% experienced loss of dignity and 42% feared choking. These percentages do not differ from the number of patients who did not explicitly request EAS. The frequency of consultations of professional caregivers and availability of appliances was similar in both groups. Our findings do not support continuous deep sedation being used as a substitute for EAS. In this prospective study, no evidence was found for a relation between EAS and the quality and quantity of care received, quality of life and symptoms of depression in patients with ALS. Our study does not support the notion that unmet palliative care needs are related to EAS.

Pregnancy outcomes in Lebanese women with multiple sclerosis (the LeMS study): a prospective multicentre study

PubMed Central

Fares, Jawad; Nassar, Anwar H; Gebeily, Souheil; Kobeissy, Firas; Fares, Youssef

2016-01-01

Objective The Lebanese Multiple Sclerosis (LeMS) study aims to assess the influence of pregnancy and delivery on the clinical course of multiple sclerosis (MS) in Lebanese women. Setting This prospective multicentre study took place in three MS referral university medical centres in Lebanon. Participants Included were 29 women over 18 years who had been diagnosed with MS according to the McDonald criteria, and became pregnant between 1995 and 2015. Participating women should have stopped treatment 3 months before conception and become pregnant after the onset of MS. Women were followed up from 1 year preconceptionally and for 4 years postpartum. Main outcome measures The annualised relapse rates per participant during each 3-month period during pregnancy and each year postpartum were compared with the relapse rate during the year before pregnancy using the paired two-tailed t test. p Values <0.05 were considered statistically significant for all analyses (95% CI). Results 64 full-term pregnancies were recorded. All pregnancies (100%) resulted in live births, with no complications or other diseases. In comparison with the prepregnancy year, in which the mean relapse rate±SE was 0.17±0.07, there was a significant reduction in the relapse rate during pregnancy and in the first year postpartum (p=0.02), but an increase in the rate in the second year postpartum (0.21±0.08). Thereafter, from the third year postpartum through the following fourth year, the annualised relapse rate fell slightly but did not differ from the annualised relapse rate recorded in the prepregnancy year (0.17±0.07). Conclusions Pregnancy in Lebanese women with MS does not seem to increase the risk of complications. No relapses were observed during pregnancy and in the first year postpartum; however, relapses rebounded in the second year postpartum, and over the long term, returned to the levels that preceded pregnancy. PMID:27178979

Physical activity correlates with neurological impairment and disability in multiple sclerosis.

PubMed

Motl, Robert W; Snook, Erin M; Wynn, Daniel R; Vollmer, Timothy

2008-06-01

This study examined the correlation of physical activity with neurological impairment and disability in persons with multiple sclerosis (MS). Eighty individuals with MS wore an accelerometer for 7 days and completed the Symptom Inventory (SI), Performance Scales (PS), and Expanded Disability Status Scale. There were large negative correlations between the accelerometer and SI (r = -0.56; rho = -0.58) and Expanded Disability Status Scale (r = -0.60; rho = -0.69) and a moderate negative correlation between the accelerometer and PS (r = -0.39; rho = -0.48) indicating that physical activity was associated with reduced neurological impairment and disability. Such findings provide a preliminary basis for using an accelerometer and the SI and PS as outcome measures in large-scale prospective and experimental examinations of the effect of physical activity behavior on disability and dependence in MS.

[Sacral neuromodulation as second-line treatment strategy for lower urinary tract symptoms of various aetiologies: experience of a German high-volume clinic].

PubMed

Otto, W; Nowrotek, A; Burger, M; Wieland, W F; Rößler, W; Denzinger, S

2012-05-01

Lower urinary tract symptoms (LUTS) are a common and multiform micturition disorder of various possible origins. Several second-line techniques are available in the event of first-line medicinal treatment failure. These include the intravesical injection of Botulinum toxin, bladder augmentation and sacral neuromodulation (SNM). This study presents current data and results from a prospective study of patients with LUTS of various aetiologies. Clinical success was investigated for all patients who underwent SNM for LUTS with or without urge incontinence caused by chronic pelvic pain syndrome, multiple sclerosis and idiopathic disease between May 2007 and December 2010. The preoperatively determined symptoms were compared with current follow-up data. Median follow-up time was 11 months (1 - 43). A total of 47 patients were indicated for SNM over the investigated period. 80.9 % were female, median patient age was 67 years (19 - 84). The testing phase was successful in 38 cases (80.9 %) with 9 electrodes being explanted (19.1 %). In the case of idiopathic LUTS we could show a statistically significant increase of micturition volume and reduction of incontinence pad use. There was no statistically significant improvement of any micturition parameter for patients with multiple sclerosis, patients with chronic pelvic pain syndrome showed a statistically significant reduction of micturition frequency and a subjective improvement of symptoms in 75 %. In the selected patient groups SNM is a promising and, in experienced hands, a low-complication second-line therapy for the treatment of LUTS of idiopathic aetiology. However, the general recommendation of SNM for multiple sclerosis and chronic pelvic pain syndrome patients cannot be given on the basis of our results. Further prospective, randomised multicentre studies are need to further refine the indications for SNM in LUTS of neurogenic and non-neurogenic origins. © Georg Thieme Verlag KG Stuttgart · New York.

High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial.

PubMed

Beck, Roy W; Trobe, Jonathan D; Moke, Pamela S; Gal, Robin L; Xing, Dongyuan; Bhatti, M Tariq; Brodsky, Michael C; Buckley, Edward G; Chrousos, Georgia A; Corbett, James; Eggenberger, Eric; Goodwin, James A; Katz, Barrett; Kaufman, David I; Keltner, John L; Kupersmith, Mark J; Miller, Neil R; Nazarian, Sarkis; Orengo-Nania, Silvia; Savino, Peter J; Shults, William T; Smith, Craig H; Wall, Michael

2003-07-01

To identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis. Three hundred eighty-eight patients who experienced acute optic neuritis between July 1, 1988, and June 30, 1991, were followed up prospectively for the development of multiple sclerosis. Consenting patients were reassessed after 10 to 13 years. The 10-year risk of multiple sclerosis was 38% (95% confidence interval, 33%-43%). Patients (160) who had 1 or more typical lesions on the baseline magnetic resonance imaging (MRI) scan of the brain had a 56% risk; those with no lesions (191) had a 22% risk (P<.001, log rank test). Among the patients who had no lesions on MRI, male gender and optic disc swelling were associated with a lower risk of multiple sclerosis, as was the presence of the following atypical features for optic neuritis: no light perception vision; absence of pain; and ophthalmoscopic findings of severe optic disc edema, peripapillary hemorrhages, or retinal exudates. The 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion; higher numbers of lesions do not appreciably increase that risk. However, even when brain lesions are seen on MRI, more than 40% of the patients will not develop clinical multiple sclerosis after 10 years. In the absence of MRI lesions, certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis. This natural history information is a critical input for estimating a patient's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system.

A multicenter, prospective, quasi-experimental evaluation study of a patient education program to foster multiple sclerosis self-management competencies.

PubMed

Feicke, Janine; Spörhase, Ulrike; Köhler, Jürgen; Busch, Claudia; Wirtz, Markus

2014-12-01

To determine the impact of the self-management training program "S.MS" for new multiple sclerosis (MS) patients. Multicenter, prospective, quasi-experimental study with 31 MS patients in the intervention group (training program) and 33 participants in the control group (CG) (brochures). Data were collected before, after and 6 months after the interventions. Analysis of change was done by ANCOVA with repeated measurements. At baseline, participants in CG were younger at the time of diagnosis, suffered more frequently from relapsing-remitting MS and took more MS-medication on a permanent basis. The intervention had a stable significant effect on each dimension of self-management ability, on total self-management ability (ES=0.194, p<0.001), on anxiety (ES=0.193, p=0.001), and on disease-specific quality of life (ES=0.120, p=0.007). Regarding depression, a significant interaction effect of time and intervention could be observed (ES=0.106, p=0.011). No effect was found on disease-specific knowledge. High participant acceptance was reported. "S.MS" participation was associated with a significant and sustained improvement of self-management abilities, anxiety and disease-specific quality of life in a quasi-experimental study design. Using RCT or CRT-designs would be desirable to further improve the evidence of treatment effectiveness. This study provides substantial evidence that "S.MS" fosters patients' self-management ability. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Noninvasive ventilation improves sleep in amyotrophic lateral sclerosis: a prospective polysomnographic study.

PubMed

Vrijsen, Bart; Buyse, Bertien; Belge, Catharina; Robberecht, Wim; Van Damme, Philip; Decramer, Marc; Testelmans, Dries

2015-04-15

To evaluate the effects of noninvasive ventilation (NIV) on sleep in patients with amyotrophic lateral sclerosis (ALS) after meticulous titration with polysomnography (PSG). In this prospective observational study, 24 ALS patients were admitted to the sleep laboratory during 4 nights for in-hospital NIV titration with PSG and nocturnal capnography. Questionnaires were used to assess subjective sleep quality and quality of life (QoL). Patients were readmitted after one month. In the total group, slow wave sleep and REM sleep increased and the arousal-awakening index improved. The group without bulbar involvement (non-bulbar) showed the same improvements, together with an increase in sleep efficiency. Nocturnal oxygen and carbon dioxide levels improved in the total and non-bulbar group. Except for oxygen saturation during REM sleep, no improvement in respiratory function or sleep structure was found in bulbar patients. However, these patients showed less room for improvement. Patient-reported outcomes showed improvement in sleep quality and QoL for the total and non-bulbar group, while bulbar patients only reported improvements in very few subscores. This study shows an improvement of sleep architecture, carbon dioxide, and nocturnal oxygen saturation at the end of NIV titration and after one month of NIV in ALS patients. More studies are needed to identify the appropriate time to start NIV in bulbar patients. Our results suggest that accurate titration of NIV by PSG improves sleep quality. A commentary on this article appears in this issue on page 511. © 2015 American Academy of Sleep Medicine.

Social consequences of multiple sclerosis: clinical and demographic predictors - a historical prospective cohort study.

PubMed

Pfleger, C C H; Flachs, E M; Koch-Henriksen, N

2010-11-01

Time to disability pension is one of the endpoints to be used to determine the prognosis of multiple sclerosis (MS) in prospective studies.   To assess the time to cessation of work and receiving disability pension in MS, and how it may depend on gender, type of work and age and symptom at onset. A total of 2240 Danes with onset of definite/probable MS 1980-1989, identified from the Danish MS-Registry, were included. Information on social endpoints was retrieved from Statistics Denmark. Cox regression analyses were used with onset as starting point. Afferent onset symptoms [hazard ratio (HR 0.57)] and non-physical type of work (HR 0.70) were favourable prognostic factors compared with high age at onset, physical work and efferent symptoms at onset. The mean time to disability pension was 13 years for patients with afferent/brainstem onset symptom but 8.7 years for those with efferent onset symptoms (P < 0.0001). The effect of onset symptom was reduced and the effect of sex became significant when all covariates and age at onset were included in multivariate Cox regression. Onset age, type of onset symptom and work are robust predictors of disability pension in MS. Disability pension proves to be a reliable milestone in estimation of the prognosis of MS. © 2010 The Author(s). Journal compilation © 2010 EFNS.

Age at onset in patients with medically refractory temporal lobe epilepsy and mesial temporal sclerosis: impact on clinical manifestations and postsurgical outcome.

PubMed

Asadi-Pooya, Ali A; Sperling, Michael R

2015-08-01

To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE. In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure below 10 years) and those with adult-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure 20 years or above). One hundred and twelve patients had childhood-onset MTS-TLE and 76 had adult-onset MTS-TLE. Demographic, clinical, EEG and MRI characteristics of these two groups were similar. Postoperative outcome was not statistically different between these two groups of patients (P=0.9). Temporal lobe epilepsy due to mesial temporal sclerosis is a common cause of epilepsy that can start from early childhood to late adulthood. The etiology of MTS-TLE may be different in various age groups, but it seems that when mesial temporal sclerosis is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with childhood-onset MTS-TLE compared to those with adult-onset disease. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The MS@Work study: a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis.

PubMed

van der Hiele, Karin; van Gorp, Dennis A M; Heerings, Marco A P; van Lieshout, Irma; Jongen, Peter J; Reneman, Michiel F; van der Klink, Jac J L; Vosman, Frans; Middelkoop, Huub A M; Visser, Leo H

2015-08-12

Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading up to unemployment, many may experience a reduction in hours or work responsibilities and increased time missed from work. The MS@Work study examines various factors that may influence work participation in relapsing-remitting MS patients, including disease-related factors, the working environment and personal factors. The MS@Work study is a multicenter, 3-year prospective observational study on work participation in patients with relapsing-remitting MS. We aim to include 350 patients through 15-18 MS outpatient clinics in the Netherlands. Eligible participants are 18 years and older, and either currently employed or within three years since their last employment. At baseline and after 1, 2 and 3 years, the participants are asked to complete online questionnaires (including questions on work participation, work problems and accommodations, cognitive and physical ability, anxiety, depression, psychosocial stress, quality of life, fatigue, empathy, personality traits and coping strategies) and undergo cognitive and neurological examinations. After six months, patients are requested to only complete online questionnaires. Patient perspectives on maintaining and improving work participation and reasons to stop working are gathered through semi-structured interviews in a sub-group of patients. Prospective studies with long-term follow-up on work participation in MS are rare, or take into account a limited number of factors. The MS@Work study provides a 3-year follow-up on various factors that may influence work participation in patients with relapsing-remitting MS. We aim to identify factors that relate to job loss and to provide information about preventative measures for physicians, psychologists and other professionals working in the field of occupational health.

Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools

PubMed Central

Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

2015-01-01

Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. PMID:26295258

Clinical characteristics of patients with multiple sclerosis enrolled in a new registry in Egypt.

PubMed

Zakaria, Magd; Zamzam, Dina A; Abdel Hafeez, Mohamed A; Swelam, Mahmoud S; Khater, Shaimaa S; Fahmy, Mai F; Abdel Hady, Ayman; Fouad, Mohamed M; Abdel Nasser, Azza; Aref, Hany; Gadallah, Mohsen

2016-11-01

Epidemiological studies of multiple sclerosis (MS) are lacking in Egypt. To study the characteristics of Egyptian patients with multiple sclerosis in a new registry in a major tertiary referral centre in Cairo, Egypt. Patients were from the project MS database of the Multiple Sclerosis Unit at Ain Shams University Hospitals (N=950). We conducted a detailed medical history and examination including the Expanded Disability Status Scale (EDSS). Females represented 72% of subjects (female: male ratio 2.57:1). The mean age of disease onset was 26.1±7.6 years. Relapsing-remitting MS (RRMS) was the most common presentation (74.6%). Visual or sensory symptoms were the most common at presentation with RRMS, while motor symptoms were the most common presentation in other types of MS. Time to diagnosis was delayed up to 2 years in 27.8% of patients. The mean EDSS score was 3.6±2.1; 55% had EDSS≤3. About half (49%) received a disease-modifying drug. Progressive MS and motor presentation were associated with higher disability. This is the first documented MS registry from Egypt. The clinical characteristics of MS in Egypt was similar to other Arab countries and western countries. MS is more common among females in Egypt, with RRMS being the most common presentation. Visual symptoms and motor symptoms were the most common presentations in RRMS and progressive MS, respectively. Our findings also highlight the value of establishing registries in Egypt in order to be able to study, prospectively, the clinical course of the disease, the response to various DMD's and the epidemiology of MS in Egypt. Copyright © 2016 Elsevier B.V. All rights reserved.

Intrathecal oligoclonal IgG synthesis in multiple sclerosis.

PubMed

Petzold, Axel

2013-09-15

The diagnosis of multiple sclerosis is based on dissemination in time and space. Before 2010 lack of evidence for dissemination in space could be substituted by a paraclinical test, cerebrospinal fluid (CSF) oligoclonal bands (OCBs). The present meta-analysis (13,467 patients) shows that the diagnostic specificity of OCB drops from 94% to 61% if inflammatory etiologies are considered. Importantly, this was not caused by poor laboratory practice. This review on CSF OCB further illustrates the conceptional problem of substituting dissemination in space with a biomarker. The potential prognostic value of intrathecal OCB will need to be tested prospectively. © 2013 Elsevier B.V. All rights reserved.

Electrophysiological Evaluation of Dysphagia in the Mild or Moderate Patients with Multiple Sclerosis: A Concept of Subclinical Dysphagia.

PubMed

Beckmann, Yesim; Gürgör, Nevin; Çakır, Ahmet; Arıcı, Şehnaz; İncesu, Tülay Kurt; Seçil, Yaprak; Ertekin, Cumhur

2015-06-01

Swallowing mechanism and neurogenic dysphagia in MS have been rarely studied by electromyographical (EMG) methods. This study aims to evaluate the presence of subclinical dysphagia in patients with mild multiple sclerosis (MS) using electrophysiological methods. A prospective study of 51 patients with relapsing remitting multiple sclerosis and 18 age-matched healthy adults was investigated. We used electromyography to measure the activity of the submental muscles during swallowing. Electrophysiological recordings of patients were obtained during relapse, after relapse, and at any time in remission period. Clinical dysphagia was found in 12% of MS patients, while electrophysiological swallowing abnormalities were encountered in 33% of patients. Subclinical dysphagia was determined in 35% of patients during an MS relapse, in 20% of patients after a relapse, and in 25% of all 51 patients in the remission period based on EMG findings. Duration of swallowing signal of submental muscles in all MS patients was found to be longer than in normal subjects (p = 0.001). During swallowing of 50 ml of sequential water, the compensatory respiratory cycles occurred more often in MS patients than normal subjects, especially during a relapse (p = 0.005). This is the first study investigating swallowing abnormalities and subclinical dysphagia from the electrophysiological aspect in MS patients with mild disability. The electrophysiological tests described in this study are useful to uncover subclinical dysphagia since they have the advantage of being rapid, easy to apply, non-invasive, and without risk for the patients.

Role of executive functions in prospective memory in multiple sclerosis: Impact of the strength of cue-action association.

PubMed

Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

2016-01-01

Patients diagnosed with multiple sclerosis (MS) often report prospective memory (PM) deficits. Although PM is important for daily functioning, it is not formally assessed in clinical practice. The aim of this study was to examine the role of executive functions in MS patients' PM revealed by the effect of strength of cue-action association on PM performance. Thirty-nine MS patients were compared to 18 healthy controls matched for age, gender, and education on a PM task modulating the strength of association between the cue and the intended action. Deficits in MS patients affecting both prospective and retrospective components of PM were confirmed using 2 × 2 × 2 mixed analyses of variance (ANOVAs). Among patients, multiple regression analyses revealed that the impairment was modulated by the efficiency of executive functions, whereas retrospective memory seemed to have little impact on PM performance, contrary to expectation. More specifically, results of 2 × 2 × 2 mixed-model analyses of covariance (ANCOVAs) showed that low-executive patients had more difficulty detecting and, especially, retrieving the appropriate action when the cue and the action were unrelated, whereas high-executive patients' performance seemed to be virtually unaffected by the cue-action association. Using an objective measure, these findings confirm the presence of PM deficits in MS. They also suggest that such deficits depend on executive functioning and can be reduced when automatic PM processes are engaged through semantic cue-action association. They underscore the importance of assessing PM in clinical settings through a cognitive evaluation and offer an interesting avenue for rehabilitation.

Sexual Dysfunction Management and Expectations Assessment in Multiple Sclerosis-Female (SEA-MS-F): creation and validation of a specific questionnaire.

PubMed

Bisseriex, Hélène; Guinet-Lacoste, Amandine; Chevret-Méasson, Marie; Costa, Pierre; Sheikh Ismael, Samer; Rousseau, Alexandra; Amarenco, Gerard

2014-12-01

Until now, no questionnaire has been developed to study specific expectations concerning sexual dysfunction management and the availability of information on sexuality in the female population affected by multiple sclerosis (MS). Understanding and meeting the patient's expectations is an issue of considerable importance in the evaluation of medical care. We present the development and validation of a specific questionnaire designed for women with MS in order to assess their expectations in terms of sexual dysfunction management: the SEA-MS-F (Sexual Dysfunction Management and Expectations Assessment in Multiple Sclerosis-Female). This questionnaire was created and validated by an expert panel, using the Delphi method. The psychometric evaluation was obtained with a sample of 40 female MS patients. Cronbach's alpha index and principal component analysis were used to measure the questionnaire's internal consistency. A consensus on the questionnaire was reached with the Delphi method. The SEA-MS-F is fully compliant with the criteria for psychometric validation among female MS patients, and its internal consistency is excellent (Cronbach's alpha 0.948). The SEA-MS-F appears to be a useful tool that could be used either in routine medical situations or in prospective studies of MS in order to ascertain women's expectations concerning the management of their sexual dysfunction. © 2014 International Society for Sexual Medicine.

Ethanol sclerotherapy of ovarian endometrioma: a safe and effective minimal invasive procedure. Preliminary results.

PubMed

García-Tejedor, Amparo; Castellarnau, Marta; Ponce, Jordi; Fernández, Ma Eulalia; Burdio, Fernando

2015-04-01

To study if ultrasound-guided aspiration with ethanol sclerosis is a safe and effective treatment for endometriomas. We conducted a prospective study of 25 women with 27 endometriomas (two bilateral) measuring 4-10cm in diameter with no suspected malignancy, who underwent ultrasound-guided aspiration and ethanol sclerosis between August 2010 and July 2014. Patients were followed up by ultrasound at 6, 12, 24, and 36 months to identify rates of complication and recurrence. Clinical characteristics of the patients (age, history of infertility, previous surgery, and abdominal pain), the cysts (location, diameter, and volume) and the procedure (duration and complications) were recorded. Kaplan-Meier survival curves were used to analyze the recurrence rates by SPSS statistical software. The recurrence rate after sclerosis was 12%. The mean length of follow-up was 17 (SD 9.9) months. Although no major procedure-related complications were recorded, minor complications included three cases of low abdominal pain during the procedure (10.7%) and two cases of abdominal ethanol extravasation (7.1%). Ultrasound-guided aspiration and ethanol sclerotherapy are a safe and effective treatment for endometriomas measuring 4-10cm in diameter with no evidence of malignancy. This conservative treatment could possibly achieve a symptomatic cure while preserving healthy ovarian tissue, thereby improving fertility outcomes and avoiding early menopause. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pregnancy outcomes in Lebanese women with multiple sclerosis (the LeMS study): a prospective multicentre study.

PubMed

Fares, Jawad; Nassar, Anwar H; Gebeily, Souheil; Kobeissy, Firas; Fares, Youssef

2016-05-13

The Lebanese Multiple Sclerosis (LeMS) study aims to assess the influence of pregnancy and delivery on the clinical course of multiple sclerosis (MS) in Lebanese women. This prospective multicentre study took place in three MS referral university medical centres in Lebanon. Included were 29 women over 18 years who had been diagnosed with MS according to the McDonald criteria, and became pregnant between 1995 and 2015. Participating women should have stopped treatment 3 months before conception and become pregnant after the onset of MS. Women were followed up from 1 year preconceptionally and for 4 years postpartum. The annualised relapse rates per participant during each 3-month period during pregnancy and each year postpartum were compared with the relapse rate during the year before pregnancy using the paired two-tailed t test. p Values <0.05 were considered statistically significant for all analyses (95% CI). 64 full-term pregnancies were recorded. All pregnancies (100%) resulted in live births, with no complications or other diseases. In comparison with the prepregnancy year, in which the mean relapse rate±SE was 0.17±0.07, there was a significant reduction in the relapse rate during pregnancy and in the first year postpartum (p=0.02), but an increase in the rate in the second year postpartum (0.21±0.08). Thereafter, from the third year postpartum through the following fourth year, the annualised relapse rate fell slightly but did not differ from the annualised relapse rate recorded in the prepregnancy year (0.17±0.07). Pregnancy in Lebanese women with MS does not seem to increase the risk of complications. No relapses were observed during pregnancy and in the first year postpartum; however, relapses rebounded in the second year postpartum, and over the long term, returned to the levels that preceded pregnancy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study.

PubMed

Cutolo, Maurizio; Herrick, Ariane L; Distler, Oliver; Becker, Mike O; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Chadha-Boreham, Harbajan; Cottreel, Emmanuelle; Pfister, Thomas; Rosenberg, Daniel; Torres, Juan V; Smith, Vanessa

2016-10-01

To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681-0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510-0.756). This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. © 2016, American College of Rheumatology.

Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study

PubMed Central

Herrick, Ariane L.; Distler, Oliver; Becker, Mike O.; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Chadha‐Boreham, Harbajan; Cottreel, Emmanuelle; Pfister, Thomas; Rosenberg, Daniel; Torres, Juan V.; Cutolo, Maurizio; Herrick, Ariane L.; Distler, Oliver; Becker, Mike; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Smith, Vanessa; Erlacher, L; Hirschl, M; Kiener, HP; Pilger, E; Smith, V; Blockmans, D; Wautrecht, J‐C; Becvár, R; Carpentier, P; Frances, C; Lok, C; Sparsa, A; Hachulla, E; Quere, I; Allanore, Y; Agard, C; Riemekasten, G; Hunzelmann, N; Stücker, M; Ahmadi‐Simab, K; Sunderkötter, C; Wohlrab, J; Müller‐Ladner, U; Schneider, M; Vlachoyianopoulos, P; Vassilopoulos, D; Drosos, A; Antonopoulos, A; Balbir‐Gurman, A; Langevitz, P; Rosner, I; Levy, Y; Cutolo, M; Bombardieri, S; Ferraccioli, G; Mazzuca, S; Grassi, W; Lunardi, C; Airó, P; Riccieri, V; Voskuyl, AE; Schuerwegh, A; Santos, L; Rodrigues, AC; Grilo, A; Amaral, MC; Román Ivorra, JA; Castellvi, I; Distler, O; Spertini, F; Müller, R; Inanç, M; Oksel, F; Turkcapar, N; Herrick, A; Denton, C; McHugh, N; Chattopadhyay, C; Hall, F; Buch, M

2016-01-01

Objective To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6‐month period in patients with systemic sclerosis (SSc). Methods In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Results Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow‐up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756). Conclusion This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. PMID:27111549

Presentation and Diagnosis of Tuberous Sclerosis Complex in Infants.

PubMed

Davis, Peter E; Filip-Dhima, Rajna; Sideridis, Georgios; Peters, Jurriaan M; Au, Kit Sing; Northrup, Hope; Bebin, E Martina; Wu, Joyce Y; Krueger, Darcy; Sahin, Mustafa

2017-12-01

Tuberous sclerosis complex (TSC) is a neurocutaneous genetic disorder with a high prevalence of epilepsy and neurodevelopmental disorders. TSC can be challenging to diagnose in infants because they often do not show many clinical signs early in life. In this study, we describe the timing and pattern of presenting and diagnostic features in a prospective longitudinal study of infants with TSC. Two multicenter, prospective studies enrolled 130 infants with definite TSC by clinical or genetic criteria and followed them longitudinally up to 36 months of age. Periodic study visits included medical and seizure histories, physical and neurologic examinations, and developmental assessments. Ages at which major and minor features of TSC and seizures were first identified were analyzed. The most common initial presenting features of TSC were cardiac rhabdomyomas (59%) and hypomelanotic macules or other skin findings (39%), and 85% of infants presented with either or both. Ultimately, the most prevalent diagnostic TSC features were hypomelanotic macules (94%), tubers or other cortical dysplasias (94%), subependymal nodules (90%), and cardiac rhabdomyomas (82%). Thirty-five percent of infants presented prenatally, 41% presented at birth or within the first month of life, and 74% met criteria for TSC diagnosis at or within 30 days of presentation. Seizure onset occurred before or at initial presentation in only 15% of infants, but 73% developed epilepsy within the first year of life. Infants with TSC can often be identified early, before the onset of neurologic sequelae, enabling earlier diagnosis, surveillance, and possibly disease-modifying treatment. Copyright © 2017 by the American Academy of Pediatrics.

Potentially Modifiable Factors Associated With Physical Activity in Individuals With Multiple Sclerosis.

PubMed

Reider, Nadia; Salter, Amber R; Cutter, Gary R; Tyry, Tuula; Marrie, Ruth Ann

2017-04-01

Physical activity levels among persons with multiple sclerosis (MS) are worryingly low. We aimed to identify the factors associated with physical activity for people with MS, with an emphasis on factors that have not been studied previously (bladder and hand dysfunction) and are potentially modifiable. This study was a secondary analysis of data collected in the spring of 2012 during the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. NARCOMS participants were surveyed regarding smoking using questions from the Behavioral Risk Factor Surveillance Survey; disability using the Patient Determined Disease Steps; fatigue, cognition, spasticity, sensory, bladder, vision and hand function using self-reported Performance Scales; health literacy using the Medical Term Recognition Test; and physical activity using questions from the Health Information National Trends Survey. We used a forward binary logistic regression to develop a predictive model in which physical activity was the outcome variable. Of 8,755 respondents, 1,707 (19.5%) were classified as active and 7,068 (80.5%) as inactive. In logistic regression, being a current smoker, moderate or severe level of disability, depression, fatigue, hand, or bladder dysfunction and minimal to mild spasticity were associated with lower odds of meeting physical activity guidelines. MS type was not linked to activity level. Several modifiable clinical and lifestyle factors influenced physical activity in MS. Prospective studies are needed to evaluate whether modification of these factors can increase physical activity participation in persons with MS. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Stem cell transplantation and mesenchymal cells to treat autoimmune diseases.

PubMed

Tyndall, Alan; van Laar, Jacob M

2016-06-01

Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes mellitus have received MSC therapeutically. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Clinical epidemiology of amyotrophic lateral sclerosis in Liguria, Italy: An update of LIGALS register.

PubMed

Scialò, Carlo; Novi, Giovanni; Bandettini di Poggio, Monica; Canosa, Antonio; Sormani, Maria Pia; Mandich, Paola; Origone, Paola; Truffelli, Romina; Mancardi, Giovanni Luigi; Caponnetto, Claudia

Our objectives were: (1) to assess amyotrophic lateral sclerosis (ALS) incidence and its trend over time in Liguria, an Italian north-western region, performing an analysis of data prospectively collected from 1 January 2009 to 31 December 2014; (2) to determine the mean and median survival in the 2009-2014 Ligurian ALS incident cases; and (3) to evaluate the presence of disease prognostic factors. The Liguria Register for ALS (LIGALS) is an ongoing, multicentre prospective register enrolling all ALS incident cases in Liguria. Cases were identified using several concurrent sources. ALS diagnosis was based on El Escorial revised criteria (EEC-R). Two hundred and ninety-eight patients were enrolled in this study. The mean annual crude incidence rate in the 2009-2014 period was 3.11/100,000 population (95% CI 2.77-3.49); the point prevalence at 31 December 2014 was 7.85/100,000 (95% CI 6.54-9.36) population. Survival analysis demonstrated a median survival from symptom onset of 37.0 months (95% CI 32.0-42.0). In conclusion, ALS crude incidence in Liguria is higher compared to other Italian regions. Clinical and epidemiological data are comparable with those of the Italian ALS population. Survival analysis showed that higher age at onset, bulbar onset, definite EEC-R diagnostic category and a shorter diagnostic delay are related with worse outcomes.

Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients.

PubMed

Assouline, Avi; Levy, Antonin; Abdelnour-Mallet, Maya; Gonzalez-Bermejo, Jesus; Lenglet, Timothée; Le Forestier, Nadine; Salachas, François; Bruneteau, Gaelle; Meininger, Vincent; Delanian, Sylvie; Pradat, Pierre-François

2014-03-01

This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10(-6)). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (-77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiation Therapy for Hypersalivation: A Prospective Study in 50 Amyotrophic Lateral Sclerosis Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Assouline, Avi, E-mail: avi.assouline@ccpsc.fr; Department of Radiation Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris; Levy, Antonin

Purpose: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Methods and Materials: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scalemore » (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. Results: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10{sup −6}). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (−77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Conclusion: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.« less

Neuropathology of supercentenarians - four autopsy case studies.

PubMed

Takao, Masaki; Hirose, Nobuyoshi; Arai, Yasumichi; Mihara, Ban; Mimura, Masaru

2016-09-02

Supercentenarians (aged 110 years old or more) are extremely rare in the world population (the number of living supercentenarians is estimated as 47 in the world), and details about their neuropathological information are limited. Based on previous studies, centenarians (aged 100-109 years old) exhibit several types of neuropathological changes, such as Alzheimer's disease and Lewy body disease pathology, primary age-related tauopathy, TDP-43 pathology, and hippocampal sclerosis. In the present study, we provide results from neuropathological analyses of four supercentenarian autopsy cases using conventional and immunohistochemical analysis for neurodegenerative disorders. In particular, we focused on the pathology of Alzheimer's disease and Lewy body disease, as well as the status of hippocampal sclerosis, TDP-43 pathology, aging-related tau astrogliopathy, and cerebrovascular diseases. Three cases were characterized as an "intermediate" level of Alzheimer's disease changes (NIA-AA guideline) and one was characterized as primary age-related tauopathy. TDP-43 deposits were present in the hippocampus in two cases. Neither Lewy body pathology nor hippocampal sclerosis was observed. Aging-related tau astrogliopathy was consistently observed, particularly in the basal forebrain. Small vessel diseases were also present, but they were relatively mild for cerebral amyloid-beta angiopathy and arteriolosclerosis. Although our study involved a small number of cases, the results provide a better understanding about human longevity. Neuropathological alterations associated with aging were mild to moderate in the supercentenarian brain, suggesting that these individuals might have some neuroprotective factors against aging. Future prospective studies and extensive molecular analyses are needed to determine the mechanisms of human longevity.

The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice.

PubMed

Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

2015-06-18

Fingolimod (Gilenya) is an oral medication for patients with highly active relapsing-remitting Multiple Sclerosis (RRMS). Clinical trials and post-marketing experience on more than 114,000 patients have established a detailed safety profile. Total patient exposure now exceeds 195,000 patient-years as stated in the last financial report (Dec 2014) of the Novartis Pharma AG, Basel, Switzerland. However, less is known about the safety of long-term fingolimod use in daily practice. Here, we describe the study design of PANGAEA (Post-Authorization Non-interventional German sAfety of GilEnyA in RRMS patients), a prospective, multicenter, non-interventional, long-term study to collect safety, efficacy, and pharmacoeconomic data on RRMS patients treated with fingolimod (0.5 mg/daily) under real-world conditions in Germany. PANGAEA is striving to assess a real-world safety and efficacy profile of fingolimod, based on data from 4,000 RRMS patients, obtained during a 60-month observational phase. A pharmacoeconomic sub-study of 800 RRMS patients further collects patient-reported outcome measures of disability, quality of life, compliance, treatment satisfaction, and usage of resources during a 24-month observational phase. Descriptive statistical analyses of the safety set as well as of stratified subgroups such as patients with concomitant diabetes mellitus and pretreated patients (e.g., natalizumab) will be conducted. PANGAEA seeks to confirm the current safety profile of fingolimod obtained in phase I-III clinical trials. The study design presented here will additionally provide guidance on the therapeutic use of fingolimod in clinical practice and possibly assists physicians in making evidence-based decisions.

Impact of glatiramer acetate on paraclinical markers of neuroprotection in multiple sclerosis: A prospective observational clinical trial.

PubMed

Ehling, Rainer; Di Pauli, Franziska; Lackner, Peter; Rainer, Carolyn; Kraus, Viktoria; Hegen, Harald; Lutterotti, Andreas; Kuenz, Bettina; De Zordo, Tobias; Schocke, Michael; Glatzl, Susanne; Löscher, Wolfgang N; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

2015-10-15

Data from in vitro and animal studies support a neuroprotective role of glatiramer acetate (GA) in multiple sclerosis (MS). We investigated prospectively whether treatment with GA leads to clinical and paraclinical changes associated with neuroprotection in patients with relapsing-remitting (RR) MS. Primary aim of this clinical study was to determine serum BDNF levels in RR-MS patients who were started on GA as compared to patients who remained therapy-naive throughout 24 months. Secondary outcomes included relapses and EDSS, cognition, quality of life, fatigue and depression, BDNF expression levels on peripheral immune cells (FACS, RT-PCR), serum anti-myelin basic peptide (MBP) antibody status, evoked potential and cerebral MRI studies. While GA treatment did not alter serum levels or expression levels on peripheral immune cells of BDNF over time it resulted in a transient increase of serum IgG antibody response to MBP, mainly due to subtype IgG1 (p<0.05), after 3 months. However, no significant differences were found between GA treated and therapy-naive patients with regard to serum BDNF and intracellular BDNF expression levels, nerve conduction (including median and tibial nerve somatosensory, pattern-shift visual and upper and lower limb motor evoked potentials) or MRI (including volume of hyperintense lesions, volume of hypointense lesions after CE, mean diffusivity and fractional anisotropy) outcome parameters. In conclusion, our findings do not support a major impact of GA treatment on paraclinical markers of neuroprotection in human RR-MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Autogenous Bone Marrow Aspirate Concentrate on Radiographic Integration of Femoral Condylar Osteochondral Allografts.

PubMed

Oladeji, Lasun O; Stannard, James P; Cook, Cristi R; Kfuri, Mauricio; Crist, Brett D; Smith, Matthew J; Cook, James L

2017-10-01

Transplantation of fresh osteochondral allografts (OCAs) is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Because the lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. To determine if autogenous bone marrow aspirate concentrate (BMC) treatment of large femoral condylar OCAs would be associated with superior radiographic OCA bone integration compared with nontreated allografts during the critical first 6 months after surgery. Cohort study; Level of evidence, 3. A review of patients enrolled in a prospective registry who were treated with transplantation of large OCAs to one or both femoral condyles at our institution from March 12, 2013 to March 14, 2016 was performed. Patients were stratified into 2 groups based on BMC treatment versus no BMC treatment; the treatment was nonrandomized and was rooted in a shift in practice and a continuing effort to optimize OCA transplantation at our institution. Patients were excluded if they did not have orthogonal view radiographs performed at 6 weeks, 3 months, and 6 months postoperatively. Each condyle undergoing OCA transplantation was assessed individually by an independent musculoskeletal radiologist, who was blinded to the treatment group and time point. OCAs were assessed with respect to graft integration (0%-100%; 0 = no integration, 100 = complete integration) and degree of sclerosis (0-3; 0 = normal, 1 = mild sclerosis, 2 = moderate sclerosis, and 3 = severe sclerosis) of the graft at each time point. This study identified 17 condyles in 15 patients who underwent OCA transplantation without BMC and 29 condyles in 22 patients who underwent OCA transplantation with BMC. The BMC group had significantly ( P = .033) higher graft integration scores at 6 weeks, 3 months, and 6 months after surgery. Graft sclerosis was significantly ( P = .017) less in the BMC group at 6 weeks and 3 months, with no significant difference at 6 months after surgery. When combining the groups to examine the influence of smoking on graft integration, nonsmokers had significantly ( P = .007) higher graft integration scores at 6 months. Large femoral condylar OCAs treated with autogenous BMC before implantation showed superior radiographic integration to bone and less sclerosis during the initial 6-month postoperative period. BMC treatment of OCAs may mitigate the failure of OCA bone healing.

Depression in amyotrophic lateral sclerosis

PubMed Central

ATASSI, NAZEM; COOK, AMANDA; PINEDA, CRISTIANA M. E.; YERRAMILLI-RAO, PADMAJA; PULLEY, DARLENE; CUDKOWICZ, MERIT

2011-01-01

Depression is an under-recognized comorbidity associated with amyotrophic lateral sclerosis (ALS). The goals of this study were to prospectively estimate the prevalence of depression and other ALS related symptoms and to study the impact of depression on enrollment in research studies. One hundred and twenty-seven people with ALS completed the ALS Depression Inventory (ADI-12) and answered questions about ALS related symptoms and research study enrollment preferences. Demographics, ALS symptoms, medications, functional status, and research enrollment were compared between depressed and non-depressed patients. Results showed that the prevalence of mild and severe depression was 29% and 6%, respectively. More than one-third of our ALS patients were receiving anti-depressants to treat depression, sialorrhea, and pseudobulbar affect. Depression prevalence was not correlated with disease duration or progression. Except for anxiety, none of the ALS related symptoms predicted depression. The presence of depression did not have an effect on the decision to enroll in research studies. In conclusion, major depression is less common in our ALS cohort than in the general population. The diagnosis of depression can be masked by some ALS related symptoms and it has no impact on enrollment in ALS clinical trials. PMID:21091399

Preliminary evidence that self-efficacy predicts physical activity in multiple sclerosis.

PubMed

Motl, Robert W; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S

2009-09-01

Individuals with multiple sclerosis (MS) are less physically active than non diseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and prospective correlates of objectively measured physical activity in 16 individuals with a diagnosis of MS. The participants completed two measures of self-efficacy and then wore an accelerometer for a 5-day period at baseline and then at 3 months follow-up. Self-efficacy for continued physical activity was associated with baseline and follow-up levels of physical activity. Self-efficacy for overcoming barriers was associated with follow-up levels of physical activity and change in physical activity across a 3-month period. Researchers should consider self-efficacy as a possible component of an intervention that is designed to increase physical activity levels in those with MS. International Journal of Rehabilitation Research

Role of the HLA system in the association between multiple sclerosis and infectious mononucleosis.

PubMed

Ramagopalan, Sreeram V; Meier, Ute C; Conacher, Margaret; Ebers, George C; Giovannoni, Gavin; Crawford, Dorothy H; McAulay, Karen A

2011-04-01

To determine whether multiple sclerosis (MS) and infectious mononucleosis (IM) share common HLA associations. A prospective cohort study was conducted from October 1, 1999, through September 30, 2003. University of Edinburgh Richard Verney Health Centre, Edinburgh, Scotland. Participants included 179 individuals who underwent asymptomatic Epstein-Barr virus seroconversion and 175 patients who developed IM. Genotyping for 5 classical HLA loci (HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1). Diagnosis of IM and allele frequency. Allelic analysis showed that HLA-DRB1*01:01 was significantly associated with the development of IM (odds ratio, 3.2; P < .001). Patients with IM and HLA-DRB1*01:01 had a lower Epstein-Barr virus viral load compared with those without the allele (median, 783 vs 7366 copies/10(6) peripheral blood mononuclear cells; P = .03). HLA-DRB1*01:01 is protective against developing MS; thus, a common genetic basis between IM and MS is not supported.

Interferon-alpha and transfer factor in the treatment of multiple sclerosis: a double-blind, placebo-controlled trial. AUSTIMS Research Group.

PubMed Central

1989-01-01

The role of interferon-alpha (IFN-alpha) and transfer factor (TF) in the treatment of multiple sclerosis was investigated in a prospective, multi-centric, three year, double-blind, placebo-controlled trial. One hundred and eighty two patients with clinically definite multiple sclerosis were randomised into three treatment groups whose compositions were found to be similar for demographic and prognostic variables including HLA status. Subcutaneous injections of IFN-alpha (3 x 10(6) units), TF (0.5 units) manufactured from leucocytes of cohabiting donors, or placebo were given twice weekly for two months, once weekly for 10 months then fortnightly for 24 months. One hundred and fifty three patients completed the injection regimen. There was no significant difference in the progression of disability for multiple sclerosis patients in either the IFN-alpha or TF-treated groups compared with the placebo group. Similarly, change in visual evoked responses (VER), and in number of oligoclonal bands (OCB) and the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) over the trial period did not differ significantly between the three groups. However, the IFN-alpha-treated group had significantly more reported adverse drug reactions and patient withdrawals than either of the other two groups. PMID:2659737

Baseline predictors of DMT reinitiation among patients with multiple sclerosis following an MI-CBT intervention.

PubMed

Thelen, Joanie; Bruce, Amanda; Catley, Delwyn; Lynch, Sharon; Goggin, Kathy; Bradley-Ewing, Andrea; Glusman, Morgan; Norouzinia, Abigail; Strober, Lauren; Bruce, Jared

2018-04-01

Patients with multiple sclerosis (MS) are often nonadherent to their disease modifying therapy (DMT). While recent studies demonstrate enhanced DMT adherence following intervention grounded in motivational interviewing (MI), little is known about how to address DMT reinitiation among MS patients who have prematurely discontinued DMT against medical advice and do not intend to reinitiate. We examined baseline predictors of DMT reinitiation among patients with MS who discontinued medications against medical advice following a telephone-based MI and Cognitive Behavioral Therapy (MI-CBT) intervention. Following MI-CBT intervention, 66 patients reported whether or not they opted to reinitiate DMT. Rate of disease progression (β = 0.295) and perceived personal control (β = - 0.131) emerged as unique significant predictors of DMT reinitiation following intervention. Clinical characteristics and health-related beliefs may be used to prospectively identify patients most likely to reinitiate DMT following MI-CBT intervention, furthering the goal of preserving brain health and preventing neurologic decline in MS via appropriate DMT utilization. Further study is warranted to delineate potential mediators and moderators of DMT reinitiation outcomes.

Prevalence of fatigue in patients with multiple sclerosis and its effect on the quality of life

PubMed Central

Nagaraj, Karthik; Taly, Arun B.; Gupta, Anupam; Prasad, Chandrajit; Christopher, Rita

2013-01-01

Objective: This prospective study was carried out to observe the prevalence of fatigue in patients with multiple sclerosis (MS) and its effect on quality-of-life (QoL). Study Design and Setting: Prospective observational study in a University Tertiary Research Hospital in India. Patients and Methods: A total of 31 patients (25 females) with definite MS according to McDonald's criteria presented in out-patient/admitted in the Department of Neurology (between February 2010 and December 2011) were included in the study. Disease severity was evaluated using the Kurtzke's expanded disability status scale (EDSS). Fatigue was assessed using Krupp's fatigue severity scale (FSS). QoL was assessed by the World Health Organization QoL-BREF questionnaire. Results: The mean age of patients was 30.1 ± 9.1 years. The mean age at first symptom was 25.23 ± 6.4 years. The mean number of relapses was 4.7 ± 3.6 in the patients. The mean duration of illness was 4.9 ± 4.4 years. The mean EDSS score was 3.5 ± 2.2. Mean fatigue score was 38.7 ± 18.5 (cut-off value 36 in FSS). The prevalence of fatigue in patients with MS was 58.1% (18/31). MS patients with fatigue were significantly more impaired (P < 0.05) on all QoL domains (i.e., physical, psychosocial, social, and environment) than MS patients without fatigue. Conclusion: Prevalence of fatigue was found to be high in the MS patients in the study. All four domains of QoL were significantly more impaired in the group with fatigue than in those without fatigue. PMID:24250159

Effects of prolonged fasting on fatigue and quality of life in patients with multiple sclerosis.

PubMed

Etemadifar, Masoud; Sayahi, Farnaz; Alroughani, Raed; Toghianifar, Nafiseh; Akbari, Mojtaba; Nasr, Zahra

2016-06-01

Fasting is one of the recommended worships of several great religions in the world. During the month of Ramadan, circadian rhythm and pattern of eating changes result in physiological, biochemical and hormonal changes in the body. Many Muslims with medical conditions ask their physicians about the feasibility and safety of fasting during Ramadan. In this study, we aim to assess the effect of Ramadan fasting on the quality of life and fatigue in multiple sclerosis (MS) patients. Relapsing-remitting MS (RRMS) patients according to McDonald's criteria who had mild disability (EDSS score ≤3) were included in this study. Fatigue and quality of life were were assessed using the validated Persian versions of modified fatigue impact scale (MFIS) and multiple sclerosis quality of life-54 (MSQOL-54) questionnaires, respectively. 218 patients (150 females and 68 males) were enrolled in our study. There was no statistically significant difference between the mean total score of MSIF before and after fasting (25.50 ± 13.81 versus 26.94 ± 16.65; p = 0.58). The mean physical health and mental health composites of quality of life increased significantly after fasting (p = 0.008 and p = 0.003 respectively). Despite the observed lack of favorable effects on fatigue, our results showed increased quality of life of MS patients once Ramadan has ended. Whether this is specifically related to Ramadan-related fasting deserves further testing in appropriately designed larger prospective clinical studies.

Systematic Review of Correlates and Determinants of Physical Activity in Persons With Multiple Sclerosis.

PubMed

Streber, René; Peters, Stefan; Pfeifer, Klaus

2016-04-01

To review the current evidence regarding correlates and determinants of physical activity (PA) in persons with multiple sclerosis (pwMS). PubMed and Scopus (1980 to January 2015) and reference lists of eligible studies. Eligible studies include adults with multiple sclerosis; have a cross-sectional or prospective observational design; or examine the effect of a theory-based intervention trial on PA, including a mediation analysis. Eligible studies also apply a quantitative assessment of PA and correlates or proposed mediators and are published in English or German language. Two reviewers independently evaluated the risk of bias, extracted data, and categorized variables according to the International Classification of Functioning, Disability and Health. Consistency and the direction of associations were evaluated with a semiquantitative approach. Fifty-six publications with data from observational studies and 2 interventional studies provided evidence for 86 different variables. Consistent correlates of PA were the disability level, walking limitations in particular, PA-related self-efficacy, self-regulation constructs, employment status, and educational level. One interventional study provided evidence for a causal relation between self-regulation and PA. However, 59 of the 86 investigated variables in observational studies are based on 1 or 2 study findings, and most results stem from cross-sectional designs. Beside the importance of the general disability level and walking limitations, the results highlight the importance of personal factors (eg, PA-related self-efficacy, self-regulatory constructs, sociodemographic factors). Limitations and implications of the current review are discussed. Research that is more rigorous is needed to better understand what affects PA in pwMS. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Correlation between Forced Vital Capacity and Slow Vital Capacity for the assessment of respiratory involvement in Amyotrophic Lateral Sclerosis: a prospective study.

PubMed

Pinto, Susana; de Carvalho, Mamede

2017-02-01

Slow vital capacity (SVC) and forced vital capacity (FVC) are the most frequent used tests evaluating respiratory function in amyotrophic lateral sclerosis (ALS). No previous study has determined their interchangeability. To evaluate SVC-FVC correlation in ALS. Consecutive definite/probable ALS and primary lateral sclerosis (PLS) patients (2000-2014) in whom respiratory tests were performed at baseline/4-6months later were included. All were evaluated with revised ALS functional rating scale, the ALSFRS respiratory (R-subscore) and bulbar subscores, SVC, FVC, maximal inspiratory (MIP) and expiratory (MEP) pressures. SVC-FVC correlation was analysed by Pearson product-moment correlation test. Paired t-test compared baseline/follow-up values. Multilinear regression analysis modelled the relationship between tested variables. We included 592 ALS (332 men, mean onset age 62.6 ± 11.8 years, mean disease duration 15.4 ± 15 months) and 19 PLS (11 men, median age 54 years, median disease duration 5.5 years) patients. SVC and FVC predicted values decreased 2.15%/month and 2.08%/month, respectively. FVC and SVC were strongly correlated. Both were strongly correlated with MIP and MEP and moderately correlated with R-subscore for the all population and spinal-onset patients, but weakly correlated for bulbar-onset patients. FVC and SVC were strongly correlated and declined similarly. This correlation was preserved in bulbar-onset ALS and in spastic PLS patients.

Neurotoxicity

MedlinePlus

... disorders such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and dementia. Also being studied are the mechanisms ... disorders such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and dementia. Also being studied are the mechanisms ...

Falls in People with Multiple Sclerosis Compared with Falls in Healthy Controls

PubMed Central

Mazumder, Rajarshi; Murchison, Charles; Bourdette, Dennis; Cameron, Michelle

2014-01-01

Objective To compare the risk, circumstances, consequences and causes of prospectively recorded falls between people with multiple sclerosis (PwMS) and healthy controls of similar age and gender. Methods 58 PwMS and 58 healthy controls, who are community-dwelling, were recruited in this 6-month prospective cohort study. 90% of PwMS and 84% of healthy controls completed the study. Participants counted falls prospectively using fall calendars and noted fall location, fall-related injuries, and the cause of the falls. Kaplan Meier survival analysis and log-rank tests were performed to compare the distributions of survival without falling between PwMS and healthy controls. Results 40.8% of controls and 71.2% of PwMS fell at least once. 48.1% of PwMS and 18.4% of healthy controls fell at least twice. 42.3% of PwMS and 20.4% of health controls sustained a fall-related injury. After adjusting for age and gender, the time to first fall (HR: 1.87, p = 0.033) and the time to recurrent falls (HR: 2.87, p = 0.0082) were significantly different between PwMS and healthy controls. PwMS reported an almost equal number of falls inside and outside, 86% of the falls in healthy controls were outside. Healthy controls were more likely to fall due to slipping on a slippery surface (39.5% vs 10.4%). PwMS more often attributed falls to distraction (31% vs 7%) and uniquely attributed falls to fatigue or heat. Conclusions Fall risk, circumstances, consequences, and causes are different for PwMS than for healthy people of the same age and gender. PwMS fall more, are more likely to be injured by a fall, and often fall indoors. PwMS, but not healthy controls, frequently fall because they are distracted, fatigued or hot. PMID:25254633

[Comparing the activity of multiple sclerosis (MS) at the minute and at 20 minutes of gadolinium application in magnetic resonance imaging (MRI) of the brain?

PubMed

Saldívar-Uribe, Christina; de la Portilla-Villanueva, Mario Alberto; Esau-Mendoza-García, Alberto

2017-01-01

The aim was to compare active disease in patients diagnosed with multiple sclerosis, brain by MRI after gadolinium application at one minute and 20 minutes. A longitudinal, prospective, observational, analytical and comparative study was conducted in 18 patients over 18 years of age diagnosed with multiple sclerosis (MS). An analysis was made for each patient, watching for inflammatory activity in MS lesions, comparing the results to one minute and 20 minutes after the application of gadolinium. For the descriptive analysis, absolute frequencies and percentages were used, as well as means and standard deviations or medians with ranges for the inferential analysis comparing the presence or absence of enhancement in lesions at one minute and 20 minutes; the exact probability test used was Fisher. Finally, the results were analyzed, looking at the gender distribution: 14 (77.8%) were female. The average age was 36.2 ± 9.5 years, with a minimum age of 18 years and a maximum of 55 years; four patients (22.2%) presented further highlight active lesions at 20 minutes, and two patients (11.1%) presented enhancement at one minute. Concluding that MRI in the diagnosis of MS is very important for the detection of activity in lesions caused by the disease, it is evident that the optimum time for evaluation of postcontrast sequences is 20 minutes.

Non-invasive ventilation in amyotrophic lateral sclerosis: a 10 year population based study.

PubMed

Chiò, Adriano; Calvo, Andrea; Moglia, Cristina; Gamna, Federica; Mattei, Alessio; Mazzini, Letizia; Mora, Gabriele

2012-04-01

To evaluate the clinical characteristics and outcome of non-invasive ventilation (NIV) in an epidemiological based series of amyotrophic lateral sclerosis (ALS) patients. The study was performed using data from the Piemonte and Valle d'Aosta Register for ALS, a prospective epidemiological register enrolling all ALS incident cases in two Italian regions. Among the 1260 patients incident in the period 1995-2004, 259 (20.6%) underwent NIV. Young male patients and subjects attending the tertiary ALS centres were more likely to undergo NIV. There was a progressive significant increase in the use of NIV during the study but was limited to patients attending the ALS tertiary centres. Median survival after NIV was 289 days (95% CI 255 to 333). In an epidemiological setting, NIV represents an increasingly utilised option for the treatment of respiratory disturbances in ALS and has favourable effects on survival, in particular among patients followed by tertiary ALS centres. Sociocultural factors, such as age, gender and marital status, strongly influence the probability of undergoing NIV. Efforts should be made to remove these obstacles in order to spread the use of NIV in all ALS patients with respiratory failure.

Biopsychosocial correlates of lifetime major depression in a multiple sclerosis population.

PubMed

Patten, S B; Metz, L M; Reimer, M A

2000-04-01

The objective of this paper was to evaluate the lifetime and point prevalence of major depression in a population-based Multiple Sclerosis (MS) clinic sample, and to describe associations between selected biopsychosocial variables and the prevalence of lifetime major depression in this sample. Subjects who had participated in an earlier study were re-contacted for additional data collection. Eighty-three per cent (n=136) of those eligible consented to participate. Each subject completed the Composite International Diagnostic Interview (CIDI) and an interviewer-administered questionnaire evaluating a series of biopsychosocial variables. The lifetime prevalence of major depression in this sample was 22.8%, somewhat lower than previous estimates in MS clinic populations. Women, those under 35, and those with a family history of major depression had a higher prevalence. Also, subjects reporting high levels of stress and heavy ingestion of caffeine (>400 mg) had a higher prevalence of major depression. As this was a cross-sectional analysis, the direction of causal effect for the observed associations could not be determined. By identifying variables that are associated with lifetime major depression, these data generate hypotheses for future prospective studies. Such studies will be needed to further understand the etiology of depressive disorders in MS.

The ability of clinical balance measures to identify falls risk in multiple sclerosis: a systematic review and meta-analysis.

PubMed

Quinn, Gillian; Comber, Laura; Galvin, Rose; Coote, Susan

2018-05-01

To determine the ability of clinical measures of balance to distinguish fallers from non-fallers and to determine their predictive validity in identifying those at risk of falls. AMED, CINAHL, Medline, Scopus, PubMed Central and Google Scholar. First search: July 2015. Final search: October 2017. Inclusion criteria were studies of adults with a definite multiple sclerosis diagnosis, a clinical balance assessment and method of falls recording. Data were extracted independently by two reviewers. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale and the modified Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was conducted for the cross-sectional studies using Review Manager 5. The mean difference with 95% confidence interval in balance outcomes between fallers and non-fallers was used as the mode of analysis. We included 33 studies (19 cross-sectional, 5 randomised controlled trials, 9 prospective) with a total of 3901 participants, of which 1917 (49%) were classified as fallers. The balance measures most commonly reported were the Berg Balance Scale, Timed Up and Go and Falls Efficacy Scale International. Meta-analysis demonstrated fallers perform significantly worse than non-fallers on all measures analysed except the Timed Up and Go Cognitive ( p < 0.05), but discriminative ability of the measures is commonly not reported. Of those reported, the Activities-specific Balance Confidence Scale had the highest area under the receiver operating characteristic curve value (0.92), but without reporting corresponding measures of clinical utility. Clinical measures of balance differ significantly between fallers and non-fallers but have poor predictive ability for falls risk in people with multiple sclerosis.

Effectiveness, safety and health-related quality of life of multiple sclerosis patients treated with fingolimod: results from a 12-month, real-world, observational PERFORMS study in the Middle East.

PubMed

Achiron, Anat; Aref, Hany; Inshasi, Jihad; Harb, Mohamad; Alroughani, Raed; Bijarnia, Mahendra; Cooke, Kathryn; Yuksel, Ozgur

2017-08-07

Evidence on the use of fingolimod in real-world clinical practice and data on patient-reported health-related quality of life (HRQoL) in countries such as the Middle East are sparse. The Prospective Evaluation of Treatment with Fingolimod for Multiple Sclerosis (PERFORMS) study assessed HRQoL and effectiveness and safety of fingolimod in patients with relapsing-remitting multiples sclerosis (RRMS), primarily in Middle Eastern countries. This 12-month, observational, multicentre, prospective, real-world study was conducted in patients with RRMS who initiated fingolimod or another approved disease-modifying treatment (DMT) within 4 weeks before study entry. Patients were enrolled in a 2:1 ratio to obtain more data in fingolimod and parallel in other DMTs cohort by physicians during routine medical care. Key study outcomes included HRQoL assessed using MS International QoL (MusiQoL), MS relapses and disability. Safety was assessed throughout the study period. Due to the observational nature of the study, no neuroimaging assessments were mandated and central reading was not performed. Of 249 enrolled patients, 247 were included in the analysis (fingolimod cohort 172; other DMTs cohort 75). Overall, the mean age of patients was 36.5 years, 64.4% were women and ~90% were Caucasians. At baseline, mean MS duration since diagnosis was 7.2 years in the fingolimod and 4.8 years in the other DMTs cohorts. Overall, mean changes in MusiQoL index scores were -2.1 in the fingolimod cohort and -0.7 in the other DMTs cohort at Month 12, but improvement was not significant vs. baseline in both cohorts. Proportion of relapse-free patients increased significantly during the study vs. 0-12 months before the study in the fingolimod cohort (80.2% vs. 24.4%; p < 0.0001). Proportion of patients free from disability progression was 86.5% in the fingolimod cohort. The incidences of AEs were 59.9% and 50.6% in the fingolimod and other DMTs cohorts, respectively. First-dose monitoring of fingolimod observed no cases of symptomatic bradyarrhythmia. Three cases of bradycardia were reported in the fingolimod cohort: one after the first dose and two during the study. No cases of macular oedema were observed during the study. Fingolimod treatment maintained QoL over 12 months and was effective in reducing relapse rate and disability progression. No new safety findings were observed in this real-world observational study in Middle Eastern countries.

Prospective memory in multiple sclerosis: The impact of cue distinctiveness and executive functioning.

PubMed

Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

2016-11-01

Prospective memory (PM), the ability to remember to do something at the appropriate time in the future, is crucial in everyday life. One way to improve PM performance is to increase the salience of a cue announcing that it is time to act. Multiple sclerosis (MS) patients often report PM failures and there is growing evidence of PM deficits among this population. However, such deficits are poorly characterized and their relation to cognitive status remains unclear. To better understand PM deficits in MS patients, this study investigated the impact of cue salience on PM, and its relation to retrospective memory (RM) and executive deficits. Thirty-nine (39) MS patients were compared to 18 healthy controls on a PM task modulating cue salience during an ongoing general knowledge test. MS patients performed worse than controls on the PM task, regardless of cue salience. MS patients' executive functions contributed significantly to the variance in PM performance, whereas age, education and RM did not. Interestingly, low- and high-executive patients' performance differed when the cue was not salient, but not when it was, suggesting that low-executive MS patients benefited more from cue salience. These findings add to the growing evidence of PM deficits in MS and highlight the contribution of executive functions to certain aspects of PM. In low-executive MS patients, high cue salience improves PM performance by reducing the detection threshold and need for environmental monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple sclerosis and pregnancy: a single-centre prospective comparative study.

PubMed

Cuello, J P; Martínez Ginés, M L; Martin Barriga, M L; de Andrés, C

2017-03-01

Multiple sclerosis (MS) is a autoimmune disorder which preferentially affects young women of childbearing age. During pregnancy, the annualized relapse rate (AAR) is modified, but pregnancy has no harm effect on the long-term course of the disease. We aimed to study the clinical course of our MS patients during pregnancy, and compare their obstetrics outcomes with a control group of non-MS patients. A single centre prospective observational study was conducted. We assessed the reproductive history, MS history, pregnancy course and new-born outcome of a cohort of MS patients who had had a pregnancy between january 2007 and july 2012. We compared the global outcomes with a control cohort of 58 age-matched healthy pregnancies. Complete data from 35 consecutive women were analyzed, 40 deliveries. Control groups: 58 patients, 60 deliveries. EDSS at pregnancy 0,7. ARR before pregnancy 0,5. During pregnancy 0,3, after pregnancy 0,4. Twelve patients were on disease-modifying drugs (DMD) before pregnancy, 4 prenatal exposure occurs. The comparison between relapse rate and EDSS before, during and after delivery showed no statistically significant difference. In addition, compared to control group, there were also no differences in the obstetric outcomes. In MS cohort, we found a higher incidence of assisted reproductive treatments and lower breastfeeding rate, both statistically significant. Our series confirms that pregnancy has no negative long term impact on the progression of MS and also suggest that there is no additional morbidity in the pregnancy, comparing to the rest of the population. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Glatiramer acetate treatment persistence - but not adherence - in multiple sclerosis patients is predicted by health-related quality of life and self-efficacy: a prospective web-based patient-centred study (CAIR study).

PubMed

Jongen, Peter Joseph; Lemmens, Wim A; Hoogervorst, Erwin L; Donders, Rogier

2017-03-14

In patients with relapsing remitting multiple sclerosis (RRMS) the persistence of and adherence to disease modifying drug (DMD) treatment is inadequate. To take individualised measures there is a need to identify patients with a high risk of non-persistence or non-adherence. As patient-related factors have a major influence on persistence and adherence, we investigated whether health-related quality of life (HRQoL) and self-efficacy could predict persistence or adherence. In a prospective web-based patient-centred study in 203 RRMS patients, starting treatment with glatiramer acatete (GA) 20 mg subcutaneously daily, we measured physical and mental HRQoL (Multiple Sclerosis Quality of Life-54 questionnaire), functional and control self-efficacy (Multiple Sclerosis Self-Efficacy Scale), the 12-month persistence rate and, in persistent patients, the percentage of missed doses. HRQoL and self-efficacy were compared between persistent and non-persistent patients, and between adherent and non-adherent patients. Logistic regression analysis was used to assess whether persistence and adherence were explained by HRQoL and self-efficacy. Persistent patients had higher baseline physical (mean 58.1 [standard deviation, SD] 16.9) and mental HRQoL (63.8 [16.8]) than non-persistent patients (49.5 [17.6]; 55.9 [20.4]) (P = 0.001; P = 0.003) with no differences between adherent and non-adherent patients (P = 0.46; P = 0.54). Likewise, in persistent patients function (752 [156]) and control self-efficacy (568 [178]) were higher than in non-persistent patients (689 [173]; 491 [192]) (P = 0.009; P = 0.004), but not in adherent vs. non-adherent patients (P = 0.26; P = 0.82). Logistic regression modelling identified physical HRQoL and control self-efficacy as factors that explained persistence. Based on predicted scores from the model, patients were classified into quartiles and the percentage of non-persistent patients per quartile was calculated: non-persistence in the highest quartile was 23.4 vs. 53.2% in the lowest quartile. Risk differentiation with respect to adherence was not possible. Based on these findings we propose a practical work-up scheme to identify patients with a high risk of non-persistence and to identify persistence-related factors. Findings suggest that pre-treatment physical HRQoL and control self-efficacy may identify RRMS patients with a high risk of early discontinuation of injectable DMD treatment. Targeting of high-risk patients may enable the efficient use of persistence-promoting measures. Nederlands Trial Register code: NTR2432 .

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1.

PubMed

Abreu, Pedro; Pedrosa, Rui; Sá, Maria José; Cerqueira, João; Sousa, Lívia; Da Silva, Ana Martins; Pinheiro, Joaquim; De Sá, João; Batista, Sónia; Simões, Rita Moiron; Pereira, Daniela Jardim; Vilela, Pedro; Vale, José

2018-05-30

Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.

Prospective risk of rheumatologic disease associated with occupational exposure in a cohort of male construction workers.

PubMed

Blanc, Paul D; Järvholm, Bengt; Torén, Kjell

2015-10-01

The association between occupational exposure and autoimmune disease is well recognized for silica, and suspected for other inhalants. We used a large cohort to estimate the risks of rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis associated with silica and other occupational exposures. We analyzed data for male Swedish construction industry employees. Exposure was defined by a job-exposure matrix for silica and for other inorganic dusts; those with other job-exposure matrix exposures but not to either of the 2 inorganic dust categories were excluded. National hospital treatment data were linked for International Classification of Diseases, 10(th) Revision-coded diagnoses of rheumatoid arthritis (seronegative and positive), systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. The 2 occupational exposures were tested as independent predictors of prospective hospital-based treatment for these diagnoses using age-adjusted Poisson multivariable regression analyses to calculate relative risk (RR). We analyzed hospital-based treatment data (1997 through 2010) for 240,983 men aged 30 to 84 years. There were 713 incident cases of rheumatoid arthritis (467 seropositive, 195 seronegative, 51 not classified) and 128 cases combined for systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. Adjusted for smoking and age, the 2 occupational exposures (silica and other inorganic dusts) were each associated with increased risk of rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis combined: RR 1.39 (95% confidence interval [CI], 1.17-1.64) and RR 1.31 (95% CI, 1.11-1.53), respectively. Among ever smokers, both silica and other inorganic dust exposure were associated with increased risk of rheumatoid arthritis (RRs 1.36; 95% CI, 1.11-1.68 and 1.42; 95% CI, 1.17-1.73, respectively), while among never smokers, neither exposure was associated with statistically significant increased risk of rheumatoid arthritis. This analysis reaffirms the link between occupational silica and a range of autoimmune diseases, while also suggesting that other inorganic dusts may also impart excess risk of such disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

PubMed

Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

2009-06-09

Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

Cognitive and Language Deficits in Multiple Sclerosis: Comparison of Relapsing Remitting and Secondary Progressive Subtypes

PubMed Central

Ntoskou, Katerina; Messinis, Lambros; Nasios, Grigorios; Martzoukou, Maria; Makris, Giorgos; Panagiotopoulos, Elias; Papathanasopoulos, Panagiotis

2018-01-01

Objective: The objective of this study was to investigate the pattern and severity of cognitive and language impairment in Greek patients with Relapsing-remitting (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS), relative to control participants. Method: A prospective study was conducted in 27 patients with multiple sclerosis (PwMS), (N= 15) with RRMS, (N= 12) with SPMS, and (N= 12) healthy controls. All participants were assessed with a flexible comprehensive neuropsychological – language battery of tests that have been standardized in Greece and validated in Greek MS patients. They were also assessed on measures of disability (Expanded Disability Status Scale; EDSS), fatigue (Fatigue Severity Scale; FSS) and depression (Beck Depression Inventory - fast screen; BDI-FS). Results: Our results revealed that groups were well matched on baseline demographic and clinical characteristics. The two clinical groups (RRMS; SPMS) did not differ on overall global cognitive impairment but differed in the initial encoding of verbal material, mental processing speed, response inhibition and set-shifting. RRMS patients differed from controls in the initial encoding of verbal material, learning curve, delayed recall of verbal information, processing speed, and response inhibition. SPMS patients differed in all utilized measures compared to controls. Moreover, we noted increased impairment frequency on individualized measures in the progressive SPMS group. Conclusion: We conclude that MS patients, irrespective of clinical subtype, have cognitive deficits compared to healthy participants, which become increasingly worse when they convert from RRMS to SPMS.On the contrary,the pattern of impairment remains relatively stable. PMID:29576812

The vestibular evoked myogenic potentials (VEMP) score: a promising tool for evaluation of brainstem involvement in multiple sclerosis.

PubMed

Gabelić, T; Krbot Skorić, M; Adamec, I; Barun, B; Zadro, I; Habek, M

2015-02-01

Concerning the great importance of brainstem involvement in multiple sclerosis (MS), the aim of this study was to explore the role of the newly developed vestibular evoked myogenic potentials (VEMP) score as a possible marker of brainstem involvement in MS patients. This was a prospective case-control study which included 100 MS patients divided into two groups (without and with clinical signs of brainstem involvement) and 50 healthy controls. Ocular VEMP (oVEMP) and cervical VEMP (cVEMP) measurements were performed in all participants and analyzed for latencies, conduction block and amplitude asymmetry ratio. Based on this the VEMP score was calculated and compared with Expanded Disability Status Scale (EDSS), disease duration and magnetic resonance imaging data. Multiple sclerosis patients with clinical signs of brainstem involvement (group 2) had a statistically significant higher percentage of VEMP conduction blocks compared with patients without clinical signs of brainstem involvement (group 1) and healthy controls (P = 0.027 and P < 0.0001, respectively). Similarly, the VEMP score was significantly higher in group 2 compared with group 1 (P = 0.018) and correlated with EDSS and disease duration (P = 0.011 and P = 0.032, respectively). Multivariate linear regression analysis showed that the VEMP score has a statistically significant influence on the EDSS score (P < 0.001, R(2) = 0.239). Interpretation of the oVEMP and cVEMP results in the form of the VEMP score enables better evaluation of brainstem involvement than either of these evoked potentials alone and correlates well with disability. © 2014 EAN.

Accounting for disease modifying therapy in models of clinical progression in multiple sclerosis.

PubMed

Healy, Brian C; Engler, David; Gholipour, Taha; Weiner, Howard; Bakshi, Rohit; Chitnis, Tanuja

2011-04-15

Identifying predictors of clinical progression in patients with relapsing-remitting multiple sclerosis (RRMS) is complicated in the era of disease modifying therapy (DMT) because patients follow many different DMT regimens. To investigate predictors of progression in a treated RRMS sample, a cohort of RRMS patients was prospectively followed in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB). Enrollment criteria were exposure to either interferon-β (IFN-β, n=164) or glatiramer acetate (GA, n=114) for at least 6 months prior to study entry. Baseline demographic and clinical features were used as candidate predictors of longitudinal clinical change on the Expanded Disability Status Scale (EDSS). We compared three approaches to account for DMT effects in statistical modeling. In all approaches, we analyzed all patients together and stratified based on baseline DMT. Model 1 used all available longitudinal EDSS scores, even those after on-study DMT changes. Model 2 used only clinical observations prior to changing DMT. Model 3 used causal statistical models to identify predictors of clinical change. When all patients were considered using Model 1, patients with a motor symptom as the first relapse had significantly larger change in EDSS scores during follow-up (p=0.04); none of the other clinical or demographic variables significantly predicted change. In Models 2 and 3, results were generally unchanged. DMT modeling choice had a modest impact on the variables classified as predictors of EDSS score change. Importantly, however, interpretation of these predictors is dependent upon modeling choice. Copyright © 2011 Elsevier B.V. All rights reserved.

A prospective study of physical trauma and multiple sclerosis.

PubMed Central

Sibley, W A; Bamford, C R; Clark, K; Smith, M S; Laguna, J F

1991-01-01

During an eight year period 170 multiple sclerosis (MS) patients and 134 controls without physical impairment were followed closely to record all episodes of physical trauma and to measure their effect on exacerbation rate and progression of MS. There was a total of 1407 instances of trauma, which were sorted into various categories. Overall there was no significant correlation between all-traumas and disease activity. There was, however, a statistically significant negative correlation between traumatic episodes and exacerbations in 95 patients who had exacerbations during the programme, due primarily to less activity of the disease during a three month period following surgical procedures and fractures. Electrical injury had a significant positive association with exacerbation using a three month at-risk period, but there were no other significant positive correlations in any other category of trauma, including minor head injuries; there were no cases of head injury with prolonged unconsciousness. There was no linkage between the frequency of trauma and progression of disability. MS patients had two to three times more trauma than controls. PMID:1895121

Cerebrospinal Fluid B Cells Correlate with Early Brain Inflammation in Multiple Sclerosis

PubMed Central

Kuenz, Bettina; Lutterotti, Andreas; Ehling, Rainer; Gneiss, Claudia; Haemmerle, Monika; Rainer, Carolyn; Deisenhammer, Florian; Schocke, Michael; Berger, Thomas; Reindl, Markus

2008-01-01

Background There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS). Methodology/Principal Findings In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF) cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS), relapsing-remitting (RR) and chronic progressive (CP) MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD138−) and plasma blasts (CD19+CD138+) in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matrix metalloproteinase (MMP)-9 and the B cell chemokine CxCL-13. Conclusions Our data support an important role of CSF B cells in acute brain inflammation in CIS and RRMS. PMID:18596942

Social consequences of multiple sclerosis. Part 2. Divorce and separation: a historical prospective cohort study.

PubMed

Pfleger, C C H; Flachs, E M; Koch-Henriksen, Nils

2010-07-01

There is a need for follow-up studies of the familial situation of multiple sclerosis (MS) patients. To evaluate the probability of MS patients to remain in marriage or relationship with the same partner after onset of MS in comparison with the population. All 2538 Danes with onset of MS 1980-1989, retrieved from the Danish MS-Registry, and 50,760 matched and randomly drawn control persons were included. Information on family status was retrieved from Statistics Denmark. Cox analyses were used with onset as starting point. Five years after onset, the cumulative probability of remaining in the same relationship was 86% in patients vs. 89% in controls. The probabilities continued to deviate, and at 24 years, the probability was 33% in patients vs. 53% in the control persons (p < 0.001). Among patients with young onset (< 36 years of age), those with no children had a higher risk of divorce than those having children less than 7 years (Hazard Ratio 1.51; p < 0.0001), and men had a higher risk of divorce than women (Hazard Ratio 1.33; p < 0.01). MS significantly affects the probability of remaining in the same relationship compared with the background population.

Accepting or declining non-invasive ventilation or gastrostomy in amyotrophic lateral sclerosis: patients' perspectives.

PubMed

Greenaway, L P; Martin, N H; Lawrence, V; Janssen, A; Al-Chalabi, A; Leigh, P N; Goldstein, L H

2015-01-01

The objective was to identify factors associated with decisions made by patients with amyotrophic lateral sclerosis (ALS) to accept or decline non-invasive ventilation (NIV) and/or gastrostomy in a prospective population-based study. Twenty-one people with ALS, recruited from the South-East ALS Register who made an intervention decision during the study timeframe underwent a face-to-face in-depth interview, with or without their informal caregiver present. Sixteen had accepted an intervention (11 accepted gastrostomy, four accepted NIV and one accepted both interventions). Five patients had declined gastrostomy. Thematic analysis revealed three main themes: (1) patient-centric factors (including perceptions of control, acceptance and need, and aspects of fear); (2) external factors (including roles played by healthcare professionals, family, and information provision); and (3) the concept of time (including living in the moment and the notion of 'right thing, right time'). Many aspects of these factors were inter-related. Decision-making processes for the patients were found to be complex and multifaceted and reinforce arguments for individualised (rather than 'algorithm-based') approaches to facilitating decision-making by people with ALS who require palliative interventions.

Progression and effect of cognitive-behavioral changes in patients with amyotrophic lateral sclerosis.

PubMed

Bock, Meredith; Duong, Y-Nhy; Kim, Anthony; Allen, Isabel; Murphy, Jennifer; Lomen-Hoerth, Catherine

2017-12-01

To prospectively evaluate the progression of cognitive-behavioral function in amyotrophic lateral sclerosis (ALS) and examine the association of cognitive-behavioral deficits with disease progression, patient quality of life (QOL), and caregiver burden. We evaluated cognitive-behavioral function using the Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen at enrollment and after 7 months in a cohort of patients with ALS. Paired t tests were used to evaluate the change in the 2 assessments. Linear regression and Kruskal-Wallis tests were applied to investigate how initial cognitive or behavioral status related to outcomes. The mean test-retest interval was 6.8 months (SD 1.6). Cognitive status of the study population (n = 49) overall did not change over the study period ( p = 0.06) despite progression of motor weakness ( p < 0.001), though small subsets of the sample demonstrate cognitive change. Patients initially classified as behaviorally normal showed increased behavioral problems over time ( t = -2.8, p = 0.009). Decline in cognitive (β = -1.3, p = 0.03) and behavioral (β = -0.76, p = 0.002) status predicted increasing caregiver burden. Behavioral abnormalities predicted decline in forced vital capacity and ALS Functional Rating Scale-Revised score ( p = 0.008, 0.012) in the study population and patient QOL in the most severely affected group ( t = 4.3, p = 0.003). Cognitive-behavioral change is a key aspect of disease heterogeneity in ALS. Executive function in ALS overall remains stable over 7 months as detected by an administered screening tool. However, patients may develop caregiver-reported behavioral symptoms in that time period. Screening for caregiver-reported symptoms has a particular utility in predicting future clinical decline, increased caregiver burden, and worsening patient QOL.

Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis.

PubMed

Fröhlich, Kilian; Winder, Klemens; Linker, Ralf A; Engelhorn, Tobias; Dörfler, Arnd; Lee, De-Hyung; Hilz, Max J; Schwab, Stefan; Seifert, Frank

2018-06-01

Background It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients. Methods We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test. Results From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia. Conclusions Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.

Progressive solitary sclerosis

PubMed Central

Kaufmann, Timothy J.; Weinshenker, Brian G.; Kantarci, Orhun H.; Schmalstieg, William F.; Paz Soldan, M. Mateo; Flanagan, Eoin P.

2016-01-01

Objective: To report patients with progressive motor impairment resulting from an isolated CNS demyelinating lesion in cerebral, brainstem, or spinal cord white matter that we call progressive solitary sclerosis. Methods: Thirty patients were identified with (1) progressive motor impairment for over 1 year with a single radiologically identified CNS demyelinating lesion along corticospinal tracts, (2) absence of other demyelinating CNS lesions, and (3) no history of relapses affecting other CNS pathways. Twenty-five were followed prospectively in our multiple sclerosis (MS) clinic and 5 were identified retrospectively from our progressive MS database. Patients were excluded if an alternative etiology for progressive motor impairment was found. Multiple brain and spinal cord MRI were reviewed by a neuroradiologist blinded to the clinical details. Results: The patients' median age was 48.5 years (range 23–71) and 15 (50%) were women. The median follow-up from symptom onset was 100 months (range 15–343 months). All had insidiously progressive upper motor neuron weakness attributable to the solitary demyelinating lesion found on MRI. Clinical presentations were hemiparesis/monoparesis (n = 24), quadriparesis (n = 5), and paraparesis (n = 1). Solitary MRI lesions involved cervical spinal cord (n = 18), cervico-medullary/brainstem region (n = 6), thoracic spinal cord (n = 4), and subcortical white matter (n = 2). CSF abnormalities consistent with MS were found in 13 of 26 (50%). Demyelinating disease was confirmed pathologically in 2 (biopsy, 1; autopsy, 1). Conclusions: Progressive solitary sclerosis results from an isolated CNS demyelinating lesion. Future revisions to MS diagnostic criteria could incorporate this presentation of demyelinating disease. PMID:27638926

Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex

DTIC Science & Technology

2012-09-01

in the formation of visible facial angiofibromas over time. The lesions appear as red or pink papules distributed over the central face...especially on the nasolabial folds, cheeks, and chin. Lesions appear in early childhood and are present in up to 80% of TSC patients. Facial angiofibromas ...facial angiofibromas without causing side effects seen with systemic administration. This project is a multi-center prospective, randomized

Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons of current clinical diagnostic criteria.

PubMed

Cortés-Vicente, Elena; Pradas, Jesús; Marín-Lahoz, Juan; De Luna, Noemi; Clarimón, Jordi; Turon-Sans, Janina; Gelpí, Ellen; Díaz-Manera, Jordi; Illa, Isabel; Rojas-Garcia, Ricard

2017-08-01

To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis. We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation. Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA). Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.

Association between nailfold capillaroscopy findings and pulmonary function tests in patients with systemic sclerosis.

PubMed

Castellví, Ivan; Simeón-Aznar, Carmen Pilar; Sarmiento, Mónica; Fortuna, Ana; Mayos, Mercedes; Geli, Carme; Diaz-Torné, César; Moya, Patricia; De Llobet, Josep Maria; Casademont, Jordi

2015-02-01

To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.

Numeracy of multiple sclerosis patients: A comparison of patients from the PERCEPT study to a German probabilistic sample.

PubMed

Gaissmaier, Wolfgang; Giese, Helge; Galesic, Mirta; Garcia-Retamero, Rocio; Kasper, Juergen; Kleiter, Ingo; Meuth, Sven G; Köpke, Sascha; Heesen, Christoph

2018-01-01

A shared decision-making approach is suggested for multiple sclerosis (MS) patients. To properly evaluate benefits and risks of different treatment options accordingly, MS patients require sufficient numeracy - the ability to understand quantitative information. It is unknown whether MS affects numeracy. Therefore, we investigated whether patients' numeracy was impaired compared to a probabilistic national sample. As part of the larger prospective, observational, multicenter study PERCEPT, we assessed numeracy for a clinical study sample of German MS patients (N=725) with a standard test and compared them to a German probabilistic sample (N=1001), controlling for age, sex, and education. Within patients, we assessed whether disease variables (disease duration, disability, annual relapse rate, cognitive impairment) predicted numeracy beyond these demographics. MS patients showed a comparable level of numeracy as the probabilistic national sample (68.9% vs. 68.5% correct answers, P=0.831). In both samples, numeracy was higher for men and the highly educated. Disease variables did not predict numeracy beyond demographics within patients, and predictability was generally low. This sample of MS patients understood quantitative information on the same level as the general population. There is no reason to withhold quantitative information from MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Home telemonitoring of non-invasive ventilation decreases healthcare utilisation in a prospective controlled trial of patients with amyotrophic lateral sclerosis.

PubMed

Pinto, Anabela; Almeida, José Pedro; Pinto, Susana; Pereira, João; Oliveira, António Gouveia; de Carvalho, Mamede

2010-11-01

Non-invasive ventilation (NIV) is an efficient method for treating respiratory failure in patients with amyotrophic lateral sclerosis (ALS). However, it requires a process of adaptation not always achieved due to poor compliance. The role of telemonitoring of NIV is not yet established. To test the advantage of using modem communication in NIV of ALS patients. Prospective, single blinded controlled trial. Population and methods According to their residence, 40 consecutive ventilated ALS patients were assigned to one of two groups: a control group (G1, n=20) in which compliance and ventilator parameter settings were assessed during office visits; or an intervention group (G2, n=20) in which patients received a modem device connected to the ventilator. The number of office and emergency room visits and hospital admissions during the entire span of NIV use and the number of parameter setting changes to achieve full compliance were the primary outcome measurements. Demographic and clinical features were similar between the two groups at admission. No difference in compliance was found between the groups. The incidence of changes in parameter settings throughout the survival period with NIV was lower in G2 (p<0.0001) but it was increased during the initial period needed to achieve full compliance. The number of office or emergency room visits and inhospital admissions was significantly lower in G2 (p<0.0001). Survival showed a trend favouring G2 (p=0.13). This study shows that telemonitoring reduces health care utilisation with probable favourable implications on costs, survival and functional status.

The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis.

PubMed

Cottrell, D A; Kremenchutzky, M; Rice, G P; Koopman, W J; Hader, W; Baskerville, J; Ebers, G C

1999-04-01

We report a natural history study of 216 patients with primary progressive (PP)- multiple sclerosis defined by at least 1 year of exacerbation-free progression at onset. This represents 19.8% of a largely population-based patient cohort having a mean longitudinal follow-up of 23 years. This subgroup of PP-multiple sclerosis patients had a mean age of onset of 38.5 years, with females predominating by a ratio of 1.3:1.0. The rate of deterioration from disease onset was substantially more rapid than for relapsing-remitting multiple sclerosis, with a median time to disability status score (DSS) 6 and DSS 8 of 8 and 18 years, respectively. Forty-nine percent of patients were followed through to death. Examination of the early disease course revealed two groups with adverse prognostic profiles. Firstly, a shorter time to reach DSS 3 from onset of PP-multiple sclerosis significantly adversely influenced time to DSS 8. Second, involvement of three or more neurological systems at onset resulted in a median time to DSS 10 of 13.5 years in contrast to PP-multiple sclerosis patients with one system involved at onset where median time to death from multiple sclerosis was 33.2 years. However, age, gender and type of neurological system involved at onset appeared to have little influence on prognosis. Life expectancy, cause of mortality and familial history profile were similar in PP-multiple sclerosis and non-PP-multiple sclerosis (all other multiple sclerosis patients from the total population). From clinical onset, rate of progression was faster in the PP-multiple sclerosis group than in the secondary progressive (SP)-multiple sclerosis group. When the rates of progression from onset of the progressive phase to DSS 6, 8 and 10 were compared, SP-multiple sclerosis had a more rapid progressive phase. A substantial minority (28%) of the PP-multiple sclerosis cohort had a distinct relapse even decades after onset of progressive deterioration. These studies establish natural history outcomes for the subgroup of multiple sclerosis patients with primary progressive disease.

Patients' self-perceived burden, caregivers' burden and quality of life for amyotrophic lateral sclerosis patients: a cross-sectional study.

PubMed

Geng, Dan; Ou, RuWei; Miao, XiaoHui; Zhao, LiHong; Wei, QianQian; Chen, XuePing; Liang, Yan; Shang, HuiFang; Yang, Rong

2017-10-01

This study surveys the quality of life of amyotrophic lateral sclerosis patients and the factors associated with amyotrophic lateral sclerosis patients' self-perceived burden and their caregivers' burden. Burdens of patients with amyotrophic lateral sclerosis and their caregivers in Chinese population are largely unknown. A cross-sectional study was conducted among 81 pairs of amyotrophic lateral sclerosis patients and their caregivers. Amyotrophic lateral sclerosis patients' self-perceived burden and caregivers' burden were assessed by the Self-Perceived Burden Scale and Zarit-Burden Interview, respectively. Quality of life of amyotrophic lateral sclerosis patients was measured using the World Health Organization Quality of Life-Bref. The amyotrophic lateral sclerosis Functional Rating Scale-Revised questionnaire was used to estimate patients' physical function. Both patients and caregivers reported a mild to moderate burden. The World Health Organization quality of life-Bref scores were decreased in respondents with lower amyotrophic lateral sclerosis Functional Rating Scale-Revised, higher Self-Perceived Burden Scale and higher Zarit-Burden Interview scores. Self-Perceived Burden Scale scores were associated with patients' knowledge of amyotrophic lateral sclerosis, respiratory function and female sex. Zarit-Burden Interview scores were associated with caregivers' age, patients' motor function and out-of-pocket payment. With increase in amyotrophic lateral sclerosis patients' self-perceived burden and caregivers' burden, quality of life of amyotrophic lateral sclerosis patients decreased. Female patients, who had known more about the disease, and those with severe respiratory dysfunction were subject to higher self-perceived burden. Older caregivers and caregivers of patients with severe motor dysfunction and more out-of-pocket payment experienced more care burdens. Our study suggests that paying more attention to female amyotrophic lateral sclerosis patients might benefit patients in China or other South-East Asian countries under the Confucian concept of ethics. There is an urgent demand to expand medical insurance coverage to cover amyotrophic lateral sclerosis in China and other developing countries. Long and adequate supports are needed for relieving caregiver's burden. To improve the quality of life of patients, relieving the patients' SBP and caregivers' burden is likely to be not only required, but also essential. © 2016 John Wiley & Sons Ltd.

Study of the relationship between tuberous sclerosis complex and autistic disorder.

PubMed

Wong, Virginia

2006-03-01

There has been increasing awareness that there are behavioral phenotypes in tuberous sclerosis complex with neuropsychiatric symptom complex such as autistic disorder and attention-deficit hyperactivity disorder (ADHD). However, the neurobiologic basis of autistic disorder in tuberous sclerosis complex is still unknown. We studied two cohorts of children followed up since 1986 until 2003, one cohort with tuberous sclerosis complex and another cohort with autistic disorder, to determine the incidence of autistic disorder in tuberous sclerosis complex and the incidence of tuberous sclerosis complex in autistic disorder respectively. We established a Tuberous Sclerosis Complex Registry in 1985 at the University of Hong Kong. In 2004, 44 index cases (the male to female ratio was 0.75:1) were registered. Three had a positive family history of tuberous sclerosis complex. Thus, the total number of tuberous sclerosis complex cases was 47. We adopted the diagnostic criteria of tuberous sclerosis complex for case ascertainment. The period prevalence rate of tuberous sclerosis complex for children and adolescents aged < 20 years is 3.5 per 10,000 (on Hong Kong island, excluding the eastern region with 125,100 aged < 20 years in 2003). Of 44 cases with tuberous sclerosis complex, 7 had autistic disorder. Thus, the incidence of autistic disorder in tuberous sclerosis complex is 16%. During the 17-year period (1986-2003), we collected a database of 753 children (668 boys and 84 girls; male to female ratio 8:1) with autistic disorder and pervasive developmental disorders. For all children with autistic disorder or pervasive developmental disorders, we routinely examined for any features of tuberous sclerosis complex by looking for neurocutaneous markers such as depigmented spots, which appear in 50% of children with tuberous sclerosis complex by the age of 2 years. For those with infantile spasm or epilepsy, the clinical features of tuberous sclerosis complex were monitored regularly during follow-up. Of these, seven had tuberous sclerosis complex. Thus, the incidence of tuberous sclerosis complex in autistic disorder is 0.9%. All of these children are mentally retarded, with moderate to severe grades in an intellectual assessment conducted by a clinical psychologist. Future studies should be directed toward looking at the various behavioral phenotypes in tuberous sclerosis complex and defining these with standardized criteria to look for any real association with the underlying genetic mutation of TSC1 or TSC2 gene or even the site of tubers in the brain.

The effect of nabilone on neuropsychological functions related to driving ability: an extended case series.

PubMed

Kurzthaler, Ilsemarie; Bodner, Thomas; Kemmler, Georg; Entner, Tanja; Wissel, Joerg; Berger, Thomas; Fleischhacker, W Wolfgang

2005-06-01

The primary goal of this prospective extended case series was to obtain the first data about the potential influence of nabilone intake on driving ability related neuropsychological functions. Six patients were investigated within a placebo controlled, double-blind crossover study of this synthetic cannabinoid (2 mg/day) in patients with multiple sclerosis and spasticity associated pain. Five neuropsychological functions (reaction time, working memory, divided attention, psychomotor speed and mental flexibility) were assessed. No indication was found of a deterioration of any of the five investigated neuropsychological functions during the 4-week treatment period with nabilone. Copyright 2005 John Wiley & Sons, Ltd.

Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: results of a reduced-dose whole-body MDCT study.

PubMed

Schulze, Maximilian; Weisel, Katja; Grandjean, Caroline; Oehrlein, Katharina; Zago, Manola; Spira, Daniel; Horger, Marius

2014-01-01

The objective of our study was to assess the frequency, location, extent, and patterns of bone sclerosis occurring in patients with multiple myeloma (MM) during bortezomib-based therapy. From June 2003 through December 2011, 593 whole-body reduced-dose MDCT studies were performed of 79 consecutive patients receiving bortezomib. The median surveillance time was 21 months (range, 3-67 months). Baseline studies were compared with follow-up studies during therapy (follow-up 1), at the end of therapy (follow-up 2), and 12 months after cessation of bortezomib therapy (follow-up 3). We recorded any sclerotic change occurring inside or along the margins of the osteolytic lesions, in the cancellous bone, or inside preexistent medullary or extramedullary lesions. The time point of occurrence of bone sclerosis was correlated with the best hematologic response category. Fourteen (17.7%) patients developed focal (n = 11) or diffuse (n = 3) bone sclerosis. The time window from bortezomib initiation to radiographic detection of bone sclerosis was 8 months (SD, 7 months). Sclerosis occurred at multiple sites (n = 7) or at an isolated site (n = 7). On subsequent whole-body reduced-dose MDCT studies, sclerosis further increased in seven (50%) patients. Hematologic best response during bortezomib treatment was complete response (n = 1), very good partial response (n = 2), partial response (n = 8), and stable disease (n = 3). Radiologic response at the time of sclerosis detection was partial response (n = 8), stable disease (n = 2), and progressive disease (n = 4). Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

Viral exposures and MS outcome in a prospective cohort of children with acquired demyelination.

PubMed

Makhani, Naila; Banwell, Brenda; Tellier, Raymond; Yea, Carmen; McGovern, Suzanne; O'Mahony, Julia; Ahorro, Jean M; Arnold, Douglas; Sadovnick, A Dessa; Marrie, Ruth A; Bar-Or, Amit

2016-03-01

Epstein-Barr virus (EBV) infection is associated with increased multiple sclerosis (MS) risk. Recently, cytomegalovirus (CMV) infection has been proposed as a protective factor against MS development. We determined EBV, herpes simplex virus, varicella-zoster virus and CMV seroprevalence in 247 prospectively followed children with acquired demyelinating syndromes (ADS). Remote EBV infection was more common in children with MS than those with monophasic ADS while CMV infection was more common in children with monophasic ADS. Children displaying evidence of remote EBV without CMV infection were at highest risk of subsequent MS diagnosis. Viral infection repertoire detected at ADS provides important prognostic information. © The Author(s), 2015.

Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

PubMed

Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

2016-06-01

It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. © The Author(s) 2016.

Comparison of corneal endothelial changes following phacoemulsification with transversal and torsional phacoemulsification machines

PubMed Central

Ataş, Mustafa; Demircan, Süleyman; Karatepe Haşhaş, Arzu Seyhan; Gülhan, Ahmet; Zararsız, Gökmen

2014-01-01

AIM To compare and evaluate the phacoemulsification parameters and postoperative endothelial cell changes of two different phacoemulsification machines, each with different modes, but also to assess the relationship between postoperative endothelial cell loss and the phacoemulsification parameters, as well as the other factors in both groups. METHODS This prospective observational study was comprised of consecutive eligible cataract patients operated with phacoemulsification technique performed by the same surgeon using either a WHITESTAR Signature Ellips FX (transversal, group 1) or Infiniti OZil IP (torsional, group 2) machine. RESULTS The study included 86 patients. Baseline characteristics in the groups were similar. The median nuclear sclerosis grade was 3 (2-4) in the first group and 2 (2-4) in the second group (P=0.265). Both groups had similar phacoemulsification needle times (group 1: 60.63±36 s; group 2: 55.98±30 s; P=0.789). The percentage of endothelial cell loss 30d after surgery ranged from 3% to 15% with a median of 7% in group 1, and from 2% to 13% with a median of 6% in group 2; however, there was no statistically significant difference between the groups (P=0.407). Hexagonality (P=0.794) and the coefficient of variation (CV; P=0.142) did not differ significantly between the groups before and 30d after surgery. A significant positive correlation was found between the endothelial cell loss and nuclear sclerosis grade (group 1: P<0.001; group 2: P<0.001) and between the endothelial cell loss and average phacoemulsification power (group 1: P=0.007; group 2: P=0.008). CONCLUSION Both of these machines were efficient, with similar endothelial cell loss. This endothelial cell loss was related to the increased nuclear sclerosis grade and increased phacoemulsification power. PMID:25349800

Comparison of corneal endothelial changes following phacoemulsification with transversal and torsional phacoemulsification machines.

PubMed

Ataş, Mustafa; Demircan, Süleyman; Karatepe Haşhaş, Arzu Seyhan; Gülhan, Ahmet; Zararsız, Gökmen

2014-01-01

To compare and evaluate the phacoemulsification parameters and postoperative endothelial cell changes of two different phacoemulsification machines, each with different modes, but also to assess the relationship between postoperative endothelial cell loss and the phacoemulsification parameters, as well as the other factors in both groups. This prospective observational study was comprised of consecutive eligible cataract patients operated with phacoemulsification technique performed by the same surgeon using either a WHITESTAR Signature Ellips FX (transversal, group 1) or Infiniti OZil IP (torsional, group 2) machine. The study included 86 patients. Baseline characteristics in the groups were similar. The median nuclear sclerosis grade was 3 (2-4) in the first group and 2 (2-4) in the second group (P=0.265). Both groups had similar phacoemulsification needle times (group 1: 60.63±36 s; group 2: 55.98±30 s; P=0.789). The percentage of endothelial cell loss 30d after surgery ranged from 3% to 15% with a median of 7% in group 1, and from 2% to 13% with a median of 6% in group 2; however, there was no statistically significant difference between the groups (P=0.407). Hexagonality (P=0.794) and the coefficient of variation (CV; P=0.142) did not differ significantly between the groups before and 30d after surgery. A significant positive correlation was found between the endothelial cell loss and nuclear sclerosis grade (group 1: P<0.001; group 2: P<0.001) and between the endothelial cell loss and average phacoemulsification power (group 1: P=0.007; group 2: P=0.008). Both of these machines were efficient, with similar endothelial cell loss. This endothelial cell loss was related to the increased nuclear sclerosis grade and increased phacoemulsification power.

Associations of HLA DRB1 alleles with IgG oligoclonal bands and their influence on multiple sclerosis course and disability status.

PubMed

Balnytė, Renata; Rastenytė, Daiva; Vaitkus, Antanas; Skrodenienė, Erika; Vitkauskienė, Astra; Ulozienė, Ingrida

2016-01-01

Oligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). The aim of this study was to evaluate the associations between HLA DRB1 alleles and oligoclonal bands (OCBs) in the disease course and disability of multiple sclerosis (MS) patients. This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analyzed using isoelectric focusing and IgG specific immunofixation to test for the presence of intrathecal specific OCB. HLA DRB1*08 allele was related to a lower degree of disability. Oligoclonal bands were an independent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *13, *15 and *16 alleles. Age at the onset and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. Detection of OCBs in the CSF was associated with the higher possibility of RR MS progression in all cases, except when the *08 allele was present. OCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Predictors of need for noninvasive ventilation during respiratory tract infections in medically stable, non-ventilated subjects with amyotrophic lateral sclerosis.

PubMed

Sancho, Jesus; Servera, Emilio; Bañuls, Pilar; Marin, Julio

2015-04-01

Acute lower respiratory infections can impair muscle strength in patients with amyotrophic lateral sclerosis (ALS). When associated with an increase in load on the respiratory system, this situation may precipitate hypercapnic respiratory failure in non-ventilated patients with ALS. The aim of this study was to determine whether a clinical or functional parameter can predict the need for noninvasive ventilation (NIV) during an acute respiratory infection for medically stable, non-ventilated patients with ALS. This was a prospective study involving all non-ventilated subjects with ALS admitted due to an acute respiratory infection to a respiratory care unit from a tertiary hospital. Thirty-two non-ventilated subjects with ALS were admitted to our respiratory care unit due to an acute respiratory infection: 60.72 ± 10.54 y, 13 males, 23 with spinal onset, FVC of 1.58 ± 0.83 L, FVC of 56.21 ± 23.15% of predicted, peak cough flow of 3.41 ± 1.77 L/s, maximum insufflation capacity of 1.87 ± 0.94 L, revised Amyotrophic Lateral Sclerosis Functional Rating Scale score of 22.80 ± 8.83, and Norris bulbar score of 23.48 ± 12.14. Fifteen subjects required NIV during the episode. Logistic regression analysis showed that the only predictors of need for NIV were percent-of-predicted FVC (odds ratio of 1.06, 95% CI 1.01-1.11, P = .02) and peak cough flow (odds ratio of 2.57, 95% CI 1.18-5.59, P = .02). In medically stable, non-ventilated patients with ALS, measurement of percent-of-predicted FVC and peak cough flow can predict the need for NIV during an acute lower respiratory tract infection. Copyright © 2015 by Daedalus Enterprises.

Reserve-building activities in multiple sclerosis patients and healthy controls: a descriptive study.

PubMed

Schwartz, Carolyn E; Ayandeh, Armon; Ramanathan, Murali; Benedict, Ralph; Dwyer, Michael G; Weinstock-Guttman, Bianca; Zivadinov, Robert

2015-08-12

Cognitive reserve has been implicated as a possible protective factor in multiple sclerosis (MS) but to date no study has compared reserve-building activities across disease course or to healthy controls. This study aims to describe differences in reserve-building activities across the MS disease course and healthy controls. Secondary analysis of a cross-sectional cohort study that included 276 healthy controls, and subjects with clinically isolated syndrome (CIS; n = 67), relapsing-remitting MS (RRMS; n = 358) and secondary progressive MS (PMS; n = 109). Past reserve-building activities were operationalized as occupational attainment and education. Current activities comprised 6 strenuous and 6 non-strenuous activities, including 5 reserve-building activities and television-watching. Multivariate Analysis of Variance models examined group differences in past and current activities, after adjusting for covariates. There were group differences in past and current reserve-building activities. SPMS patients had lower past reserve-building activities than healthy controls. All forms of MS engaged in fewer strenuous current reserve-building pursuits than healthy controls. RRMS read less than healthy controls. SPMS engaged in fewer job-related non-strenuous activities. All MS groups watched more television than healthy controls. MS patients show significantly fewer past and present reserve-building activities. Although it is difficult to establish causality without future prospective studies, lifestyle-modifying interventions should prioritize expanding MS patients' repertoire of strenuous and non-strenuous activities.

Long-term management of patients with multiple sclerosis.

PubMed

Weightman, Cherie

2006-07-01

This article explores the challenges of long-term case management for patients who have multiple sclerosis (MS). Currently there is scant research into district nursing input into long-term management of patients who have MS. Until now the role of the community nurses has been confined to palliation or terminal care, focusing on the more physical manifestations of MS. The contemporary role of district nurse is going to evolve to include proactive approaches. Governmental initiatives demand proactive services, and place emphasis on self-care for patients with MS. Themes that emerge from this article relate to the pre-existing skills--such as managing patients with complex needs and the advanced assessment skills--that will be required to achieve this. What is clear is that community nurses already possess many of the prerequisite skills needed for long-term management, and they should not be daunted by this prospect.

Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

ERIC Educational Resources Information Center

Mackenzie, Catherine; Green, Jan

2009-01-01

Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: a Case-Control and Genotype-Phenotype Study.

PubMed

Křenek, Pavel; Benešová, Yvonne; Bienertová-Vašků, Julie; Vašků, Anna

2018-04-01

Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, p a = 0.02; Taq, p g = 0.02, p a = 0.02; BsmI, p g = 0.02, p a = 0.04; ApaI, p g = 0.008, p a = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: p g = 0.01, p a = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT p corr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.

Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review.

PubMed

Lu, Ellen; Wang, Bing Wei; Guimond, Colleen; Synnes, Anne; Sadovnick, Dessa; Tremlett, Helen

2012-09-11

To systematically review the literature regarding safety of disease-modifying drug (DMD) use during pregnancy on perinatal and developmental outcomes in offspring of patients with multiple sclerosis (MS). A PubMed and EMBASE search up to February 2012 was conducted with a manual search of references from relevant articles. Selected studies were evaluated using internationally accepted criteria. Fifteen studies identified 761 interferon β-, 97 glatiramer acetate-, and 35 natalizumab-exposed pregnancies. Study quality ranged from poor to good; no study was rated excellent. Small sample sizes limited most studies. Compared with data for unexposed pregnancies, fair- to good-quality prospective cohort studies reported that interferon β exposure was associated with lower mean birth weight, shorter mean birth length, and preterm birth (<37 weeks), but not low birth weight (<2,500 g), cesarean delivery, congenital anomaly (including malformation), or spontaneous abortion. Fewer studies of fair quality were available for glatiramer acetate and natalizumab. Glatiramer acetate exposure was not associated with lower mean birth weight, congenital anomaly, preterm birth, or spontaneous abortion. Natalizumab exposure did not appear to be associated with shorter mean birth length, lower mean birth weight, or lower mean gestational age. No studies examined mitoxantrone or fingolimod exposure. One study of paternal DMD use during conception found no effect on gestational age or birth weight. Few studies examined longer-term developmental outcomes. Further studies are needed to determine the potential risks associated with preconceptional and in utero DMD exposure in patients with MS. Discontinuation of DMDs before conception is still recommended.

Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study.

PubMed

Gilio, Francesca; Iacovelli, Elisa; Frasca, Vittorio; Gabriele, Maria; Giacomelli, Elena; Picchiori, Floriana; Soldo, Pietro; Cipriani, Anna Maria; Ruoppolo, Giovanni; Inghilleri, Maurizio

2010-08-01

Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

Tolerance of Volume Control Noninvasive Ventilation in Subjects With Amyotrophic Lateral Sclerosis.

PubMed

Martínez, Daniel; Sancho, Jesús; Servera, Emilio; Marín, Julio

2015-12-01

Noninvasive ventilation (NIV) tolerance has been identified as an independent predictor of survival in amyotrophic lateral sclerosis (ALS). Volume control continuous mandatory ventilation (VC-CMV) NIV has been associated with poor tolerance. The aim of this study was to determine the tolerance of subjects with ALS to VC-CMV NIV. This was a prospective study involving subjects with ALS who were treated with VC-CMV NIV. Respiratory and functional parameters were recorded when the subjects began ventilatory support. NIV tolerance was evaluated after 3 months. Eighty-seven subjects with ALS were included. After 3 months, 80 subjects (92%) remained tolerant of NIV. Tolerant subjects presented greater survival (median 22.0 months, 95% CI 14.78-29.21) than intolerant subjects (median 6.0 months, 95% CI 0.86-11.13) (P = .03). The variables that best predicted NIV tolerance were mechanically assisted cough peak flow (P = .01) and percentage of time spent with SpO2 < 90% at night while on NIV (P = .03) CONCLUSIONS: VC-CMV NIV provides high rates of NIV tolerance in subjects with ALS. Mechanically assisted cough peak flow and percentage of time spent with SpO2 < 90% at night while using NIV are the 2 factors associated with tolerance of VC-CMV NIV in subjects with ALS. Copyright © 2015 by Daedalus Enterprises.

"Cure" for multiple sclerosis (MS)-Evolving views of therapy goals in patients on different stages of the disease: A pilot study in a cohort of Polish MS patients.

PubMed

Chacińska, Weronika; Brzostowska, Marta; Nojszewska, Monika; Podlecka-Piętowska, Aleksandra; Jędrzejczak, Wiesław W; Snarski, Emilian

2017-06-01

New aggressive treatments promise improvement of results in the treatment of multiple sclerosis (MS), however, with high risk of serious complications. In this study, we analyzed patients' acceptance for risks connected with the MS treatment. The study was designed as a prospective nonanonymous online questionnaire. Responders were asked about the definition of the "cure" for MS and crucial goals in the treatment. One hundred and eighty patients filled in the questionnaire (129 women and 51 men), and the mean age was 33 years ( SD  = 10.29). The MS forms were as follows: relapsing-remitting (65%), secondary progressive (14%), primary progressive (10%), and other (11%), with mean EDSS score of 3 points ( SD  = 2.6). For 50% of the patients, relief of symptoms such as fatigue (72%), paresis (66%), and balance disorders (65%) was synonymous with "cure." The patients with faster progression of the disease were likely to accept risky "curative" treatments-with average 68% accepted mortality risk ( p  = .003). Over 81% of patients accepted mortality rates over 1% for the treatment that achieves self-defined cure. The study shows that the MS patients are likely to accept even very risky treatments as long as they promise patient-defined "cure."

Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

PubMed

Di Gennaro, Giancarlo; Casciato, Sara; Quarato, Pier Paolo; Mascia, Addolorata; D'Aniello, Alfredo; Grammaldo, Liliana G; De Risi, Marco; Meldolesi, Giulio N; Romigi, Andrea; Esposito, Vincenzo; Picardi, Angelo

2015-01-01

To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome. Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001). Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Association between alcohol consumption and amyotrophic lateral sclerosis: a meta-analysis of five observational studies.

PubMed

E, Meng; Yu, Sufang; Dou, Jianrui; Jin, Wu; Cai, Xiang; Mao, Yiyang; Zhu, Daojian; Yang, Rumei

2016-08-01

The purpose of this study is to examine the association between alcohol consumption and amyotrophic lateral sclerosis. Published literature on the association between alcohol consumption and amyotrophic lateral sclerosis was retrieved from the PubMed and Embase databases. Two authors independently extracted the data. The quality of the identified studies was evaluated according to the Newcastle-Ottawa scale. Subgroup and sensitivity analyses were performed and publication bias was assessed. Five articles, including one cohort study and seven case-control studies, and a total of 431,943 participants, were identified. The odds ratio for the association between alcohol consumption and amyotrophic lateral sclerosis was 0.57 (95 % confidence interval 0.51-0.64). Subgroup and sensitivity analyses confirmed the result. Evidence for publication bias was detected. Alcohol consumption reduced the risk of developing amyotrophic lateral sclerosis compared with non-drinking. Alcohol, therefore, has a potentially neuroprotective effect on the development of amyotrophic lateral sclerosis.

Noninvasive ventilation in amyotrophic lateral sclerosis: effects on sleep quality and quality of life.

PubMed

Vandoorne, Eva; Vrijsen, Bart; Belge, Catharina; Testelmans, Dries; Buyse, Bertien

2016-12-01

Little is known about the effects of noninvasive ventilation (NIV) on sleep quality in amyotrophic lateral sclerosis (ALS). We aim to evaluate the long-term effects of NIV on sleep quality and quality of life in patients with ALS. In this prospective observational study, 13 ALS patients were followed for one year after initiating NIV. We evaluated sleep quality, quality of life and functional status with several questionnaires: Epworth sleepiness Scale (ESS), Pittsburg sleep quality index (PSQI), Short Form 36 Health Questionnaire (SF-36), McGill Quality of Life questionnaire (McGillQoL) and revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores (ALSFRS-R). Median and interquartile range (IQR) at the start of NIV was 59 (53-65) years. The ALSFRS-R at start was 30 (24-37) (median, IQR), with three patients having severe bulbar impairment (ALSFRS-R-bulbar ≤ 9). The P a CO 2 at start of NIV treatment was 48 (43-52) mmHg (median, IQR). During the one-year follow-up period, a significant decrease in the ALSFRS-R was observed. The impact of NIV in a short term (1 month) revealed a statistically significant decrease in ESS, decrease in total PSQI and of four PSQI subscales and improvement of almost all subscales of the McGill questionnaire. Long-term analyses (9 months to 1 year) revealed that amelioration in ESS and total PSQI was sustained. We conclude that accurately titrated NIV in ALS patients can stabilize sleep quality and quality of life for at least one year, despite significant disease progression.

Progressive solitary sclerosis: Gradual motor impairment from a single CNS demyelinating lesion.

PubMed

Keegan, B Mark; Kaufmann, Timothy J; Weinshenker, Brian G; Kantarci, Orhun H; Schmalstieg, William F; Paz Soldan, M Mateo; Flanagan, Eoin P

2016-10-18

To report patients with progressive motor impairment resulting from an isolated CNS demyelinating lesion in cerebral, brainstem, or spinal cord white matter that we call progressive solitary sclerosis. Thirty patients were identified with (1) progressive motor impairment for over 1 year with a single radiologically identified CNS demyelinating lesion along corticospinal tracts, (2) absence of other demyelinating CNS lesions, and (3) no history of relapses affecting other CNS pathways. Twenty-five were followed prospectively in our multiple sclerosis (MS) clinic and 5 were identified retrospectively from our progressive MS database. Patients were excluded if an alternative etiology for progressive motor impairment was found. Multiple brain and spinal cord MRI were reviewed by a neuroradiologist blinded to the clinical details. The patients' median age was 48.5 years (range 23-71) and 15 (50%) were women. The median follow-up from symptom onset was 100 months (range 15-343 months). All had insidiously progressive upper motor neuron weakness attributable to the solitary demyelinating lesion found on MRI. Clinical presentations were hemiparesis/monoparesis (n = 24), quadriparesis (n = 5), and paraparesis (n = 1). Solitary MRI lesions involved cervical spinal cord (n = 18), cervico-medullary/brainstem region (n = 6), thoracic spinal cord (n = 4), and subcortical white matter (n = 2). CSF abnormalities consistent with MS were found in 13 of 26 (50%). Demyelinating disease was confirmed pathologically in 2 (biopsy, 1; autopsy, 1). Progressive solitary sclerosis results from an isolated CNS demyelinating lesion. Future revisions to MS diagnostic criteria could incorporate this presentation of demyelinating disease. © 2016 American Academy of Neurology.

Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival

PubMed Central

Henkel, Jenny S; Beers, David R; Wen, Shixiang; Rivera, Andreana L; Toennis, Karen M; Appel, Joan E; Zhao, Weihua; Moore, Dan H; Powell, Suzanne Z; Appel, Stanley H

2013-01-01

In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients. PMID:23143995

Characteristics and correlates of coping with multiple sclerosis: a systematic review.

PubMed

Keramat Kar, Maryam; Whitehead, Lisa; Smith, Catherine M

2017-10-10

The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client-centered rehabilitation for people living with multiple sclerosis based on their individual responses and perceptions for coping. Implications for rehabilitation Engagement in coping with multiple sclerosis has been associated with individual factors and neuropsychological functions. Considering individual and disease-related factors would allow healthcare professionals to provide more tailored interventions to maintain and master coping with multiple sclerosis. People living with multiple sclerosis should be empowered to appraise and manage ability to cope based on the contextual evidence (individual and clinical condition). Rehabilitation services should move beyond physical management incorporating behavioral aspects for better functioning in living with multiple sclerosis.

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

PubMed Central

Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

2015-01-01

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

The long-term outcomes of epilepsy surgery

PubMed Central

Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections. PMID:29768433

The long-term outcomes of epilepsy surgery.

PubMed

Mohan, Midhun; Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1-27). Kaplan-Meier estimates showed that 47% (95% CI 40-58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31-45) at 10 years after surgery. 74% (95% CI 69-80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64-77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections.

Prospective study to evaluate the clinical and radiological outcome of patients with scleroderma of the face.

PubMed

Careta, Mariana Figueiroa; Leite, Claudia da Costa; Cresta, Fernando; Albino, Jose; Tsunami, Mirian; Romiti, Ricardo

2013-09-01

Scleroderma featuring rare connective tissue disease that manifests as skin sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement and localized scleroderma or morphea which classically presents benign evolution and self-limited, confined to the skin and/or underlying tissue. Recent studies show that the localized form may possibly course with involvement of internal organs and variable morbidity. This study aimed to determine the demographic characteristics, the prevalence of systemic manifestations and laboratory findings, as well as the association with autoimmune diseases, and the evolution of neurological findings, both clinical as brain MRI in patients with scleroderma of the face and its relation with the activity skin. Patients with localized scleroderma with facial involvement were evaluated and underwent neurological examination, magnetic resonance imaging and ophthalmology evaluation. After 3years, the patients were subjected again to MRI. We studied 12 patients with localized scleroderma of the face. Of this total, headache being the most frequent complaint found in 66.7% of patients, 33.3% had neurological changes possibly associated with scleroderma. As for ophthalmologic evaluation, 25% of patients showed abnormalities. The most frequent parenchymal finding was the presence of lesions with hyperintense or hypointense signal in 75% of patients, followed by ventricular asymmetry at 16.7%. Of the patients who had neurological deficits, 75% also had a change to MRI. In all patients, imaging findings after 3years were unchanged. During this interval of 3years, 25% of patients showed signs of activity of scleroderma. Patients with localized scleroderma of the face have a high prevalence of neurological and ophthalmological changes. Based on these findings, we suggest that all cases of localized scleroderma of the face should be thoroughly examined for the presence of systemic changes. Copyright © 2013 Elsevier B.V. All rights reserved.

Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach.

PubMed

Cappa, Ryan; Theroux, Liana; Brenton, J Nicholas

2017-10-01

Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth. Genetic predisposition contributes to the risk of multiple sclerosis, and the major histocompatibility complex on chromosome 6 makes the single largest contribution to susceptibility to multiple sclerosis. With the use of large-scale genome-wide association studies, other non-major histocompatibility complex alleles have been identified as independent risk factors for the disease. The bridge between environment and genes likely lies in the study of epigenetic processes, which are environmentally-influenced mechanisms through which gene expression may be modified. This article will review these topics to provide a framework for discussion of a comprehensive approach to counseling and ultimately treating the pediatric patient with multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Acoustic reflex patterns in amyotrophic lateral sclerosis.

PubMed

Canale, Andrea; Albera, Roberto; Lacilla, Michelangelo; Canosa, Antonio; Albera, Andrea; Sacco, Francesca; Chiò, Adriano; Calvo, Andrea

2017-02-01

The aim of the study is to investigate acoustic reflex testing in amyotrophic lateral sclerosis patients. Amplitude, latency, and rise time of stapedial reflex were recorded for 500 and 1000 Hz contralateral stimulus. Statistical analysis was performed by the Wilcoxon test and the level of significance was set at 5 %. Fifty-one amyotrophic lateral sclerosis patients and ten sex- and age-matched control subjects were studied. Patients were further divided in two groups: amyotrophic lateral sclerosis-bulbar (38 cases, with bulbar signs at evaluation) and amyotrophic lateral sclerosis-spinal (13 cases, without bulbar signs at evaluation). Stapedial reflex was present in all patients. There was a statistically significant difference in the mean amplitude, latency, and rise time between the amyotrophic lateral sclerosis patients as compared with the controls. Amplitude was lower in both the amyotrophic lateral sclerosis-bulbar and the amyotrophic lateral sclerosis-spinal patients than in the controls (p < 0.05) and rise time was longer in both patient groups compared with the controls (p < 0.05). These results confirm the presence of abnormal acoustic reflex patterns in amyotrophic lateral sclerosis cases with bulbar signs and, moreover, suggesting a possible subclinical involvement of the stapedial motor neuron even in amyotrophic lateral sclerosis-spinal patients. Amplitude and rise time seem to be good sensitive parameters for investigating subclinical bulbar involvement.

Effects of Acupuncture on Gait of Patients with Multiple Sclerosis.

PubMed

Criado, Maria Begoña; Santos, Maria João; Machado, Jorge; Gonçalves, Arminda Manuela; Greten, Henry Johannes

2017-11-01

Multiple sclerosis is considered a complex and heterogeneous disease. Approximately 85% of patients with multiple sclerosis indicate impaired gait as one of the major limitations in their daily life. Acupuncture studies found a reduction of spasticity and improvement of fatigue and imbalance in patients with multiple sclerosis, but there is a lack of studies regarding gait. We designed a study of acupuncture treatment, according to the Heidelberg model of Traditional Chinese Medicine (TCM), to investigate if acupuncture can be a useful therapeutic strategy in patients with gait impairment in multiple sclerosis of relapsing-remitting type. The sample consisted of 20 individuals with diagnosis of multiple sclerosis of relapsing-remitting type. Gait impairment was evaluated by the 25-foot walk test. The results showed differences in time to walk 25 feet following true acupuncture. In contrast, there was no difference in time to walk 25 feet following sham acupuncture. When using true acupuncture, 95% of cases showed an improvement in 25-foot walk test, compared with 45% when sham acupuncture was done. Our study protocol provides evidence that acupuncture treatment can be an attractive option for patients with multiple sclerosis, with gait impairment.

Military Service and Amyotrophic Lateral Sclerosis in a Population-based Cohort

PubMed Central

Cudkowicz, Merit E.; Johnson, Norman

2015-01-01

Background: Military service has been suggested to be associated with an increased risk of amyotrophic lateral sclerosis (ALS), but only one prospective study—of a volunteer cohort—has examined this question. Methods: We prospectively assessed the relation between service in the military and ALS mortality among participants in the National Longitudinal Mortality Study, a population-representative cohort of U.S. men and women surveyed from 1973 through 2002. Participant follow-up was conducted from 1979 through 2002 for ALS mortality. There were 696,743 men and 392,571 women who were 25 years old or more with military service data. In this group, there were 375 male ALS deaths and 96 female ALS deaths. Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards. Results: Men who served in the military had an increased adjusted ALS death rate [HR: 1.23; 95% confidence interval (CI): 0.98, 1.53] compared with those who did not serve. An increase in ALS mortality was found among those who served during World War II (HR: 1.47; 95% CI: 1.13, 1.91) but not during other time periods. This pattern of results was similar for women, but with larger confidence intervals (HR for military service: 1.26; 95% CI: 0.29, 5.59; HR for service during World War II: 2.03; 95% CI: 0.45, 9.05). Conclusions: Military personnel have an increased risk of ALS, which may be specific to certain service periods although there was no data on actual deployment. Because of the longer follow-up time for World War II veterans, we cannot rule out that increased risk for those who served during other periods would be seen with further follow-up. PMID:26414854

Pediatric multiple sclerosis: Clinical features and outcome.

PubMed

Waldman, Amy; Ness, Jayne; Pohl, Daniela; Simone, Isabella Laura; Anlar, Banu; Amato, Maria Pia; Ghezzi, Angelo

2016-08-30

Multiple sclerosis (MS) in children manifests with a relapsing-remitting MS (RRMS) disease course. Acute relapses consist of new neurologic deficits persisting greater than 24 hours, in the absence of intercurrent illness, and occur with a higher frequency early in the disease as compared to adult-onset RRMS. Most pediatric patients with MS recover well from these early relapses, and cumulative physical disability is rare in the first 10 years of disease. Brainstem attacks, poor recovery from a single attack, and a higher frequency of attacks portend a greater likelihood of future disability. Although prospective pediatric-onset MS cohorts have been established in recent years, there remains very limited prospective data detailing the longer-term clinical outcome of pediatric-onset MS into adulthood. Whether the advent of MS therapies, and the largely off-label access to such therapies in pediatric MS, has improved prognosis is unknown. MS onset during the key formative academic years, concurrent with active cognitive maturation, is an important determinant of long-term outcome, and is discussed in detail in another article in this supplement. Finally, increasing recognition of pediatric MS worldwide, recent launch of phase III trials for new agents in the pediatric MS population, and the clear imperative to more fully appreciate health-related quality of life in pediatric MS through adulthood highlight the need for standardized, validated, and robust outcome measures. © 2016 American Academy of Neurology.

Recent advances in the understanding of infectious mononucleosis: are prospects improved for treatment or control?

PubMed

Auwaerter, Paul G

2006-12-01

Symptomatic primary Epstein-Barr virus infection is known more commonly as infectious mononucleosis, an illness known for afflicting adolescents and younger adults as a febrile illness accompanied by pharyngitis and lymphadenopathy. Historically believed to be generally benign, infectious mononucleosis has been linked more recently to increased risks of developing Hodgkin's lymphoma and multiple sclerosis. Advances in the understanding of host immune responses to Epstein-Barr virus have begun to elucidate the reasons why younger children typically experience subclinical infection whereas older individuals develop infectious mononucleosis. This review will highlight recent advances in the understanding of primary Epstein-Barr virus infection, and whether prospective treatments or vaccine strategies may affect native infection and its sequelae.

Antecedents of Coping with the Disease in Patients with Multiple Sclerosis: A Qualitative Content Analysis

PubMed Central

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2017-01-01

ABSTRACT Background: Due to many physical and mental disorders that occur in multiple sclerosis patients, identifying the factors affecting coping based on the experiences of patients using qualitative study is essential to improve their quality of life. This study was conducted to explore the antecedents of coping with the disease in patients with multiple sclerosis. Methods: This is a qualitative study conducted on 11 patients with multiple sclerosis in 2015 in Tehran, Iran. These patients were selected based on purposive sampling. Data were collected using semi-structured and in-depth interviews and coded. These data were analyzed using the conventional content analysis. The rigor of qualitative data using the criteria proposed by Guba and Lincoln were assessed. Results: Five main categories were revealed: (1) social support, (2) lenience, (3) reliance on faith, (4) knowledge of multiple sclerosis and modeling, and (5) economic and environmental situation. Each category had several distinct sub-categories. Conclusions: The results of this study showed that coping with multiple sclerosis is a complex, multidimensional and contextual concept that is affected by various factors in relation to the context of Iran. The findings of the study can provide the healthcare professionals with deeper recognition and understanding of these antecedents to improve successful coping in Iranian patients suffering from multiple sclerosis. PMID:28097178

A prospective pilot study measuring muscle volumetric change in amyotrophic lateral sclerosis.

PubMed

Jenkins, Thomas M; Burness, Christine; Connolly, Daniel J; Rao, D Ganesh; Hoggard, Nigel; Mawson, Susan; McDermott, Christopher J; Wilkinson, Iain D; Shaw, Pamela J

2013-09-01

Our objective was to investigate the potential of muscle volume, measured with magnetic resonance (MR), as a biomarker to quantify disease progression in patients with amyotrophic lateral sclerosis (ALS). In this longitudinal pilot study, we first sought to determine the stability of volumetric muscle MR measurements in 11 control subjects at two time-points. We assessed feasibility of detecting atrophy in four patients with ALS, followed at three-month intervals for 12 months. Muscle power and MR volume were measured in thenar eminence (TEm), first dorsal interosseous (1DIO), tibialis anterior (TA) and tongue. Changes over time were assessed using linear regression models and t-tests. Results demonstrated that, in controls, no volumetric MR changes were seen (mean volume variation in all muscles < 5%, p > 0.1). In patients, between-subject heterogeneity was identified. Trends for volume loss were found in TEm (mean, - 26.84%, p = 0.056) and TA (- 8.29%, p = 0.077), but not in 1DIO (- 18.47%, p = 0.121) or tongue (< 5%, p = 0.367). In conclusion, volumetric muscle MR appears a stable measure in controls, and progressive volume loss was demonstrable in individuals with ALS in whom clinical weakness progressed. In this small study, subclinical atrophy was not demonstrable using muscle MR. Clinico-radiological discordance between muscle weakness and MR atrophy could reflect a contribution of upper motor neuron pathology.

Clinical presentation of neurocysticercosis-related epilepsy.

PubMed

Duque, Kevin R; Burneo, Jorge G

2017-11-01

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and a major risk factor for seizures and epilepsy. Seizure types in NCC vary largely across studies and seizure semiology is poorly understood. We discuss here the studies regarding seizure types and seizure semiology in NCC, and examine the clinical presentation in patients with NCC and drug-resistant epilepsy. We also provide evidence of the role of MRI and EEG in the diagnosis of NCC-related epilepsy. Focal seizures are reported in 60-90% of patients with NCC-related epilepsy, and around 90% of all seizures registered prospectively are focal not evolving to bilateral tonic-clonic seizures. A great number of cases suggest that seizure semiology is topographically related to NCC lesions. Patients with hippocampal sclerosis and NCC have different clinical and neurophysiological characteristics than those with hippocampal sclerosis alone. Different MRI protocols have allowed to better differentiate NCC from other etiologies. Lesions' stages might account on the chances of finding an interictal epileptiform discharge. Studies pursuing the seizure onset in patients with NCC are lacking and they are specially needed to determine both whether the reported events of individual cases are seizures, and whether they are related to the NCC lesion or lesions. This article is part of a Special Issue entitled "Neurocysticercosis and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study.

PubMed

Krupp, Lauren B; Pohl, Daniela; Ghezzi, Angelo; Boyko, Alexey; Tenembaum, Silvia; Chen, Liang; Aycardi, Ernesto; Banwell, Brenda

2016-04-15

To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon β-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [<12 years] and adolescents [12-17 years]). US adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5 kg/m(2)), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon β-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon β-1a to another DMT before the end of the observation period. This retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon β-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Hippocampal sclerosis in advanced age: clinical and pathological features.

PubMed

Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

2011-05-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P<0.015) and also 5.5-6.5 years before death (P<0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer's disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing.

Hippocampal sclerosis in advanced age: clinical and pathological features

PubMed Central

Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

2011-01-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer’s disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer’s Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n = 106). For individuals aged ≥95 years at death (n = 179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ‘definite’ Alzheimer’s disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n = 10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P < 0.015) and also 5.5–6.5 years before death (P < 0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer’s disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing. PMID:21596774

In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

DTIC Science & Technology

2014-09-01

and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI PRINCIPAL INVESTIGATOR: Dr. Caterina Mainero...studies in multiple sclerosis (MS) suggested that cortical demyelinating lesions, which are hardly detected in vivo on conventional magnetic resonance...disease progression in many MS cases. 15. SUBJECT TERMS Multiple sclerosis ; cortex; cortical sulci; neuroinflammation; microglia; cortical

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial

PubMed Central

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-01-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists. PMID:27134355

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.

PubMed

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-03-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists.

What's new in multiple sclerosis spasticity research? Poster session highlights.

PubMed

Linker, Ralf

2017-11-01

Each year at the Multiple Sclerosis Experts Summit, relevant research in the field of multiple sclerosis spasticity is featured in poster sessions. The main studies presented at this year's meeting are summarized herein.

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

PubMed

Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study.

PubMed

Cleanthous, Sophie; Strzok, Sara; Pompilus, Farrah; Cano, Stefan; Marquis, Patrick; Cohan, Stanley; Goldman, Myla D; Kresa-Reahl, Kiren; Petrillo, Jennifer; Castrillo-Viguera, Carmen; Cadavid, Diego; Chen, Shih-Yin

2018-01-01

ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

PubMed

Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

2018-01-01

Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

A Systematic Review and Meta-Analysis of Strength Training in Individuals With Multiple Sclerosis Or Parkinson Disease

PubMed Central

Cruickshank, Travis M.; Reyes, Alvaro R.; Ziman, Melanie R.

2015-01-01

Abstract Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%–83.2%) and multiple sclerosis (4.5%–36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson disease after strength training. Furthermore, significant improvements in fatigue (8.2%), functional capacity (21.5%), quality of life (8.3%), power (17.6%), and electromyography activity (24.4%) were found in individuals with multiple sclerosis after strength training. The limitations of the study were the heterogeneity of interventions and study outcomes in Parkinson disease and multiple sclerosis trials. Strength training is useful for increasing muscle strength in Parkinson disease and to a lesser extent multiple sclerosis. PMID:25634170

A systematic review and meta-analysis of strength training in individuals with multiple sclerosis or Parkinson disease.

PubMed

Cruickshank, Travis M; Reyes, Alvaro R; Ziman, Melanie R

2015-01-01

Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%-83.2%) and multiple sclerosis (4.5%-36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson disease after strength training. Furthermore, significant improvements in fatigue (8.2%), functional capacity (21.5%), quality of life (8.3%), power (17.6%), and electromyography activity (24.4%) were found in individuals with multiple sclerosis after strength training. The limitations of the study were the heterogeneity of interventions and study outcomes in Parkinson disease and multiple sclerosis trials. Strength training is useful for increasing muscle strength in Parkinson disease and to a lesser extent multiple sclerosis.

Does vagotomy protect against multiple sclerosis?

PubMed

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Adelborg, Kasper; Svensson, Elisabeth

2017-07-01

To examine the association between vagotomy and multiple sclerosis. We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. We found no association between vagotomy and later risk of late onset multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

The Practice of Sport in Multiple Sclerosis: Update.

PubMed

Donze, Cecile; Massot, Caroline; Hautecoeur, Patrick; Cattoir-Vue, Helene; Guyot, Marc-Alexandre

The practice of sport by multiple sclerosis patients has long been controversial. Recent studies, however, show that both sport and physical activity are essential for these patients. Indeed, they help to cope with the effects of multiple sclerosis, such as fatigue, reduced endurance, loss of muscle mass, and reduction of muscle strength. The beneficial effects of physical activity on these patients have been underlined in several studies, whereas those of practicing sport have been the subject of fewer evaluations and assessments. The aim of this update is to report on the effects of sport on multiple sclerosis patients. The benefits of sport have been demonstrated in several studies. It helps multiple sclerosis patients to increase their balance, resistance to fatigue, mobility and quality of life. Several biases in these studies do not enable us to recommend the practice of some of these sports on a routine basis.

Vitamin D and Multiple Sclerosis (MS): Is There Any Connection?

MedlinePlus

... protective effect and lower the risk of developing multiple sclerosis (MS). Another study conducted at Maastricht University in ... D. Raghuwanshi A, et al. Vitamin D and multiple sclerosis. Journal of Cell Biochemistry. 2008;105:338. Ramagopalan ...

Sun Exposure across the Life Course Significantly Modulates Early Multiple Sclerosis Clinical Course.

PubMed

Simpson, Steve; van der Mei, Ingrid; Lucas, Robyn M; Ponsonby, Anne-Louise; Broadley, Simon; Blizzard, Leigh; Taylor, Bruce

2018-01-01

Low vitamin D and/or sun exposure have been associated with increased risk of multiple sclerosis (MS) onset. However, comparatively, few studies have prospectively examined associations between these factors and clinical course. To evaluate the association of sun exposure parameters and vitamin D levels with conversion to MS and relapse risk in a prospectively monitored cohort of 145 participants followed after a first demyelinating event up to 5-year review (AusLong Study). Sun exposure prior to and after onset measured by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS conversion and relapse assessed by neurologist assessment and medical record review. Over two-thirds (69%) of those followed to 5-year review (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun exposure was associated with reduced risk of MS conversion, with internal consistency between measures and dose-response relationships. Analogous associations were also seen with risk of relapse, albeit less strong. No consistent associations were observed between postonset sun exposure and clinical course, however. Notably, those who increased their sun exposure during follow-up had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D levels and vitamin D supplementation were not associated with conversion to MS or relapse hazard. We found that preonset sun exposure was protective against subsequent conversion to MS and relapses. While consistent associations between postonset sun exposure or serum 25(OH)D level and clinical course were not evident, possibly masked by behavior change, those participants who markedly increased their sun exposure demonstrated a reduced MS conversion and relapse hazard, suggesting beneficial effects of sun exposure on clinical course.

Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study.

PubMed

Avouac, Jérôme; Walker, Ulrich A; Hachulla, Eric; Riemekasten, Gabriela; Cuomo, Giovanna; Carreira, Patricia E; Caramaschi, Paola; Ananieva, Lidia P; Matucci-Cerinic, Marco; Czirjak, Laszlo; Denton, Christopher; Ladner, Ulf Müller; Allanore, Yannick

2016-01-01

To determine whether joint synovitis and tendon friction rubs (TFRs) can predict the progression of systemic sclerosis (SSc) over time. We performed a prospective cohort study that included 1301 patients with SSc from the EUSTAR database with disease duration ≤3 years at inclusion and with a follow-up of at least 2 years. Presence or absence at clinical examination of synovitis and TFRs was extracted at baseline. Outcomes were skin, cardiovascular, renal and lung progression. Overall disease progression was defined according to the occurrence of at least one organ progression. Joint synovitis (HR: 1.26, 95% CI 1.01 to 1.59) and TFRs (HR: 1.32, 95% CI 1.03 to 1.70) were independently predictive of overall disease progression, as were also the diffuse cutaneous subset (HR: 1.30, 95% CI 1.05 to 1.61) and positive antitopoisomerase-I antibodies (HR: 1.25, 95% CI 1.02 to 1.53). Regarding skin progression, joint synovitis (HR: 1.67, 95% CI 1.06 to 2.64) and TFRs (HR: 1.69, 95% CI 1.02 to 2.77) were also independently predictive of worsening of the modified Rodnan skin score. For cardiovascular progression, joint synovitis was predictive of the occurrence of new digital ulcer(s) (HR: 1.45, 95% CI 1.08 to 1.96) and decreased left ventricular ejection fraction (HR: 2.20, 95% CI 1.06 to 4.57); TFRs were confirmed to be an independent predictor of scleroderma renal crisis (HR: 2.33, 95% CI 1.03 to 6.19). Joint synovitis and TFRs are independent predictive factors for disease progression in patients with early SSc. These easily detected clinical markers may be useful for the risk stratification of patients with SSc. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Preference-based Health status in a German outpatient cohort with multiple sclerosis

PubMed Central

2013-01-01

Background To prospectively determine health status and health utility and its predictors in patients with multiple sclerosis (MS). Methods A total of 144 MS patients (mean age: 41.0 ±11.3y) with different subtypes (patterns of progression) and severities of MS were recruited in an outpatient university clinic in Germany. Patients completed a questionnaire at baseline (n = 144), 6 months (n = 65) and 12 months (n = 55). Health utilities were assessed using the EuroQol instrument (EQ-5D, EQ VAS). Health status was assessed by several scales (Expanded Disability Severity Scale (EDSS), Modified Fatigue Impact Scale (M-FIS), Functional Assessment of MS (FAMS), Beck Depression Inventory (BDI-II) and Multiple Sclerosis Functional Composite (MSFC)). Additionally, demographic and socioeconomic parameters were assessed. Multivariate linear and logistic regressions were applied to reveal independent predictors of health status. Results Health status is substantially diminished in MS patients and the EQ VAS was considerably lower than that of the general German population. No significant change in health-status parameters was observed over a 12-months period. Multivariate analyses revealed M-FIS, BDI-II, MSFC, and EDSS to be significant predictors of reduced health status. Socioeconomic and socio-demographic parameters such as working status, family status, number of household inhabitants, age, and gender did not prove significant in multivariate analyses. Conclusion MS considerably impairs patients’ health status. Guidelines aiming to improve self-reported health status should include treatment options for depression and fatigue. Physicians should be aware of depression and fatigue as co-morbidities. Future studies should consider the minimal clinical difference when health status is a primary outcome. PMID:24089999

An endovascular treatment of Chronic Cerebro-Spinal Venous Insufficiency in multiple sclerosis patients - 6 month follow-up results.

PubMed

Kostecki, Jacek; Zaniewski, Maciej; Ziaja, Krzysztof; Urbanek, Tomasz; Kuczmik, Waclaw; Krzystanek, Ewa; Ziaja, Damian; Korzeniowski, Tomasz; Majewski, Eugeniusz; Hartel, Marcin; Swiat, Maciej; Sioma-Markowska, Urszula

2011-01-01

In this study, the mid-term results (6 month follow-up) of the endovascular treatment in patients with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and multiple sclerosis (MS) were prospectively evaluated. Thirty-six patients with confirmed MS and CCSVI underwent endovascular treatment by the means of the uni- or bilateral jugular vein angioplasty with optional stent placement. All the patients completed 6 month follow-up. Their MS-related disability status and quality of life were evaluated 1, 3 and 6 months postoperatively by means of the following scales: Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), Epworth Sleepiness Scale (ESS), Heat Intolerance scale (HIS) and Fatigue Severity Scale (FSS). For patency and restenosis rate assessment, the control US duplex Doppler examination was used. Six months after the procedure, restenosis in post-PTA jugular veins was found in 33% of cases. Among 17 patients who underwent stent implantation into the jugular vein, restenosis or partial in-stent thrombosis was identified in 55% of the cases. At the 6 month follow-up appointment, there was no significant improvement in the EDSS or the ESS. The endovascular treatment of the CCSVI improved the quality of life according to the MSIS-29 scale but only up to 3 months after the procedure (with no differences in the 6 month follow-up assessment). Six months after the jugular vein angioplasty (with or without stent placement), a statistically significant improvement was observed only in the FSS and the HIS. The endovascular treatment in patients with MS and concomitant CCSVI did not have an influence on the patient's neurological condition; however, in the mid-term follow-up, an improvement in some quality-of-life parameters was observed.

Scleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies.

PubMed

Fett, Nicole

2013-01-01

Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options. Published by Elsevier Inc.

Ocrelizumab: a B-cell depleting therapy for multiple sclerosis.

PubMed

Jakimovski, Dejan; Weinstock-Guttman, Bianca; Ramanathan, Murali; Kolb, Channa; Hojnacki, David; Minagar, Alireza; Zivadinov, Robert

2017-09-01

Multiple sclerosis (MS) is the most common neurological disease responsible for early disability in the young working population. In the last two decades, based on retrospective/prospective data, the use of disease-modifying therapies has been shown to slow the rate of disability progression and prolonged the time to conversion into secondary-progressive MS (SPMS). However, despite the availability of several approved therapies, disability progression cannot be halted significantly in all MS patients. Areas covered: This article reviews the immunopathology of the B-cells, and their role in pathogenesis of MS and their attractiveness as a potential therapeutic target in MS. The review focuses on the recently published ocrelizumab phase III trials in terms of its efficacy, safety, and tolerability as well as its future considerations. Expert opinion: B lymphocyte cell depletion therapy offers a compelling and promising new option for MS patients. Nonetheless, there is a need for heightened vigilance and awareness in detecting potential long-term consequences that currently remain unknown.

Living with uncertainty and hope: A qualitative study exploring parents' experiences of living with childhood multiple sclerosis.

PubMed

Hinton, Denise; Kirk, Susan

2017-06-01

Background There is growing recognition that multiple sclerosis is a possible, albeit uncommon, diagnosis in childhood. However, very little is known about the experiences of families living with childhood multiple sclerosis and this is the first study to explore this in depth. Objective Our objective was to explore the experiences of parents of children with multiple sclerosis. Methods Qualitative in-depth interviews with 31 parents using a grounded theory approach were conducted. Parents were sampled and recruited via health service and voluntary sector organisations in the United Kingdom. Results Parents' accounts of life with childhood multiple sclerosis were dominated by feelings of uncertainty associated with four sources; diagnostic uncertainty, daily uncertainty, interaction uncertainty and future uncertainty. Parents attempted to manage these uncertainties using specific strategies, which could in turn create further uncertainties about their child's illness. However, over time, ongoing uncertainty appeared to give parents hope for their child's future with multiple sclerosis. Conclusion Illness-related uncertainties appear to play a role in generating hope among parents of a child with multiple sclerosis. However, this may lead parents to avoid sources of information and support that threatens their fragile optimism. Professionals need to be sensitive to the role hope plays in supporting parental coping with childhood multiple sclerosis.

Long-term treatment of epilepsy with everolimus in tuberous sclerosis

PubMed Central

Wilfong, Angus A.; Mays, Maxwell; Talley, Christina M.; Agricola, Karen; Tudor, Cindy; Capal, Jamie; Holland-Bouley, Katherine; Franz, David Neal

2016-01-01

Objective: To evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC). Methods: Everolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life. Results: Of the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months. Conclusions: Improved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC. Classification of evidence: This study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control. PMID:27815402

Association between retinal nerve fiber layer thickness and magnetic resonance imaging findings and intelligence in patients with multiple sclerosis.

PubMed

Ashtari, Fereshteh; Emami, Parisa; Akbari, Mojtaba

2015-01-01

Multiple Sclerosis (MS) is a neurological disease in which demyelination and axonal loss leads to progressive disability. Cognition impairment is among the most common complication. Studying axonal loss in the retina is a new marker for MS. The main goal of our study is to search for correlations between magnetic resonance imaging (MRI) findings and the retinal nerve fiber layer (RNFL) thickness at the macula and head of the optic nerve and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Scores that assess multiple domains of intelligence, and to explore the relationship between changes in the RNFL thickness with intellectual and cognitive dysfunction. A prospective cross-sectional study was conducted at the University Hospital of Kashani, Isfahan, Iran, from September to December 2013. All patients were assessed with a full-scale intelligence quotient (IQ) on the WAIS-R. An optical coherence tomography study and brain MRI were performed in the same week for all the patients. Statistical analysis was conducted by using a bivariate correlation, by utilizing SPSS 20.0. A P value ≤ 0.05 was the threshold of statistical significance. Examination of a 100 patients showed a significant correlation between the average RNFL thickness of the macula and the verbal IQ (P value = 0.01) and full IQ (P value = 0.01). There was a significant correlation between brain atrophy and verbal IQ. The RNFL loss was correlated with verbal IQ and full IQ.

Transanal irrigation for bowel symptoms in patients with multiple sclerosis.

PubMed

Preziosi, Giuseppe; Gosling, Jonathan; Raeburn, Amanda; Storrie, Julie; Panicker, Jalesh; Emmanuel, Anton

2012-10-01

Constipation and fecal incontinence affect 68% of patients with multiple sclerosis, but management is empirical. Transanal irrigation has been used successfully in patients with neurogenic bowel dysfunction. The aim of this study was to evaluate the effect of transanal irrigation on the bowel symptoms and general health status in these patients and the characteristics of those that had successful treatment and to obtain data for power calculations necessary for future randomized controlled studies. This was a prospective observational study in which pre- and posttreatment questionnaires (bowel symptoms and health status) were compared. Patients for whom treatment resulted in at least 50% improvement in bowel symptoms were considered responders. Baseline variables including anorectal physiology tests and rectal compliance were compared between responders and nonresponders. This study was conducted at a specialist neurogastroenterology clinic, tertiary referral center. Included were 30 patients who had multiple sclerosis and constipation, fecal incontinence, or both. Transanal irrigation was performed. The primary outcomes measured were the Wexner Constipation and Wexner Incontinence scores. The secondary outcomes was the SF-36 health survey. All scores were recorded before and after 6 weeks of treatment. At 6 weeks posttreatment, the Wexner Constipation score significantly improved (12 (8.75/16) pretreatment vs 8 (4/12.5) posttreatment, p = 0.001), as well as the Wexner Incontinence score (12 (4.75/16) pretreatment vs 4 (2/8) posttreatment, p < 0.001). The SF-36 score did not improve significantly (51.3 ± 7.8 pretreatment vs 50.4 ± 7.8 posttreatment, p = 0.051). Sixteen patients were responders and had higher baseline Wexner Incontinence scores (14 (11/20) responders vs 9 (4/15) nonresponders, p = 0.038) and SF-36 (53.9 ± 6.3 responders vs 47.9 ± 7.8 nonresponders, p = 0.027), as well as greater maximum tolerated volume to rectal balloon distension (310 (220/320) mL responders vs 168 (108/305) mL nonresponders, p = 0.017) and rectal compliance (15.2 (14.5/17.2) mL/mmHg responders vs 9.2 (7.2/15.3) mL/mmHg nonresponders, p = 0.019). This study was limited by its small sample size and the lack of control group with alternative treatment. Transanal irrigation is effective to treat bowel symptoms in patients with multiple sclerosis. Responders (53%) had higher baseline incontinence symptoms and better perception of their health, as well as a more capacious and compliant rectum.

Effects of severe spasticity treatment with intrathecal Baclofen in multiple sclerosis patients: Long term follow-up.

PubMed

Stampacchia, Giulia; Gerini, Adriana; Mazzoleni, Stefano

2016-04-06

Intrathecal Baclofen is available to treat severe generalized spasticity in Multiple Sclerosis (MS) unresponsive to oral drug delivery. The aims of this study were to investigate the effects and the drug dosage of intrathecal Baclofen in a selected population of MS patients, affected by severe spasticity at long term follow-up. A prospective cohort study of 14 MS patients is presented. Spasticity and pain were periodically assessed and the Baclofen dosage was adjusted. The initial Baclofen dosage was 136.2 ± 109.3 μg, then it was increased at 12 months to 228.6 ± 179.2 μg (p < 0.05). The subsequent dose adjustments did not result in significant changes up to 76 months. Spasticity on the lower limbs decreased significantly from pre-implantation assessment (median: 3.5, IQR: 3.0-4.0) to 12 months evaluation (median: 0.5, IQR: 0.0-2.0) (p < 0.001); no further decrease was observed after 24 months (median: 0.5, IQR: 0.0-1.5); when pain was present, it decreased. Some effects on cerebellar symptoms were observed. Botulinum toxin injections were used with intrathecal Baclofen therapy. A reduced spasticity and pain was observed after the intrathecal Baclofen infusion for at least 76 months. To obtain these results a dosage adjustment was needed only in the first year after the implantation.

The influence of coping styles on long-term employment in multiple sclerosis: A prospective study.

PubMed

Grytten, Nina; Skår, Anne Br; Aarseth, Jan Harald; Assmus, Jorg; Farbu, Elisabeth; Lode, Kirsten; Nyland, Harald I; Smedal, Tori; Myhr, Kjell Morten

2017-06-01

The aim was to investigate predictive values of coping styles, clinical and demographic factors on time to unemployment in patients diagnosed with multiple sclerosis (MS) during 1998-2002 in Norway. All patients ( N = 108) diagnosed with MS 1998-2002 in Hordaland and Rogaland counties, Western Norway, were invited to participate in the long-term follow-up study in 2002. Baseline recordings included disability scoring (Expanded Disability Status Scale (EDSS)), fatigue (Fatigue Severity Scale (FSS)), depression (Beck Depression Inventory (BDI)), and questionnaire assessing coping (the Dispositional Coping Styles Scale (COPE)). Logistic regression analysis was used to identify factors associated with unemployed at baseline, and Cox regression analysis to identify factors at baseline associated with time to unemployment during follow-up. In all, 41 (44%) were employed at baseline. After 13 years follow-up in 2015, mean disease duration of 22 years, 16 (17%) were still employed. Median time from baseline to unemployment was 6 years (±5). Older age at diagnosis, female gender, and depression were associated with patients being unemployed at baseline. Female gender, long disease duration, and denial as avoidant coping strategy at baseline predicted shorter time to unemployment. Avoidant coping style, female gender, and longer disease duration were associated with shorter time to unemployment. These factors should be considered when advising patients on MS and future employment.

Interferon-β1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in multiple sclerosis

PubMed Central

Sheremata, William A; Jy, Wenche; Delgado, Sylvia; Minagar, Alireza; McLarty, Jerry; Ahn, Yeon

2006-01-01

Background A correlation between plasma CD31+ endothelial microparticles (CD31+EMP) levels and clinical, as well as brain MRI activity, in multiple sclerosis (MS) patients has been previously reported. However, the effect(s) of treatment with interferon-β1a (IFN-β1a) on plasma levels of CD31+EMP has not been assessed. In a prospective study, we measured plasma CD31+EMP levels in 30 patients with relapsing-remitting MS. Methods Using flow cytometry, in a blinded study, we measured plasma CD31+EMP in 30 consecutive patients with relapsing-remitting MS (RRMS) prior to and 4, 12, 24 and 52 weeks after initiation of intramuscular therapy with interferon-β1a (IFN-β1a), 30 micrograms weekly. At each visit, clinical examination was performed and expanded disability status scale (EDSS) scores were assessed. Results Plasma levels of CD31+EMP were significantly reduced from 24 through 52 weeks following initiation of treatment with IFN-β1a. Conclusion Our data suggest that serial measurement of plasma CD31+EMP levels may be used as a surrogate marker of response to therapy with INF-β1a. In addition, the decline in plasma levels of CD31+EMP further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells in pathogenesis of MS. PMID:16952316

Interferon-beta1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in multiple sclerosis.

PubMed

Sheremata, William A; Jy, Wenche; Delgado, Sylvia; Minagar, Alireza; McLarty, Jerry; Ahn, Yeon

2006-09-04

A correlation between plasma CD31+ endothelial microparticles (CD31+EMP) levels and clinical, as well as brain MRI activity, in multiple sclerosis (MS) patients has been previously reported. However, the effect(s) of treatment with interferon-beta1a (IFN-beta1a) on plasma levels of CD31+EMP has not been assessed. In a prospective study, we measured plasma CD31+EMP levels in 30 patients with relapsing-remitting MS. Using flow cytometry, in a blinded study, we measured plasma CD31+EMP in 30 consecutive patients with relapsing-remitting MS (RRMS) prior to and 4, 12, 24 and 52 weeks after initiation of intramuscular therapy with interferon-beta1a (IFN-beta1a), 30 micrograms weekly. At each visit, clinical examination was performed and expanded disability status scale (EDSS) scores were assessed. Plasma levels of CD31+EMP were significantly reduced from 24 through 52 weeks following initiation of treatment with IFN-beta1a. Our data suggest that serial measurement of plasma CD31+EMP levels may be used as a surrogate marker of response to therapy with INF-beta1a. In addition, the decline in plasma levels of CD31+EMP further supports the concept that IFN-beta1a exerts stabilizing effect on the cerebral endothelial cells in pathogenesis of MS.

Disease-specific molecular events in cortical multiple sclerosis lesions

PubMed Central

Wimmer, Isabella; Höftberger, Romana; Gerlach, Susanna; Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Mahad, Don; Binder, Christoph J.; Krumbholz, Markus; Bauer, Jan; Bradl, Monika

2013-01-01

Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene expression studies with neuropathological analysis. In our study, we showed that the combination of inflammation, plaque-like primary demyelination and neurodegeneration in the cortex is specific for multiple sclerosis and is not seen in other chronic inflammatory diseases mediated by CD8-positive T cells (Rasmussen’s encephalitis), B cells (B cell lymphoma) or complex chronic inflammation (tuberculous meningitis, luetic meningitis or chronic purulent meningitis). In addition, we performed genome-wide microarray analysis comparing micro-dissected active cortical multiple sclerosis lesions with those of tuberculous meningitis (inflammatory control), Alzheimer’s disease (neurodegenerative control) and with cortices of age-matched controls. More than 80% of the identified multiple sclerosis-specific genes were related to T cell-mediated inflammation, microglia activation, oxidative injury, DNA damage and repair, remyelination and regenerative processes. Finally, we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis. PMID:23687122

Information-seeking Behavior and Information Needs in Patients With Amyotrophic Lateral Sclerosis: Analyzing an Online Patient Community.

PubMed

Oh, Juyeon; Kim, Jung A

2017-07-01

A few studies have examined the specific informational needs of the population with amyotrophic lateral sclerosis. The aims of this study were to describe the information-seeking behavior and information needs of patients with amyotrophic lateral sclerosis and their families in Korea by analyzing messages from an online patient community. A total of 1047 messages from the question and answer forum of the "Lou Gehrig's Disease Network" (http://cafe.daum.net/alsfree) from January 2010 to September 2015 were collected. The word frequency, main questions, and asker of the messages were analyzed and coded. Terms such as "hospital," "mother," "father," "gastrostomy," and "ALS" were most frequently identified. The most commonly mentioned main topic was about disease-specific information, while the most frequent subcategory was symptoms or management of symptoms. Other prominent categories concerned information about treatment, rehabilitation, and the medical system. The people who wrote the questions were mostly the son/daughter of patients with amyotrophic lateral sclerosis. Patients with amyotrophic lateral sclerosis and their family members commonly obtained information by posting their inquiries online and have a variety of questions regarding amyotrophic lateral sclerosis in this study. The findings of this study can be used as a base of information for developing educational programs and resources for patients with amyotrophic lateral sclerosis and their families.

Edaravone and its clinical development for amyotrophic lateral sclerosis.

PubMed

Takei, Koji; Watanabe, Kazutoshi; Yuki, Satoshi; Akimoto, Makoto; Sakata, Takeshi; Palumbo, Joseph

2017-10-01

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress may be one of the major mechanisms involved. In vitro and in vivo data of edaravone suggest that it may possess broad free radical scavenging activity and protect neurons, glia, and vascular endothelial cells against oxidative stress. During the 1980s and 1990s, edaravone was developed for the treatment of acute ischemic stroke. In 2001, a clinical program in ALS was initiated and five clinical studies were conducted in Japan. Phase III studies were designed to rapidly evaluate (within a 24-week double-blind study window) functional changes using the Revised ALS Functional Rating Scale (ALSFRS-R) as a primary endpoint. The study populations were selected according to these considerations and were further refined as the studies proceeded. Although the first phase III study did not meet its primary endpoint, post-hoc analyses showed an apparent effect of edaravone, when additional patient inclusion criteria defined by ALSFRS-R score, pulmonary function, certainty of ALS diagnosis, and duration of disease were applied. This population was hypothesized not only to have retained broad functionality and normal respiratory function at study baseline but also to be likely to show measurable disease progression over 24 weeks. A second confirmatory phase III study applying these refinements in patient selection was prospectively designed and successfully documented a statistically significant difference between the edaravone and placebo groups in the ALSFRS-R primary endpoint. This paper describes and reviews data pertinent to the potential mechanism of action of edaravone, and reviews the development history of edaravone for the treatment of ALS.

Allelic imbalance of multiple sclerosis susceptibility genes IKZF3 and IQGAP1 in human peripheral blood.

PubMed

Keshari, Pankaj K; Harbo, Hanne F; Myhr, Kjell-Morten; Aarseth, Jan H; Bos, Steffan D; Berge, Tone

2016-04-14

Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown. Consistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively. Using multiple sclerosis patients and healthy controls heterozygous for rs907091 and rs11609, we showed that the multiple sclerosis risk alleles at IKZF3 and IQGAP1 are expressed at higher levels as compared to the protective allele. Furthermore, individuals homozygous for the multiple sclerosis risk allele at IQGAP1 had a significantly higher total expression of IQGAP1 compared to individuals homozygous for the protective allele. Our data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. We suggest that such cis-acting mechanisms may contribute to the multiple sclerosis association of single nucleotide polymorphisms at IKZF3 and IQGAP1.

Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis.

PubMed

Okada, Masamitsu; Yamashita, Satoshi; Ueyama, Hidetsugu; Ishizaki, Masatoshi; Maeda, Yasushi; Ando, Yukio

2018-06-01

Oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients. We retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016. The differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients. Our retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS.

Does environmental confounding mask pleiotropic effects of a multiple sclerosis susceptibility variant on vitamin D in psychosis?

PubMed

Iyegbe, Conrad O; Acharya, Anita; Lally, John; Gardner-Sood, Poonam; Smith, Louise S; Smith, Shubulade; Murray, Robin; Howes, Oliver; Gaughran, Fiona

2015-01-01

This work addresses the existing and emerging evidence of overlap within the environmental and genetic profiles of multiple sclerosis (MS) and schizophrenia. To investigate whether a genetic risk factor for MS (rs703842), whose variation is indicative of vitamin D status in the disorder, could also be a determinant of vitamin D status in chronic psychosis patients. A cohort of 224 chronic psychosis cases was phenotyped and biologically profiled. The relationship between rs703842 and physiological vitamin D status in the blood plasma was assessed by logistic regression. Deficiency was defined as a blood plasma concentration below 10 ng/µl. Potential environmental confounders of the vitamin D status were considered as part of the analysis. We report suggestive evidence of an association with vitamin D status in established psychosis (ß standardized=0.51, P=0.04). The logistic model fit significantly benefited from controlling for body mass index, depression and ethnicity (χ (2)=91.7; 2 degrees of freedom (df); P=1.2×10(20)). The results suggest that, in addition to lifestyle changes that accompany the onset of illness, vitamin D dysregulation in psychosis has a genetic component that links into MS. Further, comprehensive studies are needed to evaluate this prospect.

The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.

PubMed

Warrender-Sparkes, Matthew; Spelman, Tim; Izquierdo, Guillermo; Trojano, Maria; Lugaresi, Alessandra; Grand'Maison, François; Havrdova, Eva; Horakova, Dana; Boz, Cavit; Oreja-Guevara, Celia; Alroughani, Raed; Iuliano, Gerardo; Duquette, Pierre; Girard, Marc; Terzi, Murat; Hupperts, Raymond; Grammond, Pierre; Petersen, Thor; Fernandez-Bolaños, Ricardo; Fiol, Marcela; Pucci, Eugenio; Lechner-Scott, Jeannette; Verheul, Freek; Cristiano, Edgardo; Van Pesch, Vincent; Petkovska-Boskova, Tatjana; Moore, Fraser; Kister, Ilya; Bergamaschi, Roberto; Saladino, Maria Laura; Slee, Mark; Barnett, Michael; Amato, Maria Pia; Shaw, Cameron; Shuey, Neil; Young, Carolyn; Gray, Orla; Kappos, Ludwig; Butzkueven, Helmut; Kalincik, Tomas; Jokubaitis, Vilija

2016-04-01

We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p<0.001) while more patients switched to fingolimod than any other therapy (42.3% of switches). Patients switched to fingolimod due to convenience. Patients treated with fingolimod were less likely to discontinue treatment compared with other therapies (p<0.001). Female sex, country of residence, younger age, a high Expanded Disability Status Scale score and relapse activity were all independently associated with higher rates of treatment discontinuation. Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications. © The Author(s), 2015.

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry.

PubMed

Denton, Christopher P; Krieg, Thomas; Guillevin, Loic; Schwierin, Barbara; Rosenberg, Daniel; Silkey, Mariabeth; Zultak, Maurice; Matucci-Cerinic, Marco

2012-05-01

The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies.

Disclosure of diagnosis of multiple sclerosis in the workplace positively affects employment status and job tenure.

PubMed

Kirk-Brown, A K; Van Dijk, P A; Simmons, R D; Bourne, M P; Cooper, B K

2014-06-01

For many employees with multiple sclerosis (MS), disclosure of their diagnosis at work is seen as a high-risk strategy that might lead to diminished perceptions of their capabilities by supervisors and colleagues, if not outright discrimination. The consequence of this mistrust surrounding the disclosure process is that employees with MS may leave it until too late to effectively manage symptoms at work. The objective of this paper is to statistically evaluate the relationship between disclosure of diagnosis at work and maintenance of employment. Three annual, large-sample self-report surveys of MS patients prospectively examined the relationship between disclosure of diagnosis at work and employment status. A total of 1438 people responded to all three surveys. Of employed persons in 2010 (n = 946), 673 also responded to the 2012 survey. Of these 673 respondents 564 were still employed. People who had disclosed their MS status to an employer were more likely to remain in employment in Year 3. The effect of disclosure in predicting employment status remained after controlling for age, gender, hours worked and level of disability. This study provides the first empirical support for the positive role of disclosure in maintaining employment status, measured both as job retention and tenure in current employment. © The Author(s) 2013.

Diaphragm pacing improves sleep in patients with amyotrophic lateral sclerosis.

PubMed

Gonzalez-Bermejo, Jesus; Morélot-Panzini, Capucine; Salachas, François; Redolfi, Stefania; Straus, Christian; Becquemin, Marie-Hélène; Arnulf, Isabelle; Pradat, Pierre-François; Bruneteau, Gaëlle; Ignagni, Anthony R; Diop, Moustapha; Onders, Raymond; Nelson, Teresa; Menegaux, Fabrice; Meininger, Vincent; Similowski, Thomas

2012-01-01

In amyotrophic lateral sclerosis (ALS) patients, respiratory insufficiency is a major burden. Diaphragm conditioning by electrical stimulation could interfere with lung function decline by promoting the development of type 1 muscle fibres. We describe an ancillary study to a prospective, non-randomized trial (NCT00420719) assessing the effects of diaphragm pacing on forced vital capacity (FVC). Sleep-related disturbances being early clues to diaphragmatic dysfunction, we postulated that they would provide a sensitive marker. Stimulators were implanted laparoscopically in the diaphragm close to the phrenic motor point in 18 ALS patients for daily conditioning. ALS functioning score (ALSFRS), FVC, sniff nasal inspiratory pressure (SNIP), and polysomnographic recordings (PSG, performed with the stimulator turned off) were assessed before implantation and after four months of conditioning (n = 14). Sleep efficiency improved (69 ± 15% to 75 ± 11%, p = 0.0394) with fewer arousals and micro-arousals. This occurred against a background of deterioration as ALSFRS-R, FVC, and SNIP declined. There was, however, no change in NIV status or the ALSFRS respiratory subscore, and the FVC decline was mostly due to impaired expiration. Supporting a better diaphragm function, apnoeas and hypopnoeas during REM sleep decreased. In conclusion, in these severe patients not expected to experience spontaneous improvements, diaphragm conditioning improved sleep and there were hints at diaphragm function changes.

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

PubMed

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J; Dreyer, Lene; Gislason, Gunnar; Ahlehoff, Ole

2018-03-13

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

Impact of a Pelvic Floor Training Program Among Women with Multiple Sclerosis: A Controlled Clinical Trial.

PubMed

Ferreira, Ana Paula Silva; Pegorare, Ana Beatriz Gomes de Souza; Salgado, Pedro Rippel; Casafus, Filemón Silva; Christofoletti, Gustavo

2016-01-01

The objective of this study was to investigate the effects of two programs for strengthening the pelvic floor on the urinary incontinence of patients with multiple sclerosis (MS). This is a prospective study of the clinical trial type, monitored for 6 mos, in which 24 women in the moderate stage of MS participated in a program of exercises for strengthening the pelvic floor-associated (experimental group) or not (control group) with electrotherapy. The variables analyzed were as follows: quality-of-life, overactivity of the bladder, perineal contraction, and level of anxiety and depression. The statistical procedures involved multivariate analyses of repeated measurements, with a significance of 5%. Initial homogeneity being observed in the anthropometric and clinical variables, both protocols resulted in improvements in quality-of-life (P = 0.001), overactive bladder (P = 0.001), perineal contraction (P = 0.004), and level of anxiety (P = 0.001) and depression (P = 0.001), in relation to the initial comparison. The association of electrotherapy with strengthening exercises increased the improvement of the patients regarding overactive bladder (P = 0.039) and perineal contraction (P = 0.001), in comparison with the control group. The results reinforce the benefit of exercises for strengthening the musculature of the pelvic floor in women with overactive bladder in MS and demonstrate a potential of the action when associated with electrotherapy. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Identify common dysfunctions of the lower urinary tract in women with multiple sclerosis; (2) Discuss the relationship between quality-of-life, level of anxiety and depression, degree of perineal contraction, and overactive bladder; and (3) Recognize the benefits promoted by physical therapy for strengthening the pelvic floor in patients with multiple sclerosis. Advanced : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.

Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

PubMed

Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

2014-11-01

Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included headache, fatigue, infusion site reactions, and urinary tract infection. PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis patients. No paradoxical worsening of lesion counts was noted with either dose. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Relationship Between Physiological and Perceived Fall Risk in People With Multiple Sclerosis: Implications for Assessment and Management.

PubMed

Gunn, Hilary; Cameron, Michelle; Hoang, Phu; Lord, Stephen; Shaw, Steve; Freeman, Jennifer

2018-04-24

This study evaluated the relationship between physiological and perceived fall risk in people with multiple sclerosis (MS). Secondary analysis of data from prospective cohort studies undertaken in Australia, the United Kingdom, and the United States. Community. Ambulatory people with MS (N=416) (age 51.5±12.0 years; 73% female; 62% relapsing-remitting MS; 13.7±9.9 years disease duration). Not applicable. All participants completed measures of physiological (Physiological Profile Assessment [PPA]) and perceived (Falls Efficacy Scale-international [FESi]) fall risk and prospectively recorded falls for 3 months. 155 (37%) of the participants were recurrent fallers (≥2 falls). Mean PPA and FESi scores were high (PPA 2.14±1.87, FESi 34.27±11.18). The PPA and the FESi independently predicted faller classification in logistic regression, which indicated that the odds of being classified as a recurrent faller significantly increased with increasing scores (PPA odds ratio [OR] 1.30 [95% CI 1.17-1.46], FESi OR 1.05 [95% CI 1.03-1.07]). Classification and regression tree analysis divided the sample into four groups based on cutoff values for the PPA: (1) low physiological/low perceived risk (PPA <2.83, FESi <27.5), (2) low physiological/high perceived risk (PPA <2.83, FESi >27.5), (3) high physiological/low perceived risk (PPA >2.83, FESi <35.5), and (4) high physiological/high perceived risk (PPA <2.83, FESi >35.5). Over 50% of participants had a disparity between perceived and physiological fall risk; most were in group 2. It is possible that physiological risk factors not detected by the PPA may also be influential. This study highlights the importance of considering both physiological and perceived fall risk in MS and the need for further research to explore the complex interrelationships of perceptual and physiological risk factors in this population. This study also supports the importance of developing behavioral and physical interventions that can be tailored to the individual's needs. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

PubMed

Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

2016-04-01

Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic lateral sclerosis mouse models based on TDP-43 (Tardbp) and FUS mutations. Finally, we demonstrate that the melanocortin defect is primarily caused by serotonin loss in mutant SOD1(G86R) mice. Altogether, the current study combined clinical evidence and experimental studies in rodents to provide a mechanistic explanation for abnormalities in food intake and weight control observed in patients with amyotrophic lateral sclerosis. Importantly, these results also show that amyotrophic lateral sclerosis progression impairs responsiveness to classical drugs leading to weight gain. This has important implications for pharmacological management of weight loss in amyotrophic lateral sclerosis. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Incidence and prevalence of systemic sclerosis in Campo Grande, State of Mato Grosso do Sul, Brazil.

PubMed

Horimoto, Alex Magno Coelho; Matos, Erica Naomi Naka; Costa, Márcio Reis da; Takahashi, Fernanda; Rezende, Marcelo Cruz; Kanomata, Letícia Barrios; Locatelli, Elisangela Possebon Pradebon; Finotti, Leandro Tavares; Maegawa, Flávia Kamy Maciel; Rondon, Rosa Maria Ribeiro; Machado, Natália Pereira; Couto, Flávia Midori Arakaki Ayres Tavares do; Figueiredo, Túlia Peixoto Alves de; Ovidio, Raphael Antonio; Costa, Izaias Pereira da

Systemic sclerosis is an autoimmune disease which shows extreme heterogeneity in its clinical presentation and that follows a variable and unpredictable course. Although some discrepancies in the incidence and prevalence rates between geographical regions may reflect methodological differences in the definition and verification of cases, they may also reflect true local differences. To determine the prevalence and incidence of systemic sclerosis in the city of Campo Grande, state capital of Mato Grosso do Sul (MS), Brazil, during the period from January to December 2014. All health care services of the city of Campo Grande - MS with attending in the specialty of Rheumatology were invited to participate in the study through a standardized form of clinical and socio-demographic assessment. Physicians of any specialty could report a suspected case of systemic sclerosis, but necessarily the definitive diagnosis should be established by a rheumatologist, in order to warrant the standardization of diagnostic criteria and exclusion of other diseases resembling systemic sclerosis. At the end of the study, 15 rheumatologists reported that they attended patients with systemic sclerosis and sent the completed forms containing epidemiological data of patients. The incidence rate of systemic sclerosis in Campo Grande for the year 2014 was 11.9 per million inhabitants and the prevalence rate was 105.6 per million inhabitants. Systemic sclerosis patients were mostly women, white, with a mean age of 50.58 years, showing the limited form of the disease with a mean duration of the disease of 8.19 years. Regarding laboratory tests, 94.4% were positive for antinuclear antibody, 41.6% for anti-centromere antibody and 19.1% for anti-Scl70; anti-RNA Polymerase III was performed in 37 patients, with 16.2% positive. The city of Campo Grande, the state capital of MS, presented a lower incidence/prevalence of systemic sclerosis in comparison with those numbers found in US studies and close to European studies' data. Published by Elsevier Editora Ltda.

A proposal of criteria for the classification of systemic sclerosis.

PubMed

Nadashkevich, Oleg; Davis, Paul; Fritzler, Marvin J

2004-11-01

Sensitive and specific criteria for the classification of systemic sclerosis are required by clinicians and investigators to achieve higher quality clinical studies and approaches to therapy. A clinical study of systemic sclerosis patients in Europe and Canada led to a set of criteria that achieve high sensitivity and specificity. Both clinical and laboratory investigations of patients with systemic sclerosis, related conditions and diseases with clinical features that can be mistaken as part of the systemic sclerosis spectrum were undertaken. Laboratory investigations included the detection of autoantibodies to centromere proteins, Scl-70 (topoisomerase I), and fibrillarin (U3-RNP). Based on the investigation of 269 systemic sclerosis patients and 720 patients presenting with related and confounding conditions, the following set of criteria for the classification of systemic sclerosis was proposed: 1) autoantibodies to: centromere proteins, Scl-70 (topo I), fibrillarin; 2) bibasilar pulmonary fibrosis; 3) contractures of the digital joints or prayer sign; 4) dermal thickening proximal to the wrists; 5) calcinosis cutis; 6) Raynaud's phenomenon; 7) esophageal distal hypomotility or reflux-esophagitis; 8) sclerodactyly or non-pitting digital edema; 9) teleangiectasias. The classification of definite SSc requires at least three of the above criteria. Criteria for the classification of systemic sclerosis have been proposed. Preliminary testing has defined the sensitivity and specificity of these criteria as high as 99% and 100%, respectively. Testing and validation of the proposed criteria by other clinical centers is required.

Prevalence of Hippocampal Sclerosis in a Clinicopathologically Characterized Cohort.

PubMed

Malek-Ahmadi, Michael; Kahlon, Vickram; Adler, Charles H; Obradov, Aleksandra; Thind, Kabir; Shill, Holly A; Sue, Lucia I; Caviness, John N; Jacobson, Sandra; Sabbagh, Marwan N

2013-01-01

Hippocampal sclerosis (HS) is a neuropathological finding that frequently occurs with pathologies, such as Alzheimer's disease (AD). Prevalence estimates of HS in autopsy-confirmed dementia samples have varied between 0.4% and 24.5%. However, the prevalence of HS within other pathologic groups has not been well characterized. Utilizing a sample of 910 prospectively followed and clinicopathologically confirmed dementia cases, we determined the prevalence of HS among the sample and within specific pathologic groups. HS prevalence of the sample was compared to reported HS prevalence rates in other autopsy-confirmed dementia samples. The age range of the sample was 43 to 106 years, with a mean of 81.49±8.45. Of the 910 cases, 505 were male and 405 were female. For the entire sample, the average educational level was 14.59±2.65years. Of the 910 individuals, 47 (5.16%) cases had HS pathology present at autopsy. Among the 561 AD cases, 26 (4.43%) had HS pathology present. The frontotemporal dementia (FTD)/Pick's group had the highest percentage of cases with HS pathology (23.08%) followed by primary progressive aphasia (PPA) (16.67%) and Parkinson's disease with dementia (PDD) (5.34%). The HS prevalence rate of this study was not significantly different from all but 2 studies. The prevalence of HS pathology in this sample of autopsy-confirmed dementia cases was similar to other reported HS prevalence rates. This study is the first to report the presence of HS pathology in PDD cases.

Percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis: Mortality and complications.

PubMed

Carbó Perseguer, J; Madejón Seiz, A; Romero Portales, M; Martínez Hernández, J; Mora Pardina, J S; García-Samaniego, J

2018-03-26

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes severe dysphagia and weight loss. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for the enteral nutrition of these patients. To analyse mortality and complications in a series of patients diagnosed with ALS who underwent PEG, and to evaluate factors related to patient survival after the procedure. We performed a prospective, observational study including all patients diagnosed with ALS and treated by our hospital's Gastroenterology Department in the period 1997-2013. We studied mortality, complications, and clinical and biochemical parameters, and correlated these with the survival rate. The study included a total of 57 patients, of whom 49 were ultimately treated with PEG. ALS onset was bulbar in 30 patients and spinal in 19. Mortality during the procedure and at 30 days was 2% (n = 1). Six patients (12.2%) experienced major complications; 17 (34.7%) experienced less serious complications which were easily resolved with conservative treatment. No significant differences were observed in forced vital capacity, albumin level, or age between patients with (n = 6) and without (n = 43) major complications. PEG is an effective, relatively safe procedure for the enteral nutrition of patients with ALS, although not without morbidity and mortality. Neither forced vital capacity nor the form of presentation of ALS were associated with morbidity in PEG. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Physical activity and exercise priorities in community dwelling people with multiple sclerosis: a Delphi study.

PubMed

Stennett, Andrea; De Souza, Lorraine; Norris, Meriel

2018-07-01

Exercise and physical activity have been found to be beneficial in managing disabilities caused by multiple sclerosis. Despite the known benefits, many people with multiple sclerosis are inactive. This study aimed to identify the prioritised exercise and physical activity practices of people with multiple sclerosis living in the community and the reasons why they are engaged in these activities. A four Round Delphi questionnaire scoped and determined consensus of priorities for the top 10 exercise and physical activities and the reasons why people with multiple sclerosis (n = 101) are engaged in these activities. Data were analysed using content analysis, descriptive statistics, and non-parametric tests. The top 10 exercise and physical activity practices and the top 10 reasons why people with multiple sclerosis (n = 70) engaged in these activities were identified and prioritised. Consensus was achieved for the exercise and physical activities (W = 0.744, p < .0001) and for the reasons they engaged in exercise and physical activity (W = 0.723, p < .0001). The exercise and physical activity practices and the reasons people with multiple sclerosis engaged in exercise and physical activity were diverse. These self-selected activities and reasons highlighted that people with multiple sclerosis might conceptualise exercise and physical activity in ways that may not be fully appreciated or understood by health professionals. Considerations of the views of people with multiple sclerosis may be essential if the goal of increasing physical activity in this population is to be achieved. Implications for Rehabilitation Health professionals should work collaboratively with people with multiple sclerosis to understand how they prioritise activities, the underlying reasons for their prioritisations and embed these into rehabilitation programmes. Health professionals should utilise activities prioritised by people with multiple sclerosis in the community as a way to support, promote, and sustain exercise and physical activity in this population. Rehabilitation interventions should include both the activities people with multiple sclerosis prioritise and the reasons why they engage in exercise and physical activity as another option for increasing physical activity levels and reducing sedentary behaviours.

Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology.

PubMed

Kassubek, Jan; Müller, Hans-Peter; Del Tredici, Kelly; Brettschneider, Johannes; Pinkhardt, Elmar H; Lulé, Dorothée; Böhm, Sarah; Braak, Heiko; Ludolph, Albert C

2014-06-01

Diffusion tensor imaging can identify amyotrophic lateral sclerosis-associated patterns of brain alterations at the group level. Recently, a neuropathological staging system for amyotrophic lateral sclerosis has shown that amyotrophic lateral sclerosis may disseminate in a sequential regional pattern during four disease stages. The objective of the present study was to apply a new methodological diffusion tensor imaging-based approach to automatically analyse in vivo the fibre tracts that are prone to be involved at each neuropathological stage of amyotrophic lateral sclerosis. Two data samples, consisting of 130 diffusion tensor imaging data sets acquired at 1.5 T from 78 patients with amyotrophic lateral sclerosis and 52 control subjects; and 55 diffusion-tensor imaging data sets at 3.0 T from 33 patients with amyotrophic lateral sclerosis and 22 control subjects, were analysed by a tract of interest-based fibre tracking approach to analyse five tracts that become involved during the course of amyotrophic lateral sclerosis: the corticospinal tract (stage 1); the corticorubral and the corticopontine tracts (stage 2); the corticostriatal pathway (stage 3); the proximal portion of the perforant path (stage 4); and two reference pathways. The statistical analyses of tracts of interest showed differences between patients with amyotrophic lateral sclerosis and control subjects for all tracts. The significance level of the comparisons at the group level was lower, the higher the disease stage with corresponding involved fibre tracts. Both the clinical phenotype as assessed by the amyotrophic lateral sclerosis functional rating scale-revised and disease duration correlated significantly with the resulting staging scheme. In summary, the tract of interest-based technique allowed for individual analysis of predefined tract structures, thus making it possible to image in vivo the disease stages in amyotrophic lateral sclerosis. This approach can be used not only for individual clinical work-up purposes, but enlarges the spectrum of potential non-invasive surrogate markers as a neuroimaging-based read-out for amyotrophic lateral sclerosis studies within a clinical context. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database.

PubMed

Brand, Monika; Hollaender, Rebecca; Rosenberg, Daniel; Scott, Martin; Hunsche, Elke; Tyndall, Alan; Denaro, Valentina; Carreira, Patricia; Varju, Cecilia; Gabrielli, Barbara; Zingarelli, Stefania; Caramaschi, Paola; Simic-Pasalic, Katarina; Müller-Ladner, Ulf; Vasile, Massimiliano; Mihai, Carina; Rosato, Edoardo; Vacca, Alessandra; Zenone, Thierry; Mohamed, Walid A; Ancuta, Codrina; Zampogna, Giuseppe; Rednic, Simona; Jabaar, Nadia; Belloli, Laura; Pozzi, Maria R; Foti, Rosario; Walker, Ulrich A

2015-01-01

This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon β1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study).

PubMed

Lanzillo, Roberta; Quarantelli, Mario; Pozzilli, Carlo; Trojano, Maria; Amato, Maria Pia; Marrosu, Maria G; Francia, Ada; Florio, Ciro; Orefice, Giuseppe; Tedeschi, Gioacchino; Bellantonio, Paolo; Annunziata, Pasquale; Grimaldi, Luigi M; Comerci, Marco; Brunetti, Arturo; Bonavita, Vincenzo; Alfano, Bruno; Marini, Stefano; Brescia Morra, Vincenzo

2016-08-01

A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis. This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis. © The Author(s), 2015.

Sit less and move more: perspectives of adults with multiple sclerosis.

PubMed

Aminian, Saeideh; Ezeugwu, Victor E; Motl, Robert W; Manns, Patricia J

2017-12-20

Multiple sclerosis is a chronic neurological disease with the highest prevalence in Canada. Replacing sedentary behavior with light activities may be a feasible approach to manage multiple sclerosis symptoms. This study explored the perspectives of adults with multiple sclerosis about sedentary behavior, physical activity and ways to change behavior. Fifteen adults with multiple sclerosis (age 43 ± 13 years; mean ± standard deviation), recruited through the multiple sclerosis Clinic at the University of Alberta, Edmonton, Canada, participated in semi-structured interviews. Interview audios were transcribed verbatim and coded. NVivo software was used to facilitate the inductive process of thematic analysis. Balancing competing priorities between sitting and moving was the primary theme. Participants were aware of the benefits of physical activity to their overall health, and in the management of fatigue and muscle stiffness. Due to fatigue, they often chose sitting to get their energy back. Further, some barriers included perceived fear of losing balance or embarrassment while walking. Activity monitoring, accountability, educational and individualized programs were suggested strategies to motivate more movement. Adults with multiple sclerosis were open to the idea of replacing sitting with light activities. Motivational and educational programs are required to help them to change sedentary behavior to moving more. IMPLICATIONS FOR REHABILITATION One of the most challenging and common difficulties of multiple sclerosis is walking impairment that worsens because of multiple sclerosis progression, and is a common goal in the rehabilitation of people with multiple sclerosis. The deterioration in walking abilities is related to lower levels of physical activity and more sedentary behavior, such that adults with multiple sclerosis spend 8 to 10.5 h per day sitting. Replacing prolonged sedentary behavior with light physical activities, and incorporating education, encouragement, and self-monitoring strategies are feasible approaches to manage the symptoms of multiple sclerosis.

Physician compensation for industry-sponsored clinical trials in multiple sclerosis influences patient trust.

PubMed

Klein, E; Solomon, A J; Corboy, J; Bernat, J

2016-07-01

Perceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust. To understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials. An anonymous online instrument was developed. 597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials. Results of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust. Copyright © 2016 Elsevier B.V. All rights reserved.

Incidence of multiple sclerosis among European Economic Area populations, 1985-2009: the framework for monitoring

PubMed Central

2013-01-01

Background A debate surrounding multiple sclerosis epidemiology has centred on time-related incidence increases and the need of monitoring. The purpose of this study is to reassess multiple sclerosis incidence in the European Economic Area. Methods We conducted a systematic review of literature from 1965 onwards and integrated elements of original research, including requested or completed data by surveys authors and specific analyses. Results The review of 5323 documents yielded ten studies for age- and sex-specific analyses, and 21 studies for time-trend analysis of single data sets. After 1985, the incidence of multiple sclerosis ranged from 1.12 to 6.96 per 100,000 population, was higher in females, tripled with latitude, and doubled with study midpoint year. The north registered increasing trends from the 1960s and 1970s, with a historic drop in the Faroe Islands, and fairly stable data in the period 1980-2000; incidence rose in Italian and French populations in the period 1970-2000, in Evros (Greece) in the 1980s, and in the French West Indies in around 2000. Conclusions We conclude that the increase in multiple sclerosis incidence is only apparent, and that it is not specific to women. Monitoring of multiple sclerosis incidence might be appropriate for the European Economic Area. PMID:23758972

[The efficacy of the exoskeleton ExoAtlet to restore walking in patients with multiple sclerosis].

PubMed

Kotov, S V; Lijdvoy, V Yu; Sekirin, A B; Petrushanskaya, K A; Pismennaya, E V

2017-01-01

To investigate the efficacy and safety of the exoskeleton ExoAtlet in complex therapy of patients with multiple sclerosis (MS). A pilot study within the prospective open controlled program was conducted. Eighteen patients with relapsing-remitting MS (RRMS) in remission and secondary progressive MS (SPMS) with the level of neurological deficit on the EDSS from 3 to 7 points have completed the study. EDSS, MSFC, HADS, MoCA scales were administered and the force measuring insoles F-Scan Tekscan (USA) were used to study the biomechanics of walking. Good tolerability of workload within 30-40 min. was observed. The improvement in the EDSS was detected in 9 patients, in whole, a significant positive trend (p<0.01) was shown. The study of the biomechanics of the walk showed its significant impairment compared to healthy individuals: reduction of parameters of rate, speed and step length, significant instability, pronounced asymmetry, the decrease in support and shock lower limb function, high coefficient of variability of the parameters, the phenomenon of recurrence of the vertical component of support reactions. After a course of exercise of walking in the exoskeleton, the walking speed and stability increased, oscillation of the body decreased, support function increased, the phenomenon of cyclical changes of the vertical component of support reactions reduced. The results of the pilot study showed promising future research opportunities for robotic-assisted walking and maintenance of the vertical posture with the help of the exoskeleton ExoAtlet to restore the abilities of movement in MS patients with locomotor disorders.

Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

2004-01-01

This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

The Relevance of Depressive Symptoms and Social Support to Disability in Women with Multiple Sclerosis or Fibromyalgia

ERIC Educational Resources Information Center

Phillips, Lorraine J.

2010-01-01

Multiple sclerosis and fibromyalgia syndrome may spur substantial disability for those affected. Using structural equation modeling, this secondary analysis examined predictors of disability in women with multiple sclerosis (n = 118) and fibromyalgia syndrome (n = 197) recruited for separate wellness studies. Greater functional limitations, lower…

[Causes of death in amyotrophic lateral sclerosis : Results from the Rhineland-Palatinate ALS registry].

PubMed

Wolf, J; Safer, A; Wöhrle, J C; Palm, F; Nix, W A; Maschke, M; Grau, A J

2017-08-01

Amyotrophic lateral sclerosis (ALS) is associated with an increased mortality. Knowledge of possible causes of death could lead to an individualization of the palliative treatment concept and result in a differentiated palliative treatment pathway. Currently, only few systematic data are available on the heterogeneity of causes of death associated with ALS. Analysis of the various causes of death in a prospective population-based German cohort of ALS patients. Analysis of data of the Rhineland-Palatinate ALS registry in which newly diagnosed patients who had been identified between October 2009 and September 2012 were prospectively enrolled and followed up at regular intervals. From this prospective cohort study the causes of death were elicited based on information provided by the attending physicians, family members and by means of death certificates registered by the regional health authorities in Rhineland-Palatinate. Out of 200 ALS patients registered 148 died between register initiation on 1 October 2009 and the end of follow-up on 30 September 2015 (78 males and 70 females, death rate 74%). The most frequent cause of death was respiratory failure as a consequence of weakness of respiratory muscles (n = 91, 61%). Less frequent causes of death were pneumonia (n = 13, 9%), terminal cachexia (n = 9, 6%) and death from cardiovascular causes including sudden death (n = 9, 6%). Cases of suicide were rare (n = 3, 2%) as were deaths due to concurrent diseases (n = 2). In 21 cases (14%) the exact cause of death could not be clarified. Differences in the causes of death only showed a tendency towards the ALS phenotype. Respiratory failure was the cause of death in all patients with a respiratory phenotype and in 78% of patients with flail arm syndrome. Despite the low number of patients (8%) with additional frontotemporal dementia (FTD) a distinct difference in causes of death between those with and without FTD could be observed. Death due to respiratory failure was less frequent in ALS patients with FTD (33% vs. 65%) while pneumonia was more frequent (27% vs. 7%). Respiratory failure was the most frequent cause of death in our cohort of ALS patients. In contrast, pneumonia and nutritional disorders played a less important role as the cause of death. The phenotypic expression of ALS might in part allow the cause of the prospective death to be predicted. Differentiation of ALS phenotypes is an important foundation for patient counseling on the process of dying to be expected and for the determination of an individual palliative concept.

"Understanding my ALS". Experiences and reflections of persons with amyotrophic lateral sclerosis and relatives on participation in peer group rehabilitation.

PubMed

Madsen, Louise Sofia; Jeppesen, Jørgen; Handberg, Charlotte

2018-01-26

The aim of this study was to gain insight into experiences and reflections of persons with amyotrophic lateral sclerosis and relatives concerning the peer group rehabilitation programme "More Life - Less Illness". This qualitative study used the Interpretive Description methodology with Symbolic Interactionism as the analytical framework. Eighteen programme participants representing persons with amyotrophic lateral sclerosis (n = 8) and relatives (n = 10) were included. Data consisted of individual interviews and participant observation. The analysis revealed two categorical themes, "Sense of Community Building" and "Understanding my ALS", which represented the participants' experiences and reflections on peer group rehabilitation. Through the analysis, it became apparent that "Sense of Community Building" gave rise to an increased and personalised understanding of amyotrophic lateral sclerosis among the participants. As a part of the continuous processing of the knowledge gained, "Facing Facts" and "Retaining Normality" appeared as subthemes regarding the participants' ability to live a less dependent and more meaningful life. This study of peer group rehabilitation for persons with amyotrophic lateral sclerosis and relatives indicates that programme participation leads to positive experiences in terms of living a shared meaningful life despite severe disability. The findings may guide practice to develop longitudinal peer group rehabilitation programmes with joint inclusion of persons with amyotrophic lateral sclerosis and relatives. Implications for Rehabilitation Peer group rehabilitation may facilitate an increased and personalised understanding of what it means to live with amyotrophic lateral sclerosis. A programme design with six months of sequential sessions enables a continuous processing of shared experiences and gained knowledge. Joint participation of persons with amyotrophic lateral sclerosis and their relatives supports both their internal relationship and social networking. Peer group rehabilitation in amyotrophic lateral sclerosis should help overcome obstacles concerning the needs of participants, accessibility, and geographical distance.

Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers.

PubMed

Freischmidt, Axel; Müller, Kathrin; Zondler, Lisa; Weydt, Patrick; Volk, Alexander E; Božič, Anže Lošdorfer; Walter, Michael; Bonin, Michael; Mayer, Benjamin; von Arnim, Christine A F; Otto, Markus; Dieterich, Christoph; Holzmann, Karlheinz; Andersen, Peter M; Ludolph, Albert C; Danzer, Karin M; Weishaupt, Jochen H

2014-11-01

Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effectiveness of applying progressive muscle relaxation technique on quality of life of patients with multiple sclerosis.

PubMed

Ghafari, Somayeh; Ahmadi, Fazlolah; Nabavi, Masoud; Anoshirvan, Kazemnejad; Memarian, Robabe; Rafatbakhsh, Mohamad

2009-08-01

To identify the effects of applying Progressive Muscle Relaxation Technique on Quality of Life of patients with multiple Sclerosis. In view of the growing caring options in Multiple Sclerosis, improvement of quality of life has become increasingly relevant as a caring intervention. Complementary therapies are widely used by multiple sclerosis patients and Progressive Muscle Relaxation Technique is a form of complementary therapies. Quasi-experimental study. Multiple Sclerosis patients (n = 66) were selected with no probability sampling then assigned to experimental and control groups (33 patients in each group). Means of data collection included: Individual Information Questionnaire, SF-8 Health Survey, Self-reported checklist. PMRT performed for 63 sessions by experimental group during two months but no intervention was done for control group. Statistical analysis was done by SPSS software. Student t-test showed that there was no significant difference between two groups in mean scores of health-related quality of life before the study but this test showed a significant difference between two groups, one and two months after intervention (p < 0.05). anova test with repeated measurements showed that there is a significant difference in mean score of whole and dimensions of health-related quality of life between two groups in three times (p < 0.05). Although this study provides modest support for the effectiveness of Progressive Muscle Relaxation Technique on quality of life of multiple sclerosis patients, further research is required to determine better methods to promote quality of life of patients suffer multiple sclerosis and other chronic disease. Progressive Muscle Relaxation Technique is practically feasible and is associated with increase of life quality of multiple sclerosis patients; so that health professionals need to update their knowledge about complementary therapies.

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

PubMed

Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved in progressive multiple sclerosis, correlations between histopathology and magnetic resonance imaging studies, along with possible new therapeutic approaches. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The liminal self in people with multiple sclerosis: an interpretative phenomenological exploration of being diagnosed.

PubMed

Strickland, Karen; Worth, Allison; Kennedy, Catriona

2017-06-01

To explore the lived experience of the meaning of being diagnosed with multiple sclerosis on the individual's sense of self. The time leading up to and immediately following the diagnosis of multiple sclerosis has been identified as a time period shrouded by uncertainty and one where individuals have a heightened desire to seek accurate information and support. The diagnosis brings changes to the way one views the self which has consequences for biographical construction. A hermeneutic phenomenological study. In-depth qualitative interviews were conducted with 10 people recently diagnosed with multiple sclerosis. The data were analysed using interpretative phenomenological analysis. This study presents the three master themes: the 'road to diagnosis', 'the liminal self' and 'learning to live with multiple sclerosis'. The diagnosis of multiple sclerosis may be conceptualised as a 'threshold moment' where the individual's sense of self is disrupted from the former taken-for-granted way of being and propose a framework which articulates the transition. The findings highlight the need for healthcare professionals to develop interventions to better support people affected by a new diagnosis of multiple sclerosis. The conceptual framework which has been developed from the data and presented in this study provides a new way of understanding the impact of the diagnosis on the individual's sense of self when affected by a new diagnosis of multiple sclerosis. This framework can guide healthcare professionals in the provision of supportive care around the time of diagnosis. The findings provide practitioners with a new way of understanding the impact of the diagnosis on the individual's sense of self and a framework which can guide them in the provision of supportive care around the time of diagnosis. © 2016 John Wiley & Sons Ltd.

Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study

PubMed Central

Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

2016-01-01

The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. PMID:26785711

Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study.

PubMed

Riccio, Paolo; Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

2016-03-01

The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. © 2016 by the Society for Experimental Biology and Medicine.

Progression of regional grey matter atrophy in multiple sclerosis

PubMed Central

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis. PMID:29741648

Progression of regional grey matter atrophy in multiple sclerosis.

PubMed

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.

Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden

PubMed Central

Westerlind, Helga; Ramanujam, Ryan; Uvehag, Daniel; Kuja-Halkola, Ralf; Boman, Marcus; Bottai, Matteo; Lichtenstein, Paul

2014-01-01

Data on familial recurrence rates of complex diseases such as multiple sclerosis give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias. Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 patients with multiple sclerosis were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of patients with multiple sclerosis. Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42–7.86). Surprisingly, despite a well-established lower prevalence of multiple sclerosis amongst males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called ‘Carter effect’ could not be excluded. We estimated the heritability of multiple sclerosis using 74 757 twin pairs with known zygosity, of which 315 were affected with multiple sclerosis, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36–0.76), whereas the shared environmental component was estimated to be 0.01 (0.00–0.18). In summary, whereas multiple sclerosis is to a great extent an inherited trait, the familial relative risks may be lower than usually reported. PMID:24441172

Exercising away the blues: can it help multiple sclerosis-related depression?

PubMed

Feinstein, Anthony; Rector, Neil; Motl, Robert

2013-12-01

The present review focuses on exercise as a treatment for depression in multiple sclerosis. While exercise has emerged as a potentially useful treatment in the general psychiatry-depression literature, the findings from a small number of multiple sclerosis-related treatment trials are equivocal. Methodological limitations, including the absence of depression as a primary endpoint, characterize all the studies completed to date. Given that limitations in study design can be rectified, it is time to put exercise to the test once more. Depressed multiple sclerosis patients and those involved in their care are looking for guidance here because the prevailing zeitgeist promotes the benefits of exercise to mood. But first, some clarity is needed.

Predictive value of vascular disease biomarkers for digital ulcers in systemic sclerosis patients.

PubMed

Silva, Ivone; Teixeira, Andreia; Oliveira, José; Almeida, Isabel; Almeida, Rui; Vasconcelos, Carlos

2015-01-01

To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients. Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. After the 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9 pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of endoglin>4.215 ng/ml (p=0.053) was associated to a new DU episode. No predictive serum value was found for ADMA (p=0.075) and endostatin (p=0.130). Endothelial dysfunction and angiogenic vascular biomarkers have an important role in the underlying and in the progression of microvascular disease in systemic sclerosis. Increased serum levels of ET-1, ADMA and VEGF are strong predictors of severe microangiopathy complications, namely ischaemic digital ulcers.

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

PubMed

Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

2018-03-01

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

[Effects of nutritional status on the multiple sclerosis disease: systematic review].

PubMed

Ródenas Esteve, Irene; Wanden-Berghe, Carmina; Sanz-Valero, Javier

2018-01-19

To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.

Impact of multiple sclerosis on employment and use of job-retention strategies: The situation in France in 2015.

PubMed

Fantoni-Quinton, Sophie; Kwiatkowski, Arnaud; Vermersch, Patrick; Roux, Bastien; Hautecoeur, Patrick; Leroyer, Ariane

2016-06-13

The main objective of this survey of persons with multiple sclerosis was to describe their employment situation. Secondary objectives were to ascertain when and how multiple sclerosis symptoms first impact employment per se and what strategies persons with multiple sclerosis use to cope with their employment problems. A retrospective survey was conducted to collect data from persons with multiple sclerosis aged 18 years and over, using a computer-assisted web tool. A total of 941 respondents were working at the time of multiple sclerosis diagnosis or had worked subsequently. Median time since diagnosis was 10 years. Multiple sclerosis had an impact on employment for 74.3% of respondents. The overall employment rate at the time of the survey was 68.1%; 27.2% had discontinued their occupational activity for a multiple sclerosis-related reason. Median time from diagnosis to multiple sclerosis-related cessation of occupational activity was 24.0 years (95% confidence interval (CI) 21.7-26.3 years). Respondents were poorly aware of available tools designed to assist them in retaining employment. This study highlights the importance of early intervention by the occupational medicine physician in order to favour job retention and use of available tools by all workers with MS and not only those with a recognized status as a disabled worker.

Patterns of Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis.

PubMed

Markovic, Nevena; Povitz, Marcus; Smith, Joanne; Leasa, David; Shoesmith, Christen; Gofton, Teneille E

2018-06-06

Non-invasive ventilation (NIV) improves quality of life and survival in patients with amyotrophic lateral sclerosis (ALS) and respiratory symptoms. Little is known about the patterns of NIV use over time and the impact of NIV on end-of-life decision-making in ALS. This study assessed the pattern of NIV use over the course of the disease and the timing of end-of-life discussions in people living with ALS. A retrospective single-center cohort study was performed at London Health Sciences Centre. Daily NIV duration of use was evaluated at 3-month intervals. The timing of diagnosis, NIV initiation, discussions relating to do-not-attempt-resuscitation (DNAR) and death were examined. In total, 48 patients were included in the analysis. Duration of NIV use increased over time, and tolerance to NIV was observed to be better than expected in patients with bulbar-onset ALS. There was a high degree of variability in the timing of end-of-life discussions in patients with ALS (356±451 days from diagnosis). In this cohort, there was a strong association between the timing of discussions regarding code status and establishment of a DNAR order (r2=0.93). This retrospective cohort study suggests that the use of NIV in ALS increases over time and that there remains a great deal of variability in the timing of end-of-life discussions in people living with ALS. Future prospective studies exploring the use NIV over the disease trajectory and how NIV affects end-of-life decision-making in people with ALS are needed.

Clinical commentary on "Paroxysmal kinesigenic dyskinesia-like phenotype in multiple sclerosis" and "Secondary paroxysmal dyskinesia in multiple sclerosis: Clinical-radiological features and treatment. Case report of seven patients".

PubMed

Pareés, Isabel

2017-11-01

This clinical commentary discusses the phenomenology and treatment of paroxysmal dyskinesia in patients with multiple sclerosis. It calls for a consensus on the definition as well as for larger studies to better understand this unusual clinical association.

Reliability and Clinical Significance of Mobility and Balance Assessments in Multiple Sclerosis

ERIC Educational Resources Information Center

Learmonth, Yvonne C.; Paul, Lorna; McFadyen, Angus K.; Mattison, Paul; Miller, Linda

2012-01-01

The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures--the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale--in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended…

Psychopathology in Tuberous Sclerosis: An Overview and Findings in a Population-Based Sample of Adults with Tuberous Sclerosis

ERIC Educational Resources Information Center

Raznahan, A.; Joinson, C.; O'Callaghan, F.; Osborne, J. P.; Bolton, P. F.

2006-01-01

Background: Tuberous sclerosis (TS) is a multi- system disorder with complex genetics. The neurodevelopmental manifestations of TS are responsible for considerable morbidity. The prevalence of epilepsy and intellectual disabilities among individuals with TS have been well described. Ours is the first study that explores the prevalence and pattern…

Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis.

PubMed

Panas, M; Karadima, G; Kalfakis, N; Psarrou, O; Floroskoufi, P; Kladi, A; Petersen, M B; Vassilopoulos, D

2000-12-01

The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n = 72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

Radiographic changes of the distal phalangeal tuft of the hands in subjects with systemic sclerosis. Systematic review.

PubMed

Izquierdo, Yojhan Edilberto; Calvo Páramo, Enrique; Castañeda, Luisa María; Gómez, Sandra Viviana; Zambrano, Fernán Santiago

To determine abnormal plain radiograph findings of the distal phalanx tuft of the hand (DPTH) associated with systemic sclerosis in adults. A systematic review was developed following the parameters of the PRISMA guidelines in databases: MEDLINE, EMBASE, BIREME, Scielo, Google Scholar and others including as primary outcomes alterations of DPTH (erosions, resorption, sclerosis and proliferation) detected by simple radiography in subjects with systemic sclerosis. The prevalence of radiographic findings was synthesized using the fixed effects model. The statistical associations were expressed in terms of relative risk or odds ratio with their respective confidence intervals and p values. Twenty-two observational studies were included; the prevalence of DPTH resorption was 28.3% (95% CI: 0.256-0.312; p < .001); I 2 =80.4%, the prevalence of calcinosis was 15.6% (95% CI: 0.113-0.210; p < .001); I 2 =0%. No study reported proliferation or erosions and only one study described sclerosis of DPTH in 5 individuals. Resorption and calcinosis of DPTH are the characteristic radiographic findings in patients with systemic sclerosis. However, new studies with greater methodological strength are needed to establish associations between these phenomena and their presence in other connective tissue diseases. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Effect of glatiramer acetate on disease reactivation in MS patients discontinuing natalizumab.

PubMed

Rossi, S; Motta, C; Studer, V; De Chiara, V; Barbieri, F; Monteleone, F; Fornasiero, A; Coarelli, G; Bernardi, G; Cutter, G; Stüve, O; Salvetti, M; Centonze, D

2013-01-01

Multiple sclerosis (MS) patients discontinuing natalizumab are at risk of rebound of disease activity. In the present multi-center, open-label, non-randomized, prospective, pilot study, we tested whether treatment with glatiramer acetate (GA) is safe and effective after natalizumab in MS patients. The study was performed at academic tertiary medical centers. Forty active relapsing-remitting MS patients who never failed GA therapy and who discontinued natalizumab after 12-18 months of therapy were enrolled. GA was initiated 4 weeks after the last dose of natalizumab. 62.5% of patients were relapse-free 12 months after GA initiation. Annualized relapse rate and time to relapse were significantly lower than before natalizumab. Notably, the frequency of relapses was significantly lower amongst those patients who had experienced ≤2 relapses the year before initiation of natalizumab therapy, compared with patients who had had three or more relapses. No evidence of rebound was observed in magnetic resonance imaging scans. Furthermore, Expanded Disability Status Scale and Multiple Sclerosis Functional Composite were stable in our patients, again suggesting that 12 months of post-natalizumab-GA therapy is not associated with clinical deterioration. Following discontinuation of natalizumab, 12 months of therapy with GA is safe and well tolerated in MS patients. GA can reduce the risk of early reactivation/rebound of disease activity in this setting. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab.

PubMed

Diotti, Roberta Antonia; Capra, Ruggero; Moiola, Lucia; Caputo, Valeria; De Rossi, Nicola; Sangalli, Francesca; Martinelli, Vittorio; Burioni, Roberto; Clementi, Massimo; Mancini, Nicasio

2016-05-07

The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment.

Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.

PubMed

Bourne, Theresa; Waltz, Michael; Casper, T C; Kavak, K; Aaen, G; Belman, A; Benson, L; Candee, M; Chitnis, T; Graves, J; Greenberg, B; Gorman, M; Harris, Y; Krupp, L; Lotze, T; Mar, S; Ness, J; Olsen, C; Roalstad, S; Rodriguez, M; Rose, J; Rubin, J; Schreiner, T; Tillema, J M; Kahn, I; Waldman, A; Barcellos, L; Waubant, E; Weinstock-Guttman, B

2017-04-15

Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). We included 271 cases (mean age at disease onset of 15.7years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p=0.01). While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies. Copyright © 2017 Elsevier B.V. All rights reserved.

Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice.

PubMed

Vermersch, Patrick; Trojano, Maria

2016-01-01

Tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) is an add-on therapy for moderate-to-severe multiple sclerosis (MS)-related drug-resistant spasticity (MSS). The MOVE-2 EU study collected data from everyday clinical practice concerning the effectiveness and tolerability of THC:CBD. This was an observational, prospective, multicentre, non-interventional study. Patients with resistant MSS prescribed add-on THC:CBD oromucosal spray according to approved labelling, were followed for 3 months. After 1 month, only responders (≥20% improvement in spasticity) continued treatment. The main endpoints were the evolution of MSS and associated symptoms, quality of life (QoL) and tolerability. Four hundred and thirty three patients (55% female) were recruited (98% in Italy). The mean duration of MSS was 7.4 years and baclofen was used by 78.1% of participants. Three hundred and forty nine participants continued with THC:CBD oromucosal spray after 1 month, and 281 after 3 months. THC:CBD mean dosage was 6 sprays/day. MSS scores and spasticity-related symptoms (spasms, fatigue, pain, sleep quality and bladder dysfunction) were significantly improved by THC:CBD at 3 months, as were activities of daily living, and QoL (EQ-5D VAS). Adverse events, none of which were severe or serious, were reported by 10.4% of patients. In everyday clinical practice, THC:CBD oromucosal spray provided symptomatic relief of MSS and related troublesome symptoms. © 2016 S. Karger AG, Basel.

Nabiximols (THC/CBD oromucosal spray, Sativex®) in clinical practice--results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity.

PubMed

Flachenecker, Peter; Henze, Thomas; Zettl, Uwe K

2014-01-01

Nabiximols (Sativex®), a cannabinoid-based oromucosal spray, is an add-on therapy for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other medications. The primary objective was to provide real-life observational data of clinical experience of nabiximols in contrast to formal clinical trials of effectiveness. This was an observational, prospective, multicenter, non-interventional study with a follow-up period of 3-4 months, conducted in routine care setting in Germany. Patients with moderate to severe MSS were included at nabiximols' initiation. Structured documentation forms, questionnaires and validated instruments were used for data collection at inclusion, 1 and 3 months after inclusion. Overall, 335 patients were assessed of whom 276 fitted the criteria and were included in the effectiveness analysis. After 1 month, nabiximols provided relief of resistant MSS in 74.6% of patients according to specialist assessment; mean spasticity 0-10 numerical rating scale (NRS) score decreased from 6.1 ± 1.8 to 5.2 ± 2.0 points; in patients with NRS improvement ≥20% mean NRS score decreased by 40%. After 3 months, 55.3% of patients had continued to use nabiximols and the mean NRS score had decreased by 25% from baseline. 17% of patients reported adverse events. Real-life data confirm nabiximols as an effective and well-tolerated treatment option for resistant MSS in clinical practice. © 2014 S. Karger AG, Basel.

Comorbidities Are Associated with Altered Health Services Use in Multiple Sclerosis: A Prospective Cohort Study.

PubMed

McKay, Kyla A; Marrie, Ruth Ann; Fisk, John D; Patten, Scott B; Tremlett, Helen

2018-05-15

Persons with multiple sclerosis (MS) use health resources with greater frequency than the general population. However, little is known regarding which patient characteristics might contribute. The study aimed to evaluate characteristics associated with healthcare use in MS patients. Consecutive MS clinic attendees were recruited (September-November 2010), with clinical, demographic, and patient-completed questionnaires collected at 3 visits over 2 years. Linkage with administrative data (hospital, physician, and pharmacy records) provided healthcare use outcomes until December 31, 2013. Findings were reported as adjusted rate ratios (adjRRs) using negative binomial regression. A total of 340 MS patients with a mean (SD) age of 48.4 (12.0) years and subsequent follow-up of 3.1 (0.34) years were included. Fatigue and high physical comorbidity count (≥3 vs. none) were significantly associated with higher rates of physician encounters (adjRRs: 1.37 and 1.52, respectively), prescriptions filled (adjRRs: 1.25 and 1.40), and hospitalizations (adjRRs: 4.02 and 3.45). In addition, anxiety, disruptive pain, and perceived functional cognitive difficulties were associated with higher rates of physician encounters and prescriptions dispensed (adjRR ranged from 1.28 to 1.48). The presence of fatigue and higher physical comorbidity burden were associated with higher rates of health services use. Findings have implications for those examining healthcare burden or organizing health services for persons with MS. © 2018 S. Karger AG, Basel.

MRI in multiple sclerosis: current status and future prospects

PubMed Central

Bakshi, Rohit; Thompson, Alan J; Rocca, Maria A; Pelletier, Daniel; Dousset, Vincent; Barkhof, Frederik; Inglese, Matilde; Guttmann, Charles R G; Horsfield, Mark A; Filippi, Massimo

2008-01-01

Many promising MRI approaches for research or clinical management of multiple sclerosis (MS) have recently emerged, or are under development or refinement. Advanced MRI methods need to be assessed to determine whether they allow earlier diagnosis or better identification of phenotypes. Improved post-processing should allow more efficient and complete extraction of information from images. Magnetic resonance spectroscopy should improve in sensitivity and specificity with higher field strengths and should enable the detection of a wider array of metabolites. Diffusion imaging is moving closer to the goal of defining structural connectivity and, thereby, determining the functional significance of lesions at specific locations. Cell-specific imaging now seems feasible with new magnetic resonance contrast agents. The imaging of myelin water fraction brings the hope of providing a specific measure of myelin content. Ultra-high-field MRI increases sensitivity, but also presents new technical challenges. Here, we review these recent developments in MRI for MS, and also look forward to refinements in spinal-cord imaging, optic-nerve imaging, perfusion MRI, and functional MRI. Advances in MRI should improve our ability to diagnose, monitor, and understand the pathophysiology of MS. PMID:18565455

Use of the 2010 McDonald criteria can facilitate early diagnosis of pediatric multiple sclerosis in a predominantly black cohort.

PubMed

Williams, Mitchel T; Tapos, Daniela O; Juhász, Csaba

2014-12-01

Pediatric-onset multiple sclerosis represents around 3-5% of all patients with multiple sclerosis. Both the 2005 and 2010 McDonald criteria for multiple sclerosis have been suggested for the possible use in pediatric-onset multiple sclerosis. Modifications incorporated into the 2010 criteria enabled the fulfillment of dissemination in time to be met with the initial magnetic resonance imaging. The present study was designed to compare the diagnostic sensitivity of these criteria at initial presentation, the time to fulfilling them, and secondary effects of ethnicity in pediatric-onset multiple sclerosis. Twenty-five children with clinically definite multiple sclerosis (mean age, 14.6 ± 3.1 years; 15 girls) from a single center between 2005 and 2012 were analyzed using both the 2005 and 2010 McDonald criteria based on initial clinical presentation and neuroimaging findings comparing diagnostic sensitivity, time interval to meet diagnosis, and ethnicity. Initial multiple sclerosis diagnosis rates applying the 2005 McDonald criteria were 32% compared with 92% for the 2010 criteria (P = 0.0003). The mean time after initial signs until the 2005 and 2010 McDonald criteria for multiple sclerosis were met was 5.0 vs 0.7 months, respectively (P = 0.001). Time to diagnosis using the 2010 criteria was shorter in black children than the European white (P = 0.005). The 2010 McDonald criteria are an appropriate tool for the timely diagnosis of pediatric multiple sclerosis, especially in black children, potentially allowing an earlier initiation of disease-modifying therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of Neuromyelitis Optica: Review and Recommendations

PubMed Central

Kimbrough, Dorlan J; Fujihara, Kazuo; Jacob, Anu; Lana-Peixoto, Marco A; Leite, Maria Isabel; Levy, Michael; Marignier, Romain; Nakashima, Ichiro; Palace, Jacqueline; de Seze, Jérôme; Stuve, Olaf; Tenembaum, Silvia N; Traboulsee, Anthony; Waubant, Emmanuelle; Weinshenker, Brian G; Wingerchuk, Dean M

2014-01-01

Neuromyelitis optica (NMO) is an autoimmune demyelinating disease preferentially targeting the optic nerves and spinal cord. Once regarded as a variant of multiple sclerosis (MS), NMO is now recognized to be a different disease with unique pathology and immunopathogenesis that does not respond to traditional MS immunomodulators such as interferons. Preventive therapy in NMO has focused on a range of immunosuppressive medications, none of which have been validated in a rigorous randomized trial. However, multiple retrospective and a few recent prospective studies have provided evidence for the use of six medications for the prevention of NMO exacerbations: azathioprine, rituximab, mycophenolate mofetil, prednisone, methotrexate and mitoxantrone. This review provides a comprehensive analysis of each of these medications in NMO and concludes with a set of recommended consensus practices. PMID:24555176

Prospective study of Centurion® versus Infiniti® phacoemulsification systems: surgical and visual outcomes.

PubMed

Oh, Lawrence J; Nguyen, Chu Luan; Wong, Eugene; Wang, Samuel S Y; Francis, Ian C

2017-01-01

To evaluate surgical outcomes (SOs) and visual outcomes (VOs) in cataract surgery comparing the Centurion ® phacoemulsification system (CPS) with the Infiniti ® phacoemulsification system (IPS). Prospective, consecutive study in a single-site private practice. Totally 412 patients undergoing cataract surgery with either the CPS using the 30-degree balanced ® tip ( n =207) or the IPS using the 30-degree Kelman ® tip ( n =205). Intraoperative and postoperative outcomes were documented prospectively up to one month follow-up. Nuclear sclerosis (NS) grade, cumulated dissipated energy (CDE), preoperative corrected distance visual acuity (CDVA), and CDVA at one month were recorded. CDE was 13.50% less in the whole CPS compared with the whole IPS subcohort. In eyes with NS grade III or greater, CDE was 28.87% less with CPS ( n =70) compared with IPS ( n =44) ( P =0.010). Surgical complications were not statistically different between the two subcohorts ( P =0.083), but in the one case of vitreous loss using the CPS, CDVA of 6/4 was achieved at one month. The mean CDVAs (VOs) at one month for NS grade III and above cataracts were -0.17 logMAR (6/4.5) in the CPS and -0.15 logMAR (6/4.5) in the IPS subcohort respectively ( P =0.033). CDE is 28.87% less, and VOs are significantly improved, in denser cataracts in the CPS compared with the IPS. The authors recommend the CPS for cases with denser nuclei.

Glucose uptake heterogeneity of the leg muscles is similar between patients with multiple sclerosis and healthy controls during walking.

PubMed

Kindred, John H; Ketelhut, Nathaniel B; Rudroff, Thorsten

2015-02-01

Difficulties in ambulation are one of the main problems reported by patients with multiple sclerosis. A previous study by our research group showed increased recruitment of muscle groups during walking, but the influence of skeletal muscle properties, such as muscle fiber activity, has not been fully elucidated. The purpose of this investigation was to use the novel method of calculating glucose uptake heterogeneity in the leg muscles of patients with multiple sclerosis and compare these results to healthy controls. Eight patients with multiple sclerosis (4 men) and 8 healthy controls (4 men) performed 15 min of treadmill walking at a comfortable self-selected speed following muscle strength tests. Participants were injected with ≈ 8 mCi of [(18)F]-fluorodeoxyglucose during walking after which positron emission tomography/computed tomography imaging was performed. No differences in muscle strength were detected between multiple sclerosis and control groups (P>0.27). Within the multiple sclerosis, group differences in muscle volume existed between the stronger and weaker legs in the vastus lateralis, semitendinosus, and semimembranosus (P<0.03). Glucose uptake heterogeneity between the groups was not different for any muscle group or individual muscle of the legs (P>0.16, P≥0.05). Patients with multiple sclerosis and healthy controls showed similar muscle fiber activity during walking. Interpretations of these results, with respect to our previous study, suggest that walking difficulties in patients with multiple sclerosis may be more associated with altered central nervous system motor patterns rather than alterations in skeletal muscle properties. Published by Elsevier Ltd.

Hepatic steatosis is associated with aortic valve sclerosis in the general population: the Study of Health in Pomerania (SHIP).

PubMed

Markus, Marcello Ricardo Paulista; Baumeister, Sebastian Edgar; Stritzke, Jan; Dörr, Marcus; Wallaschofski, Henri; Völzke, Henry; Lieb, Wolfgang

2013-07-01

We aimed to analyze the association between hepatic steatosis and aortic valve sclerosis in the general population. Cross-sectional data of 2212 men and women, aged 45 to 81 years, from the baseline examination of the population-based Study of Health in Pomerania (SHIP-0) were analyzed. Hepatic steatosis was primarily defined as the presence of a hyperechogenic ultrasound pattern of the liver. Aortic valve sclerosis was determined by echocardiography. In our sample, hepatic steatosis was present in 877 (39.7%) individuals. Among participants with hepatic steatosis, aortic valve sclerosis was more common (n=323; 36.8%) compared with participants without hepatic steatosis (n=379; 28.4%; P<0.001). After adjustment for potential confounders, individuals with hepatic steatosis had 33% higher odds of aortic valve sclerosis compared with those without hepatic steatosis (95% confidence interval, 6%-66%; P=0.014). Additional adjustment for high-sensitive C-reactive protein, serum ferritin levels, and white blood cells slightly reduced the association to 32% (95% confidence interval, 4%-66%; P=0.021). Our findings add evidence that hepatic steatosis and aortic valve sclerosis are interrelated after adjustment for major confounders. The release of proatherogenic substances by the steatotic liver or its contribution to insulin resistance and dyslipidemia may contribute to the development of calcification and sclerosis of the aortic valve.

Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years.

PubMed

Fragoso, Yara Dadalti; Alves-Leon, Soniza Vieira; Barreira, Amilton Antunes; Callegaro, Dagoberto; Brito Ferreira, Maria Lucia; Finkelsztejn, Alessandro; Gomes, Sidney; Magno Goncalves, Marcus Vinicius; Moraes Machado, Maria Iris; Marques, Vanessa Daccach; Cunha Matta, Andre Palma; Papais-Alvarenga, Regina Maria; Apostolos Pereira, Samira Luisa; Tauil, Carlos Bernardo

2015-08-01

There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control. Copyright © 2015 Elsevier Inc. All rights reserved.

A palliative care hotline for multiple sclerosis: A pilot feasibility study.

PubMed

Knies, Andrea K; Golla, Heidrun; Strupp, Julia; Galushko, Maren; Schipper, Sabine; Voltz, Raymond

2015-08-01

Research findings suggest that patients severely affected by multiple sclerosis benefit from palliative care. Our objectives were to (1) implement a pilot palliative care counseling hotline for severely affected multiple sclerosis patients and their caregivers in order to connect them to palliative care, and (2) evaluate its preliminary feasibility through a pilot study. The hotline was designed in cooperation with the local state association of the German Multiple Sclerosis Society and based on a review of the literature. The initial study setting for the hotline was the broader region of the cities Cologne and Bonn in Germany. The hotline was introduced through a magazine published by the German Multiple Sclerosis Society and leaflets sent to local healthcare providers. Calls were conducted using a semistructured interview guide and documented by a standardized case report form. Measures to assess feasibility were both quantitative (e.g., number of calls) and qualitative (e.g., criteria for eligibility for palliative care). During its pilot year, the hotline received 18 calls. Some 15 callers were included in the analysis, and 10 of these 15 were deemed eligible for palliative care due to such criteria as medical characteristics, care or nursing conditions, caregiver strain, and concerns regarding death and dying. Access to palliative care services could be provided for all 10 callers. Based on our pilot feasibility study, the hotline seems to be a valuable service for patients severely affected by multiple sclerosis (MS) and their caregivers in order to gain information about and access to palliative care. It will be extended on a nationwide scale through a grant of the German Multiple Sclerosis Society. Awareness of the hotline needs to be enhanced in order to attract and support a significant number of new callers.

Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis.

PubMed

Launay, David; Montani, David; Hassoun, Paul M; Cottin, Vincent; Le Pavec, Jérôme; Clerson, Pierre; Sitbon, Olivier; Jaïs, Xavier; Savale, Laurent; Weatherald, Jason; Sobanski, Vincent; Mathai, Stephen C; Shafiq, Majid; Cordier, Jean-François; Hachulla, Eric; Simonneau, Gérald; Humbert, Marc

2018-01-01

Pre-capillary pulmonary hypertension (PH) in systemic sclerosis (SSc) is a heterogeneous condition with an overall bad prognosis. The objective of this study was to identify and characterize homogeneous phenotypes by a cluster analysis in SSc patients with PH. Patients were identified from two prospective cohorts from the US and France. Clinical, pulmonary function, high-resolution chest tomography, hemodynamic and survival data were extracted. We performed cluster analysis using the k-means method and compared survival between clusters using Cox regression analysis. Cluster analysis of 200 patients identified four homogenous phenotypes. Cluster C1 included patients with mild to moderate risk pulmonary arterial hypertension (PAH) with limited or no interstitial lung disease (ILD) and low DLCO with a 3-year survival of 81.5% (95% CI: 71.4-88.2). C2 had pre-capillary PH due to extensive ILD and worse 3-year survival compared to C1 (adjusted hazard ratio [HR] 3.14; 95% CI 1.66-5.94; p = 0.0004). C3 had severe PAH and a trend towards worse survival (HR 2.53; 95% CI 0.99-6.49; p = 0.052). Cluster C4 and C1 were similar with no difference in survival (HR 0.65; 95% CI 0.19-2.27, p = 0.507) but with a higher DLCO in C4. PH in SSc can be characterized into distinct clusters that differ in prognosis.

Cranberry versus placebo in the prevention of urinary infections in multiple sclerosis: a multicenter, randomized, placebo-controlled, double-blind trial.

PubMed

Gallien, Philippe; Amarenco, Gérard; Benoit, Nicolas; Bonniaud, Véronique; Donzé, Cécile; Kerdraon, Jacques; de Seze, Marianne; Denys, Pierre; Renault, Alain; Naudet, Florian; Reymann, Jean Michel

2014-08-01

Our aim was to assess the usefulness of cranberry extract in multiple sclerosis (MS) patients suffering from urinary disorders. In total, 171 adult MS outpatients with urinary disorders presenting at eight centers were randomized (stratification according to center and use of clean intermittent self-catheterization) to cranberry versus placebo in a 1-year, prospective, double-blind study that was analyzed using a sequential method on an intent-to-treat basis. An independent monitoring board analyzed the results of the analyses each time 40 patients were assessed on the main endpoint. Cranberry extract (36 mg proanthocyanidins per day) or a matching placebo was taken by participants twice daily for 1 year. The primary endpoint was the time to first symptomatic urinary tract infection (UTI), subject to validation by a validation committee. The second sequential analyses allowed us to accept the null hypothesis (no difference between cranberry and placebo). There was no difference in time to first symptomatic UTI distribution across 1 year, with an estimated hazard ratio of 0.99, 95% CI [0.61, 1.60] (p = 0.97). Secondary endpoints and tolerance did not differ between groups. Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders. Trial Registration NCT00280592. © The Author(s) 2014.

Effectiveness of assisted and unassisted cough capacity in amyotrophic lateral sclerosis patients.

PubMed

Sancho, Jesús; Servera, Emilio; Bañuls, Pilar; Marín, Julio

2017-11-01

Decreased cough capacity during a respiratory infection is one of the main causes of acute respiratory failure and hospitalisation in amyotrophic lateral sclerosis (ALS). To determine whether a respiratory measurement could identify the effectiveness of cough capacity in ALS during a respiratory infection. This was a prospective study of all ALS patients who were treated at a respiratory care unit due to a respiratory infection from 2012 to 2016. The effectiveness of unassisted and assisted coughing was evaluated and respiratory function tests were performed during the acute episode. Forty-eight ALS patients were enrolled, with only four having an effective unassisted cough. The variable which predicted unassisted cough effectiveness was peak cough flow (PCF) (OR 4499.27; 95%CI 3.60-3219086.19; p = 0.022) with a cut-off point of 2.77 L/s (166 L/min). For manually assisted coughing, the predictor of cough effectiveness was manually assisted PCF (cut-off point of 2.82-169 L/min) (OR 2198.602; 95% CI 3.750-1351691.42; p = 0.019). Mechanically assisted PCF (cut-off point of 2.95-177 L/min) was found to be the predictor of mechanically assisted coughing effectiveness (OR 23.40; 95% CI 2.11-258.96; p = 0.010). During a respiratory infection in ALS patients, the effectiveness of assisted and unassisted cough capacity depends on the PCF generated.

The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis.

PubMed

Choi, Bo Young; Jung, Jong Won; Suh, Sang Won

2017-09-28

Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 ( ZnT3 ) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

Hippocampal Sclerosis in Older Patients: Practical Examples and Guidance With a Focus on Cerebral Age-Related TDP-43 With Sclerosis.

PubMed

Cykowski, Matthew D; Powell, Suzanne Z; Schulz, Paul E; Takei, Hidehiro; Rivera, Andreana L; Jackson, Robert E; Roman, Gustavo; Jicha, Gregory A; Nelson, Peter T

2017-08-01

- Autopsy studies of the older population (≥65 years of age), and particularly of the "oldest-old" (≥85 years of age), have identified a significant proportion (∼20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. - To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). - Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. - In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology.

The effects of Tai Chi on physical and psychosocial function among persons with multiple sclerosis: A systematic review.

PubMed

Taylor, Emily; Taylor-Piliae, Ruth E

2017-04-01

Conduct a systematic review to evaluate the effects of Tai Chi on physical and psychosocial function among individuals with Multiple Sclerosis. An electronic literature search of 12 databases using controlled vocabulary function and keywords from inception through August 2016. All Tai Chi intervention studies assessing physical and psychosocial function among persons with Multiple Sclerosis were included. Study quality was scored using an established tool examining 16 study elements (range=0-32). A total of 91 articles were retrieved, with 3 additional articles identified through reviewing bibliographies of relevant articles. A total of 8 studies (randomized controlled trials, n=3; quasi-experimental, n=5) enrolled 193 participants with Multiple Sclerosis. Studies were conducted in the USA (n=3), Europe (n=3), Iran, (n=1), and India (n=1). A total of 3 studies reported using the Yang style of Tai Chi (not specified, n=5 studies). The Tai Chi intervention averaged 27 sessions over 11 weeks. Study quality scores for the randomized controlled trials had a mean score of 23 (range 19-26), while quality scores for quasi-experimental studies had a mean score of 20 (range 13-26). Overall, participants enrolled in Tai Chi had better balance, gait and flexibility, less fatigue and depression, and better quality of life after the intervention; though mixed results were reported. The results indicate that Tai Chi is likely safe and may provide physical and psychosocial benefits in individuals with Multiple Sclerosis. Further research is needed using more rigorous study designs to assess the benefits of Tai Chi for individuals with Multiple Sclerosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical benefits to vestibular rehabilitation in multiple sclerosis. Report of 4 cases.

PubMed

Zeigelboim, Bianca; Liberalesso, Paulo; Jurkiewicz, Ari; Klagenberg, Karlin

2010-01-01

Balance difficulties are common among multiple sclerosis patients. To evaluate the effectiveness of the Cawthorne and Cooksey protocol of vestibular rehabilitation (VR) exercises in reducing the physical, functional and emotional impact of multiple sclerosis among individuals who complained of vertigo. Four patients with remittent-recurrent multiple sclerosis underwent an interview, otorhinolaryngological and vestibular evaluation, VR exercises and the Dizziness Handicap Inventory pre- and post-intervention. There was significant improvement in the physical, functional and emotional aspects of the DHI after the completion of the VR. The VR exercises appeared useful in reducing subjective complaints of the study participants.

Change in quality of life and predictors of change among patients with multiple sclerosis: a prospective cohort study.

PubMed

Tepavcevic, Darija Kisic; Pekmezovic, Tatjana; Stojsavljevic, Nebojsa; Kostic, Jelena; Basuroski, Irena Dujmovic; Mesaros, Sarlota; Drulovic, Jelena

2014-04-01

The aim of this study was to determine the changes in the health-related quality of life (HRQoL) and predictors of change among patients with multiple sclerosis (MS) at 3 and 6 years during the follow-up period. A group of 109 consecutive MS patients (McDonald's criteria) referred to the Clinic of Neurology, Belgrade, were enrolled in the study. At three time points during the study (baseline, and at 3 and 6 years during the follow-up period), the HRQoL (measured by MSQoL-54), Expanded Disability Status Scale, and Hamilton Rating Scale for Depression and Fatigue Severity Scale were assessed. During the study period, 93 patients provided both follow-up assessments. Statistically significant deterioration in the HRQoL at each subsequent time point was detected for all scales of the MSQoL-54 except for the pain and change in health scales. A higher level of education was a significant prognostic factor for a better HRQoL on the cognitive function scale throughout the entire period of observation, while marital status (single, including divorced and widowed) and increased age at the onset of MS had significant predictive values of poorer quality-of-life scores on the overall quality-of-life scale at 6-year follow-up. Higher levels of physical disability and depression at baseline were statistically significant prognostic markers for deterioration in HRQoL for the majority of MSQoL-54 scales during the entire follow-up period. Our study suggests that baseline demographic and clinical characteristics could be applied as prognostic markers of the HRQOL for patients diagnosed with MS.

Cognitive rehabilitation and mindfulness in multiple sclerosis (REMIND-MS): a study protocol for a randomised controlled trial.

PubMed

Nauta, Ilse M; Speckens, Anne E M; Kessels, Roy P C; Geurts, Jeroen J G; de Groot, Vincent; Uitdehaag, Bernard M J; Fasotti, Luciano; de Jong, Brigit A

2017-11-21

Cognitive problems frequently occur in patients with multiple sclerosis (MS) and profoundly affect their quality of life. So far, the best cognitive treatment options for MS patients are a matter of debate. Therefore, this study aims to investigate the effectiveness of two promising non-pharmacological treatments: cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT). Furthermore, this study aims to gain additional knowledge about the aetiology of cognitive problems among MS patients, since this may help to develop and guide effective cognitive treatments. In a dual-centre, single-blind randomised controlled trial (RCT), 120 MS patients will be randomised into one of three parallel groups: CRT, MBCT or enhanced treatment as usual (ETAU). Both CRT and MBCT consist of a structured 9-week program. ETAU consists of one appointment with an MS specialist nurse. Measurements will be performed at baseline, post-intervention and 6 months after the interventions. The primary outcome measure is the level of subjective cognitive complaints. Secondary outcome measures are objective cognitive function, functional brain network measures (using magnetoencephalography), psychological symptoms, well-being, quality of life and daily life functioning. To our knowledge, this will be the first RCT that investigates the effect of MBCT on cognitive function among MS patients. In addition, studying the effect of CRT on cognitive function may provide direction to the contradictory evidence that is currently available. This study will also provide information on changes in functional brain networks in relation to cognitive function. To conclude, this study may help to understand and treat cognitive problems among MS patients. This trial was prospectively registered at the Dutch Trial Registration (number NTR6459 , registered on 31 May 2017).

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

PubMed Central

Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

2013-01-01

Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value < 1.0 × 10-4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value < 5.0 × 10-8); three found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

Treatment of progressive multiple sclerosis: what works, what does not, and what is needed.

PubMed

Feinstein, Anthony; Freeman, Jenny; Lo, Albert C

2015-02-01

Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely to these symptoms in progressive multiple sclerosis, which translates to few proven therapeutic options in the clinic. A new strategy that can be used in future rehabilitation trials is therefore needed, with the adoption of approaches that look beyond single interventions to concurrent, potentially synergistic, treatments that maximise what remains of neural plasticity in patients with progressive multiple sclerosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group.

PubMed

Foocharoen, Chingching; Tyndall, Alan; Hachulla, Eric; Rosato, Edoardo; Allanore, Yannick; Farge-Bancel, Dominique; Caramaschi, Paola; Airó, Paolo; Nikolaevna, Starovojtova M; Pereira da Silva, José António; Stamenkovic, Bojana; Riemekasten, Gabriela; Rednic, Simona; Sibilia, Jean; Wiland, Piotr; Tarner, Ingo; Smith, Vanessa; Onken, Anna T; Abdel Atty Mohamed, Walid Ahmed; Distler, Oliver; Morović-Vergles, Jadranka; Himsel, Andrea; de la Peña Lefebvre, Paloma Garcia; Hügle, Thomas; Walker, Ulrich A

2012-02-20

Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known. This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively. Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients. Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder.

PubMed

Vázquez-Costa, Juan Francisco; Arlandis, Salvador; Hervas, David; Martínez-Cuenca, Esther; Cardona, Fernando; Pérez-Tur, Jordi; Broseta, Enrique; Sevilla, Teresa

2017-07-15

Lower urinary tract symptoms (LUTS) are frequent in motor neuron disease (MND) patients, but clinical factors related to them are unknown. We describe differences in LUTS among MND phenotypes and their relationship with other clinical characteristics, including prognosis. For this study, we collected clinical data of a previously published cohort of patients diagnosed with classical amyotrophic lateral sclerosis (cALS), progressive muscular atrophy (PMA) or primary lateral sclerosis (PLS) with and without LUTS. Familial history was recorded and the C9ORF72 expansion was analysed in the entire cohort. Patients were followed-up for survival until August 2016. Fifty-five ALS patients (37 cALS, 10 PMA and 8 PLS) were recruited. Twenty-four reported LUTS and neurogenic bladder (NB) could be demonstrated in nine of them. LUTS were not influenced by age, phenotype, disability, cognitive or behavioural impairment, or disease progression, but female sex appeared to be a protective factor (OR=0.39, p=0.06). Neither family history nor the C9ORF72 expansion was linked to LUTS or NB. In the multivariate analysis, patients reporting LUTS early in the disease course tended to show poorer survival. In this study, LUTS appear to be more frequent in male MND patients, but are not related to age, clinical or genetic characteristics. When reported early, LUTS could be a sign of rapid disease spread and poor prognosis. Further prospective longitudinal and neuroimaging studies are warranted to confirm this hypothesis. Copyright © 2017 Elsevier B.V. All rights reserved.

[Current aspects of therapy conversion for multiple sclerosis].

PubMed

Kolber, P; Luessi, F; Meuth, S G; Klotz, L; Korn, T; Trebst, C; Tackenberg, B; Kieseier, B; Kümpfel, T; Fleischer, V; Tumani, H; Wildemann, B; Lang, M; Flachenecker, P; Meier, U; Brück, W; Limmroth, V; Haghikia, A; Hartung, H-P; Stangel, M; Hohlfeld, R; Hemmer, B; Gold, R; Wiendl, H; Zipp, F

2015-10-01

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

Connective tissue disease-associated pulmonary arterial hypertension

PubMed Central

Howard, Luke S.

2015-01-01

Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

Tuberous Sclerosis Associated Neuropsychiatric Disorders (TAND) and the TAND Checklist

PubMed Central

de Vries, Petrus J.; Whittemore, Vicky H.; Leclezio, Loren; Byars, Anna W.; Dunn, David; Ess, Kevin C.; Hook, Dena; King, Bryan H.; Sahin, Mustafa; Jansen, Anna

2015-01-01

BACKGROUND Tuberous sclerosis complex is a multisystem genetic disorder with a range of physical manifestations that require evaluation, surveillance, and management. Individuals with tuberous sclerosis complex also have a range of behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial difficulties. These may represent the greatest burden of the disease. Around 90% of individuals with tuberous sclerosis complex will have some of these difficulties during their lifetime, yet only about 20% ever receive evaluation and treatment. The Neuropsychiatry Panel at the 2012 Tuberous Sclerosis Complex International Consensus Conference expressed concern about the significant “treatment gap” and about confusion regarding terminology relating to the biopsychosocial difficulties associated with tuberous sclerosis complex. METHODS The Tuberous Sclerosis Complex Neuropsychiatry Panel coined the term TAND—tuberous sclerosis complex-associated neuropsychiatric disorders—to bring together these multidimensional manifestations of the disorder, and recommended annual screening for TAND. In addition, the Panel agreed to develop a TAND Checklist as a guide for screening. RESULTS Here, we present an outline of the conceptualization of TAND, rationale for the structure of the TAND Checklist, and include the full US English version of the TAND Checklist. CONCLUSION We hope that the unified term TAND and the TAND Checklist will raise awareness of the importance of tuberous sclerosis complex-associated neuropsychiatric disorders and of the major burden of disease associated with it, provide a shared language and a simple tool to describe and evaluate the different levels of TAND, alert clinical teams and families or individuals of the importance of screening, assessment, and treatment of TAND, and provide a shared framework for future studies of tuberous sclerosis complex-associated neuropsychiatric disorders. PMID:25532776

Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist.

PubMed

de Vries, Petrus J; Whittemore, Vicky H; Leclezio, Loren; Byars, Anna W; Dunn, David; Ess, Kevin C; Hook, Dena; King, Bryan H; Sahin, Mustafa; Jansen, Anna

2015-01-01

Tuberous sclerosis complex is a multisystem genetic disorder with a range of physical manifestations that require evaluation, surveillance, and management. Individuals with tuberous sclerosis complex also have a range of behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial difficulties. These may represent the greatest burden of the disease. Around 90% of individuals with tuberous sclerosis complex will have some of these difficulties during their lifetime, yet only about 20% ever receive evaluation and treatment. The Neuropsychiatry Panel at the 2012 Tuberous Sclerosis Complex International Consensus Conference expressed concern about the significant "treatment gap" and about confusion regarding terminology relating to the biopsychosocial difficulties associated with tuberous sclerosis complex. The Tuberous Sclerosis Complex Neuropsychiatry Panel coined the term TAND-tuberous sclerosis complex-associated neuropsychiatric disorders-to bring together these multidimensional manifestations of the disorder, and recommended annual screening for TAND. In addition, the Panel agreed to develop a TAND Checklist as a guide for screening. Here, we present an outline of the conceptualization of TAND, rationale for the structure of the TAND Checklist, and include the full US English version of the TAND Checklist. We hope that the unified term TAND and the TAND Checklist will raise awareness of the importance of tuberous sclerosis complex-associated neuropsychiatric disorders and of the major burden of disease associated with it, provide a shared language and a simple tool to describe and evaluate the different levels of TAND, alert clinical teams and families or individuals of the importance of screening, assessment, and treatment of TAND, and provide a shared framework for future studies of tuberous sclerosis complex-associated neuropsychiatric disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular analysis of HLA-DPB1 alleles in idiopathic systemic sclerosis patients and uranium miners with systemic sclerosis.

PubMed

Rihs, H P; Conrad, K; Mehlhorn, J; May-Taube, K; Welticke, B; Frank, K H; Baur, X

1996-03-01

According to clinical mainifestation and autoantibody pattern [anti-Scl-70, anti-centromere antibodies (ACAs)], systemic sclerosis is a connective tissue disease with heterogenous subgroups. PCR-sequence-specific-oligonucleotide typing was used to study the genetic association of HLA-DPB1 alleles in 54 patients with idiopathic systemic sclerosis, 26 uranium miners with systemic sclerosis and 70 unrelated healthy control subjects. Systemic sclerosis patients with and without former employment in mines were divided into two subgroups according to their scleroderma-typical autoantibody specificities--anti-Scl-70 positive and ACA positive--and third subgroup comprising the rest. Statistical analysis revealed a significantly increased frequency of DPB1*1301(p=0.0001, corrected p=0.011) in idiopathic anti-Scl-70-positive systemic sclerosis cases when compared with unexposed controls. In the same group, we observed an enhanced frequency of DPB1*0601 and *1701 alleles. Since these three alleles carry the information for a glutamic acid residue in position 69 of DPB1, we tested the association of this residue with anti-Scl-70 expression. A strong association between anti-Scl-70 positivity in idiopathic systemic sclerosis patients and amino acid residue 69 of DPB1 was observed when compared with anti-Scl-70-negative idiopathic systemic sclerosis patients (p=0.0009) or unrelated controls (p=0.0007). ACA expression was not associated with the presence of any DPB1 allele tested. The data show that anti-Scl-70 expression in idiopathic systemic sclerosis patients is linked with DPB1*1301 whereas anti-Scl-70-positive miners do not show such a DPB1 association. Futhermore, the data indicate that glutamate 69 of DPB1 might be involved in the susceptibility to idiopathic anti-Scl-70 expression.

Gut microbiota in MS: possible influence of immunomodulators

PubMed Central

Cantarel, Brandi L.; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z.; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M.; Mowry, Ellen M.

2015-01-01

Objectives Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in multiple sclerosis patients and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Methods Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Multiple sclerosis patients were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5,000 IU/day) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. Results While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in multiple sclerosis patients. Glatiramer acetate-treated MS subjects showed differences in community composition compared to untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and Other Clostridiales. Compared to the other groups, untreated multiple sclerosis subjects had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. Conclusions While overall bacterial communities were similar, specific operational taxonomic units differed between healthy and multiple sclerosis subjects. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results. PMID:25775034

Features of Coping with Disease in Iranian Multiple Sclerosis Patients: a Qualitative Study.

PubMed

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2018-03-01

Introduction: Coping with disease is of the main components improving the quality of life in multiple sclerosis patients. Identifying the characteristics of this concept is based on the experiences of patients. Using qualitative research is essential to improve the quality of life. This study was conducted to explore the features of coping with the disease in patients with multiple sclerosis. Method: In this conventional content analysis study, eleven multiple sclerosis patients from Iran MS Society in Tehran (Iran) participated. Purposive sampling was used to select participants. Data were gathered using semi structured interviews. To analyze data, a conventional content analysis approach was used to identify meaning units and to make codes and categories. Results: Results showed that features of coping with disease in multiple sclerosis patients consists of (a) accepting the current situation, (b) maintenance and development of human interactions, (c) self-regulation and (d) self-efficacy. Each of these categories is composed of sub-categories and codes that showed the perception and experience of patients about the coping with disease. Conclusion: Accordingly, a unique set of features regarding features of coping with the disease were identified among the patients with multiple sclerosis. Therefore, working to ensure the emergence of, and subsequent reinforcement of these features in MS patients can be an important step in improving the adjustment and quality of their lives.

[Assessment of exposure to tobacco smoke in a selected group of patients with multiple sclerosis from the Upper Silesia region].

PubMed

Dobosz, Cezary; Tyrpień, Krystyna; Pierzchała, Krystyna

2012-01-01

In recent years, the increase in the incidence of multiple sclerosis (MS - Multiple Sclerosis) is observed. and the direct cause of the symptoms of multiple sclerosis is myelin nerves damage. It can be concluded that the environmental factor is at least partly responsible for the occurrence of this disease. For the development of this disease are responsible, in addition to genetic factors, compounds present in many parts of the environment. Many of these compounds may adversely affect the redox equilibrium of the body, exacerbating radicalgenesis and decreasing antioxidant defenses. Multiple sclerosis is usually diagnosed in early adulthood, during most daily activities. Effects of SM on living standards includes not only the medical aspect, but also social, economic and emotional aspect. Polish population is a high risk zone regarding multiple sclerosis. The aim of this study was a preliminary assessment of selected environmental exposure factors in the pathogenesis of multiple sclerosis with regard to exposure to tobacco smoke with the author's survey of patients from the region of Upper Silesia. Most MS patients (32) in the study group (suffering from MS from 2 to 44 years) are inhabitants of agglomeration of over 50 thousand citizens, from the area of Gliwice, Bytom and Zabrze (43.75%). In investigated group 46.88% MS patients from Silesia region were exposed to tobacco smoke, of which 21.88% actively smoke. Patients with MS, in order not to worsen their disease manifestation, should stop smoking and increase, if possible, any physical activities. These data will be incorporated into a wide-ranging research to clarify the role of selected environmental factors in a very complex and still not fully explored the pathogenesis of multiple sclerosis in Upper Silesia.

Remote infarct of the temporal lobe with coexistent hippocampal sclerosis in mesial temporal lobe epilepsy.

PubMed

Gales, Jordan M; Prayson, Richard A

2016-02-01

In patients undergoing surgery for temporal lobe epilepsy, hippocampal sclerosis remains the most commonly observed pathology. In addition to hippocampal sclerosis, 5% to 30% of these resections on magnetic resonance imaging contain a second independently epileptogenic lesion, commonly referred to as dual pathology. A second etiology of seizure activity, as seen in dual pathology, may serve as an important cause of treatment failure in striving for post-operative seizure control. Dual pathology, consisting of hippocampal sclerosis and a remote infarct of the adjacent cortex, has been rarely reported. Cases of pathologically confirmed hippocampal sclerosis diagnosed between January 2000 and December 2012 (n = 349) were reviewed, and 7 cases of coexistent infarct (2%) formed the study group. Seven individuals (mean age, 29years; range, 5-47 years) with a mean epilepsy duration of 12.5years (3.3-25 years) and a mean pre-surgery frequency of 15 seizures per week (range, 0.5-56 seizures/week) were followed up postoperatively for a mean duration of 64months (range, 3-137 months). Pathologically, the most common form of hippocampal sclerosis observed was International League against Epilepsy type Ib or severe variant (n = 4). Four of the six individuals with post-surgery follow-up were seizure free at last encounter. The reported incidence of dual pathology, including hippocampal sclerosis and remote infarct, is low (2% in the present study) but may indicate a slightly increased risk of developing hippocampal sclerosis in the setting of a remote infarct. Surgical intervention for such cases anecdotally appears effective in achieving seizure control. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypertrophic lichen sclerosus sine sclerosis: clues to histopathologic diagnosis when presenting as psoriasiform lichenoid dermatitis.

PubMed

Weyers, Wolfgang

2015-02-01

The histopathologic diagnosis of lichen sclerosus (LS) is usually facilitated by a subepidermal zone of sclerosis. In the absence of sclerosis, LS mostly presents itself as a psoriasiform lichenoid dermatitis that may be difficult to distinguish from other diseases. We sought to assess histopathologic findings that allow recognition of LS in the absence of sclerosis. We studied 28 criteria in 100 biopsy specimens of LS from genital or perianal skin, including 55 cases with marked sclerosis, 16 cases with mild sclerosis confined to foci of the papillary dermis and 29 cases without sclerosis. Fifteen cases each of the early plaque stage of mycosis fungoides, lichen planus and lichen simplex chronicus were studied for comparison. Some histopathologic hallmarks of LS were seen chiefly in sclerotic lesions and, therefore, did not contribute to the diagnosis of difficult cases, such as dissolution of elastic fibers. Others were seen rarely in non-sclerotic lesions but might be helpful in individual cases, including follicular hyperkeratosis and thickening of the basement membrane. Findings that were more common and may be utilized as clues to the histopathologic diagnosis of non-sclerotic LS include tiny foci of homogenized tissue in dermal papillae, marked fibrosis with thickening of the papillary dermis, marked thickening of individual collagen fibers, lymphocytes aligned in rows between those fibers, necrotic keratinocytes, often with preserved pyknotic nuclei, in all reaches of the epidermis, including the cornified layer, clustering of necrotic keratinocytes above elongated dermal papillae and vertical columns of parakeratosis with distinct dyskeratotic parakeratotic cells. In the absence of sclerosis, histopathologic diagnosis of LS depends on findings that are less distinctive. Nonetheless, a constellation of those findings allows a specific diagnosis to be made. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An ImmunoChip study of multiple sclerosis risk in African Americans

PubMed Central

Isobe, Noriko; Madireddy, Lohith; Khankhanian, Pouya; Matsushita, Takuya; Caillier, Stacy J.; Moré, Jayaji M.; Gourraud, Pierre-Antoine; McCauley, Jacob L.; Beecham, Ashley H.; Piccio, Laura; Herbert, Joseph; Khan, Omar; Cohen, Jeffrey; Stone, Lael; Santaniello, Adam; Cree, Bruce A. C.; Onengut-Gumuscu, Suna; Rich, Stephen S.; Hauser, Stephen L.; Sawcer, Stephen

2015-01-01

The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10−4), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 × 10−5). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk. PMID:25818868

An ImmunoChip study of multiple sclerosis risk in African Americans.

PubMed

Isobe, Noriko; Madireddy, Lohith; Khankhanian, Pouya; Matsushita, Takuya; Caillier, Stacy J; Moré, Jayaji M; Gourraud, Pierre-Antoine; McCauley, Jacob L; Beecham, Ashley H; Piccio, Laura; Herbert, Joseph; Khan, Omar; Cohen, Jeffrey; Stone, Lael; Santaniello, Adam; Cree, Bruce A C; Onengut-Gumuscu, Suna; Rich, Stephen S; Hauser, Stephen L; Sawcer, Stephen; Oksenberg, Jorge R

2015-06-01

The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10(-4)), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 × 10(-5)). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The multiple sclerosis work difficulties questionnaire: translation and cross-cultural adaptation to Turkish and assessment of validity and reliability.

PubMed

Kahraman, Turhan; Özdoğar, Asiye Tuba; Honan, Cynthia Alison; Ertekin, Özge; Özakbaş, Serkan

2018-05-09

To linguistically and culturally adapt the Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) for use in Turkey, and to examine its reliability and validity. Following standard forward-back translation of the MSWDQ-23, it was administered to 124 people with multiple sclerosis (MS). Validity was evaluated using related outcome measures including those related to employment status and expectations, disability level, fatigue, walking, and quality of life. Randomly selected participants were asked to complete the MSWDQ-23 again to assess test-retest reliability. Confirmatory factor analysis on the MSWDQ-23 demonstrated a good fit for the data, and the internal consistency of each subscale was excellent. The test-retest reliability for the total score, psychological/cognitive barriers, physical barriers, and external barriers subscales were high. The MSWDQ-23 and its subscales were positively correlated with the employment, disability level, walking, and fatigue outcome measures. This study suggests that the Turkish version of MSWDQ-23 has high reliability and adequate validity, and it can be used to determine the difficulties faced by people with multiple sclerosis in workplace. Moreover, the study provides evidence about the test-retest reliability of the questionnaire. Implications for rehabilitation Multiple sclerosis affects young people of working age. Understanding work-related problems is crucial to enhance people with multiple sclerosis likelihood of maintaining their job. The Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) is a valid and reliable measure of perceived workplace difficulties in people with multiple sclerosis: we presented its validation to Turkish. Professionals working in the field of vocational rehabilitation may benefit from using the MSWDQ-23 to predict the current work outcomes and future employment expectations.

Impact of systemic sclerosis oral manifestations on patients' health-related quality of life: a systematic review.

PubMed

Smirani, Rawen; Truchetet, Marie-Elise; Poursac, Nicolas; Naveau, Adrien; Schaeverbeke, Thierry; Devillard, Raphaël

2018-06-01

Oropharyngeal features are frequent and often understated in the treatment clinical guidelines of systemic sclerosis in spite of important consequences on comfort, esthetics, nutrition and daily life. The aim of this systematic review was to assess a correlation between the oropharyngeal manifestations of systemic sclerosis and patients' health-related quality of life. A systematic search was conducted using four databases [PubMed ® , Cochrane Database ® , Dentistry & Oral Sciences Source ® , and SCOPUS ® ] up to January 2018, according to the Preferred reporting items for systematic reviews and meta analyses. Grey literature and hand search were also included. Study selection, risk bias assessment (Newcastle-Ottawa scale) and data extraction were performed by two independent reviewers. The review protocol was registered on PROSPERO database with the code CRD42018085994. From 375 screened studies, 6 cross-sectional studies were included in the systematic review. The total number of patients included per study ranged from 84 to 178. These studies reported a statistically significant association between oropharyngeal manifestations of systemic sclerosis (mainly assessed by maximal mouth opening and the mouth handicap in systemic sclerosis scale) and an impaired quality of life (measured by different scales). Studies were unequal concerning risk of bias mostly because of low level of evidence, different recruiting sources of samples, and different scales to assess the quality of life. This systematic review demonstrates a correlation between oropharyngeal manifestations of systemic sclerosis and impaired quality of life, despite the low level of evidence of included studies. Large-scaled studies are needed to provide stronger evidence of this association. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Enantioselectivity in the Metabolism of Cyclophosphamide in Patients With Multiple or Systemic Sclerosis.

PubMed

de Castro, Francine Attié; Simões, Belinda Pinto; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

2017-06-01

The aim of this study was to evaluate the enantioselective pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide and carboxyethylphosphoramide mustard in patients with systemic or multiple sclerosis. Patients with systemic sclerosis (n = 10) or multiple sclerosis (n = 10), genotyped for the allelic variants of CYP2C9*2 and CYP2C9*3 and of the CYP2B6 G516T polymorphism, were treated with 50 mg cyclophosphamide/kg daily for 4 days. Serial blood samples were collected up to 24 hours after administration of the last cyclophosphamide dose. Cyclophosphamide, 4-hydroxycyclophosphamide, and carboxyethylphosphoramide enantiomers were analyzed in plasma samples using liquid chromatography-tandem mass spectrometry coupled to chiral column Chiralcel OD-R or Chiralpak AD-RH. Cytokines IL-2, IL-4, IL-6, IL-8, IL-10, IL- 12p70, IL-17, TNF-α, and INT-δ in the plasma samples collected before cyclophosphamide infusion were analyzed by Milliplex MAP human cytokine/chemokine. Pharmacokinetic parameters showed higher plasma concentrations of (S)-(-)-cyclophosphamide (AUC 215.0 vs 186.2 μg·h/mL for multiple sclerosis patients and 219.1 vs 179.2 μg·h/mL for systemic sclerosis patients) and (R)-4-hydroxycyclophosphamide (AUC 5.6 vs 3.7 μg·h/mL for multiple sclerosis patients and 6.3 vs 5.6 μg·h/mL for systemic sclerosis patients) when compared to their enantiomers in both groups of patients, whereas the pharmacokinetics of the carboxyethylphosphoramide metabolite was not enantioselective. Cytokines' plasma concentrations were similar between multiple and systemic sclerosis groups. The pharmacokinetics of cyclophosphamide is enantioselective in patients with systemic sclerosis and multiple sclerosis, with higher plasma concentrations of the (S)-(-)-cyclophosphamide enantiomer due to the preferential formation of the (R)-4-hydroxycyclophosphamide metabolite. © 2017, The American College of Clinical Pharmacology.

A pragmatic investigation into the effects of massage therapy on the self efficacy of multiple sclerosis clients.

PubMed

Finch, Paul; Bessonnette, Susan

2014-01-01

This research was conducted to examine changes in self self-efficacy, (the perception/belief that one can competently cope with a challenging situation) in multiple sclerosis clients following a series of massage therapy treatments. This small practical trial investigated the effects of a pragmatic treatment protocol using a prospective randomized pretest posttest waitlist control design. Self-Efficacy scores were obtained before the first treatment, mid-treatment series, after the last treatment in the series, four weeks after the final treatment and again eight weeks after the final treatment had been received. The intervention involved a series of weekly one hour therapeutic massage treatments conducted over eight weeks and a subsequent eight week follow up period. All treatments were delivered by supervised student therapists in the final term of their two year massage therapy program. Self-Efficacy [SE] was the outcome for the study, measured using the Multiple Sclerosis Self-Efficacy survey [MSSE]. Descriptive statistics for SE scores were assessed and inferential analysis involved the testing of between group differences at each of the measurement points noted above. Statistically significant improvement in self-efficacy was noted between treatment (n = 8) and control (n = 7) groups at mid treatment series (t = 2.32; p < 0.02), post treatment series (t = 1.81; p < 0.05) and at four week follow up (t = 2.24; p < 0.02). At the eight week follow up self-efficacy scores had decreased and there was no statistically significant difference between groups (t = 0.87; p < 0.2). Study results support previous findings indicating that massage therapy increases the self-efficacy of clients with multiple sclerosis, potentially resulting in a better overall adjustment to the disease and an improvement in psycho-emotional state. The increase in self-efficacy after 4 weeks of treatment suggests that positive response occurs more rapidly that was previously demonstrated. The improvement in self-efficacy endured 4 weeks after the end of the treatment series, which suggests that massage therapy may have longer term effects on self-efficacy that were not previously noted. Lack of inter group difference at the eight week follow up reinforces the notion that on-going treatment is required in order to maintain the positive changes observed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functional identification of pathogenic autoantibody responses in patients with multiple sclerosis

PubMed Central

Elliott, Christina; Lindner, Maren; Arthur, Ariel; Brennan, Kathryn; Jarius, Sven; Hussey, John; Chan, Andrew; Stroet, Anke; Olsson, Tomas; Willison, Hugh; Barnett, Susan C.; Meinl, Edgar

2012-01-01

Pathological and clinical studies implicate antibody-dependent mechanisms in the immunopathogenesis of multiple sclerosis. We tested this hypothesis directly by investigating the ability of patient-derived immunoglobulins to mediate demyelination and axonal injury in vitro. Using a myelinating culture system, we developed a sensitive and reproducible bioassay to detect and quantify these effects and applied this to investigate the pathogenic potential of immunoglobulin G preparations obtained from patients with multiple sclerosis (n = 37), other neurological diseases (n = 10) and healthy control donors (n = 13). This identified complement-dependent demyelinating immunoglobulin G responses in approximately 30% of patients with multiple sclerosis, which in two cases was accompanied by significant complement-dependent antibody mediated axonal loss. No pathogenic immunoglobulin G responses were detected in patients with other neurological disease or healthy controls, indicating that the presence of these demyelinating/axopathic autoantibodies is specific for a subset of patients with multiple sclerosis. Immunofluorescence microscopy revealed immunoglobulin G preparations with demyelinating activity contained antibodies that specifically decorated the surface of myelinating oligodendrocytes and their contiguous myelin sheaths. No other binding was observed indicating that the response is restricted to autoantigens expressed by terminally differentiated myelinating oligodendrocytes. In conclusion, our study identifies axopathic and/or demyelinating autoantibody responses in a subset of patients with multiple sclerosis. This observation underlines the mechanistic heterogeneity of multiple sclerosis and provides a rational explanation why some patients benefit from antibody depleting treatments. PMID:22561643

Effect of the cooling suit method applied to individuals with multiple sclerosis on fatigue and activities of daily living.

PubMed

Özkan Tuncay, Fatma; Mollaoğlu, Mukadder

2017-12-01

To determine the effects of cooling suit on fatigue and activities of daily living of individuals with multiple sclerosis. Fatigue is one of the most common symptoms in people with multiple sclerosis and adversely affects their activities of daily living. Studies evaluating fatigue associated with multiple sclerosis have reported that most of the fatigue cases are related to the increase in body temperature and that cooling therapy is effective in coping with fatigue. This study used a two sample, control group design. The study sample comprised 75 individuals who met the inclusion criteria. Data were collected with study forms. After the study data were collected, cooling suit treatment was administered to the experimental group. During home visits paid at the fourth and eighth weeks after the intervention, the aforementioned scales were re-administered to the participants in the experimental and control groups. The analyses performed demonstrated that the severity levels of fatigue experienced by the participants in the experimental group wearing cooling suit decreased. The experimental group also exhibited a significant improvement in the participants' levels of independence in activities of daily living. The cooling suit worn by individuals with multiple sclerosis was determined to significantly improve the participants' levels of fatigue and independence in activities of daily living. The cooling suit therapy was found to be an effective intervention for the debilitating fatigue suffered by many multiple sclerosis patients, thus significantly improving their level of independence in activities of daily living. © 2017 John Wiley & Sons Ltd.

The Validity and Test-Retest Reliability of the Leeds Multiple Sclerosis Quality of Life Scale in Turkish Patients

ERIC Educational Resources Information Center

Akbiyik, Derya Iren; Sumbuloglu, Vildan; Guney, Zafer; Armutlu, Kadriye; Korkmaz, Nilufer; Keser, Ilke; Yuksel, Muazzez Merve; Karabudak, Rana

2009-01-01

The aim of the study was to translate and test the reliability and validity of the Leeds Multiple Sclerosis Quality of Life Scale (LMSQoL) in Turkish patients with multiple sclerosis (MS). Demographic data of MS patients who had a registration in and followed up by a university hospital were recorded. The LMSQoL and Turkish Quality of Life…

The Effects of Gain- versus Loss-Framed Messages Following Health Risk Information on Physical Activity in Individuals With Multiple Sclerosis.

PubMed

Lithopoulos, Alexander; Bassett-Gunter, Rebecca L; Martin Ginis, Kathleen A; Latimer-Cheung, Amy E

2017-06-01

Few people with multiple sclerosis engage in physical activity. Messaging interventions may motivate more physical activity among these individuals. The purpose of this online study was to evaluate an intervention presenting participants with multiple sclerosis (N = 237) with risk information (i.e., information demonstrating people with multiple sclerosis are more likely to experience certain health issues) or no risk information followed by gain- or loss-framed physical activity messages. Participants completed questionnaires on Days 1, 6, and 28 and received information material on Days 2-5. The dependent variables were as follows: physical activity intentions and behavior, response and task efficacy, perceived threat (i.e., perception of threat to health issues relevant to people with multiple sclerosis), and avoidance (i.e., avoiding thinking about/doing something about the health issues presented in the messages). Analyses indicated physical activity and response efficacy increased over time. Also, participants receiving risk information had higher levels of physical activity and perceived threat. However, manipulation checks showed no differences between participants regarding perceptions of risk information or gain/loss-framed messages. Despite the lack of impact of the framing intervention, this study suggests that a brief informational intervention can positively influence physical activity and certain correlates of physical activity among people with multiple sclerosis.

Lateral interactions and speed of information processing in highly functioning multiple sclerosis patients.

PubMed

Nagy, Helga; Bencsik, Krisztina; Rajda, Cecília; Benedek, Krisztina; Janáky, Márta; Beniczky, Sándor; Kéri, Szabolcs; Vécsei, László

2007-06-01

Visual impairment is a common feature of multiple sclerosis. The aim of this study was to investigate lateral interactions in the visual cortex of highly functioning patients with multiple sclerosis and to compare that with basic visual and neuropsychologic functions. Twenty-two young, visually unimpaired multiple sclerosis patients with minimal symptoms (Expanded Disability Status Scale <2) and 30 healthy controls subjects participated in the study. Lateral interactions were investigated with the flanker task, during which participants were asked to detect the orientation of a low-contrast Gabor patch (vertical or horizontal), flanked with 2 collinear or orthogonal Gabor patches. Stimulus exposure time was 40, 60, 80, and 100 ms. Digit span forward/backward, digit symbol, verbal fluency, and California Verbal Learning Test procedures were used for background neuropsychologic assessment. Results revealed that patients with multiple sclerosis showed intact visual contrast sensitivity and neuropsychologic functions, whereas orientation detection in the orthogonal condition was significantly impaired. At 40-ms exposure time, collinear flankers facilitated the orientation detection performance of the patients resulting in normal performance. In conclusion, the detection of briefly presented, low-contrast visual stimuli was selectively impaired in multiple sclerosis. Lateral interactions between target and flankers robustly facilitated target detection in the patient group.

Application of laser radiation and magnetostimulation in therapy of patients with multiple sclerosis.

PubMed

Kubsik, Anna; Klimkiewicz, Robert; Janczewska, Katarzyna; Klimkiewicz, Paulina; Jankowska, Agnieszka; Woldańska-Okońska, Marta

2016-01-01

Multiple sclerosis is one of the most common neurological disorders. It is a chronic inflammatory demyelinating disease of the CNS, whose etiology is not fully understood. Application of new rehabilitation methods are essential to improve functional status. The material studied consisted of 120 patients of both sexes (82 women and 38 men) aged 21-81 years. The study involved patients with a diagnosis of multiple sclerosis. The aim of the study was to evaluate the effect of laser radiation and other therapies on the functional status of patients with multiple sclerosis. Patients were randomly divided into four treatment groups. The evaluation was performed three times - before the start of rehabilitation, immediately after rehabilitation (21 days of treatment) and subsequent control - 30 days after the patients leave the clinic. The following tests were performed for all patients to assess functional status: Expanded Disability Status Scale (EDSS) of Kurtzke and Barthel Index. Results of all testing procedures show that the treatment methods are improving the functional status of patients with multiple sclerosis, with the significant advantage of the synergistic action of laser and magneto stimulation. The combination of laser and magneto stimulation significantly confirmed beneficial effect on quality of life. The results of these studies present new scientific value and are improved compared to program of rehabilitation of patients with multiple sclerosis by laser radiation which was previously used. This study showed that synergic action of laser radiation and magneto stimulation has a beneficial effect on improving functional status, and thus improves the quality of life of patients with multiple sclerosis. The effects of all methods of rehabilitation are persisted after cessation of treatment applications, with a particular advantage of the synergistic action of laser radiation and magneto stimulation, which indicates the possibility to elicitation in these methods the phenomenon of the biological hysteresis.

Exploring change in a group-based psychological intervention for multiple sclerosis patients.

PubMed

Borghi, Martina; Bonino, Silvia; Graziano, Federica; Calandri, Emanuela

2018-07-01

The study is focused on a group-based cognitive behavioral intervention aimed at promoting the quality of life and psychological well-being of multiple sclerosis patients. The study investigates how the group intervention promoted change among participants and fostered their adjustment to the illness. The intervention involved six groups of patients (a total of 41 patients) and included four consecutive sessions and a 6-month follow-up. To explore change, verbatim transcripts of the intervention sessions were analyzed using a mixed-methods content analysis with qualitative data combined with descriptive statistics. The categories of resistance and openness to change were used to describe the process of change. Resistance and openness to change coexisted during the intervention. Only in the first session did resistance prevail over openness to change; thereafter, openness to change gradually increased and stabilized over time, and openness to change was then always stronger than resistance. The study builds on previous research on the effectiveness of group-based psychological interventions for multiple sclerosis patients and gives methodological and clinical suggestions to health care professionals working with multiple sclerosis patients. Implications for rehabilitation The study suggests that a group-based cognitive behavioral intervention for multiple sclerosis patients focused on the promotion of identity redefinition, a sense of coherence and self-efficacy in dealing with multiple sclerosis fosters the process of change and may be effective in promoting patients' adjustment to their illness. Health care professionals leading group-based psychological interventions for multiple sclerosis patients should be aware that resistance and openness to change coexist in the process of change. The study suggests that the duration of the intervention is a crucial factor: a minimum of three sessions appears to be necessary for group participants to develop greater openness to change and follow-up sessions should be implemented to maintain positive changes among participants. The use of qualitative instruments to evaluate group interventions captures the complexity of processes and gives useful indications to health professionals to improve rehabilitation programs.

Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

PubMed

García-Merino, A; Fernández, O; Montalbán, X; de Andrés, C; Oreja-Guevara, C; Rodríguez-Antigüedad, A; Arbizu, T

2013-01-01

Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Effects of physiotherapy interventions on balance in multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Paltamaa, Jaana; Sjögren, Tuulikki; Peurala, Sinikka H; Heinonen, Ari

2012-10-01

To determine the effects of physiotherapy interventions on balance in people with multiple sclerosis. A systematic literature search was conducted in Medline, Cinahl, Embase, PEDro, both electronically and by manual search up to March 2011. Randomized controlled trials of physiotherapy interventions in people with multiple sclerosis, with an outcome measure linked to the International Classification of Functioning, Disability and Health (ICF) category of "Changing and maintaining body position", were included. The quality of studies was determined by the van Tulder criteria. Meta-analyses were performed in subgroups according to the intervention. After screening 233 full-text papers, 11 studies were included in a qualitative analysis and 7 in a meta-analysis. The methodological quality of the studies ranged from poor to moderate. Low evidence was found for the efficacy of specific balance exercises, physical therapy based on an individualized problem-solving approach, and resistance and aerobic exercises on improving balance among ambulatory people with multiple sclerosis. These findings indicate small, but significant, effects of physiotherapy on balance in people with multiple sclerosis who have a mild to moderate level of disability. However, evidence for severely disabled people is lacking, and further research is needed.

Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis.

PubMed

Snook, Erin M; Motl, Robert W

2009-02-01

The study used meta-analytic procedures to examine the overall effect of exercise training interventions on walking mobility among individuals with multiple sclerosis. A search was conducted for published exercise training studies from 1960 to November 2007 using MEDLINE, PsychINFO, CINAHL, and Current Contents Plus. Studies were selected if they measured walking mobility, using instruments identified as acceptable walking mobility constructs and outcome measures for individuals with neurologic disorders, before and after an intervention that included exercise training. Forty-two published articles were located and reviewed, and 22 provided enough data to compute effect sizes expressed as Cohen's d. Sixty-six effect sizes were retrieved from the 22 publications with 600 multiple sclerosis participants and yielded a weighted mean effect size of g = 0.19 (95% confidence interval, 0.09-0.28). There were larger effects associated with supervised exercise training ( g = 0.32), exercise programs that were less than 3 months in duration (g = 0.28), and mixed samples of relapsing-remitting and progressive multiple sclerosis (g = 0.52). The cumulative evidence supports that exercise training is associated with a small improvement in walking mobility among individuals with multiple sclerosis.

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PubMed

Bobholz, Julie A; Rao, Stephen M

2003-06-01

Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

No association between dietary sodium intake and the risk of multiple sclerosis.

PubMed

Cortese, Marianna; Yuan, Changzheng; Chitnis, Tanuja; Ascherio, Alberto; Munger, Kassandra L

2017-09-26

To prospectively investigate the association between dietary sodium intake and multiple sclerosis (MS) risk. In this cohort study, we assessed dietary sodium intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (NHS) (1984-2002) and to 94,511 in the Nurses' Health Study II (NHSII) (1991-2007), and calibrated it using data from a validation study. There were 479 new MS cases during follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the effect of energy-adjusted dietary sodium on MS risk, adjusting also for age, latitude of residence at age 15, ancestry, body mass index at age 18, supplemental vitamin D intake, cigarette smoking, and total energy intake in each cohort. The results in both cohorts were pooled using fixed effects models. Total dietary intake of sodium at baseline was not associated with MS risk (highest [medians: 3.2 g/d NHS; 3.5 g/d NHSII] vs lowest [medians: 2.5 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 0.98, 95% CI 0.74-1.30, p for trend = 0.75). Cumulative average sodium intake during follow-up was also not associated with MS risk (highest [medians: 3.3 g/d NHS; 3.4 g/d NHSII] vs lowest [medians: 2.7 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 1.02, 95% CI 0.76-1.37, p for trend = 0.76). Comparing more extreme sodium intake in deciles yielded similar results ( p for trend = 0.95). Our findings suggest that higher dietary sodium intake does not increase the risk of developing MS. © 2017 American Academy of Neurology.

Work-related problems in multiple sclerosis: a literature review on its associates and determinants.

PubMed

Raggi, Alberto; Covelli, Venusia; Schiavolin, Silvia; Scaratti, Chiara; Leonardi, Matilde; Willems, Michelle

2016-01-01

To explore which variables are associated to or determinants of work-related difficulties or unemployment in persons with multiple sclerosis (MS). Papers published between 1993 and February 2015 were included. Quality was judged as poor, acceptable, good or excellent. Determinants were extracted from prospective and retrospective data, associated variables from cross-sectional data; variables were grouped by similarity. Evidence was judged as strong if there were at least two good studies reporting the same results; limited if there was only one good and some acceptable studies. Forty-two papers were selected, for a total of 31,192 patients (75% females). Work-related difficulties were referred as unemployment, lower amount of worked hours or job cessation. Strong evidence of impact over work-related difficulties was found for a core set of variables, i.e., expanded disability status scale, MS duration, patients' age, fatigue and walking problems. Little evidence exists on the impact of contextual factors. Most of the variables identified as associated to or determinants of work-related difficulties can be treated through rehabilitative interventions. It is important that future research addresses not only unemployment issues in MS, but also the amount and severity of problems affecting work-related tasks relying on specific assessment instruments. Multiple sclerosis (MS) affects young persons of working age and limitation in work activities is part of MS-related disability, but they are not consistently addressed in MS research: EDSS, MS duration, patients' age, fatigue, walking problems, cognitive and neuropsychological impairments were the factors most commonly found as associated to or determinant of difficulties with work. Evidence exists that rehabilitation interventions are effective for fatigue, cognitive impairment, mobility and walking difficulties. However, research did not address the impact of rehabilitation programmes on vocational outcomes. Rehabilitation researchers should include MS-specific assessment instruments for work-related difficulties to standardised clinical protocols, so that the benefits of rehabilitation on persons' ability to work can be demonstrated directly: in this way, cost-benefit balance analyses can be added to the evaluation of treatment effectiveness.

A regenerative approach to the treatment of multiple sclerosis.

PubMed

Deshmukh, Vishal A; Tardif, Virginie; Lyssiotis, Costas A; Green, Chelsea C; Kerman, Bilal; Kim, Hyung Joon; Padmanabhan, Krishnan; Swoboda, Jonathan G; Ahmad, Insha; Kondo, Toru; Gage, Fred H; Theofilopoulos, Argyrios N; Lawson, Brian R; Schultz, Peter G; Lairson, Luke L

2013-10-17

Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission. To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

Effects of physiotherapy treatment for urinary incontinence in patient with multiple sclerosis.

PubMed

Pereira, Carla Maria de Abreu; Castiglione, Mariane; Kasawara, Karina Tamy

2017-07-01

[Purpose] The aim of the study was to evaluate the benefits of physical therapy for urinary incontinence in patients with multiple sclerosis and to verify the impact of urinary incontinence on the patient's quality of life. [Subject and Methods] A case study of a 55-year-old female patient diagnosed with multiple sclerosis and mixed urinary incontinence was conducted. Physical therapy sessions were conducted once a week, in total 15 sessions, making use of targeted functional electrical vaginal stimulation, along with active exercises for the pelvic floor muscles and electrical stimulation of the posterior tibial nerve, behavioral rehabilitation and exercise at home. [Results] After 15 physical therapy sessions, a patient diagnosed with multiple sclerosis and mixed urinary incontinence showed continued satisfactory results after five months. She showed better quality of life, higher strength of pelvic floor muscle and reduced urinary frequency without nocturia and enuresis. [Conclusion] The physical therapy protocol in this patient with multiple sclerosis and mixed urinary incontinence showed satisfactory results reducing urinary incontinence symptomatology and improving the patient's quality of life.

The experiences of support persons of people newly diagnosed with multiple sclerosis: an interpretative phenomenological study.

PubMed

Strickland, Karen; Worth, Allison; Kennedy, Catriona

2015-12-01

This study explores the experience of the diagnosis of Multiple Sclerosis for the support person and identifies the impact on their lives. At the time of diagnosis, the support person may not be readily identified in a traditional caring role; however, the diagnosis itself brings with it the possibility of changes to the roles in the relationship and possible consequences for biographical construction. A hermeneutic phenomenological study. A convenience sample of nine support persons was interviewed between December 2008-March 2010. The data were analysed using interpretative phenomenological analysis. The participants in this study were often not readily identifiable as 'carers'; however, the diagnosis of Multiple Sclerosis implied a shift towards a caring role at some point in the future. The uncertainty surrounding the nature and progression of the condition left this identity hanging, incomplete and as such contributed to a liminal way of being. This paper reveals that biographical disruption is not limited to the person diagnosed with Multiple Sclerosis but that the support person also undergoes a transition to their sense of self to that of 'anticipatory carer'. The findings provide insight into the biographical and emotional impact of Multiple Sclerosis on the support persons early in the development of the condition. © 2015 John Wiley & Sons Ltd.

Dealing with Chronic Illness: Experiences of Iranian Families of Persons with Multiple Sclerosis—A Qualitative Study

PubMed Central

Ebrahimi, Hossein; Hasankhani, Hadi; Namdar, Hossein; Fooladi, Marjaneh

2017-01-01

Background Today family members are providing care and support to each other during illness. In particular, in chronic illness, such as multiple sclerosis, the families are more involved in caring for and supporting their patients, so they use several strategies to cope with this situation. The purpose of this study was to explore the coping strategies in family caregivers of persons with multiple sclerosis in Iran. Methods This is a qualitative study that was conducted through 18 family caregivers of persons with multiple sclerosis. A purposeful sampling method was used. Data were collected through semistructured and in-depth interviews conducted in Multiple Sclerosis Society and hospitals of Tabriz in Iran. The collected data was analyzed according to qualitative content analysis. Results Five main categories were elicited from interviews: “using spirituality,” “living with hope,” “experiencing persistence and stability,” “seeking support,” and “seeking alternative treatments.” Conclusion. The study findings can help to inform the support given to families to help them cope with the effects of caring for someone with multiple sclerosis. Health system managers and professionals by using these results are able to support patients and their families appropriately in order to improve their quality of life and alleviate the complications of disease. PMID:29082042

Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis.

PubMed

Crespi, Chiara; Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Falini, Andrea; Cappa, Stefano F

2016-01-01

Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia.

Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis

PubMed Central

Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Falini, Andrea; Cappa, Stefano F.

2016-01-01

Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia. PMID:27513746

'Normal' and 'failing' mothers: Women's constructions of maternal subjectivity while living with multiple sclerosis.

PubMed

Parton, Chloe; Katz, Terri; Ussher, Jane M

2017-10-01

Multiple sclerosis causes physical and cognitive impairment that can impact women's experiences of motherhood. This study examined how women construct their maternal subjectivities, or sense of self as a mother, drawing on a framework of biographical disruption. A total of 20 mothers with a multiple sclerosis diagnosis took part in semi-structured interviews. Transcripts were analysed using thematic decomposition to identify subject positions that women adopted in relation to cultural discourses of gender, motherhood and illness. Three main subject positions were identified: 'The Failing Mother', 'Fear of Judgement and Burdening Others' and 'The Normal Mother'. Women's sense of self as the 'Failing Mother' was attributed to the impact of multiple sclerosis, contributing to biographical disruption and reinforced through 'Fear of Judgement and Burdening Others' within social interactions. In accounts of the 'Normal Mother', maternal subjectivity was renegotiated by adopting strategies to manage the limitations of multiple sclerosis on mothering practice. This allowed women to self-position as 'good' mothers. Health professionals can assist women by acknowledging the embodied impact of multiple sclerosis on maternal subjectivities, coping strategies that women employ to address potential biographical disruption, and the cultural context of mothering, which contributes to women's experience of subjectivity and well-being when living with multiple sclerosis.

Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis.

PubMed

Albert, Monika; Barrantes-Freer, Alonso; Lohrberg, Melanie; Antel, Jack P; Prineas, John W; Palkovits, Miklós; Wolff, Joachim R; Brück, Wolfgang; Stadelmann, Christine

2017-11-01

In multiple sclerosis, cerebellar symptoms are associated with clinical impairment and an increased likelihood of progressive course. Cortical atrophy and synaptic dysfunction play a prominent role in cerebellar pathology and although the dentate nucleus is a predilection site for lesion development, structural synaptic changes in this region remain largely unexplored. Moreover, the mechanisms leading to synaptic dysfunction have not yet been investigated at an ultrastructural level in multiple sclerosis. Here, we report on synaptic changes of dentate nuclei in post-mortem cerebella of 16 multiple sclerosis patients and eight controls at the histological level as well as an electron microscopy evaluation of afferent synapses of the cerebellar dentate and pontine nuclei of one multiple sclerosis patient and one control. We found a significant reduction of afferent dentate synapses in multiple sclerosis, irrespective of the presence of demyelination, and a close relationship between glial processes and dentate synapses. Ultrastructurally, we show autophagosomes containing degradation products of synaptic vesicles within dendrites, residual bodies within intact-appearing axons and free postsynaptic densities opposed to astrocytic appendages. Our study demonstrates loss of dentate afferent synapses and provides, for the first time, ultrastructural evidence pointing towards neuron-autonomous and neuroglia-mediated mechanisms of synaptic degradation in chronic multiple sclerosis. © 2016 International Society of Neuropathology.

Visual Search as a Tool for a Quick and Reliable Assessment of Cognitive Functions in Patients with Multiple Sclerosis

PubMed Central

Utz, Kathrin S.; Hankeln, Thomas M. A.; Jung, Lena; Lämmer, Alexandra; Waschbisch, Anne; Lee, De-Hyung; Linker, Ralf A.; Schenk, Thomas

2013-01-01

Background Despite the high frequency of cognitive impairment in multiple sclerosis, its assessment has not gained entrance into clinical routine yet, due to lack of time-saving and suitable tests for patients with multiple sclerosis. Objective The aim of the study was to compare the paradigm of visual search with neuropsychological standard tests, in order to identify the test that discriminates best between patients with multiple sclerosis and healthy individuals concerning cognitive functions, without being susceptible to practice effects. Methods Patients with relapsing remitting multiple sclerosis (n = 38) and age-and gender-matched healthy individuals (n = 40) were tested with common neuropsychological tests and a computer-based visual search task, whereby a target stimulus has to be detected amongst distracting stimuli on a touch screen. Twenty-eight of the healthy individuals were re-tested in order to determine potential practice effects. Results Mean reaction time reflecting visual attention and movement time indicating motor execution in the visual search task discriminated best between healthy individuals and patients with multiple sclerosis, without practice effects. Conclusions Visual search is a promising instrument for the assessment of cognitive functions and potentially cognitive changes in patients with multiple sclerosis thanks to its good discriminatory power and insusceptibility to practice effects. PMID:24282604

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Impact of high-intensity concurrent training on cardiovascular risk factors in persons with multiple sclerosis - pilot study.

PubMed

Keytsman, Charly; Hansen, Dominique; Wens, Inez; O Eijnde, Bert

2017-10-27

High-intensity concurrent training positively affects cardiovascular risk factors. Because this was never investigated in multiple sclerosis, the present pilot study explored the impact of this training on cardiovascular risk factors in this population. Before and after 12 weeks of high-intense concurrent training (interval and strength training, 5 sessions per 2 weeks, n = 16) body composition, resting blood pressure and heart rate, 2-h oral glucose tolerance (insulin sensitivity, glycosylated hemoglobin, blood glucose and insulin concentrations), blood lipids (high- and low-density lipoprotein, total cholesterol, triglyceride levels) and C-reactive protein were analyzed. Twelve weeks of high-intense concurrent training significantly improved resting heart rate (-6%), 2-h blood glucose concentrations (-13%) and insulin sensitivity (-24%). Blood pressure, body composition, blood lipids and C-reactive protein did not seem to be affected. Under the conditions of this pilot study, 12 weeks of concurrent high-intense interval and strength training improved resting heart rate, 2-h glucose and insulin sensitivity in multiple sclerosis but did not affect blood C-reactive protein levels, blood pressure, body composition and blood lipid profiles. Further, larger and controlled research investigating the effects of high-intense concurrent training on cardiovascular risk factors in multiple sclerosis is warranted. Implications for rehabilitation High-intensity concurrent training improves cardiovascular fitness. This pilot study explores the impact of this training on cardiovascular risk factors in multiple sclerosis. Despite the lack of a control group, high-intense concurrent training does not seem to improve cardiovascular risk factors in multiple sclerosis.

Evolution of multiple sclerosis in France since the beginning of hepatitis B vaccination.

PubMed

Le Houézec, Dominique

2014-12-01

Since the implementation of the mass vaccination campaign against hepatitis B in France, the appearance of multiple sclerosis, sometimes occurring in the aftermath of vaccinations, led to the publication of epidemiological international studies. This was also justified by the sharp increase in the annual incidence of multiple sclerosis reported to the French health insurance in the mid-1990s. Almost 20 years later, a retrospective reflection can be sketched from these official data and also from the national pharmacovigilance agency. Statistical data from these latter sources seem to show a significant correlation between the number of hepatitis B vaccinations performed and the declaration to the pharmacovigilance of multiple sclerosis occurring between 1 and 2 years later. The application of the Hill's criteria to these data indicates that the correlation between hepatitis B vaccine and multiple sclerosis may be causal.

Application of botulinum toxin to treat sialorrhea in amyotrophic lateral sclerosis patients: a literature review

PubMed Central

de Oliveira, Ademar Francisco; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier

2016-01-01

ABSTRACT Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. PMID:27759834

Hippocampal Sclerosis in Older Patients

PubMed Central

Cykowski, Matthew D.; Powell, Suzanne Z.; Schulz, Paul E.; Takei, Hidehiro; Rivera, Andreana L.; Jackson, Robert E.; Roman, Gustavo; Jicha, Gregory A.; Nelson, Peter T.

2018-01-01

Context Autopsy studies of the older population (≥65 years of age), and particularly of the “oldest-old” (≥85 years of age), have identified a significant proportion (~20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. Objective To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). Data Sources Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. Conclusions In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology. PMID:28467211

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

PubMed

Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

2018-01-01

Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.

PubMed

Frevel, D; Mäurer, M

2015-02-01

Balance disorders are common in multiple sclerosis. Aim of the study is to investigate the effectiveness of an Internet-based home training program (e-Training) to improve balance in patients with multiple sclerosis. A randomized, controlled study. Academic teaching hospital in cooperation with the therapeutic riding center Gut Üttingshof, Bad Mergentheim. Eighteen multiple sclerosis patients (mean EDSS 3,5) took part in the trial. Outcome of patients using e-Training (N.=9) was compared to the outcome of patients receiving hippotherapy (N.=9), which can be considered as an advanced concept for the improvement of balance and postural control in multiple sclerosis. After simple random allocation patients received hippotherapy or Internet-based home training (balance, postural control and strength training) twice a week for 12 weeks. Assessments were done before and after the intervention and included static and dynamic balance (primary outcome). Isometric muscle strength of the knee and trunk extension/flexion (dynamometer), walking capacity, fatigue and quality of life served as secondary outcome parameters. Both intervention groups showed comparable and highly significant improvement in static and dynamic balance capacity, no difference was seen between the both intervention groups. However looking at fatigue and quality of life only the group receiving hippotherapy improved significantly. Since e-Training shows even comparable effects to hippotherapy to improve balance, we believe that the established Internet-based home training program, specialized on balance and postural control training, is feasible for a balance and strength training in persons with multiple sclerosis. We demonstrated that Internet-based home training is possible in patients with multiple sclerosis.

Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

PubMed

Ehinger, Johannes K; Morota, Saori; Hansson, Magnus J; Paul, Gesine; Elmér, Eskil

2015-06-01

Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease.

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

PubMed

Paquin, M-Ê; El Mendili, M M; Gros, C; Dupont, S M; Cohen-Adad, J; Pradat, P-F

2018-01-01

There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls ( P = .004) compared with spinal cord atrophy ( P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline ( R = 0.56 for gray matter and R = 0.55 for spinal cord; P < .01). Prediction at 1 year with clinical scores ( R 2 = 0.54) was improved when including a combination of gray matter and white matter cross-sectional areas ( R 2 = 0.74). Although improvements over spinal cord cross-sectional areas were modest, this study suggests the potential use of gray matter cross-sectional areas as an MR imaging structural biomarker to monitor the evolution of amyotrophic lateral sclerosis. © 2018 by American Journal of Neuroradiology.

Prediction of long-term disability in multiple sclerosis.

PubMed

Schlaeger, R; D'Souza, M; Schindler, C; Grize, L; Dellas, S; Radue, E W; Kappos, L; Fuhr, P

2012-01-01

Little is known about the predictive value of neurophysiological measures for the long-term course of multiple sclerosis (MS). To prospectively investigate whether combined visual (VEP) and motor evoked potentials (MEP) allow prediction of disability over 14 years. A total of 30 patients with relapsing-remitting and secondary progressive MS were prospectively investigated with VEPs, MEPs and the Expanded Disability Status Scale (EDSS) at entry (T0) and after 6, 12 and 24 months, and with cranial MRI scans at entry (T2-weighted and gadolinium-enhanced T1-weighted images). EDSS was again assessed at year 14 (T4). The association between evoked potential (EP), magnetic resonance (MR) data and EDSS was measured using Spearman's rank correlation. Multivariable linear regression was performed to predict EDSS(T4) as a function of z-transformed EP-latencies(T0). The model was validated using a jack-knife procedure and the potential for improving it by inclusion of additional baseline variables was examined. EDSS values(T4) correlated with the sum of z-transformed EP-latencies(T0) (rho = 0.68, p < 0.0001), but not with MR-parameters(T0). EDSS(T4) as predicted by the formula EDSS(T4) = 4.194 + 0.088 * z-score P100(T0) + 0.071 * z-score CMCT(UE, T0) correlated with the observed values (rho = 0.69, p < 0.0001). Combined EPs allow prediction of long-term disability in small groups of patients with MS. This may have implications for the choice of monitoring methods in clinical trials and for daily practice decisions.

Transient impairment of olfactory threshold in acute multiple sclerosis relapse.

PubMed

Bsteh, Gabriel; Hegen, Harald; Ladstätter, Felix; Berek, Klaus; Amprosi, Matthias; Wurth, Sebastian; Auer, Michael; Di Pauli, Franziska; Deisenhammer, Florian; Lutterotti, Andreas; Berger, Thomas

2018-05-18

Impairment of olfactory threshold is a feature of early and active relapsing remitting multiple sclerosis (RRMS). It predicts inflammatory disease activity and was reported to be transient. However, the timing of onset and resolve of olfactory threshold impairment remains unclear. To prospectively assess the development of olfactory threshold in acute MS relapse over time in comparison to stable MS patients. In a prospective observational design, we measured olfactory threshold by performing the Sniffin' Sticks test (minimum score 0, maximum score 16 reflecting optimal olfactory function) at baseline and after 4, 12 and 24 weeks. We included 30 RRMS patients with acute MS relapse and 30 clinically stable RRMS patients (defined as no relapse within the last 12 months) as a control group. Olfactory threshold was impaired in patients with acute MS relapse at baseline (median difference = -3.5; inter-quartile range [IQR] -4.5- - 2.5; p < 0.001), week 4 (-2.5; IQR -3.0 - -2.0; p < 0.001), week 12 (-1.5; IQR -2.0 - -0.5; p = 0.002) and week 24 (-0.5; IQR -1.0 - 0.0; p = 0.159) compared to stable MS patients. Of note, in relapsing patients in whom disease-modifying treatment was initiated or escalated after relapse, threshold did not differ anymore from stable patients at week 12 (-0.5; IQR -1.0 - 0.5; p = 0.247) and week 24 (0.0; IQR -1.0 - 1.0; p = 0.753). Olfactory threshold impairment seems to be a transient bystander feature of MS relapse. It may be correlated to the level of inflammation within the CNS and might be a useful biomarker in this regard. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential gene expression in dentate granule cells in mesial temporal lobe epilepsy with and without hippocampal sclerosis.

PubMed

Griffin, Nicole G; Wang, Yu; Hulette, Christine M; Halvorsen, Matt; Cronin, Kenneth D; Walley, Nicole M; Haglund, Michael M; Radtke, Rodney A; Skene, J H Pate; Sinha, Saurabh R; Heinzen, Erin L

2016-03-01

Hippocampal sclerosis is the most common neuropathologic finding in cases of medically intractable mesial temporal lobe epilepsy. In this study, we analyzed the gene expression profiles of dentate granule cells of patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations, and to shed light on the transcriptional changes associated with hippocampal sclerosis. RNA was extracted, and complementary DNA (cDNA) was prepared and amplified from dentate granule cells that had been harvested by laser capture microdissection from surgically resected hippocampi from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis. Sequencing libraries were sequenced, and the resulting sequencing reads were aligned to the reference genome. Differential expression analysis was used to ascertain expression differences between patients with and without hippocampal sclerosis. Greater than 90% of the RNA-Seq reads aligned to the reference. There was high concordance between transcriptional profiles obtained for duplicate samples. Principal component analysis revealed that the presence or absence of hippocampal sclerosis was the main determinant of the variance within the data. Among the genes up-regulated in the hippocampal sclerosis samples, there was significant enrichment for genes involved in oxidative phosphorylation. By analyzing the gene expression profiles of dentate granule cells from surgically resected hippocampal specimens from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis, we have demonstrated the utility of next-generation sequencing methods for producing biologically relevant results from small populations of homogeneous cells, and have provided insight on the transcriptional changes associated with this pathology. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Prospective study of Centurion® versus Infiniti® phacoemulsification systems: surgical and visual outcomes

PubMed Central

Oh, Lawrence J.; Nguyen, Chu Luan; Wong, Eugene; Wang, Samuel S.Y.; Francis, Ian C.

2017-01-01

AIM To evaluate surgical outcomes (SOs) and visual outcomes (VOs) in cataract surgery comparing the Centurion® phacoemulsification system (CPS) with the Infiniti® phacoemulsification system (IPS). METHODS Prospective, consecutive study in a single-site private practice. Totally 412 patients undergoing cataract surgery with either the CPS using the 30-degree balanced® tip (n=207) or the IPS using the 30-degree Kelman® tip (n=205). Intraoperative and postoperative outcomes were documented prospectively up to one month follow-up. Nuclear sclerosis (NS) grade, cumulated dissipated energy (CDE), preoperative corrected distance visual acuity (CDVA), and CDVA at one month were recorded. RESULTS CDE was 13.50% less in the whole CPS compared with the whole IPS subcohort. In eyes with NS grade III or greater, CDE was 28.87% less with CPS (n=70) compared with IPS (n=44) (P=0.010). Surgical complications were not statistically different between the two subcohorts (P=0.083), but in the one case of vitreous loss using the CPS, CDVA of 6/4 was achieved at one month. The mean CDVAs (VOs) at one month for NS grade III and above cataracts were -0.17 logMAR (6/4.5) in the CPS and -0.15 logMAR (6/4.5) in the IPS subcohort respectively (P=0.033). CONCLUSION CDE is 28.87% less, and VOs are significantly improved, in denser cataracts in the CPS compared with the IPS. The authors recommend the CPS for cases with denser nuclei. PMID:29181313

Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis.

PubMed

Håkansson, I; Tisell, A; Cassel, P; Blennow, K; Zetterberg, H; Lundberg, P; Dahle, C; Vrethem, M; Ernerudh, J

2017-05-01

Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity. © 2017 EAN.

Nutritional support in patients with systemic sclerosis.

PubMed

Ortiz-Santamaria, Vera; Puig, Celia; Soldevillla, Cristina; Barata, Anna; Cuquet, Jordi; Recasens, Asunción

2014-01-01

Systemic sclerosis (SSc) is a chronic multisystem autoimmune disease which involves the gastrointestinal tract in about 90% of cases. It may contribute to nutritional deterioration. To assess whether the application of a nutritional support protocol to these patients could improve their nutritional status and quality of life. Single center prospective study, performed on an outpatient basis, in a county hospital. The Malnutrition Universal Screening Tool (MUST) was used to screen risk for malnutrition. Health questionnaire SF-36 and the Hospital Anxiety and Depression Scale were used to assess quality of life and psychopathology respectively. Weight, height, energy and protein requirements, macronutrient intake and nutritional biochemical parameters were evaluated. Nutritional intervention was performed in patients at risk for malnutrition. Of the 72 patients, 12.5% were at risk for malnutrition. Iron deficiency anemia (18.35%) and vitamin D deficiency (54%) were the most frequently observed nutritional deficits. The questionnaires on psychopathology and quality of life showed a high prevalence of anxiety and depression, and lower level poor quality of life in the physical and mental component. No significant improvements were observed in the weight, food intake, nutritional biochemical parameters, psychopathology and quality of life follow-up. Dietary intervention was able to maintain body weight and food intake. Iron deficiency anemia and vitamin D deficiency improved with iron and vitamine D supplements. No deterioration was observed in psychological assessment or quality of life. Studies with larger numbers of patients are needed to assess the efficacy of this intervention. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Effects of natalizumab treatment on Foxp3+ T regulatory cells.

PubMed

Stenner, Max-Philipp; Waschbisch, Anne; Buck, Dorothea; Doerck, Sebastian; Einsele, Hermann; Toyka, Klaus V; Wiendl, Heinz

2008-10-06

Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4) exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs) in multiple sclerosis (MS) patients. A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4) differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25(high)CD127(low)Foxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function.

Effects of Natalizumab Treatment on Foxp3+ T Regulatory Cells

PubMed Central

Buck, Dorothea; Doerck, Sebastian; Einsele, Hermann; Toyka, Klaus V.; Wiendl, Heinz

2008-01-01

Background Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4) exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs) in multiple sclerosis (MS) patients. Methodology A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. Principal Findings Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4) differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25highCD127lowFoxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. Conclusions We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function. PMID:18836525

Prediction of Falls in Subjects Suffering From Parkinson Disease, Multiple Sclerosis, and Stroke.

PubMed

Beghi, Ettore; Gervasoni, Elisa; Pupillo, Elisabetta; Bianchi, Elisa; Montesano, Angelo; Aprile, Irene; Agostini, Michela; Rovaris, Marco; Cattaneo, Davide

2018-04-01

To compare the risk of falls and fall predictors in patients with Parkinson disease (PD), multiple sclerosis (MS), and stroke using the same study design. Multicenter prospective cohort study. Institutions for physical therapy and rehabilitation. Patients (N=299) with PD (n=94), MS (n=111), and stroke (n=94) seen for rehabilitation. Not applicable. Functional scales were applied to investigate balance, disability, daily performance, self-confidence with balance, and social integration. Patients were followed for 6 months. Telephone interviews were organized at 2, 4, and 6 months to record falls and fall-related injuries. Incidence ratios, Kaplan-Meier survival curves, and Cox proportional hazards models were used. Of the 299 patients enrolled, 259 had complete follow-up. One hundred and twenty-two patients (47.1%) fell at least once; 82 (31.7%) were recurrent fallers and 44 (17.0%) suffered injuries; and 16%, 32%, and 40% fell at 2, 4, and 6 months. Risk of falls was associated with disease type (PD, MS, and stroke in decreasing order) and confidence with balance (Activities-specific Balance Confidence [ABC] scale). Recurrent fallers were 7%, 15%, and 24% at 2, 4, and 6 months. The risk of recurrent falls was associated with disease type, high educational level, and ABC score. Injured fallers were 3%, 8%, and 12% at 2, 4, and 6 months. The only predictor of falls with injuries was disease type (PD). PD, MS, and stroke carry a high risk of falls. Other predictors include perceived balance confidence and high educational level. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort

PubMed Central

Factor-Litvak, Pam; Goetz, Raymond; Lomen-Hoerth, Catherine; Nagy, Peter L.; Hupf, Jonathan; Singleton, Jessica; Woolley, Susan; Andrews, Howard; Heitzman, Daragh; Bedlack, Richard S.; Katz, Jonathan S.; Barohn, Richard J.; Sorenson, Eric J.; Oskarsson, Björn; Fernandes Filho, J. Americo M.; Kasarskis, Edward J.; Mozaffar, Tahseen; Rollins, Yvonne D.; Nations, Sharon P.; Swenson, Andrea J.; Koczon-Jaremko, Boguslawa A.; Mitsumoto, Hiroshi

2016-01-01

Objectives: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). Methods: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. Results: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. Conclusions: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline. PMID:26802094

Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort.

PubMed

Murphy, Jennifer; Factor-Litvak, Pam; Goetz, Raymond; Lomen-Hoerth, Catherine; Nagy, Peter L; Hupf, Jonathan; Singleton, Jessica; Woolley, Susan; Andrews, Howard; Heitzman, Daragh; Bedlack, Richard S; Katz, Jonathan S; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Björn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Koczon-Jaremko, Boguslawa A; Mitsumoto, Hiroshi

2016-03-01

To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline. © 2016 American Academy of Neurology.

Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis.

PubMed

Hughes, Abbey J; Parmenter, Brett A; Haselkorn, Jodie K; Lovera, Jesus F; Bourdette, Dennis; Boudreau, Eilis; Cameron, Michelle H; Turner, Aaron P

2017-08-01

Problems with sleep and cognitive impairment are common among people with multiple sclerosis (MS). The present study examined the relationship between self-reported sleep and both objective and perceived cognitive impairment in MS. Data were obtained from the baseline assessment of a multi-centre intervention trial (NCT00841321). Participants were 121 individuals with MS. Nearly half (49%) of participants met the criteria for objective cognitive impairment; however, cognitively impaired and unimpaired participants did not differ on any self-reported sleep measures. Nearly two-thirds (65%) of participants met the criteria for 'poor' sleep, and poorer sleep was significantly associated with greater levels of perceived cognitive impairment. Moreover, the relationships between self-reported sleep and perceived cognitive impairment were significant beyond the influence of clinical and demographic factors known to influence sleep and cognitive functioning (e.g. age, sex, education level, disability severity, type of MS, disease duration, depression and fatigue). However, self-reported sleep was not associated with any measures of objective cognitive impairment. Among different types of perceived cognitive impairment, poor self-reported sleep was most commonly related to worse perceived executive function (e.g. planning/organization) and prospective memory. Results from the present study emphasize that self-reported sleep is significantly and independently related to perceived cognitive impairment in MS. In terms of clinical implications, interventions focused on improving sleep may help improve perceived cognitive function and quality of life in this population; however, the impact of improved sleep on objective cognitive function requires further investigation. © 2017 European Sleep Research Society.

Measurement of ulnar subtrochlear sclerosis using a percentage scale in labrador retrievers with minimal radiographic signs of periarticular osteophytosis.

PubMed

Smith, Thomas J; Fitzpatrick, Noel; Evans, Richard B; Pead, Mathew J

2009-02-01

To report the development of a measurement method for quantifying ulnar subtrochlear sclerosis (STS) in Labrador Retrievers. Prospective blinded study. Radiographs of Labrador Retrievers elbows (n=30) with minimal radiographic signs of periarticular osteophytosis. Measurement of STS as a % of the distance between 2 standardized radiographic landmarks (%STS) was developed. Mediolateral radiographic projections of flexed elbows were collected from 2 cohorts termed diseased (n=15; confirmed disease of the medial coronoid process) and control (n=15; free from clinically evident disease). Five observers blindly assessed each radiograph for radiographic technique, elbow positioning, periarticular osteophytosis, and STS, which, if present, was measured and assigned a %STS score. Intraobserver and interobserver variations in measuring STS and the ability to differentiate study cohorts were assessed using receiver operator curve (ROC) characteristics. A P-value of <.05 was considered significant. Median %STS for diseased elbows was 47% (range, 0-74%) and 0% (range, 0-62%) for control elbows. Correlations were not significantly different between each observer's assessments of %STS, with a median Spearman's P-value of .75 (range, .67-.86). All observers differentiated the 2 cohorts with "fair-good" accuracy, with a median ROC value of 0.81 (range, 0.75-0.88). Measurement of %STS in Labrador Retrievers was repeatable for each observer and repeatable between observers. A method for measuring STS allows comparison of Labrador Retrievers of different sizes, is easy to perform, and could be used to investigate the clinical significance of STS in this breed.

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

PubMed

Maniscalco, Giorgia Teresa; Aponte, R; Bruzzese, D; Guarcello, G; Manzo, V; Napolitano, M; Moreggia, O; Chiariello, F; Florio, C

2018-01-01

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

Subtle pathological changes in neocortical temporal lobe epilepsy.

PubMed

Ochoa, Juan G; Hentgarden, Diana; Paulzak, Audrey; Ogden, Melissa; Pryson, Richard; Lamle, Markus; Rusyniak, Walter G

2017-06-01

This was a prospective observational study to correlate the clinical symptoms, electrophysiology, imaging, and surgical pathology of patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis. We selected consecutive patients with TLE and normal MRI undergoing temporal lobe resection between April and September 2015. Clinical features, imaging, and functional data were reviewed. Intracranial monitoring and language mapping were performed when it was required according to our team recommendation. Prior to hippocampal resection, intraoperative electrocorticography was performed using depth electrodes in the amygdala and the hippocampus. The resected hippocampus was sent for pathological analysis. Five patients with diagnosis with non-lesional TLE were included. We did not find distinctive clinical features that could be a characteristic of non-lesional TLE. The mean follow-up was 13.2months (11-15months); 80% of patients achieved Engel Class I outcome. There was no distinctive electrographic findings in these patients. Histopathologic analysis was negative for mesial temporal sclerosis. A second blinded independent neuropathologist with expertise in epilepsy found ILAE type I focal cortical dysplasia in the parahippocampal gyrus in all patients. A third independent neuropathologist reported changes in layer 2 with larger pyramidal neurons in 4 cases but concluded that none of these cases met the diagnostic criteria of FCD. Subtle pathological changes could be associated with a parahippocampal epileptic zone and should be investigated in patients with MRI-negative TLE. This study also highlights the lack of interobserver reliability for the diagnosis of mild cortical dysplasia. Finally, selective amygdalo-hippocampectomy or laser ablation of the hippocampus may not control intractable epilepsy in this specific population. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired neurosteroid synthesis in multiple sclerosis

PubMed Central

Noorbakhsh, Farshid; Ellestad, Kristofor K.; Maingat, Ferdinand; Warren, Kenneth G.; Han, May H.; Steinman, Lawrence; Baker, Glen B.

2011-01-01

High-throughput technologies have led to advances in the recognition of disease pathways and their underlying mechanisms. To investigate the impact of micro-RNAs on the disease process in multiple sclerosis, a prototypic inflammatory neurological disorder, we examined cerebral white matter from patients with or without the disease by micro-RNA profiling, together with confirmatory reverse transcription–polymerase chain reaction analysis, immunoblotting and gas chromatography-mass spectrometry. These observations were verified using the in vivo multiple sclerosis model, experimental autoimmune encephalomyelitis. Brains of patients with or without multiple sclerosis demonstrated differential expression of multiple micro-RNAs, but expression of three neurosteroid synthesis enzyme-specific micro-RNAs (miR-338, miR-155 and miR-491) showed a bias towards induction in patients with multiple sclerosis (P < 0.05). Analysis of the neurosteroidogenic pathways targeted by micro-RNAs revealed suppression of enzyme transcript and protein levels in the white matter of patients with multiple sclerosis (P < 0.05). This was confirmed by firefly/Renilla luciferase micro-RNA target knockdown experiments (P < 0.05) and detection of specific micro-RNAs by in situ hybridization in the brains of patients with or without multiple sclerosis. Levels of important neurosteroids, including allopregnanolone, were suppressed in the white matter of patients with multiple sclerosis (P < 0.05). Induction of the murine micro-RNAs, miR-338 and miR-155, accompanied by diminished expression of neurosteroidogenic enzymes and allopregnanolone, was also observed in the brains of mice with experimental autoimmune encephalomyelitis (P < 0.05). Allopregnanolone treatment of the experimental autoimmune encephalomyelitis mouse model limited the associated neuropathology, including neuroinflammation, myelin and axonal injury and reduced neurobehavioral deficits (P < 0.05). These multi-platform studies point to impaired neurosteroidogenesis in both multiple sclerosis and experimental autoimmune encephalomyelitis. The findings also indicate that allopregnanolone and perhaps other neurosteroid-like compounds might represent potential biomarkers or therapies for multiple sclerosis. PMID:21908875

Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis.

PubMed

van Bon, Lenny; Affandi, Alsya J; Broen, Jasper; Christmann, Romy B; Marijnissen, Renoud J; Stawski, Lukasz; Farina, Giuseppina A; Stifano, Giuseppina; Mathes, Allison L; Cossu, Marta; York, Michael; Collins, Cindy; Wenink, Mark; Huijbens, Richard; Hesselstrand, Roger; Saxne, Tore; DiMarzio, Mike; Wuttge, Dirk; Agarwal, Sandeep K; Reveille, John D; Assassi, Shervin; Mayes, Maureen; Deng, Yanhui; Drenth, Joost P H; de Graaf, Jacqueline; den Heijer, Martin; Kallenberg, Cees G M; Bijl, Marc; Loof, Arnoud; van den Berg, Wim B; Joosten, Leo A B; Smith, Vanessa; de Keyser, Filip; Scorza, Rafaella; Lunardi, Claudio; van Riel, Piet L C M; Vonk, Madelon; van Heerde, Waander; Meller, Stephan; Homey, Bernhard; Beretta, Lorenzo; Roest, Mark; Trojanowska, Maria; Lafyatis, Robert; Radstake, Timothy R D J

2014-01-30

Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon. We isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis who had distinct clinical phenotypes. We then performed proteome-wide analysis and validated these observations in five large cohorts of patients with systemic sclerosis. Next, we compared the results with those in patients with systemic lupus erythematosus, ankylosing spondylitis, and hepatic fibrosis. We correlated plasma levels of CXCL4 protein with features of systemic sclerosis and studied the direct effects of CXCL4 in vitro and in vivo. Proteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in systemic sclerosis, both in circulation and in skin. The mean (±SD) level of CXCL4 in patients with systemic sclerosis was 25,624±2652 pg per milliliter, which was significantly higher than the level in controls (92.5±77.9 pg per milliliter) and than the level in patients with systemic lupus erythematosus (1346±1011 pg per milliliter), ankylosing spondylitis (1368±1162 pg per milliliter), or liver fibrosis (1668±1263 pg per milliliter). CXCL4 levels correlated with skin and lung fibrosis and with pulmonary arterial hypertension. Among chemokines, only CXCL4 predicted the risk and progression of systemic sclerosis. In vitro, CXCL4 down-regulated expression of transcription factor FLI1, induced markers of endothelial-cell activation, and potentiated responses of toll-like receptors. In vivo, CXCL4 induced the influx of inflammatory cells and skin transcriptome changes, as in systemic sclerosis. Levels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension. (Funded by the Dutch Arthritis Association and others.).

Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic Sclerosis

PubMed Central

van Bon, L.; Affandi, A.J.; Broen, J.; Christmann, R.B.; Marijnissen, R.J.; Stawski, L.; Farina, G.A.; Stifano, G.; Mathes, A.L.; Cossu, M.; York, M.; Collins, C.; Wenink, M.; Huijbens, R.; Hesselstrand, R.; Saxne, T.; DiMarzio, M.; Wuttge, D.; Agarwal, S.K.; Reveille, J.D.; Assassi, S.; Mayes, M.; Deng, Y.; Drenth, J.P.H.; de Graaf, J.; den Heijer, M.; Kallenberg, C.G.M.; Bijl, M.; Loof, A.; van den Berg, W.B.; Joosten, L.A.B.; Smith, V.; de Keyser, F.; Scorza, R.; Lunardi, C.; van Riel, P.L.C.M.; Vonk, M.; van Heerde, W.; Meller, S.; Homey, B.; Beretta, L.; Roest, M.; Trojanowska, M.; Lafyatis, R.; Radstake, T.R.D.J.

2014-01-01

Background Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon. Methods We isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis who had distinct clinical phenotypes. We then performed proteome-wide analysis and validated these observations in five large cohorts of patients with systemic sclerosis. Next, we compared the results with those in patients with systemic lupus erythematosus, ankylosing spondylitis, and hepatic fibrosis. We correlated plasma levels of CXCL4 protein with features of systemic sclerosis and studied the direct effects of CXCL4 in vitro and in vivo. Results Proteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in systemic sclerosis, both in circulation and in skin. The mean (±SD) level of CXCL4 in patients with systemic sclerosis was 25,624±2652 pg per milliliter, which was significantly higher than the level in controls (92.5±77.9 pg per milliliter) and than the level in patients with systemic lupus erythematosus (1346±1011 pg per milliliter), ankylosing spondylitis (1368±1162 pg per milliliter), or liver fibrosis (1668±1263 pg per milliliter). CXCL4 levels correlated with skin and lung fibrosis and with pulmonary arterial hypertension. Among chemokines, only CXCL4 predicted the risk and progression of systemic sclerosis. In vitro, CXCL4 downregulated expression of transcription factor FLI1, induced markers of endothelial-cell activation, and potentiated responses of toll-like receptors. In vivo, CXCL4 induced the influx of inflammatory cells and skin transcriptome changes, as in systemic sclerosis. Conclusions Levels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension. (Funded by the Dutch Arthritis Association and others.) PMID:24350901

Degeneration of serotonergic neurons in amyotrophic lateral sclerosis: a link to spasticity.

PubMed

Dentel, Christel; Palamiuc, Lavinia; Henriques, Alexandre; Lannes, Béatrice; Spreux-Varoquaux, Odile; Gutknecht, Lise; René, Frédérique; Echaniz-Laguna, Andoni; Gonzalez de Aguilar, Jose-Luis; Lesch, Klaus Peter; Meininger, Vincent; Loeffler, Jean-Philippe; Dupuis, Luc

2013-02-01

Spasticity is a common and disabling symptom observed in patients with central nervous system diseases, including amyotrophic lateral sclerosis, a disease affecting both upper and lower motor neurons. In amyotrophic lateral sclerosis, spasticity is traditionally thought to be the result of degeneration of the upper motor neurons in the cerebral cortex, although degeneration of other neuronal types, in particular serotonergic neurons, might also represent a cause of spasticity. We performed a pathology study in seven patients with amyotrophic lateral sclerosis and six control subjects and observed that central serotonergic neurons suffer from a degenerative process with prominent neuritic degeneration, and sometimes loss of cell bodies in patients with amyotrophic lateral sclerosis. Moreover, distal serotonergic projections to spinal cord motor neurons and hippocampus systematically degenerated in patients with amyotrophic lateral sclerosis. In SOD1 (G86R) mice, a transgenic model of amyotrophic lateral sclerosis, serotonin levels were decreased in brainstem and spinal cord before onset of motor symptoms. Furthermore, there was noticeable atrophy of serotonin neuronal cell bodies along with neuritic degeneration at disease onset. We hypothesized that degeneration of serotonergic neurons could underlie spasticity in amyotrophic lateral sclerosis and investigated this hypothesis in vivo using tail muscle spastic-like contractions in response to mechanical stimulation as a measure of spasticity. In SOD1 (G86R) mice, tail muscle spastic-like contractions were observed at end-stage. Importantly, they were abolished by 5-hydroxytryptamine-2b/c receptors inverse agonists. In line with this, 5-hydroxytryptamine-2b receptor expression was strongly increased at disease onset. In all, we show that serotonergic neurons degenerate during amyotrophic lateral sclerosis, and that this might underlie spasticity in mice. Further research is needed to determine whether inverse agonists of 5-hydroxytryptamine-2b/c receptors could be of interest in treating spasticity in patients with amyotrophic lateral sclerosis.

A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

PubMed

Sheelakumari, R; Madhusoodanan, M; Radhakrishnan, A; Ranjith, G; Thomas, B

2016-02-01

Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis. Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis. Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison showed a cutoff of 35μg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for differentiating patients with amyotrophic lateral sclerosis from controls. Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

Illness trajectories in patients with amyotrophic lateral sclerosis: How illness progression is related to life narratives and interpersonal relationships.

PubMed

Cipolletta, Sabrina; Gammino, Giorgia Rosamaria; Palmieri, Arianna

2017-12-01

To identify illness trajectories in amyotrophic lateral sclerosis by analysing personal, social and functional dimensions related to amyotrophic lateral sclerosis progression. Previous studies have considered some psychological distinct variables that may moderate illness progression, but no research has combined an extensive qualitative understanding of amyotrophic lateral sclerosis patients' psychological characteristics and illness progression. A mixed-methods approach was used to combine quantitative and qualitative measures. Illness progression was assessed through a longitudinal design. Eighteen patients with amyotrophic lateral sclerosis attending a Neurology Department in northern Italy participated in the study. Semi-structured interviews to explore personal experience, and dependency grids to assess the distribution of dependency; ALSFRS-R and neuropsychological screening were, respectively, used to measure physical and cognitive impairment. To assess the progression of the disease, ALSFRS-R was re-administered after 8 months and mortality rate was considered. Data were analysed using the grounded theory approach. Illness progression changed according to the perception of the disease, the trust placed in medical care, self-construction and the distribution of dependency. Based on these categories, cases that had similar experiences were grouped, and four illness trajectories were identified: aggressiveness, threat, constriction and guilt. The findings suggest that it is possible to identify different illness trajectories in amyotrophic lateral sclerosis. Personalised intervention strategies may be construed based on the different trajectories identified. © 2017 John Wiley & Sons Ltd.

Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

PubMed

Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

2016-07-01

Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. © The Author(s) 2016.

Hippocampal sclerosis: volumetric evaluation of the substructures of the hippocampus by magnetic resonance imaging.

PubMed

Granados Sánchez, A M; Orejuela Zapata, J F

2018-05-25

The pathological classification of hippocampal sclerosis is based on the loss of neurons in the substructures of the hippocampus. This study aimed to evaluate these substructures in patients with hippocampal sclerosis by magnetic resonance imaging and to compare the usefulness of this morphological analysis compared to that of volumetric analysis of the entire hippocampus. We included 25 controls and 25 patients with hippocampal sclerosis whose diagnosis was extracted from the institutional epilepsy board. We used FreeSurfer to process the studies and obtain the volumetric data. We evaluated overall volume and volume by substructure: fimbria, subiculum, presubiculum, hippocampal sulcus, CA1, CA2-CA3, CA4, and dentate gyrus (DG). We considered p < 0.05 statistically significant. We observed statistically significant decreases in the volume of the hippocampus ipsilateral to the epileptogenic focus in 19 (76.0%) of the 25 cases. With the exception of the hippocampal sulcus, we observed a decrease in all ipsilateral hippocampal substructures in patients with right hippocampal sclerosis (CA1, p=0.0223; CA2-CA3, p=0.0066; CA4-GD, p=0.0066; fimbria, p=0.0046; presubiculum, p=0.0087; subiculum, p=0.0017) and in those with left hippocampal sclerosis (CA1, p<0.0001; CA2-CA3, p<0. 0001; CA4-GD, p<0. 0001; fimbria, p=0.0183; presubiculum, p<0. 0001; subiculum, p<0. 0001). In four patients with left hippocampal sclerosis, none of the substructures had statistically significant alterations, although a trend toward atrophy was observed, mainly in CA2-CA3 and CA4-GD. The findings suggest that it can be useful to assess the substructures of the hippocampus to improve the performance of diagnostic imaging in patients with hippocampal sclerosis. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

PubMed Central

Kiiski, Hanni S. M.; Ní Riada, Sinéad; Lalor, Edmund C.; Gonçalves, Nuno R.; Nolan, Hugh; Whelan, Robert; Lonergan, Róisín; Kelly, Siobhán; O'Brien, Marie Claire; Kinsella, Katie; Bramham, Jessica; Burke, Teresa; Ó Donnchadha, Seán; Hutchinson, Michael; Tubridy, Niall; Reilly, Richard B.

2016-01-01

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. PMID:26726800

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

PubMed

Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

2016-03-01

Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

Long-term safety and real-world effectiveness of fingolimod in relapsing multiple sclerosis

PubMed Central

Druart, Charlotte; El Sankari, Souraya; van Pesch, Vincent

2018-01-01

With a growing number of disease-modifying therapies becoming available for relapsing multiple sclerosis, there is an important need to gather real-world evidence data regarding long-term treatment effectiveness and safety in unselected patient populations. Although not providing as high a level of evidence as randomized controlled trials, and prone to bias, real-world studies from observational studies or registries nevertheless provide crucial information on real-world outcomes of a given therapy. In addition, evaluation of treatment satisfaction and impact on quality of life are increasingly regarded as complementary outcome measures. Fingolimod was the first oral disease-modifying therapy approved for relapsing multiple sclerosis. This review aims to summarize current knowledge on the long-term effectiveness and safety outcomes of multiple sclerosis patients on fingolimod. Impact on treatment satisfaction and quality of life will be discussed according to available data. PMID:29317850

Mixed pathology is more likely in black than white decedents with Alzheimer dementia

PubMed Central

Leurgans, Sue; Aggarwal, Neelum T.; Shah, Raj C.; Arvanitakis, Zoe; James, Bryan D.; Buchman, Aron S.; Bennett, David A.; Schneider, Julie A.

2015-01-01

Objective: To compare the burden of neuropathology in black and white participants with clinical Alzheimer disease (AD). Methods: Participants included 122 persons enrolled in the Rush Alzheimer's Disease Clinical Core, a prospective cohort study of AD. Forty-one black decedents were matched two-to-one to 81 white decedents according to age at death, sex, years of education, and cognition proximate to death. We examined common brain pathologies related to dementia (AD, Lewy body, and macroscopic and microinfarct pathology) and arteriolar sclerosis and atherosclerosis. We calculated the frequency of each dementia pathology both alone and in combination (mixed pathologies). Racial differences in the odds of a single pathology vs mixed pathologies, and in the odds of vessel disease and its severity, were examined using logistic regression analyses. Results: AD pathology was confirmed in >93% of both black and white decedents with AD dementia. However, black decedents were less likely to have Alzheimer pathology as a single dementia pathology than white decedents (19.5% vs 42.0%), and were more likely to have AD mixed with an additional pathology (70.7% vs 50.6%), particularly Alzheimer pathology and Lewy bodies, and Alzheimer pathology, Lewy bodies, and infarcts. Black decedents also had more severe arteriolar sclerosis and atherosclerosis. Conclusion: Black decedents with AD dementia are more likely to have mixed brain pathologies compared with age-, sex-, education-, and cognition-matched white decedents with AD dementia. PMID:26180136

Systemic sclerosis, birth order and parity.

PubMed

Russo, Paul A J; Lester, Susan; Roberts-Thomson, Peter J

2014-06-01

A recent study identified increasing birth order to be a risk factor for the development of systemic sclerosis (SSc). This finding supports the theory that transplacental microchimerism may be a key pathological event in the initiation of SSc. We investigated the relationship between birth order and parity and the age of onset of SSc in South Australia. A retrospective analysis of patient data in the South Australian Scleroderma Register was performed. Data were obtained from a mailed questionnaire. Control data was collected prospectively using a similar questionnaire. The relationship between birth order, family size or parity and risk of subsequent development of SSc was analyzed by mixed effects logistic regression analysis. Three hundred and eighty-seven index probands were identified and compared with 457 controls. Controls were well matched for gender, but not for age. No statistically significant relationship was identified between SSc and birth order, parity in females, family size, age at first pregnancy in females or gender of first child in parous females. Our data suggests that parity, age at first pregnancy and the gender of the first child are not relevant factors in our understanding of the epidemiology and pathogenesis of SSc. Birth order and family size in both genders also appears irrelevant. These results argue against microchimerism as being relevant in the pathogenesis of SSc and add further support to the theory that stochastic events may be important in the etiopathogenesis of SSc. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Patient-ventilator asynchrony, leaks and sleep in patients with amyotrophic lateral sclerosis.

PubMed

Vrijsen, Bart; Testelmans, Dries; Belge, Catharina; Vanpee, Goele; Van Damme, Philip; Buyse, Bertien

2016-01-01

Sleeping with non-invasive ventilation (NIV) in amyotrophic lateral sclerosis appears to be accompanied by a high patient-ventilator asynchrony (PVA) index. This prospective observational cohort study quantifies PVA and leaks, and searches for effects of these events on sleep after polysomnographic NIV titration. Full-video polysomnography, with incorporation of transcutaneous carbon dioxide and ventilator software, was used to analyse sleep epoch-by-epoch and respiratory events and PVA breath-by-breath in 35 patients (17 non-bulbar). After diagnostic polysomnography, NIV was titrated during three consecutive nights. Sleep, PVA and leaks were evaluated at discharge and after one month. Results showed that non-bulbar patients improved in sleep architecture and oxygen and carbon dioxide levels while bulbar patients only improved oxygen saturation. PVA remained present at discharge (non-bulbar 54 (21-101) and bulbar 31 (9-39)/h sleep) and one month (non-bulbar 31 (9-39) and bulbar 32 (17-55)/h sleep), with ineffective effort as most prominent asynchrony. Leaks also persisted after titration (non-bulbar 16.6 (3.1-44.6) and bulbar 5.1 (0.0-19.5)% of total sleep time (TST)) and one month (non-bulbar 7.7 (1.4-29.3) and bulbar 12.7 (0.0-35.2)% TST). PVA and leaks have none to minor effect on sleep architecture. In conclusion, although PVA and leaks remain present after meticulous NIV titration, these events seem not to interfere with sleep.

Should I stay or should I go? A prospective investigation examining individual factors impacting employment status among individuals with multiple sclerosis (MS).

PubMed

Strober, Lauren B; Chiaravalloti, Nancy; DeLuca, John

2018-01-01

Rates of unemployment among individuals with multiple sclerosis (MS) are as high as 80%. While several factors for such high rates of unemployment have been identified, they do not account for the majority of the variance. This study examines person-specific factors such as personality and coping, which may better account for individuals leaving the workforce. Forty individuals with MS (20 considering reducing work hours or leaving the workforce and 20 remaining employed) were matched on age, gender, education, disease duration, and disease course, and administered a comprehensive survey of factors purported to be related to employment status. Based on multiple, logistic regression analyses certain disease factors and person-specific factors differentiate those who are considering leaving work or reducing work hours and those staying employed. In particular, those expressing the need to reduce work hours or leaving the workforce reported more fatigue, anxiety, depression, and use of behavioral disengagement as a means of coping. In contrast, those staying employed reported greater levels of extraversion, self-efficacy, and use of humor as a means of coping. Together, fatigue, use of humor, and use of behavioral disengagement as a means of coping were the most significant factors, accounting for 44% of the variance. Findings suggest that greater consideration be given to these factors and that interventions tailored to address these factors may assist individuals with MS staying employed and/or making appropriate accommodations.

Meditation as an Adjunct to the Management of Multiple Sclerosis

PubMed Central

Levin, Adam B.; Hadgkiss, Emily J.; Weiland, Tracey J.; Jelinek, George A.

2014-01-01

Background. Multiple sclerosis (MS) disease course is known to be adversely affected by several factors including stress. A proposed mechanism for decreasing stress and therefore decreasing MS morbidity and improving quality of life is meditation. This review aims to critically analyse the current literature regarding meditation and MS. Methods. Four major databases were used to search for English language papers published before March 2014 with the terms MS, multiple sclerosis, meditation, and mindfulness. Results. 12 pieces of primary literature fitting the selection criteria were selected: two were randomised controlled studies, four were cohort studies, and six were surveys. The current literature varies in quality; however common positive effects of meditation include improved quality of life (QOL) and improved coping skills. Conclusion. All studies suggest possible benefit to the use of meditation as an adjunct to the management of multiple sclerosis. Additional rigorous clinical trials are required to validate the existing findings and determine if meditation has an impact on disease course over time. PMID:25105026

Factor analysis of the Zarit Burden Interview in family caregivers of patients with amyotrophic lateral sclerosis.

PubMed

Oh, Juyeon; Kim, Jung A

2018-02-01

The Zarit Burden Interview has been used in many studies to assess caregiver burden in family caregivers of patients with amyotrophic lateral sclerosis, but the factor structure of the Zarit Burden Interview in the caregivers of amyotrophic lateral sclerosis patients is unknown. The aim of this study was to explore the factor structure of the Zarit Burden Interview in family caregivers of amyotrophic lateral sclerosis patients using exploratory factor analysis. The exploratory factor analysis was performed using generalized least squares with oblique rotation in a sample of 202 family caregivers. Three factors had an eigenvalue greater than 1 and accounted for 60.33% of the total variance. The three factors were named as follows: (factor 1) "Social restrictions" (items 2, 3, and 10-15); (factor 2) "Self-criticism" (items 20-21); and (factor 3) "Anger and frustration" (items 1, 4-6, 9, and 16-19). The correlation between factors 1 and 3 was much higher (r = 0.79) than that between factors 1 and 2 (r = 0.14) or factors 2 and 3 (r = 0.15). The findings of this study enriched our understanding of several meaningful dimensions of the caregiving burden in caregivers of an amyotrophic lateral sclerosis population and provided opportunities for future intervention.

Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis: The Study of Health in Pomerania (SHIP).

PubMed

Markus, Marcello Ricardo Paulista; Lieb, Wolfgang; Stritzke, Jan; Siewert, Ulrike; Troitzsch, Paulina; Koch, Manja; Dörr, Marcus; Felix, Stephan Burkhard; Völzke, Henry; Schunkert, Heribert; Baumeister, Sebastian Edgar

2015-05-01

In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the cross-sectional association between average daily alcohol consumption and AVS in the general population. We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%. Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted P value: 0.005). Compared with individuals with an average consumption of 10 g of alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence interval, 1.19-2.14) among current abstainers and 1.56 (95% confidence interval, 1.01-2.41) among individuals with an average consumption of 60 g per day. Our findings indicate that light to moderate alcohol consumption was associated with a lower odd of having AVS. Prospective data need to address whether alcohol consumption and related changes over time in several biological markers affect the progression of AVS. © 2015 American Heart Association, Inc.

First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence.

PubMed

Ferraro, Diana; Camera, Valentina; Baldi, Eleonora; Vacchiano, Veria; Curti, Erica; Guareschi, Angelica; Malagù, Susanna; Montepietra, Sara; Strumia, Silvia; Santangelo, Mario; Caniatti, Luisa; Foschi, Matteo; Lugaresi, Alessandra; Granella, Franco; Pesci, Ilaria; Motti, Luisa; Neri, Walter; Immovilli, Paolo; Montanari, Enrico; Vitetta, Francesca; Simone, Anna Maria; Sola, Patrizia

2018-04-12

The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation. In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued. Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences. The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.

PubMed

Dresler, Carolyn M; Olak, Jemi; Herndon, James E; Richards, William G; Scalzetti, Ernest; Fleishman, Stewart B; Kernstine, Kemp H; Demmy, Todd; Jablons, David M; Kohman, Leslie; Daniel, Thomas M; Haasler, George B; Sugarbaker, David J

2005-03-01

To demonstrate the efficacy, safety, and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions (MPEs). A prospective, randomized trial was designed to compare thoracoscopy with talc insufflation (TTI) to thoracostomy and talc slurry (TS) for patients with documented MPE. The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-expanded > 90%. Morbidity, mortality, and quality of life were also assessed. Of 501 patients registered, those eligible were randomized to TTI (n = 242) or TS (n = 240). Patient demographics and primary malignancies were similar between study arms. Overall, there was no difference between study arms in the percentage of patients with successful 30-day outcomes (TTI, 78%; TS, 71%). However, the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS (82% vs 67%). Common morbidity included fever, dyspnea, and pain. Treatment-related mortality occurred in nine TTI patients and seven TS patients. Respiratory complications were more common following TTI than TS (14% vs 6%). Respiratory failure was observed in 4% of TS patients and 8% of TTI patients, accounting for five toxic deaths and six toxic deaths, respectively. Quality-of-life measurement demonstrated less fatigue with TTI than TS. Patient ratings of comfort and safety were also higher for TTI, but there were no differences on perceived value or convenience of the procedures. Both methods of talc delivery are similar in efficacy; TTI may be better for patients with either a lung or breast primary. The etiology and incidence of respiratory complications from talc need further exploration.

Hormone therapy use and physical quality of life in postmenopausal women with multiple sclerosis.

PubMed

Bove, Riley; White, Charles C; Fitzgerald, Kathryn C; Chitnis, Tanuja; Chibnik, Lori; Ascherio, Alberto; Munger, Kassandra L

2016-10-04

To determine the association between hormone therapy (HT) and physical quality of life (QOL) in postmenopausal women with multiple sclerosis (MS). We included female participants from the prospective Nurses' Health Study, with a diagnosis of definite or probable MS, who had completed a physical functioning assessment (PF10; subscale of the 36-Item Short-Form Health Survey QOL survey) at a time point between 3 and 10 years after their final menstrual period (early postmenopause). We assessed the association between HT use at this time point (never vs at least 12 months of systemic estrogen with/without progestin) and both PF10 and the 36-Item Short-Form Health Survey Physical Component Scale. We used a linear regression model adjusting for age, MS duration, menopause type and duration, and further for additional covariates (only ancestry was significant). Among 95 participants meeting all inclusion criteria at their first postmenopausal assessment, 61 reported HT use and 34 reported none. HT users differed from non-HT users in MS duration (p = 0.02) and menopause type (p = 0.01) but no other clinical or demographic characteristics. HT users had average PF10 scores that were 23 points higher than non-HT users (adjusted p = 0.004) and average Physical Component Scale scores that were 9.1 points higher in the 59 women with these available (adjusted p = 0.02). Longer duration of HT use was also associated with higher PF10 scores (p = 0.02, adjusted p = 0.06). Systemic HT use was associated with better physical QOL in postmenopausal women with MS in this observational study. Further studies are necessary to investigate causality. © 2016 American Academy of Neurology.

Memantine may affect pseudobulbar affect in patients with Alzheimer's disease.

PubMed

Prokšelj, Tatjana; Jerin, Aleš; Kogoj, Aleš

2013-12-01

Behavioural symptoms are common in moderate to severe Alzheimer's disease (AD) and are improved by memantine with the most pronounced effect on agitation/aggression. Dextromethorphan in combination with quinidine is the only drug approved by US Food and Drug Administration for the treatment of pseudobulbar affect (PBA) on the basis of efficacy in patients with multiple sclerosis or amyotrophic lateral sclerosis. The aim of our study was to evaluate the efficacy of memantine on PBA in patients with AD. In a prospective, double-blind, case-control study to assess PBA with pathological laughter and crying scale patients were administered memantine (final dose of 20 mg daily) or citalopram (20 mg once daily), each for 10 weeks. The number of episodes of involuntary emotional expression, Neuropsychiatric Inventory (NPI) and Overt Aggression Scale-Modified (OAS-M) total scores were also recorded. Furthermore, the platelet serotonin (5-HT) concentration was measured. Although memantine had beneficial effects on PBA, it also had a crucial impact on behavioural symptoms, especially aggression and agitation (to an average of 3.5 times higher end-point scores on OAS-M and increase of NPI total scores for an average of 114% of initial value). Therefore, the study was prematurely stopped. In addition, we had evidenced a drop of platelet 5-HT concentration (to an average of 73% of initial value). Surprisingly, our research showed the opposite action of memantine on neuropsychiatric symptoms as expected. In a limited number of AD patients with PBA, memantine had a beneficial effect on involuntary emotional expression, but it potentiated agitation/aggression, irritability and caused a crucial drop of the platelet 5-HT concentration.

Determinants of non-adherence to disease-modifying therapies in multiple sclerosis: A cross-Canada prospective study

PubMed Central

McKay, Kyla A; Tremlett, Helen; Patten, Scott B; Fisk, John D; Evans, Charity; Fiest, Kirsten; Campbell, Trudy; Marrie, Ruth Ann

2016-01-01

Background: Poor adherence to the disease-modifying therapies (DMTs) for multiple sclerosis (MS) may attenuate clinical benefit. A better understanding of characteristics associated with non-adherence could improve outcomes. Objective: To evaluate characteristics associated with non-adherence to injectable DMTs. Methods: Consecutive patients from four Canadian MS Clinics were assessed at three time points over two years. Clinical and demographic information included self-reported DMT use, missed doses in the previous 30 days, health behaviors, and comorbidities. Non-adherence was defined as <80% of expected doses taken. We employed generalized estimating equations to examine characteristics associated with non-adherence at all time points with findings reported as adjusted odds ratios (OR). Results: In all, 485 participants reported use of an injectable DMT, of whom 107 (22.1%) were non-adherent over the study period. Non-adherence was associated with a lower Expanded Disability Status Scale score (0–2.5 vs 3.0–5.5, OR: 1.80; 95% confidence interval (CI): 1.06–3.04), disease duration (⩽5 vs <5 years, OR: 2.23; 95% CI: 1.10–4.52), alcohol dependence (OR: 2.14; 95% CI: 1.23–3.75), and self-reported cognitive difficulties, measured by the Health Utilities Index-3 (OR: 1.55; 95% CI: 1.08–2.22). Conclusions: Nearly one-quarter of participants were non-adherent during the study. Alcohol dependence, perceived cognitive difficulties, longer disease duration, and mild disability status were associated with non-adherence. These characteristics may help healthcare professionals identify patients at greatest risk of poor adherence. PMID:27357507

Genetics of Familial and Sporadic ALS

ClinicalTrials.gov

2018-03-27

Amyotrophic Lateral Sclerosis (ALS); Familial Amyotrophic Lateral Sclerosis; Amyotrophic Lateral Sclerosis With Frontotemporal Dementia; Lou Gehrig's Disease; Motor Neuron Disease; Primary Lateral Sclerosis

The interpretation of physical activity, exercise, and sedentary behaviours by persons with multiple sclerosis.

PubMed

Kinnett-Hopkins, Dominique; Learmonth, Yvonne; Hubbard, Elizabeth; Pilutti, Lara; Roberts, Sarah; Fanning, Jason; Wójcicki, Thomas; McAuley, Edward; Motl, Robert

2017-11-07

This study adopted a qualitative research design with directed content analysis and examined the interpretations of physical activity, exercise, and sedentary behaviour by persons with multiple sclerosis. Fifty three persons with multiple sclerosis who were enrolled in an exercise trial took part in semi-structured interviews regarding personal interpretations of physical activity, exercise, and sedentary behaviours. Forty three percent of participants indicated a consistent understanding of physical activity, 42% of participants indicated a consistent understanding of exercise, and 83% of participants indicated a consistent understanding of sedentary behaviour with the standard definitions. There was evidence of definitional ambiguity (i.e., 57, 58, and 11% of the sample for physical activity, exercise, and sedentary behaviour, respectively); 6% of the sample inconsistently defined sedentary behaviour with standard definitions. Some participants described physical activity in a manner that more closely aligned with exercise and confused sedentary behaviour with exercise or sleeping/napping. Results highlight the need to provide and utilise consistent definitions for accurate understanding, proper evaluation and communication of physical activity, exercise, and sedentary behaviours among persons with multiple sclerosis. The application of consistent definitions may minimise ambiguity, alleviate the equivocality of findings in the literature, and translate into improved communication about these behaviours in multiple sclerosis. Implications for Rehabilitation The symptoms of multiple sclerosis can be managed through participation in physical activity and exercise. Persons with multiple sclerosis are not engaging in sufficient levels of physical activity and exercise for health benefits. Rehabilitation professionals should use established definitions of physical activity, exercise, and sedentary behaviours when communicating about these behaviours among persons with multiple sclerosis.

Reliability of Classifying Multiple Sclerosis Disease Activity Using Magnetic Resonance Imaging in a Multiple Sclerosis Clinic

PubMed Central

Altay, Ebru Erbayat; Fisher, Elizabeth; Jones, Stephen E.; Hara-Cleaver, Claire; Lee, Jar-Chi; Rudick, Richard A.

2013-01-01

Objective To assess the reliability of new magnetic resonance imaging (MRI) lesion counts by clinicians in a multiple sclerosis specialty clinic. Design An observational study. Setting A multiple sclerosis specialty clinic. Patients Eighty-five patients with multiple sclerosis participating in a National Institutes of Health–supported longitudinal study were included. Intervention Each patient had a brain MRI scan at entry and 6 months later using a standardized protocol. Main Outcome Measures The number of new T2 lesions, newly enlarging T2 lesions, and gadolinium-enhancing lesions were measured on the 6-month MRI using a computer-based image analysis program for the original study. For this study, images were reanalyzed by an expert neuroradiologist and 3 clinician raters. The neuroradiologist evaluated the original image pairs; the clinicians evaluated image pairs that were modified to simulate clinical practice. New lesion counts were compared across raters, as was classification of patients as MRI active or inactive. Results Agreement on lesion counts was highest for gadolinium-enhancing lesions, intermediate for new T2 lesions, and poor for enlarging T2 lesions. In 18% to 25% of the cases, MRI activity was classified differently by the clinician raters compared with the neuroradiologist or computer program. Variability among the clinical raters for estimates of new T2 lesions was affected most strongly by the image modifications that simulated low image quality and different head position. Conclusions Between-rater variability in new T2 lesion counts may be reduced by improved standardization of image acquisitions, but this approach may not be practical in most clinical environments. Ultimately, more reliable, robust, and accessible image analysis methods are needed for accurate multiple sclerosis disease-modifying drug monitoring and decision making in the routine clinic setting. PMID:23599930

Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability.

PubMed

Studer, Valeria; Rocchi, Camilla; Motta, Caterina; Lauretti, Benedetta; Perugini, Jacopo; Brambilla, Laura; Pareja-Gutierrez, Lorena; Camera, Giorgia; Barbieri, Francesca Romana; Marfia, Girolama A; Centonze, Diego; Rossi, Silvia

2017-01-01

Sympathovagal imbalance has been associated with poor prognosis in chronic diseases, but there is conflicting evidence in multiple sclerosis. The objective of this study was to investigate the autonomic nervous system dysfunction correlation with inflammation and progression in multiple sclerosis. Heart rate variability was analysed in 120 multiple sclerosis patients and 60 healthy controls during supine rest and head-up tilt test; the normalised units of low frequency and high frequency power were considered to assess sympathetic and vagal components, respectively. Correlation analyses with clinical and radiological markers of disease activity and progression were performed. Sympathetic dysfunction was closely related to the progression of disability in multiple sclerosis: progressive patients showed altered heart rate variability with respect to healthy controls and relapsing-remitting patients, with higher rest low frequency power and lacking the expected low frequency power increase during the head-up tilt test. In relapsing-remitting patients, disease activity, even subclinical, was associated with lower rest low frequency power, whereas stable relapsing-remitting patients did not differ from healthy controls. Less sympathetic reactivity and higher low frequency power at rest were associated with incomplete recovery from relapse. Autonomic balance appears to be intimately linked with both the inflammatory activity of multiple sclerosis, which is featured by an overall hypoactivity of the sympathetic nervous system, and its compensatory plastic processes, which appear inefficient in case of worsening and progressive multiple sclerosis.

The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis.

PubMed

Sako, Wataru; Abe, Takashi; Izumi, Yuishin; Harada, Masafumi; Kaji, Ryuji

2016-05-01

Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The "suspected" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Internal jugular vein blood flow in multiple sclerosis patients and matched controls.

PubMed

Mancini, Marcello; Lanzillo, Roberta; Liuzzi, Raffaele; Di Donato, Orlando; Ragucci, Monica; Monti, Serena; Salvatore, Elena; Morra, Vincenzo Brescia; Salvatore, Marco

2014-01-01

The aim of the study was to investigate the Internal Jugular Veins dynamics using contrast enhanced ultrasonography in Multiple Sclerosis patients, clinically isolated syndrome patients and healthy controls. Contrast enhanced ultrasonography imaging of the Internal Jugular Vein was performed in fifty-eight patients with Multiple Sclerosis, seven clinically isolated syndrome patients and in thirteen healthy controls. Time-intensity curves were quantified using a semi-automated method and compared with clinical disease outcomes. Wash-out parameters were calculated and six Time-intensity curves shapes were created. Significantly reduction of wash-out rate in Internal Jugular Veins was detected in Multiple Sclerosis patients compared to healthy controls [22.2% (2.7%-65.9%) vs. 33.4% (16.2%-76.8%); P<0.005]. Internal Jugular Vein enhancement was heterogeneous in patients with Multiple Sclerosis and consisted of slow wash-out Time-intensity curves shapes, compared with almost only one type of Time-intensity curves shape in control subjects that correspond to fast enhancement and fast wash-out. The vein wash-in parameters were similar in Multiple Sclerosis group compared with controls. A significant correlation was found between Internal Jugular Vein wash-out and level of disability (R =  -0.402, p<0.05). Contrast enhanced ultrasonography of the Internal Jugular Vein with time intensity curve analysis revealed alterations of cerebral venous outflow in Multiple Sclerosis patients, however mechanisms that determine this condition remains unclear.

Community-based group aquatic programme for individuals with multiple sclerosis: a pilot study.

PubMed

Salem, Yasser; Scott, Anne Hiller; Karpatkin, Herbert; Concert, George; Haller, Leah; Kaminsky, Eva; Weisbrot, Rivky; Spatz, Eugene

2011-01-01

The purpose of this study was to determine the feasibility of providing a community-based aquatic exercise programme and to examine the effects of a group aquatic exercise programme in individuals with multiple sclerosis. This study illustrates the implementation of a multidisciplinary community-based programme in a university community wellness centre coordinated with a local advocacy group. Eleven subjects with multiple sclerosis participated in a 5-week community-based aquatic exercise programme. Aquatic exercises were held twice weekly for 60 minutes and included aerobic exercises, strength training, flexibility exercises, balance training and walking activities. The 10-Metre Walk test, the Berg Balance Scale (BBS), the 'Timed Up and Go' (TUG) test, grip strength and the Modified Fatigue Impact Scale were used to assess motor function. Analysis of the scores demonstrated improved gait speed, BBS, TUG test and grip strength. The average attendance of the training sessions was good (88%), and no incidence of injuries, no incidence of falls and no adverse effects related to the exercise programme were reported. All participants reported that they enjoyed the programme, and they had improved after the training. A community-based aquatic exercise programme is feasible and resulted in improvement in motor functions of individuals with multiple sclerosis. These findings indicate that an aquatic training programme is appropriate and beneficial for individuals with multiple sclerosis and should be considered to augment the rehabilitation of those individuals. This programme may provide a viable model for a community-based wellness programme for people with disability including individuals with multiple sclerosis.

Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28.

PubMed

Zürcher, Nicole R; Loggia, Marco L; Lawson, Robert; Chonde, Daniel B; Izquierdo-Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

2015-01-01

Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [(11)C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38-68 years) and ten age- and [(11)C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33-65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (p FWE < 0.05). Region of interest analysis revealed increased [(11)C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = -0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [(11)C]-PBR28 as a marker of treatments that target neuroinflammation.

Establishing a 1991 Veterans Research Network to Improve Characterization of Gulf War Illness and Provide a National Resource for Veterans and Investigators

DTIC Science & Technology

2015-09-01

studies have reported that 1991 Gulf War veterans have an excess rate of amyotrophic lateral sclerosis (ALS),11-13 compared to nondeployed veterans...Coffman CJ, et al. Amyotrophic Lateral Sclerosis among 1991 Gulf War Veterans: Evidence for a Time-Limited Outbreak. Neuroepidemiology.2008;31:28-32. 12...Horner RD, Kamins KG, Feussner JR, et al. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology.2003;61:742-749. 8 13. Haley

Establishing a 1991 Veterans Research Network To Improve Characterization of Gulf War Illness and Provide a National Resource for Veterans and Investigators

DTIC Science & Technology

2014-09-01

studies have reported that 1991 Gulf War veterans have an excess rate of amyotrophic lateral sclerosis (ALS),11-13 compared to nondeployed veterans of...AppendixA_Presentation04.pdf 11. Horner RD, Grambow SC, Coffman CJ, et al. Amyotrophic Lateral Sclerosis among 1991 Gulf War Veterans: Evidence for a...Time-Limited Outbreak. Neuroepidemiology.2008;31:28-32. 12. Horner RD, Kamins KG, Feussner JR, et al. Occurrence of amyotrophic lateral sclerosis

Rehabilitation and multiple sclerosis: hot topics in the preservation of physical functioning.

PubMed

Dalgas, Ulrik

2011-12-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point of their lives, emphasising the importance of rehabilitation in order to maintain quality of life. An important aspect of multiple sclerosis rehabilitation is the preservation of physical functioning. Hot topics in the rehabilitation of physical function include (1) exercise therapy, (2) robot-assisted training and (3) pharmacological interventions. Exercise therapy has for many years been a controversial issue in multiple sclerosis rehabilitation and the advice generally given to patients was not to participate in physical exercise, since it was thought to lead to a worsening of symptoms or fatigue. However, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies that have evaluated these is limited, although some promising results have been reported. Finally, recent studies have shown that certain pharmacological interventions have the potential to improve functional capacity substantially, with the potassium channel blocker fampridine being one of the most promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving everyday functioning and quality of life in patients with MS. Copyright © 2011 Elsevier B.V. All rights reserved.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Etiogenic factors present in the cerebrospinal fluid from amyotrophic lateral sclerosis patients induce predominantly pro-inflammatory responses in microglia.

PubMed

Mishra, Pooja-Shree; Vijayalakshmi, K; Nalini, A; Sathyaprabha, T N; Kramer, B W; Alladi, Phalguni Anand; Raju, T R

2017-12-16

Microglial cell-associated neuroinflammation is considered as a potential contributor to the pathophysiology of sporadic amyotrophic lateral sclerosis. However, the specific role of microglia in the disease pathogenesis remains to be elucidated. We studied the activation profiles of the microglial cultures exposed to the cerebrospinal fluid from these patients which recapitulates the neurodegeneration seen in sporadic amyotrophic lateral sclerosis. This was done by investigating the morphological and functional changes including the expression levels of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), TNF-α, IL-6, IFN-γ, IL-10, inducible nitric oxide synthase (iNOS), arginase, and trophic factors. We also studied the effect of chitotriosidase, the inflammatory protein found upregulated in the cerebrospinal fluid from amyotrophic lateral sclerosis patients, on these cultures. We report that the cerebrospinal fluid from amyotrophic lateral sclerosis patients could induce an early and potent response in the form of microglial activation, skewed primarily towards a pro-inflammatory profile. It was seen in the form of upregulation of the pro-inflammatory cytokines and factors including IL-6, TNF-α, iNOS, COX-2, and PGE2. Concomitantly, a downregulation of beneficial trophic factors and anti-inflammatory markers including VEGF, glial cell line-derived neurotrophic factor, and IFN-γ was seen. In addition, chitotriosidase-1 appeared to act specifically via the microglial cells. Our findings demonstrate that the cerebrospinal fluid from amyotrophic lateral sclerosis patients holds enough cues to induce microglial inflammatory processes as an early event, which may contribute to the neurodegeneration seen in the sporadic amyotrophic lateral sclerosis. These findings highlight the dynamic role of microglial cells in the pathogenesis of the disease, thus suggesting the need for a multidimensional and temporally guarded therapeutic approach targeting the inflammatory pathways for its treatment.

Multiple sclerosis: Left advantage for auditory laterality in dichotic tests of central auditory processing and relationship of psychoacoustic tests with the Multiple Sclerosis Disability Scale-EDSS.

PubMed

Peñaloza López, Yolanda Rebeca; Orozco Peña, Xóchitl Daisy; Pérez Ruiz, Santiago Jesús

2018-04-03

To evaluate the central auditory processing disorders in patients with multiple sclerosis, emphasizing auditory laterality by applying psychoacoustic tests and to identify their relationship with the Multiple Sclerosis Disability Scale (EDSS) functions. Depression scales (HADS), EDSS, and 9 psychoacoustic tests to study CAPD were applied to 26 individuals with multiple sclerosis and 26 controls. Correlation tests were performed between the EDSS and psychoacoustic tests. Seven out of 9 psychoacoustic tests were significantly different (P<.05); right or left (14/19 explorations) with respect to control. In dichotic digits there was a left-ear advantage compared to the usual predominance of RDD. There was significant correlation in five psychoacoustic tests and the specific functions of EDSS. The left-ear advantage detected and interpreted as an expression of deficient influences of the corpus callosum and attention in multiple sclerosis should be investigated. There was a correlation between psychoacoustic tests and specific EDSS functions. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

Vision and vision-related outcome measures in multiple sclerosis

PubMed Central

Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

[Axonopathy in the pathogenesis of multiple sclerosis, peripheral diffuse and local motor neuropathies and motor neuron disease].

PubMed

Merkulov, Iu A; Merkulova, D M; Iosifova, O A; Zavalishin, I A

2010-01-01

Two hundreds and seventy-six patients including 43 patients with multiple sclerosis, 24 - with acute inflammatory demyelinating polyneuropathy (AIDP), 144 - with chronic inflammatory demyelinating polyneuropathy (CIDP), 27 - with motor multifocal neuropathy (MMN), 38 - with lateral amyotrophic sclerosis (LAS) have been examined. Symptoms of axonal degeneration, manifested in denervation phenomena in both clinical and instrumental studies (electromyography, transcranial magnetic stimulation, MRT), were revealed in all groups of patients. The formation of excitation conduction blocks is an universal pathophysiological mechanism of the axonopathy development in AIDP, CIDP, MMN and LAS. Symptoms of axonopathy and peripheral demyelinization in patients with multiple sclerosis and LAS suggest the possibility of transformation of immunopathological process from the central nervous system to the peripheral one.

MAPT as a predisposing gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population

PubMed Central

Fang, Pu; Xu, Wenyuan; Wu, Chengsi; Zhu, Min; Li, Xiaobing; Hong, Daojun

2013-01-01

A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau (MAPT) gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population. We screened the mutation-susceptible regions of MAPT – the 3' and 5' untranslated regions as well as introns 9, 10, 11, and 12 – by direct sequencing, and identified 33 genetic variations. Two of these, 105788 A > G in intron 9 and 123972 T > A in intron 11, were not present in the control group. The age of onset in patients with the 105788 A > G and/or the 123972 T > A variant was younger than that in patients without either genetic variation. Moreover, the pa-tients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population. PMID:25206632

Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

PubMed Central

Righart, Ruthger; Biberacher, Viola; Jonkman, Laura E.; Klaver, Roel; Schmidt, Paul; Buck, Dorothea; Berthele, Achim; Kirschke, Jan S.; Zimmer, Claus; Hemmer, Bernhard; Geurts, Jeroen J. G.

2017-01-01

Objective In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown. Methods Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors. Results Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin. Interpretation The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529 PMID:28833433

Effect of Rehabilitation Technology Services on Vocational Rehabilitation Outcomes of Individuals with Multiple Sclerosis

ERIC Educational Resources Information Center

Chiu, Chung-Yi; Tansey, Timothy N.; Chan, Fong; Strauser, David; Frain, Michael P.; Arora, Simran

2015-01-01

Objectives: To examine the effect of rehabilitation technology interventions on the employment or job retention outcomes of individuals with multiple sclerosis (MS) served by the state-federal vocational rehabilitation program using a case-control study design. Participants: Data for this study were extracted from the Rehabilitation Services…

Satisfaction with Communicative Participation as Defined by Adults with Multiple Sclerosis: A Qualitative Study

ERIC Educational Resources Information Center

Yorkston, Kathryn M.; Baylor, Carolyn R.; Klasner, Estelle R.; Deitz, Jean; Dudgeon, Brian J.; Eadie, Tanya; Miller, Robert M.; Amtmann, Dagmar

2007-01-01

Purpose: This study examined satisfaction with communicative participation as reported by adults with multiple sclerosis (MS). Method: Eight community-dwelling adults with MS participated in semi-structured interviews. They were asked to discuss their satisfaction with their communication in a variety of situations. Interviews were analyzed using…

Resource utilization in children with tuberous sclerosis complex and associated seizures: a retrospective chart review study.

PubMed

Lennert, Barb; Farrelly, Eileen; Sacco, Patricia; Pira, Geraldine; Frost, Michael

2013-04-01

Seizures are a hallmark manifestation of tuberous sclerosis complex, yet data characterizing resource utilization are lacking. This retrospective chart review was performed to assess the economic burden of tuberous sclerosis complex with neurologic manifestations. Demographic and resource utilization data were collected for 95 patients for up to 5 years after tuberous sclerosis complex diagnosis. Mean age at diagnosis was 3.1 years, with complex partial and infantile spasms as the most common seizure types. In the first 5 years post-diagnosis, 83.2% required hospitalization, 30.5% underwent surgery, and the majority of patients (90.5%) underwent ≥3 testing procedures. In 79 patients with a full 5 years of data, hospitalizations, intensive care unit stays, diagnostic testing, and rehabilitation services decreased over the 5-year period. Resource utilization is cost-intensive in children with tuberous sclerosis complex and associated seizures during the first few years following diagnosis. Improving seizure control and reducing health care costs in this population remain unmet needs.

A passive exoskeleton can push your life up: application on multiple sclerosis patients.

PubMed

Di Russo, Francesco; Berchicci, Marika; Perri, Rinaldo Livio; Ripani, Francesca Romana; Ripani, Maurizio

2013-01-01

In the present study, we report the benefits of a passive and fully articulated exoskeleton on multiple sclerosis patients by means of behavioral and electrophysiological measures, paying particular attention to the prefrontal cortex activity. Multiple sclerosis is a neurological condition characterized by lesions of the myelin sheaths that encapsulate the neurons of the brain, spine and optic nerve, and it causes transient or progressive symptoms and impairments in gait and posture. Up to 50% of multiple sclerosis patients require walking aids and 10% are wheelchair-bound 15 years following the initial diagnosis. We tested the ability of a new orthosis, the "Human Body Posturizer", designed to improve the structural and functional symmetry of the body through proprioception, in multiple sclerosis patients. We observed that a single Human Body Posturizer application improved mobility, ambulation and response accuracy, in all of the tested patients. Most importantly, we associated these clinical observations and behavioral effects to changes in brain activity, particularly in the prefrontal cortex.

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

PubMed

Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

2004-01-01

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external sphincterotomy followed by condom catheter drainage is recommended. However, if external urethral sphincterotomy fails to reduce residual urine and detrusor pressure, urinary diversion or bladder reconstruction may be necessary.

Processing speed and working memory training in multiple sclerosis: a double-blind randomized controlled pilot study.

PubMed

Hancock, Laura M; Bruce, Jared M; Bruce, Amanda S; Lynch, Sharon G

2015-01-01

Between 40-65% of multiple sclerosis patients experience cognitive deficits, with processing speed and working memory most commonly affected. This pilot study investigated the effect of computerized cognitive training focused on improving processing speed and working memory. Participants were randomized into either an active or a sham training group and engaged in six weeks of training. The active training group improved on a measure of processing speed and attention following cognitive training, and data trended toward significance on measures of other domains. Results provide preliminary evidence that cognitive training with multiple sclerosis patients may produce moderate improvement in select areas of cognitive functioning.

Analysis of the quantitative dermatoglyphics of the digito-palmar complex in patients with multiple sclerosis.

PubMed

Supe, S; Milicić, J; Pavićević, R

1997-06-01

Recent studies on the etiopathogenesis of multiple sclerosis (MS) all point out that there is a polygenetical predisposition for this illness. The so called "MS Trait" determines the reactivity of the immunological system upon ecological factors. The development of the glyphological science and the study of the characteristics of the digito-palmar dermatoglyphic complex (for which it was established that they are polygenetically determined characteristics) all enable a better insight into the genetic development during early embriogenesis. The aim of this study was to estimate certain differences in the dermatoglyphics of digito-palmar complexes between the group with multiple sclerosis and the comparable, phenotypically healthy groups of both sexes. This study is based on the analysis of 18 quantitative characteristics of the digito-palmar complex in 125 patients with multiple sclerosis (41 males and 84 females) in comparison to a group of 400 phenotypically healthy patients (200 males and 200 females). The conducted analysis pointed towards a statistically significant decrease of the number of digital and palmar ridges, as well as with lower values of atd angles in a group of MS patients of both sexes. The main discriminators were the characteristic palmar dermatoglyphics with the possibility that the discriminate analysis classifies over 80% of the examinees which exceeds the statistical significance. The results of this study suggest a possible discrimination of patients with MS and the phenotypically health population through the analysis of the dermatoglyphic status, and therefore the possibility that multiple sclerosis is genetically predisposed disease.

Lockhart Clarke’s contribution to the description of amyotrophic lateral sclerosis

PubMed Central

Turner, Martin R.; Swash, Michael; Ebers, George C.

2011-01-01

The definition of the clinicopathological entity of amyotrophic lateral sclerosis evolved over half a century. Although the definitive term amyotrophic lateral sclerosis that acknowledged both upper and lower motor neuron involvement was attributed to Jean-Martin Charcot in 1874, his initial case was published nearly a decade earlier; and it is accepted that, from at least the 1830s, several others (including Charles Bell, François-Amilcar Aran and Jean Cruveilhier) had already recognized a progressive lower motor neuron-only syndrome within a broader, clinically-defined group of disorders, termed progressive muscular atrophy. Although William Gowers first grouped the three phenotypes of amyotrophic lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy together as part of the same syndrome, the term motor neuron disease, as an over-arching label, was not suggested until nearly a century later by W. Russell Brain. Augustus Jacob Lockhart Clarke (1817–80) is best known for his descriptions of spinal cord anatomy. However, in two detailed case reports from the 1860s, he carried out rigorous post-mortem neuropathological studies of what appear to be classical cases of amyotrophic lateral sclerosis. Furthermore, he recognized the additional involvement of the corticospinal tracts that distinguished this from progressive muscular atrophy. Several aspects of the exquisite clinical histories documented as part of both studies, one by Charles Bland Radcliffe, resonate with contemporary debates concerning the evolution of disease in amyotrophic lateral sclerosis. These ‘past masters’ still have much to teach us. PMID:20576696

Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review)

PubMed Central

Miller, R G.; Jackson, C E.; Kasarskis, E J.; England, J D.; Forshew, D; Johnston, W; Kalra, S; Katz, J S.; Mitsumoto, H; Rosenfeld, J; Shoesmith, C; Strong, M J.; Woolley, S C.

2009-01-01

Objective: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). Methods: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include breaking the news, multidisciplinary clinics, symptom management, cognitive and behavioral impairment, communication, and palliative care for patients with ALS. Results: The authors identified 2 Class I studies, 8 Class II studies, and 30 Class III studies in ALS, but many important areas have been little studied. More high-quality, controlled studies of symptomatic therapies and palliative care are needed to guide management and assess outcomes in patients with ALS. Recommendations: Multidisciplinary clinic referral should be considered for managing patients with ALS to optimize health care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C). For the treatment of refractory sialorrhea, botulinum toxin B should be considered (Level B) and low-dose radiation therapy to the salivary glands may be considered (Level C). For treatment of pseudobulbar affect, dextromethorphan and quinidine should be considered if approved by the US Food and Drug Administration (Level B). For patients who develop fatigue while taking riluzole, withholding the drug may be considered (Level C). Because many patients with ALS demonstrate cognitive impairment, which in some cases meets criteria for dementia, screening for cognitive and behavioral impairment should be considered in patients with ALS (Level B). Other management strategies all lack strong evidence. GLOSSARY ALS = amyotrophic lateral sclerosis; ALS-FTD = amyotrophic lateral sclerosis with a dementia meeting the Neary criteria for frontotemporal dementia; ALSbi = amyotrophic lateral sclerosis with behavioral impairment; ALSci = amyotrophic lateral sclerosis with cognitive impairment; BTxA = botulinum toxin type A; BTxB = botulinum toxin type B; DM = dextromethorphan; FDA = Food and Drug Administration; FTD = frontotemporal dementia; NIV = noninvasive ventilation; PEG = percutaneous endoscopic gastrostomy; Q = quinidine. PMID:19822873

Topical sodium metabisulfite for the treatment of calcinosis cutis: a promising new therapy.

PubMed

Del Barrio-Díaz, P; Moll-Manzur, C; Álvarez-Veliz, S; Vera-Kellet, C

2016-09-01

Calcinosis cutis is a chronic calcium-mediated disease that causes significant morbidity. Multiple treatments have been tried, with varying results; indeed, to date, no standard treatment has been generally accepted. Sodium metabisulfite is an inorganic compound that, when it reacts with oxygen, becomes sodium sulfate, a metabolite of sodium thiosulfate that has a similar ability to inhibit calcium oxalate agglomeration. Four women diagnosed with calcinosis cutis, secondary to dermatomyositis, systemic sclerosis and radiodermatitis after breast cancer, were evaluated for their response to topical 25% sodium metabisulfite. In all patients a decrease in lesion size, erythema and pain from injuries was shown, with complete resolution of the associated ulcers. One patient had a complete response. None experienced adverse effects. Topical sodium metabisulfite is a promising emerging therapy that should be considered as a valid alternative treatment in calcinosis cutis. Randomized prospective studies are required to evaluate its true efficacy. © 2016 British Association of Dermatologists.

Laboratory evaluation of suspected motor neuron disease: A survey of physicians.

PubMed

Sanderson, Alan B; Novak, John C; Nash, Steven M; Kolb, Stephen J; Kissel, John T

2015-07-01

The clinical diagnosis of amyotrophic lateral sclerosis (ALS) relies on exclusion of mimic syndromes, but there are no specific guidelines regarding the extent of laboratory testing required. A survey was sent to 274 physicians listed in the Neuromuscular Section of the American Academy of Neurology. The survey asked how often they order 21 different laboratory tests in patients suspected of having ALS. Ninety-nine responses were received (36% response rate). Greater than 75% ordered serum creatine kinase, chemistry panel, and thyroid functions often or always. Fewer than 25% tested for serum complement, hexosaminidase A, spinal muscular atrophy, Kennedy disease, heavy metals, or human T-cell lymphotrophic virus often or always. Twelve other tests had intermediate responses. There is a lack of consensus among respondents regarding the laboratory evaluation of suspected ALS. Prospective studies are needed to define the diagnostic yield and cost-effectiveness of laboratory testing in this population. © 2015 Wiley Periodicals, Inc.

Spasticity

MedlinePlus

... in association with spinal cord injury, multiple sclerosis, cerebral palsy, stroke, brain or head trauma, amyotrophic lateral sclerosis, ... in association with spinal cord injury, multiple sclerosis, cerebral palsy, stroke, brain or head trauma, amyotrophic lateral sclerosis, ...

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

PubMed

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4-) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clinical relapses. This was not found in patients who experienced relapses during natalizumab treatment. The enhanced potential of Th17.1 cells to infiltrate the central nervous system was supported by their predominance in cerebrospinal fluid of early multiple sclerosis patients and their preferential transmigration across human brain endothelial layers. These findings reveal a dominant contribution of Th1-like Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and provide a strong rationale for more specific and earlier use of T cell-targeted therapy in multiple sclerosis.

Use of the Godin leisure-time exercise questionnaire in multiple sclerosis research: a comprehensive narrative review.

PubMed

Sikes, Elizabeth Morghen; Richardson, Emma V; Cederberg, Katie J; Sasaki, Jeffer E; Sandroff, Brian M; Motl, Robert W

2018-01-17

The Godin Leisure-Time Exercise Questionnaire has been a commonly applied measure of physical activity in research among persons with multiple sclerosis over the past decade. This paper provides a comprehensive description of its application and inclusion in research on physical activity in multiple sclerosis. This comprehensive, narrative review included papers that were published between 1985 and 2017, written in English, involved participants with multiple sclerosis as a primary population, measured physical activity, and cited one of the two original Godin papers. There is a broad scope of research that has included the Godin Leisure-Time Exercise Questionnaire in persons with multiple sclerosis. Overall, 8 papers evaluated its psychometric properties, 21 evaluated patterns of physical activity, 24 evaluated correlates or determinants of physical activity, 28 evaluated outcomes or consequences of physical activity, and 15 evaluated physical activity interventions. The Godin Leisure-Time Exercise Questionnaire is a valid self-report measure of physical activity in persons with multiple sclerosis, and further is an appropriate, simple, and effective tool for describing patterns of physical activity, examining correlates and outcomes of physical activity, and provides a sensitive outcome for measuring change in physical activity after an intervention. Implications for rehabilitation There is increasing interest in physical activity and its benefits in multiple sclerosis. The study of physical activity requires appropriate and standardized measures. The Godin Leisure-Time Exercise Questionnaire is a common self-report measure of physical activity for persons with multiple sclerosis. Godin Leisure-Time Exercise Questionnaire scores are reliable measures of physical activity in persons with multiple sclerosis. The Godin Leisure-Time Exercise Questionnaire further is an appropriate, simple, and effective tool for describing patterns of physical activity, examining correlates and outcomes of physical activity participation, and is an advantageous primary outcome for measuring change in physical activity in response to an intervention.

Upper Extremity Function in Multiple Sclerosis Patients With Advanced Disability Treated With Ocrevus

ClinicalTrials.gov

2018-06-18

Multiple Sclerosis; Pathologic Processes; Demyelinating Diseases; Demyelinating Autoimmune Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Primary Progressive Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis

Childhood infections and risk of multiple sclerosis.

PubMed

Bager, Peter; Nielsen, Nete Munk; Bihrmann, Kristine; Frisch, Morten; Hjalgrim, Henrik; Wohlfart, Jan; Koch-Henriksen, Nils; Melbye, Mads; Westergaard, Tine

2004-11-01

Multiple sclerosis has been hypothesized to be the result from an aberrant immune response possibly triggered by delayed exposure to a common childhood infection. Because the vast majority of previous studies testing this hypothesis have been based on a history of childhood infections recalled years to decades later in adulthood, we investigated whether age at six common childhood infections was associated with risk of multiple sclerosis, using information recalled in the childhood of a historical cohort of school children in Denmark. Cases included all individuals with multiple sclerosis in the country born between 1940 and 1975, who had attended school in the capital, Copenhagen. Controls were age- and sex-matched peers. School health records were obtained for all subjects. The records contained information on measles, pertussis, scarlet fever, birth order, sibship size, social class of the father, school years, and name of school and attended school classes for children born since 1940 (n(cases) = 455, n(controls) = 1801). For children born since 1950, the records also contained information on rubella, varicella and mumps (n(cases) = 182, n(controls) = 690). Neither age at infection with measles, rubella, varicella, mumps, pertussis and scarlet fever (upper age limit, 14 years) nor the cumulative number of these infections between the ages of 10 and 14 years was associated with the risk of multiple sclerosis. In addition, the risk of multiple sclerosis was not associated with birth order or social class. No clustering of multiple sclerosis in school classes was observed. Our findings suggest that measles, rubella, mumps, varicella, pertussis and scarlet fever, even if acquired late in childhood, are not associated with increased risk of multiple sclerosis later in life.

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

PubMed

Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

2013-01-01

Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Impaired heel to toe progression during gait is related to reduced ankle range of motion in people with Multiple Sclerosis.

PubMed

Psarakis, Michael; Greene, David; Moresi, Mark; Baker, Michael; Stubbs, Peter; Brodie, Matthew; Lord, Stephen; Hoang, Phu

2017-11-01

Gait impairment in people with Multiple Sclerosis results from neurological impairment, muscle weakness and reduced range of motion. Restrictions in passive ankle range of motion can result in abnormal heel-to-toe progression (weight transfer) and inefficient gait patterns in people with Multiple Sclerosis. The purpose of this study was to determine the associations between gait impairment, heel-to-toe progression and ankle range of motion in people with Multiple Sclerosis. Twelve participants with Multiple Sclerosis and twelve healthy age-matched participants were assessed. Spatiotemporal parameters of gait and individual footprint data were used to investigate group differences. A pressure sensitive walkway was used to divide each footprint into three phases (contact, mid-stance, propulsive) and calculate the heel-to-toe progression during the stance phase of gait. Compared to healthy controls, people with Multiple Sclerosis spent relatively less time in contact phase (7.8% vs 25.1%) and more time in the mid stance phase of gait (57.3% vs 33.7%). Inter-limb differences were observed in people with Multiple Sclerosis between the affected and non-affected sides for contact (7.8% vs 15.3%) and mid stance (57.3% and 47.1%) phases. Differences in heel-to-toe progression remained significant after adjusting for walking speed and were correlated with walking distance and ankle range of motion. Impaired heel-to-toe progression was related to poor ankle range of motion in people with Multiple Sclerosis. Heel-to-toe progression provided a sensitive measure for assessing gait impairments that were not detectable using standard spatiotemporal gait parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Always looking for a new balance": toward an understanding of what it takes to continue working while being diagnosed with relapsing-remitting multiple sclerosis.

PubMed

Meide, Hanneke van der; Gorp, Dennis van; van der Hiele, Karin; Visser, Leo

2017-06-22

The aim of this study was to gain insight into the meaning of work in the everyday lives of people with relapsing-remitting multiple sclerosis, and the barriers and facilitators to staying in work. Nineteen employed adults diagnosed with relapsing-remitting multiple sclerosis participated in narrative interviews. All interviews were transcribed and coded for thematic analysis. For people with relapsing-remitting multiple sclerosis, continuing to work was a precarious balancing act. Five themes influenced this balance: becoming familiar with the disease, adjusting expectations, having an understanding and realistic line manager, seeing work as meaningful life activity and strategic considerations. People receiving a diagnosis of relapsing-remitting multiple sclerosis have to refamiliarize themselves with their own body in a meaningful way to be able to continue their work. Rehabilitation professionals can support them herein by taking into account not merely functional capabilities but also identity aspects of the body. Medication that stabilizes symptoms supports making the necessary adjustments. A trusting relationship with the line manager is vital for this adaptation process. Additionally, a match between being adequately challenged by work, while still having the capacity to meet those work demands, is needed, as is long-term financial stability. Implications for rehabilitation Rehabilitation professionals can support employees with relapsing-remitting multiple sclerosis by taking into account not merely functional capabilities but also identity aspects of the body. A trusting relationship with the line manager, including a timely disclosure of the diagnosis, is vital for people with relapsing-remitting multiple sclerosis to remain at work. For people with relapsing-remitting multiple sclerosis, there is a delicate balance between being adequately challenged by work while still having the capacity to meet work demands.

Older age, higher perceived disability and depressive symptoms predict the amount and severity of work-related difficulties in persons with multiple sclerosis.

PubMed

Raggi, Alberto; Giovannetti, Ambra Mara; Schiavolin, Silvia; Brambilla, Laura; Brenna, Greta; Confalonieri, Paolo Agostino; Cortese, Francesca; Frangiamore, Rita; Leonardi, Matilde; Mantegazza, Renato Emilio; Moscatelli, Marco; Ponzio, Michela; Torri Clerici, Valentina; Zaratin, Paola; De Torres, Laura

2018-04-16

This cross-sectional study aims to identify the predictors of work-related difficulties in a sample of employed persons with multiple sclerosis as addressed with the Multiple Sclerosis Questionnaire for Job Difficulties. Hierarchical linear regression analysis was conducted to identify predictors of work difficulties: predictors included demographic variables (age, formal education), disease duration and severity, perceived disability and psychological variables (cognitive dysfunction, depression and anxiety). The targets were the questionnaire's overall score and its six subscales. A total of 177 participants (108 females, aged 21-63) were recruited. Age, perceived disability and depression were direct and significant predictors of the questionnaire total score, and the final model explained 43.7% of its variation. The models built on the questionnaire's subscales show that perceived disability and depression were direct and significant predictors of most of its subscales. Our results show that, among patients with multiple sclerosis, those who were older, with higher perceived disability and higher depression symptoms have more and more severe work-related difficulties. The Multiple Sclerosis Questionnaire for Job Difficulties can be fruitfully exploited to plan tailored actions to limit the likelihood of near-future job loss in persons of working age with multiple sclerosis. Implications for rehabilitation Difficulties with work are common among people with multiple sclerosis and are usually addressed in terms of unemployment or job loss. The Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific questionnaire developed to address the amount and severity of work-related difficulties. We found that work-related difficulties were associated to older age, higher perceived disability and depressive symptoms. Mental health issues and perceived disability should be consistently included in future research targeting work-related difficulties.

THC:CBD in Daily Practice: Available Data from UK, Germany and Spain.

PubMed

Fernández, Óscar

2016-01-01

From the time Sativex (THC:CBD) oromucosal spray first became available in European Union countries in 2010 for the management of treatment-resistant multiple sclerosis (MS) spasticity, data from daily practice have been collected through various projects. A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported. The most recent analysis of a retrospective registry established in the United Kingdom (UK), Germany and Switzerland, which collected safety data on more than 900 patients, has indicated a positive risk-benefit profile for THC:CBD oromucosal spray during long-term use. Long-term continuation rates were 68% (mean follow-up time 1 year) and the mean dose was 5.4 sprays/day. No new safety concerns were identified, and adverse events of special interest for a cannabis-based medicine were limited. The UK registry has since been closed but remains open in Germany and Switzerland. A prospective safety study undertaken in Spain involved 207 patients from 13 specialized MS centres who had been prescribed THC:CBD oromucosal spray. The findings aligned closely with the UK/German/Swiss registry data in terms of 1-year continuation rates (64.7%), mean daily dose (6.6 sprays/day) and safety profile, including no evidence of addiction, abuse or misuse. The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice. © 2016 S. Karger AG, Basel.

Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial.

PubMed

Oliveria, Seth F; Rodriguez, Ramon L; Bowers, Dawn; Kantor, Daniel; Hilliard, Justin D; Monari, Erin H; Scott, Bonnie M; Okun, Michael S; Foote, Kelly D

2017-09-01

Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius-ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior-ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor. We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS-either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3-4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four stimulation conditions: VIM on, VO on, both on, and both off (the order of testing was chosen by a computer-generated random sequence, assigned by independent members of the centre, and enacted by an unmasked DBS programming nurse). Each of four stimulation settings were tested over 4 consecutive days, with stimulation settings held constant for at least 12 h before testing. The primary outcome was change in mean total TRS score at the 6-month postoperative assessment with both leads activated, compared with the preoperative baseline mean TRS score. Analysis was by intention to treat. Safety was analysed in all patients who received the surgical implantation except in one patient who discontinued before the safety assessment. This trial is registered with ClinicalTrials.gov, number NCT00954421. Between Jan 16, 2007, and Dec 17, 2013, we enrolled 12 patients who were randomly assigned either to 3 initial months of VIM-only or VO-only stimulation. One patient from the VO-only group developed an infection necessitating DBS explantation, and was excluded from the assessment of the primary outcome. Compared with the mean baseline TRS score of 57·0 (SD 10·2), the mean score at 6 months decreased to 40·1 (17·6), -29·6% reduction; t=-0·28, p=0·03. Three of 11 patients did not respond to surgical intervention. One patient died suddenly 2 years after surgery, but this was judged to be unrelated to DBS implantation. Serious adverse events included a superficial wound infection in one patient that resolved with antibiotic therapy, and transient altered mental status and late multiple sclerosis exacerbation in another patient. The most common non-serious adverse events were headache and fatigue. Dual lead thalamic DBS might be a safe and effective option for improving severe, refractory multiple sclerosis tremor. Larger studies are necessary to show whether this technique is widely applicable, safe in the long-term, and effective in treating multiple sclerosis tremor or other severe tremor disorders. US National Institutes of Health, the Cathy Donnellan, Albert E Einstein, and Birdie W Einstein Fund, and the William Merz Professorship. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Magnetic Resonance Imaging Conversion Predictors of Clinically Isolated Syndrome to Multiple Sclerosis].

PubMed

Peixoto, Sara; Abreu, Pedro

2016-11-01

Clinically isolated syndrome may be the first manifestation of multiple sclerosis, a chronic demyelinating disease of the central nervous system, and it is defined by a single clinical episode suggestive of demyelination. However, patients with this syndrome, even with long term follow up, may not develop new symptoms or demyelinating lesions that fulfils multiple sclerosis diagnostic criteria. We reviewed, in clinically isolated syndrome, what are the best magnetic resonance imaging findings that may predict its conversion to multiple sclerosis. A search was made in the PubMed database for papers published between January 2010 and June 2015 using the following terms: 'clinically isolated syndrome', 'cis', 'multiple sclerosis', 'magnetic resonance imaging', 'magnetic resonance' and 'mri'. In this review, the following conventional magnetic resonance imaging abnormalities found in literature were included: lesion load, lesion location, Barkhof's criteria and brain atrophy related features. The non conventional magnetic resonance imaging techniques studied were double inversion recovery, magnetization transfer imaging, spectroscopy and diffusion tensor imaging. The number and location of demyelinating lesions have a clear role in predicting clinically isolated syndrome conversion to multiple sclerosis. On the other hand, more data are needed to confirm the ability to predict this disease development of non conventional techniques and remaining neuroimaging abnormalities. In forthcoming years, in addition to the established predictive value of the above mentioned neuroimaging abnormalities, different clinically isolated syndrome neuroradiological findings may be considered in multiple sclerosis diagnostic criteria and/or change its treatment recommendations.

The influence of interferon β-1b on gut microbiota composition in patients with multiple sclerosis.

PubMed

Castillo-Álvarez, F; Pérez-Matute, P; Oteo, J A; Marzo-Sola, M E

2018-06-09

The association between gut microbiota and animal models of multiple sclerosis has been well established; however, studies in humans are scarce. We performed a descriptive, cross-sectional study comparing the relative composition of gut microbiota in 30 patients with multiple sclerosis (15 treated with interferon β-1b, 15 not receiving this treatment) and 14 healthy controls using next generation sequencing. Patients with multiple sclerosis and controls showed differences in the proportion of Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, and Lentisphaerae phyla and in 17 bacterial species. More specifically, we found significant differences in the proportion of Firmicutes, Actinobacteria, and Lentisphaerae and 6 bacteria species between controls and untreated patients; however, these differences disappeared when compared with treated patients. Untreated patients showed a significant reduction in the proportion of Prevotella copri compared to controls, while the bacteria was significantly more abundant in patients treated with interferon β-1b than in untreated patients, with levels resembling those observed in the healthy control group. We observed differences in gut microbiota composition between patients with multiple sclerosis and controls, and between patients treated and not treated with interferon β-1b. In most cases, no differences were observed between treated patients and healthy controls, particularly for P. copri levels. This suggests that the clinical improvements observed in patients with multiple sclerosis receiving interferon β-1b may result from the effect of the drug on gut microbiota. Longitudinal and functional studies are necessary to establish a causal relationship. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Predictors of Employment Status for People with Multiple Sclerosis

ERIC Educational Resources Information Center

Roessler, Richard T.; Rumrill, Phillip D.; Fitzgerald, Shawn M.

2004-01-01

This study examined the relevance of the disease-and-demographics model for explaining the employment outcomes of adults with multiple sclerosis (MS). Participating in a national survey of their employment concerns, 1,310 adults with MS provided data for the study (274 men, 21%; 1,020 women, 78%; 16 participants did not identify their gender).…

Neurofunctional Correlates of Personality Traits in Relapsing-Remitting Multiple Sclerosis: An fMRI Study

ERIC Educational Resources Information Center

Gioia, Maria C.; Cerasa, Antonio; Valentino, Paola; Fera, Francesco; Nistico, Rita; Liguori, Maria; Lanza, Pierluigi; Quattrone, Aldo

2009-01-01

Extraversion and Neuroticism are two fundamental dimensions of human personality that influence cognitive functioning in healthy subjects. Little is known about personality changes that may occur in patients with multiple sclerosis (MS) nor about, in particular, their neurofunctional basis. The aim of this study is to determine the impact of…

Sexual Difficulties for Persons with Multiple Sclerosis in New South Wales, Australia

ERIC Educational Resources Information Center

Redelman, Margaret Juliet

2009-01-01

This 1992 study was conducted to ascertain the incidence of sexual difficulties in individuals diagnosed with multiple sclerosis (MS) living in New South Wales, Australia. New South Wales is a state lying roughly 29-36 [degrees] south of the equator. This is currently the largest study conducted. The anonymous questionnaire completed by 283…

The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study

PubMed Central

2010-01-01

Background A community in northern Italy was previously reported to have an excess incidence of amyotrophic lateral sclerosis among residents exposed to high levels of inorganic selenium in their drinking water. Methods To assess the extent to which such association persisted in the decade following its initial observation, we conducted a population-based case-control study encompassing forty-one newly-diagnosed cases of amyotrophic lateral sclerosis and eighty-two age- and sex-matched controls. We measured long-term intake of inorganic selenium along with other potentially neurotoxic trace elements. Results We found that consumption of drinking water containing ≥ 1 μg/l of inorganic selenium was associated with a relative risk for amyotrophic lateral sclerosis of 5.4 (95% confidence interval 1.1-26) after adjustment for confounding factors. Greater amounts of cumulative inorganic selenium intake were associated with progressively increasing effects, with a relative risk of 2.1 (95% confidence interval 0.5-9.1) for intermediate levels of cumulative intake and 6.4 (95% confidence interval 1.3-31) for high intake. Conclusion Based on these results, coupled with other epidemiologic data and with findings from animal studies that show specific toxicity of the trace element on motor neurons, we hypothesize that dietary intake of inorganic selenium through drinking water increases the risk for amyotrophic lateral sclerosis. PMID:21134276

Multicenter Case-Control Study on Restless Legs Syndrome in Multiple Sclerosis: the REMS Study

PubMed Central

Manconi, Mauro; Ferini-Strambi, Luigi; Filippi, Massimo; Bonanni, Enrica; Iudice, Alfonso; Murri, Luigi; Gigli, Gian Luigi; Fratticci, Lara; Merlino, Giovanni; Terzano, Giovanni; Granella, Franco; Parrino, Liborio; Silvestri, Rosalia; Aricò, Irene; Dattola, Vincenzo; Russo, Giovanna; Luongo, Carmela; Cicolin, Alessandro; Tribolo, Antonella; Cavalla, Paola; Savarese, Mariantonietta; Trojano, Maria; Ottaviano, Salvatore; Cirignotta, Fabio; Simioni, Valentina; Salvi, Fabrizio; Mondino, Fiorella; Perla, Franco; Chinaglia, Giorgia; Zuliani, Cristina; Cesnik, Edward; Granieri, Enrico; Placidi, Fabio; Palmieri, Maria Giuseppina; Manni, Raffaele; Terzaghi, Michele; Bergamaschi, Roberto; Rocchi, Raffaele; Ulivelli, Monica; Bartalini, Sabina; Ferri, Raffaele; Fermo, Salvatore Lo; Ubiali, Emilio; Viscardi, Massimo; Rottoli, Mariarosa; Nobili, Lino; Protti, Alessandra; Ferrillo, Franco; Allena, Marta; Mancardi, Gianluigi; Guarnieri, Biancamaria; Londrillo, Francesco

2008-01-01

Study objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. Design: Prospective, multicenter, case-control epidemiologic survey. Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine. Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects. Interventions: N/A. Measures and results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56–8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs. Citation: Manconi M; Ferini-Strambi L; Filippi M; Bonanni E; Iudice A; Murri L; Gigli GL; Fratticci L; Merlino G; Terzano G; Granella F; Parrino L; Silvestri R; Aricò I; Dattola V; Russo G; Luongo C; Cicolin A; Tribolo A; Cavalla P; Savarese M; Trojano M; Ottaviano S; Cirignotta F; Simioni V; Salvi F; Mondino F; Perla F; Chinaglia G; Zuliani C; Cesnik E; Granieri E; Placidi F; Palmieri MG; Manni R; Terzaghi M; Bergamaschi R; Rocchi R; Ulivelli M; Bartalini S; Ferri R; Lo Fermo S; Ubiali E; Viscardi M; Rottoli M; Nobili L; Protti A; Ferrillo F; Allena M; Mancardi G; Guarnieri B; Londrillo F. Multicenter Case-Control Study on Restless Legs Syndrome in Multiple Sclerosis: the REMS Study. SLEEP 2008;31(7):944-952. PMID:18655317

Clinical Usefulness of Aripiprazole and Lamotrigine in Schizoaffective Presentation of Tuberous Sclerosis.

PubMed

Lee, Seung-Yup; Min, Jung-Ah; Lee, In Goo; Kim, Jung Jin

2016-08-31

Tuberous sclerosis is not as rare as once thought and has high psychiatric comorbidities. However, bipolar or psychotic features associated with tuberous sclerosis have been rarely reported. This report first presents a tuberous sclerosis patient, resembling a schizoaffective disorder of bipolar type. A patient with known tuberous sclerosis displayed mood fluctuation and psychotic features. Her symptoms did not remit along with several psychiatric medications. After hospitalization, the patient responded well with lamotrigine and aripiprazole without exacerbation. As demonstrated in this case, tuberous sclerosis may also encompass bipolar affective or psychotic features. We would like to point out the necessity to consider bipolarity in evaluating and treating tuberous sclerosis.

Micrographia associated with a parietal lobe lesion in multiple sclerosis.

PubMed Central

Scolding, N J; Lees, A J

1994-01-01

The occurrence of micrographia in a 52 year old women two years after an isolated episode of painful sensory disturbance led to the diagnosis of multiple sclerosis. Her handwriting returned to normal after a course of intravenous methylprednisolone. Previous reports of movement disorders occurring in the context of multiple sclerosis are briefly reviewed. The finding on MRI studies of an enhancing lesion in the dominant parietal white matter supports Kinnier Wilson's suggestion that the anatomical origin of micrographia lies in the cerebral hemisphere rather than the corpus striatum. Images PMID:8006658

Clinical and Demographic Profile of Patients Receiving Fingolimod in Clinical Practice in Germany and the Benefit-Risk Profile of Fingolimod After 1 Year of Treatment: Initial Results From the Observational, Noninterventional Study PANGAEA.

PubMed

Ziemssen, Tjalf; Lang, Michael; Tackenberg, Björn; Schmidt, Stephan; Albrecht, Holger; Klotz, Luisa; Haas, Judith; Lassek, Christoph; Medin, Jennie; Cornelissen, Christian

2018-01-01

The population with multiple sclerosis receiving treatment in clinical practice differs from that in randomized controlled trials (RCTs). An assessment of the real-world benefit-risk profile of therapies is needed. This analysis used data from the large, noninterventional, observational German study Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) to assess prospectively baseline characteristics and outcomes after 12 months (± 90 days) of fingolimod treatment. Patients were divided into 2 cohorts: fingolimod starter [first received fingolimod in PANGAEA (n = 3315)] and previous study [received fingolimod before enrollment in PANGAEA in RCTs (n = 875), some of whom also had baseline data at entry into RCTs (n = 505)]. At PANGAEA baseline, patients in the fingolimod starter versus the previous study cohort had a higher annualized relapse rate [ARR (95% confidence interval): 1.79 (1.75-1.83) vs 1.32 (1.25-1.40)] and Expanded Disability Status Scale score [3.11 (3.04-3.17) vs 2.55 (2.44-2.66)]. A greater proportion in the fingolimod starter versus previous study cohort had diabetes (2.0% vs 0.7%). After 12 months of fingolimod, ARRs were lower than in the 12 months before PANGAEA enrollment in the fingolimod starter [0.386 (0.360-0.414)] and previous study [0.276 (0.238-0.320)] cohorts. Expanded Disability Status Scale scores were stable versus baseline. Adverse events were experienced by similar proportions in both cohorts during fingolimod treatment. Relevant differences exist in disease activity and comorbidities between patients receiving fingolimod in clinical practice versus RCTs. Irrespective of baseline differences indicating a higher proportion at an advanced stage of multiple sclerosis in the real world versus RCTs, fingolimod remains effective, with a manageable safety profile.

Treatment of Cognitive Impairment in Multiple Sclerosis

PubMed Central

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial.

PubMed

Khalili, Mohammad; Eghtesadi, Shahryar; Mirshafiey, Abbas; Eskandari, Ghazaleh; Sanoobar, Meisam; Sahraian, Mohamad Ali; Motevalian, Abbas; Norouzi, Abbas; Moftakhar, Shirin; Azimi, Amirreza

2014-01-01

Multiple sclerosis is a neurodegenerative and demyelinating disease of central nervous system. High levels of oxidative stress are associated with inflammation and play an important role in pathogenesis of multiple sclerosis. This double-blind, randomized controlled clinical study was carried out to determine the effect of daily consumption of lipoic acid on oxidative stress among multiple sclerosis patients. A total of 52 relapsing-remitting multiple sclerosis patients, aged 18-50 years with Expanded Disability Status Scale ≤5.5 were assigned to consume either lipoic acid (1200 mg/day) or placebo capsules for 12 weeks. Fasting blood samples were collected before the first dose taken and 12 hours after the last. Dietary intakes were obtained by using 3-day dietary records. Consumption of lipoic acid resulted in a significant improvement of total antioxidant capacity (TAC) in comparison to the placebo group (P = 0.004). Although a significant change of TAC (-1511 mmol/L, P = 0.001) was found within lipoic acid group, other markers of oxidative stress including superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde levels were not affected by lipoic acid consumption. These results suggest that 1200 mg of lipoic acid improves serum TAC among multiple sclerosis patients but does not affect other markers of oxidative stress.

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

PubMed

Zikou, Anastasia K; Xydis, Vasileios G; Astrakas, Loukas G; Nakou, Iliada; Tzarouchi, Loukia C; Tzoufi, Meropi; Argyropoulou, Maria I

2016-07-01

There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

Technology-Aided Programs for Assisting Communication and Leisure Engagement of Persons with Amyotrophic Lateral Sclerosis: Two Single-Case Studies

ERIC Educational Resources Information Center

Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Ferlisi, Gabriele; Ferrarese, Giacomina; Zullo, Valeria; Addante, Luigi M.; Spica, Antonella; Oliva, Doretta

2012-01-01

Technology-aided programs for assisting communication and leisure engagement were assessed in single-case studies involving two men with amyotrophic lateral sclerosis (ALS). Study I involved a 51-year-old man with a virtually total loss of his motor repertoire and assessed a technology-aided program aimed at enabling him to (a) write and send out…

Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis

PubMed Central

Konradi, Christine; Sillivan, Stephanie E.; Clay, Hayley B.

2011-01-01

Gene expression studies of bipolar disorder (BPD) have shown changes in transcriptome profiles in multiple brain regions. Here we summarize the most consistent findings in the scientific literature, and compare them to data from schizophrenia (SZ) and major depressive disorder (MDD). The transcriptome profiles of all three disorders overlap, making the existence of a BPD-specific profile unlikely. Three groups of functionally related genes are consistently expressed at altered levels in BPD, SZ and MDD. Genes involved in energy metabolism and mitochondrial function are downregulated, genes involved in immune response and inflammation are upregulated, and genes expressed in oligodendrocytes are downregulated. Experimental paradigms for multiple sclerosis demonstrate a tight link between energy metabolism, inflammation and demyelination. These studies also show variabilities in the extent of oligodendrocyte stress, which can vary from a downregulation of oligodendrocyte genes, such as observed in psychiatric disorders, to cell death and brain lesions seen in multiple sclerosis. We conclude that experimental models of multiple sclerosis could be of interest for the research of BPD, SZ and MDD. PMID:21310238

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

PubMed

Conrad, Benjamin N; Barry, Robert L; Rogers, Baxter P; Maki, Satoshi; Mishra, Arabinda; Thukral, Saakshi; Sriram, Subramaniam; Bhatia, Aashim; Pawate, Siddharama; Gore, John C; Smith, Seth A

2018-06-01

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016.

PubMed

García Merino, A; Ramón Ara Callizo, J; Fernández Fernández, O; Landete Pascual, L; Moral Torres, E; Rodríguez-Antigüedad Zarrantz, A

2017-03-01

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics.

PubMed

Camara-Lemarroy, Carlos R; Metz, Luanne; Meddings, Jonathan B; Sharkey, Keith A; Wee Yong, V

2018-05-30

Biological barriers are essential for the maintenance of homeostasis in health and disease. Breakdown of the intestinal barrier is an essential aspect of the pathophysiology of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. A wealth of recent studies has shown that the intestinal microbiome, part of the brain-gut axis, could play a role in the pathophysiology of multiple sclerosis. However, an essential component of this axis, the intestinal barrier, has received much less attention. In this review, we describe the intestinal barrier as the physical and functional zone of interaction between the luminal microbiome and the host. Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia. We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis. Finally, we address the mechanisms by which commonly used disease-modifying drugs in multiple sclerosis could alter the intestinal barrier and the microbiome, and we discuss the potential of barrier-stabilizing strategies, including probiotics and stabilization of tight junctions, as novel therapeutic avenues in multiple sclerosis.

Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene.

PubMed

Morimoto, Nobutoshi; Nagai, Makiko; Miyazaki, Kazunori; Ohta, Yasuyuki; Kurata, Tomoko; Takehisa, Yasushi; Ikeda, Yoshio; Matsuura, Tohru; Asanuma, Masato; Abe, Koji

2010-06-01

Amyotrophic lateral sclerosis is a progressive and fatal disease caused by selective death of motor neurons, and a number of these patients carry mutations in the superoxide dismutase 1 (SOD1) gene involved in ameliorating oxidative stress. Recent studies indicate that oxidative stress and disruption of mitochondrial homeostasis is a common mechanism for motor neuron degeneration in amyotrophic lateral sclerosis and the loss of midbrain dopamine neurons in Parkinson's disease. Therefore, the present study investigated the presence and alterations of familial Parkinson's disease-related proteins, PINK1 and DJ-1, in spinal motor neurons of G93ASOD1 transgenic mouse model of amyotrophic lateral sclerosis. Following onset of disease, PINK1 and DJ-1 protein expression increased in the spinal motor neurons. The activated form of p53 also increased and translocated to the nuclei of spinal motor neurons, followed by increased expression of p53-activated gene 608 (PAG608). This is the first report demonstrating that increased expression of PAG608 correlates with activation of phosphorylated p53 in spinal motor neurons of an amyotrophic lateral sclerosis model. These results provide further evidence of the profound correlations between spinal motor neurons of amyotrophic lateral sclerosis and parkinsonism-related proteins.

Field Synopsis and Re-analysis of Systematic Meta-analyses of Genetic Association Studies in Multiple Sclerosis: a Bayesian Approach.

PubMed

Park, Jae Hyon; Kim, Joo Hi; Jo, Kye Eun; Na, Se Whan; Eisenhut, Michael; Kronbichler, Andreas; Lee, Keum Hwa; Shin, Jae Il

2018-07-01

To provide an up-to-date summary of multiple sclerosis-susceptible gene variants and assess the noteworthiness in hopes of finding true associations, we investigated the results of 44 meta-analyses on gene variants and multiple sclerosis published through December 2016. Out of 70 statistically significant genotype associations, roughly a fifth (21%) of the comparisons showed noteworthy false-positive rate probability (FPRP) at a statistical power to detect an OR of 1.5 and at a prior probability of 10 -6 assumed for a random single nucleotide polymorphism. These associations (IRF8/rs17445836, STAT3/rs744166, HLA/rs4959093, HLA/rs2647046, HLA/rs7382297, HLA/rs17421624, HLA/rs2517646, HLA/rs9261491, HLA/rs2857439, HLA/rs16896944, HLA/rs3132671, HLA/rs2857435, HLA/rs9261471, HLA/rs2523393, HLA-DRB1/rs3135388, RGS1/rs2760524, PTGER4/rs9292777) also showed a noteworthy Bayesian false discovery probability (BFDP) and one additional association (CD24 rs8734/rs52812045) was also noteworthy via BFDP computation. Herein, we have identified several noteworthy biomarkers of multiple sclerosis susceptibility. We hope these data are used to study multiple sclerosis genetics and inform future screening programs.

Creatine kinase enzyme level correlates positively with serum creatinine and lean body mass, and is a prognostic factor for survival in amyotrophic lateral sclerosis.

PubMed

Rafiq, M K; Lee, E; Bradburn, M; McDermott, C J; Shaw, P J

2016-06-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition for which there is no single diagnostic test or biomarker. The level of the creatine kinase (CK) enzyme in serum may be mild to moderately elevated in some patients with ALS, the precise cause of which and its behaviour with disease progression is unknown. The aim of this study was to examine the usefulness of monitoring CK serially during the ALS disease trajectory and to determine whether CK levels mirror disease progression. This was a prospective observational cohort study, using the clinical database of the olesoxime (TRO19622) investigational medicinal product trial. The baseline CK was raised in 52% of the trial participants with the mean CK ± SD being 257 ± 239 U/l. The mean CK was significantly higher in male participants than in female participants (P < 0.001) and amongst participants with limb onset ALS compared to participants with bulbar onset ALS (P < 0.001). There was no significant difference in the CK levels between upper limb and lower limb onset disease (P = 0.746). The CK level co-related positively with serum creatinine and estimated lean body mass but there was no relationship between CK and muscle scores and limb function. A higher CKlog was associated with significantly better survival, even when adjusted for prognostic co-variants (P = 0.013). The serum CK level seems to be an independent prognostic factor for survival in ALS. The cellular mechanism of CK enzyme suggests that it may be upregulated to provide energy in the face of metabolic stress in ALS. © 2016 EAN.

Prognostic Role of Exhaled Breath Condensate pH and Fraction Exhaled Nitric Oxide in Systemic Sclerosis Related Interstitial Lung Disease.

PubMed

Guillen-Del Castillo, Alfredo; Sánchez-Vidaurre, Sara; Simeón-Aznar, Carmen P; Cruz, María J; Fonollosa-Pla, Vicente; Muñoz, Xavier

2017-03-01

Interstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. No differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (Log Rank P=.03 and P<.01, respectively). EB and EBC could help to detect patients likely to present a deterioration on lung function during follow up. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

[Usefulness of electronic drug registers: Spanish register of patients treated with fingolimod (Gilenya ®)].

PubMed

Fernández, Óscar; Rodríguez-Antigüedad, Alfredo; Oreja-Guevara, Celia; Garcia-Garcia, Margarida; Montalban, Xavier

2014-01-16

This study outlines the design of an electronic register of patients with multiple sclerosis who began treatment with fingolimod in Spain. The system is intended to serve as a tool to monitor its utilisation in daily clinical practice and thus allow optimisation of the way it is used. To establish the profile of patients with multiple sclerosis undergoing treatment with fingolimod and to determine the effectiveness and safety of this treatment in daily clinical practice. An observation-based, retrospective and prospective, multi-centre registry is set up, which will be active for five years. Forty neurologists working in Spain will participate in the project. Patients treated with fingolimod who fulfil the selection criteria will be included in the study. The effectiveness variables that will be evaluated are: disability measured by means of the Expanded Disability Status Scale, the rate of attacks, T1 gadolinium-enhancing lesions and new lesions in T2, and the percentage of patients who were free of activity and those who require concomitant treatments. The tolerability variables that will be evaluated are: the rate of patients who present events and adverse reactions, respectively, with a separate analysis of those presenting after the first dose or that are related to the fingolimod risk management plan and the treatment dropout rate. New pharmaceuticals that have only recently been commercialised require more information about their effectiveness and safety, beyond the controlled environment of a clinical trial. Initiatives involving electronic registries such as the Gilenya register are a solution that can respond to such needs by providing information in the shortest possible time about the most suitable management in order to be able to make the best and most efficient use of it.

Controlling the digital ulcerative disease in systemic sclerosis is associated with improved hand function.

PubMed

Mouthon, Luc; Carpentier, Patrick H; Lok, Catherine; Clerson, Pierre; Gressin, Virginie; Hachulla, Eric; Bérezné, Alice; Diot, Elisabeth; Van Kien, Aurélie Khau; Jego, Patrick; Agard, Christian; Duval-Modeste, Anne-Bénédicte; Sparsa, Agnès; Puzenat, Eve; Richard, Marie-Aleth

2017-06-01

Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan. ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up. Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 (p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 (p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 (p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 (p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI (p = 0.04), CHFS (p = 0.04), and pain score (p = 0.046). In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability. Copyright © 2017 Elsevier Inc. All rights reserved.

Effectiveness and Tolerability of THC/CBD Oromucosal Spray for Multiple Sclerosis Spasticity in Italy: First Data from a Large Observational Study.

PubMed

Trojano, Maria; Vila, Carlos

2015-01-01

The prospective, non-interventional Mobility Improvement (MOVE) 2 study was designed to provide real life data on clinical outcomes of patients with treatment-resistant multiple sclerosis (MS) spasticity receiving routine treatment with tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®), subsequent to its approval in European countries. This interim analysis reports on MOVE 2 patients from Italy. Interim data from 322 patients (58.3% female; mean age 51.1 ± 10.2 years) were analyzed. From baseline to month 3 of treatment (Visit 3), the mean 0-10 Numerical Rating Scale (NRS) score decreased by -19.1% (-1.6 points, p < 0.0001) and the mean modified Ashworth score decreased from 2.6 to 2.3 points (p < 0.0001). At Visit 3, 24.6% of 203 patients with available data were clinically relevant responders (≥30% improvement from baseline NRS score; p < 0.001 vs. baseline). The mean reported dose of THC:CBD oromucosal spray was 6.1 ± 2.5 sprays/day at Visit 1 (1 month) and 5.1 ± 2.6 sprays/day at Visit 3 (range 1-12 sprays/day at both timepoints). Forty-one (13.1%) patients reported at least one adverse event (AE), which included 3 serious AEs (1 unrelated). AEs with an incidence ≥1% were dizziness (5.6%), confusion (2.5%), nausea (1.25%) and somnolence (1.25%). In everyday clinical practice in Italy, THC:CBD oromucosal spray provided symptomatic relief of MS spasticity with good tolerability in a relevant number of previously resistant patients. © 2015 S. Karger AG, Basel.

Home tracheotomy mechanical ventilation in patients with amyotrophic lateral sclerosis: causes, complications and 1-year survival.

PubMed

Sancho, Jesús; Servera, Emilio; Díaz, José Luis; Bañuls, Pilar; Marín, Julio

2011-11-01

Home tracheotomy mechanical ventilation (HTMV) can prolong survival in patients with amyotrophic lateral sclerosis (ALS) when non-invasive ventilation (NIV) fails, but knowledge about HTMV is scarce. The aim of this study was to determine the causes of tracheotomy and the main issues of 1-year HTMV in a cohort of patients with ALS. A prospective study of all patients needing HTMV was performed in a referral respiratory care unit (RCU) from April 2001 to January 2010. Patients' informed decisions about HTMV were fully respected. Caregivers were trained and could telephone the RCU. Hospital staff made home visits. All patients (n=116) agreed to participate and a tracheotomy was needed for 76, mainly due to bulbar dysfunction. Of the 38 who had a tracheotomy, in 21 it was performed in an acute setting and in 17 as a non-emergency procedure. In 19 patients the tracheotomy was related to the inadequacy of mechanically assisted coughing (MAC) to maintain normal oxygen saturation. During HTMV, 19 patients required hospitalisation, 12 with respiratory problems. The 1-year survival rate was 78.9%, with a mean survival of 10.39 months (95% CI 9.36 to 11.43). Sudden death was the main cause of death (n=9) and only one patient died from respiratory causes. No predictive factors for survival were found. Besides NIV inadequacy, the ineffectiveness of mechanically assisted coughing appears to be a relevant cause of tracheotomy for patients with ALS with severe bulbar dysfunction. Patients choosing HTMV provided by a referral RCU could have a good 1-year survival rate, respiratory problems being the main cause of hospitalisation but not of death.

Temporal trend of amyotrophic lateral sclerosis incidence in southern Europe: a population study in the health district of Ferrara, Italy.

PubMed

Govoni, Vittorio; Cesnik, Edward; Casetta, Ilaria; Tugnoli, Valeria; Tola, Maria Rosaria; Granieri, Enrico

2012-08-01

Data about the temporal trend of amyotrophic lateral sclerosis (ALS) incidence in southern Europe are scarce. Incidence studies on ALS have been carried out in the health district of Ferrara, Italy, since 1960s. We expanded the previous studies from 1964 to 2009. The study was prospective with a subsequent retrospective intensive survey of multiple sources of case ascertainment. All patients with a definite and probable ALS according to the original El Escorial criteria were selected. There were 130 incident cases in the years 1964-2009 giving an average annual crude incidence of 1.82 per 100,000 population (95% CI 1.53-2.17). An incidence increase during the study period was estimated in women (χ(2) test for trend = 7.19, p < 0.01) and in the elderly (χ(2) test for trend = 7.803, p < 0.01). The age-adjusted incidence was stable over time in both women (1.19 per 100,000, 95% CI 0.90-1.52) and men (1.45 per 100,000, 95% CI 0.12-1.84). The annual number of new ALS cases in the study population followed the Poisson distribution in both sexes as well as in the elderly group of the population. The present findings suggest that ALS incidence is nearly stable over time. The crude incidence increase we estimated over time among women is mainly explained by population ageing. The increasing incidence in the elderly population was likely the consequence of an increasing precision in ALS diagnosis in the elderly since the increasing attention and care over time of neurologic elderly patients that likely concern elderly women more than previous time periods rather than better case ascertainment of diagnosed patients. The present findings do not support the role of specific environmental factors in ALS pathogenesis.

Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis.

PubMed

Maurer, Britta; Busch, Nicole; Jüngel, Astrid; Pileckyte, Margarita; Gay, Renate E; Michel, Beat A; Schett, Georg; Gay, Steffen; Distler, Jörg; Distler, Oliver

2009-12-08

Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected. Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.

Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy

PubMed Central

Ruiz-Peña, Juan Luis; Piñero, Pilar; Sellers, Guillermo; Argente, Joaquín; Casado, Alfredo; Foronda, Jesus; Uclés, Antonio; Izquierdo, Guillermo

2004-01-01

Background What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability measured by Multiple Sclerosis Functional Composite scale, Neurological Rating Scale, Ambulation Index scale, and Expanded Disability Scale Score. Methods Thirty one patients (9 male and 22 female) with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0–5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. Results A statistically significant correlation was found (r = -0.38 p < 0.05) between disability (measured by Expanded Disability Scale Score) and N-Acetyl Aspartate (NAA/Cr ratio) levels in normal appearing white matter in these patients. No correlation was found between the NAA/Cr ratio and disability measured by any of the other disability assessment scales. Conclusions There is correlation between disability (measured by Expanded Disability Scale Score) and the NAA/Cr ratio in normal appearing white matter. The lack of correlation between the NAA/Cr ratio and the Multiple Sclerosis Functional Composite score indicates that the Multiple Sclerosis Functional Composite is not able to measure irreversible disability and would be more useful as a marker in stages where axonal damage is not a predominant factor. PMID:15191618

Clinicopathological study of 81 cases of localized and systemic scleroderma.

PubMed

Succaria, F; Kurban, M; Kibbi, A-G; Abbas, O

2013-02-01

Scleroderma is a connective tissue disease that includes localized and systemic forms. Our recent encounter with a morphea case exhibiting prominent perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with morphea/scleroderma at our institution. To describe the clinicopathological features of all patients diagnosed with morphea/scleroderma at American University of Beirut Medical Center (AUB-MC) between 1999 and 2010, and compare our findings with those published in the literature. A total of 81 cases (63 women and 18 men) were identified, of which 73 were localized (morphea) and eight were systemic scleroderma. Clinically, plaque type morphea was the most common variant both in adults and children, and seven (9%) cases of morphea were associated with lichen sclerosis et atrophicus (LSA). Histopathologically, perineural inflammation was observed in 49% of cases, and may serve, in addition to other features including lichen sclerosis-like changes (observed in exclusively nine cases of morphea), more diffuse dermal and less subcutaneous sclerosis, and intense inflammation, as clues favouring diagnosis of morphea over systemic sclerosis. The features of morphea/scleroderma patients in this study are generally comparable to those published in the literature, with few differences. Clinically, plaque type morphea was the most common variant both in adults and children and LSA was a frequent association. Histopathologically, perineural inflammation was commonly observed and may serve in addition to lichen sclerosis-like changes and intense inflammation as clues favouring diagnosis of morphea over systemic sclerosis. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Ethical Considerations of Patient-Funded Research for Multiple Sclerosis Therapeutics.

PubMed

Amezcua, Lilyana; Nelson, Flavia

2017-10-01

Patient-funded research has started to emerge in multiple sclerosis studies, such as low-dose naltrexone and stem-cell therapy. While these represent greater opportunities for the physician, scientist, and patient, ethical concerns concerning protocol review, conflict of interests, and protection of subjects are reviewed.

Therapy satisfaction and adherence in patients with relapsing–remitting multiple sclerosis: the THEPA-MS survey

PubMed Central

Haase, Rocco; Kullmann, Jennifer S.; Ziemssen, Tjalf

2016-01-01

Background: Improved clinical effectiveness and therefore positive modification of multiple sclerosis (MS) with basic therapy can be achieved by long-term regular intake of drugs as prescribed but investigations have shown that a high percentage of patients do not take their medications as prescribed. Objectives: We assessed the satisfaction and adherence of patients with MS with their current disease-modifying treatment under clinical practice conditions. We compared different facets of satisfaction as well as their internal relationship and identified predictors in an exploratory manner. Methods: Therapy satisfaction in patients with relapsing–remitting multiple sclerosis (THEPA-MS) was a noninterventional, prospective cross-sectional study performed throughout Germany in 2013 and 2014, and included patients with clinically isolated syndrome or relapsing–remitting MS. We applied a standardized approach to document satisfaction and adherence by patient-reported outcomes (Treatment Satisfaction Questionnaire for Medication) as well as by physician ratings. Results: Of 3312 patients with a mean age of 43.7 years, 73.3% were women and the mean level of disability according to the Expanded Disability Status Scale was 2.29; 13.3% did not receive any medication at the time of documentation, 21.3% received interferon β1a intramuscularly, 20.7% had interferon β1a subcutaneously, 17.0% had interferon β1b subcutaneously and 23.7% had glatiramer acetate. Adherence rates varied between 60% (lifetime) and 96.5% (current medication). Differences between current medications were found for side effects and convenience scores but not for effectiveness, satisfaction and adherence. Higher global satisfaction and effectiveness were associated with fewer relapses, longer duration of medication, lower disability score and the absence of several side effects. Conclusion: In a connected model of patient satisfaction, effectiveness, side effects, convenience and adherence, patients’ individual needs and concerns have to be addressed. Most differences were found with respect to side effects and convenience of treatment. Therefore, an improvement in these two domains seems to be the most promising proximate approach to elevate adherence levels. PMID:27366231

Speech and Pause Characteristics in Multiple Sclerosis: A Preliminary Study of Speakers with High and Low Neuropsychological Test Performance

ERIC Educational Resources Information Center

Feenaughty, Lynda; Tjaden, Kris; Benedict, Ralph H. B.; Weinstock-Guttman, Bianca

2013-01-01

This preliminary study investigated how cognitive-linguistic status in multiple sclerosis (MS) is reflected in two speech tasks (i.e. oral reading, narrative) that differ in cognitive-linguistic demand. Twenty individuals with MS were selected to comprise High and Low performance groups based on clinical tests of executive function and information…

Gender Effect According to Item Directionality on the Perceived Stress Scale for Adults with Multiple Sclerosis

ERIC Educational Resources Information Center

Gitchel, W. Dent; Roessler, Richard T.; Turner, Ronna C.

2011-01-01

Assessment is critical to rehabilitation practice and research, and self-reports are a commonly used form of assessment. This study examines a gender effect according to item wording on the "Perceived Stress Scale" for adults with multiple sclerosis. Past studies have demonstrated two-factor solutions on this scale and other scales measuring…

Speech and Pause Characteristics Associated with Voluntary Rate Reduction in Parkinson's Disease and Multiple Sclerosis

ERIC Educational Resources Information Center

Tjaden, Kris; Wilding, Greg

2011-01-01

The primary purpose of this study was to investigate how speakers with Parkinson's disease (PD) and Multiple Sclerosis (MS) accomplish voluntary reductions in speech rate. A group of talkers with no history of neurological disease was included for comparison. This study was motivated by the idea that knowledge of how speakers with dysarthria…

Dietary intake and nutritional status in patients with systemic sclerosis.

PubMed Central

Lundberg, A C; Akesson, A; Akesson, B

1992-01-01

Oesophageal dysmotility and abnormalities of intestinal function are important manifestations in systemic sclerosis and may have a significant effect on nutrient absorption and nutritional status. In this study 30 patients with systemic sclerosis with symptoms from the gastrointestinal tract were compared with matched healthy control subjects with respect to nutrient intake (four day record), anthropometric measurements, and biochemical nutritional status. The intake of energy (8.1 and 8.4 MJ/day) and its distribution among nutrients did not differ between patients and control subjects, but the lower intake of dietary fibre among patients with systemic sclerosis suggests that they avoided food with a coarse structure, such as coarse bread. The intake of vegetables and fruit also tended to be lower among patients with systemic sclerosis. Half of the patients had a subnormal arm muscle circumference, and two patients also had a subnormal triceps skinfold thickness, indicating severe malnutrition. The concentration of ascorbic acid, alpha-tocopherol, carotene, selenium, and also the proportion of linoleic acid (18:2) in serum phosphatidylcholine was lower in patients than in control subjects. PMID:1332633

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis.

PubMed

Motta, Caterina; Palermo, Eduardo; Studer, Valeria; Germanotta, Marco; Germani, Giorgio; Centonze, Diego; Cappa, Paolo; Rossi, Silvia; Rossi, Stefano

2016-01-01

The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis.

Measuring outcomes for neurological disorders: a review of disease-specific health status instruments for three degenerative neurological conditions.

PubMed

Heffernan, Catherine; Jenkinson, Crispin

2005-06-01

Health-related quality-of-life measures have been increasingly used in research into neurological disorders in recent years. The aim of this paper is to provide an objective appraisal of the evidence in regard to disease-specific quality-of-life measures used in research on health interventions for three degenerative neurological disorders: multiple sclerosis, motor neurone disease/amyotrophic lateral sclerosis and Parkinson's disease. A comprehensive search strategy was developed to include nine relevant electronic databases. Only studies pertaining to patient-based outcome measurements in multiple sclerosis, motor neurone disease and Parkinson's disease were included. We identified 76 eligible studies. As studies consisted of descriptive and cross-sectional survey study designs, results were reported qualitatively rather than in the form of a meta-analysis. Four disease-specific measures were found for Parkinson's disease, 11 for multiple sclerosis and one for motor neurone disease. We conclude that health-related quality-of-life measures are useful in assessing the impact of treatments and interventions for neurological disorders. However, further research is needed on the development of instruments using psychometric methods and on the validation, utilization and responsiveness of instruments to change.

Management of optic neuritis

PubMed Central

Menon, Vimla; Saxena, Rohit; Misra, Ruby; Phuljhele, Swati

2011-01-01

Optic neuritis is an inflammatory condition of the optic nerve characterized by a sudden onset of unilateral visual loss, usually affecting young females. Demyelination associated with multiple sclerosis (MS) is the most common cause in regions where MS is prevalent; while in other places, there are a substantial proportion of cases where infective or autoimmune causes are seen. Optic Neuritis Treatment Trial (ONTT) was the first major study that provided information on the natural history, role of steroids in treatment and risk of development of MS. Subsequently, numerous clinical trials have evaluated different modalities of management of optic neuritis and MS. The Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS); the Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis (PRISMS) Trial; and, most recently, the Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) Study have provided large amount of information on the natural history of optic neuritis and management options available. However, due to the low prevalence of MS reported in Asian studies, high cost of therapy and indefinite time period of treatment, it may not be cost effective to start interferon therapy in most cases. PMID:21350281

Infectious mononucleosis and multiple sclerosis - Updated review on associated risk.

PubMed

Sheik-Ali, Sharaf

2017-05-01

There has been substantial evidence accumulating on the role of infectious mononucleosis (IM) and the subsequent risk of obtaining Multiple Sclerosis (MS). Up to date studies not previously explored were reviewed by the author to further clarify the association. Medline and Web of Science were searched with no time constraints for articles exploring an association between Multiple Sclerosis and Infectious Mononucleosis. 24 articles were found, totalling 1063 cases and 13,227 cohort/controls. 23/24 (96%) articles reported a significant association of Infectious Mononucleosis on the risk of subsequent multiple sclerosis. Overall, new literature on IM and risk of MS categorically supports the association. Future work should focus on other risk factors such as age and gender on IM and subsequent risk of MS. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Learned helplessness in the multiple sclerosis population.

PubMed

McGuinness, S

1996-06-01

The purpose of this cross-sectional, descriptive study was to describe the relationships between learned helplessness and disease status, functional and social disability, and disease activity in the multiple sclerosis population. Additionally, the relationships between learned helplessness and age, disease duration, education and marital and employment status were evaluated. Self-report instruments with established validity and reliability in the multiple sclerosis population were used to collect the data. Learned helplessness was significantly positively correlated with social and functional disability. Although not significant at the .05 level, disease status and disease activity were also positively correlated with learned helplessness. Additionally, unemployed individuals were more likely to be helpless than employed individuals. Overall, the results suggest that learned helplessness is related to negative health indicators in the multiple sclerosis population. Nursing interventions to decrease or prevent learned helplessness may be appropriate in this population.

Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

PubMed

Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

2017-03-01

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A qualitative investigation of lay perspectives of diagnosis and self-management strategies employed by people with progressive multiple sclerosis.

PubMed

Frost, Julia; Grose, Jane; Britten, Nicky

2017-05-01

This article explores how people with progressive multiple sclerosis give meaning to their experiences. It builds upon the self-management literature, which has captured the tension between the desire for retaining normalcy and the increasing burden of self-management associated with chronic disease progression. This repeat interview study is empirically grounded in 28 interviews with 14 people with progressive multiple sclerosis. We identified gender differences in diagnosis-seeking which impacted subsequent sense-making. Male respondents found a diagnosis of multiple sclerosis difficult to come to terms with, and an enduring sense of loss or anger could inhibit further sense-making. A diagnosis of multiple sclerosis was more difficult to obtain for women respondents, and any sense of certainty that diagnosis provided framed their subsequent sense-making strategies. The complex sequelae of multiple sclerosis require that self-management strategies are both contextual and timely, although even the most accomplished self-managers can lose their sense of self with neurodegeneration. Disease progression can be associated with suicidal ideation, suggesting the need for greater dialogue to ensure that people with multiple sclerosis are adequately supported to fulfil their quality of life at all stages of neurodegeneration. These lay perspectives emphasise the articulation of affect rather than the rendering of a medical diagnosis, although diagnosis may provide a degree of certainty in the short term. The ethos of self-management ensures people attempt to retain their sense of 'normality' and existent social roles for as long as possible, but this ethos can negate both one's ability to self-manage and the management of self.

PSYCHOLOGICAL INTERVENTION IN TUBEROUS SCLEROSIS: A CASE REPORT

PubMed Central

Sharma, Puja; Rao, Kiran

2002-01-01

Tuberous sclerosis (TS) is characterized by the clinical triad of epilepsy, mental subnormality and adenoma sebaceum. TS is a multi-system disorder resulting in severe distress for the individuals and their family members. The present study illustrates an eclectic psychosocial management of a patient with TS and normal intelligence. PMID:21206610

A Study of the Nature of Information Needed by Women with Multiple Sclerosis.

ERIC Educational Resources Information Center

Baker, Lynda M.

1996-01-01

Women with MS (Multiple Sclerosis), classified by the Miller Behavioral Style Scale as actively seeking information (monitors) or rejecting information (blunters), assessed pamphlets pertaining to the disease. More monitors than blunters rated the pamphlet relevant, regardless of the nature of the information. (PEN)

Cognitive-Behavioral Classifications of Chronic Pain in Patients with Multiple Sclerosis

ERIC Educational Resources Information Center

Khan, Fary; Pallant, Julie F.; Amatya, Bhasker; Young, Kevin; Gibson, Steven

2011-01-01

The aim of this study was to replicate, in patients with multiple sclerosis (MS), the three-cluster cognitive-behavioral classification proposed by Turk and Rudy. Sixty-two patients attending a tertiary MS rehabilitation center completed the Pain Impact Rating questionnaire measuring activity interference, pain intensity, social support, and…

Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

ERIC Educational Resources Information Center

Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

2011-01-01

Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

Speech Intelligibility and Marital Communication in Amyotrophic Lateral Sclerosis: An Exploratory Study

ERIC Educational Resources Information Center

Joubert, Karin; Bornman, Juan; Alant, Erna

2011-01-01

Amyotrophic lateral sclerosis (ALS), a rapidly progressive neuromuscular disease, has a devastating impact not only on individuals diagnosed with ALS but also their spouses. Speech intelligibility, often compromised as a result of dysarthria, affects the couple's ability to maintain effective, intimate communication. The purpose of this…

A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy

PubMed Central

Sidhu, Meneka K.; Stretton, Jason; Winston, Gavin P.; Bonelli, Silvia; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Koepp, Matthias J.

2013-01-01

Functional magnetic resonance imaging has demonstrated reorganization of memory encoding networks within the temporal lobe in temporal lobe epilepsy, but little is known of the extra-temporal networks in these patients. We investigated the temporal and extra-temporal reorganization of memory encoding networks in refractory temporal lobe epilepsy and the neural correlates of successful subsequent memory formation. We studied 44 patients with unilateral temporal lobe epilepsy and hippocampal sclerosis (24 left) and 26 healthy control subjects. All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words with subsequent out-of-scanner recognition assessments. A blocked analysis was used to investigate activations during encoding and neural correlates of subsequent memory were investigated using an event-related analysis. Event-related activations were then correlated with out-of-scanner verbal and visual memory scores. During word encoding, control subjects activated the left prefrontal cortex and left hippocampus whereas patients with left hippocampal sclerosis showed significant additional right temporal and extra-temporal activations. Control subjects displayed subsequent verbal memory effects within left parahippocampal gyrus, left orbitofrontal cortex and fusiform gyrus whereas patients with left hippocampal sclerosis activated only right posterior hippocampus, parahippocampus and fusiform gyrus. Correlational analysis showed that patients with left hippocampal sclerosis with better verbal memory additionally activated left orbitofrontal cortex, anterior cingulate cortex and left posterior hippocampus. During face encoding, control subjects showed right lateralized prefrontal cortex and bilateral hippocampal activations. Patients with right hippocampal sclerosis showed increased temporal activations within the superior temporal gyri bilaterally and no increased extra-temporal areas of activation compared with control subjects. Control subjects showed subsequent visual memory effects within right amygdala, hippocampus, fusiform gyrus and orbitofrontal cortex. Patients with right hippocampal sclerosis showed subsequent visual memory effects within right posterior hippocampus, parahippocampal and fusiform gyri, and predominantly left hemisphere extra-temporal activations within the insula and orbitofrontal cortex. Correlational analysis showed that patients with right hippocampal sclerosis with better visual memory activated the amygdala bilaterally, right anterior parahippocampal gyrus and left insula. Right sided extra-temporal areas of reorganization observed in patients with left hippocampal sclerosis during word encoding and bilateral lateral temporal reorganization in patients with right hippocampal sclerosis during face encoding were not associated with subsequent memory formation. Reorganization within the medial temporal lobe, however, is an efficient process. The orbitofrontal cortex is critical to subsequent memory formation in control subjects and patients. Activations within anterior cingulum and insula correlated with better verbal and visual subsequent memory in patients with left and right hippocampal sclerosis, respectively, representing effective extra-temporal recruitment. PMID:23674488

Robot-assisted gait training in multiple sclerosis patients: a randomized trial.

PubMed

Schwartz, Isabella; Sajin, Anna; Moreh, Elior; Fisher, Iris; Neeb, Martin; Forest, Adina; Vaknin-Dembinsky, Adi; Karusis, Dimitrios; Meiner, Zeev

2012-06-01

Preservation of locomotor activity in multiple sclerosis (MS) patients is of utmost importance. Robotic-assisted body weight-supported treadmill training is a promising method to improve gait functions in neurologically impaired patients, although its effectiveness in MS patients is still unknown. To compare the effectiveness of robot-assisted gait training (RAGT) with that of conventional walking treatment (CWT) on gait and generalized functions in a group of stable MS patients. A prospective randomized controlled trial of 12 sessions of RAGT or CWT in MS patients of EDSS score 5-7. Primary outcome measures were gait parameters and the secondary outcomes were functional and quality of life parameters. All tests were performed at baseline, 3 and 6 months post-treatment by a blinded rater. Fifteen and 17 patients were randomly allocated to RAGT and CWT, respectively. Both groups were comparable at baseline in all parameters. As compared with baseline, although some gait parameters improved significantly following the treatment at each time point there was no difference between the groups. Both FIM and EDSS scores improved significantly post-treatment with no difference between the groups. At 6 months, most gait and functional parameters had returned to baseline. Robot-assisted gait training is feasible and safe and may be an effective additional therapeutic option in MS patients with severe walking disabilities.

Label-free multiphoton microscopy reveals altered tissue architecture in hippocampal sclerosis.

PubMed

Uckermann, Ortrud; Galli, Roberta; Leupold, Susann; Coras, Roland; Meinhardt, Matthias; Hallmeyer-Elgner, Susanne; Mayer, Thomas; Storch, Alexander; Schackert, Gabriele; Koch, Edmund; Blümcke, Ingmar; Steiner, Gerald; Kirsch, Matthias

2017-01-01

The properties and structure of tissue can be visualized without labeling or preparation by multiphoton microscopy combining coherent anti-Stokes Raman scattering (CARS), addressing lipid content, second harmonic generation (SHG) showing collagen, and two-photon excited fluorescence (TPEF) of endogenous fluorophores. We compared samples of sclerotic and nonsclerotic human hippocampus to detect pathologic changes in the brain of patients with pharmacoresistant temporomesial epilepsy (n = 15). Multiphoton microscopy of cryosections and bulk tissue revealed hippocampal layering and micromorphologic details in accordance with reference histology: CARS displayed white and gray matter layering and allowed the assessment of axonal myelin. SHG visualized blood vessels based on adventitial collagen. In addition, corpora amylacea (CoA) were found to be SHG-active. Pyramidal cell bodies were characterized by intense cytoplasmic endogenous TPEF. Furthermore, diffuse TPEF around blood vessels was observed that co-localized with positive albumin immunohistochemistry and might indicate degeneration-associated vascular leakage. We present a label-free and fast optical approach that analyzes pathologic aspects of HS. Hippocampal layering, loss of pyramidal cells, and presence of CoA indicative of sclerosis are visualized. Label-free multiphoton microscopy has the potential to extend the histopathologic armamentarium for ex vivo assessment of changes of the hippocampal formation on fresh tissue and prospectively in vivo. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

High EDSS can predict risk for upper urinary tract damage in patients with multiple sclerosis.

PubMed

Ineichen, Benjamin V; Schneider, Marc P; Hlavica, Martin; Hagenbuch, Niels; Linnebank, Michael; Kessler, Thomas M

2018-04-01

Neurogenic lower urinary tract dysfunction (NLUTD) is very common in patients with multiple sclerosis (MS), and it might jeopardize renal function and thereby increase mortality. Although there are well-known urodynamic risk factors for upper urinary tract damage, no clinical prediction parameters are available. We aimed to assess clinical parameters potentially predicting urodynamic risk factors for upper urinary tract damage. A consecutive series of 141 patients with MS referred from neurologists for primary neuro-urological work-up including urodynamics were prospectively evaluated. Clinical parameters taken into account were age, sex, duration, and clinical course of MS and Expanded Disability Status Scale (EDSS). Multivariate modeling revealed EDSS as a clinical parameter significantly associated with urodynamic risk factors for upper urinary tract damage (odds ratio = 1.34, 95% confidence interval (CI) = 1.06-1.71, p = 0.02). Using receiver operator characteristic (ROC) curves, an EDSS of 5.0 as cutoff showed a sensitivity of 86%-87% and a specificity of 52% for at least one urodynamic risk factor for upper urinary tract damage. High EDSS is significantly associated with urodynamic risk factors for upper urinary tract damage and allows a risk-dependent stratification in daily neurological clinical practice to identify MS patients requiring further neuro-urological assessment and treatment.

Monocyte NOTCH2 expression predicts IFN-β immunogenicity in multiple sclerosis patients.

PubMed

Adriani, Marsilio; Nytrova, Petra; Mbogning, Cyprien; Hässler, Signe; Medek, Karel; Jensen, Poul Erik H; Creeke, Paul; Warnke, Clemens; Ingenhoven, Kathleen; Hemmer, Bernhard; Sievers, Claudia; Lindberg Gasser, Raija Lp; Fissolo, Nicolas; Deisenhammer, Florian; Bocskei, Zsolt; Mikol, Vincent; Fogdell-Hahn, Anna; Kubala Havrdova, Eva; Broët, Philippe; Dönnes, Pierre; Mauri, Claudia; Jury, Elizabeth C

2018-06-07

Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β is an established treatment for MS; however, up to 30% of IFN-β-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immunogenicity remain uncertain, and reliable biomarkers to predict immunogenicity development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14+ monocytes and increased frequency of proinflammatory monocyte subsets were identified as baseline predictors of nADA development in MS patients treated with IFN-β. The association of this monocyte profile with nADA development was validated in 2 independent cross-sectional MS patient cohorts and a prospective cohort followed before and after IFN-β administration. Reduced monocyte NOTCH2 expression in nADA+ MS patients was associated with NOTCH2 activation measured by increased expression of Notch-responsive genes, polarization of monocytes toward a nonclassical phenotype, and increased proinflammatory IL-6 production. NOTCH2 activation was T cell dependent and was only triggered in the presence of serum from nADA+ patients. Thus, nADA development was driven by a proinflammatory environment that triggered activation of the NOTCH2 signaling pathway prior to first IFN-β administration.

Do Flexible Goal Adjustment and Acceptance Help Preserve Quality of Life in Patients with Multiple Sclerosis?

PubMed

Van Damme, Stefaan; De Waegeneer, Annelies; Debruyne, Jan

2016-06-01

Goal regulation strategies such as flexible goal adjustment and acceptance are believed to be protective factors in persons with chronic illness, but research on their relative contributions to quality of life in multiple sclerosis (MS) is lacking. We aimed to test the idea that acceptance and flexible goal adjustment (in contrast to tenacious goal pursuit) may help preserve the quality of life in persons with MS. A sample of 117 patients with MS was recruited. They completed questionnaires measuring quality of life (physical functioning, psychological distress), acceptance, flexible goal adjustment, and tenacious goal pursuit. Acceptance significantly accounted for variance in all three indexes of quality of life, beyond the effects of demographic and illness characteristics. The role of goal regulation style was less clear. Flexible goal adjustment significantly accounted for psychological well-being only. Surprisingly, tenacious goal pursuit predicted better psychological functioning and less psychological distress. No support was found for the hypothesis that acceptance and flexible goal adjustment would moderate the relation between illness severity and quality of life. The findings suggest the potential importance of acceptance in understanding MS patients' quality of life, although its hypothesized protective function could not be confirmed. Further conceptual work on acceptance and goal regulation style is needed, as well as prospective work investigating their causal status.

A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement

PubMed Central

Macchi, Zachary; Wang, Yunxia; Moore, Dan; Katz, Jonathan; Saperstein, David; Walk, David; Simpson, Ericka; Genge, Angela; Bertorini, Tulio; Fernandes, J Americo; Swenson, Andrea; Elman, Lauren; Dimachkie, Mazen; Herbelin, Laura; Miller, Joann; Lu, Jianghua; Wilkins, Heather; Swerdlow, Russell H; Statland, Jeffrey; Barohn, Richard

2015-01-01

OBJECTIVE Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitochondrial biomarkers. METHODS We performed a prospective open-label, multicenter screening trial of 36 ALS patients treated with 2mg oral rasagiline daily for 12 months. Outcomes included the slope of deterioration of the revised ALS Functional Rating Scale (ALSFRS-R), adverse event monitoring, time to treatment failure, and exploratory biomarkers. RESULTS Participants experienced no serious drug-related adverse events, and the most common adverse event was nausea (11.1%). Rasagiline did not improve the rate of decline in the ALSFRS-R; however, differences in symptom duration compared to historical placebo controls differentially affected ALSFRS-R slope estimates. Rasagiline changed biomarkers over 12 months, such that the mitochondrial membrane potential increased (JC-1 red/green fluorescent ratio 1.92, P=0.0001) and apoptosis markers decreased (Bcl-2/Bax ratio 0.24, P<0.0001). CONCLUSION Engagement of exploratory biomarkers and questions about comparability of baseline characteristics lead us to recommend a further placebo-controlled trial. PMID:25832828

7 Tesla Magnetic Resonance Imaging to Detect Cortical Pathology in Multiple Sclerosis

PubMed Central

van Gelderen, Peter; Merkle, Hellmuth; Chen, Christina; Lassmann, Hans; Duyn, Jeff H.; Bagnato, Francesca

2014-01-01

Background Neocortical lesions (NLs) are an important pathological component of multiple sclerosis (MS), but their visualization by magnetic resonance imaging (MRI) remains challenging. Objectives We aimed at assessing the sensitivity of multi echo gradient echo (ME-GRE) T2 *-weighted MRI at 7.0 Tesla in depicting NLs compared to myelin and iron staining. Methods Samples from two MS patients were imaged post mortem using a whole body 7T MRI scanner with a 24-channel receive-only array. Isotropic 200 micron resolution images with varying T2 * weighting were reconstructed from the ME-GRE data and converted into R2 * maps. Immunohistochemical staining for myelin (proteolipid protein, PLP) and diaminobenzidine-enhanced Turnbull blue staining for iron were performed. Results Prospective and retrospective sensitivities of MRI for the detection of NLs were 48% and 67% respectively. We observed MRI maps detecting only a small portion of 20 subpial NLs extending over large cortical areas on PLP stainings. No MRI signal changes suggestive of iron accumulation in NLs were observed. Conversely, R2 * maps indicated iron loss in NLs, which was confirmed by histological quantification. Conclusions High-resolution post mortem imaging using R2 * and magnitude maps permits detection of focal NLs. However, disclosing extensive subpial demyelination with MRI remains challenging. PMID:25303286

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

PubMed Central

Weygandt, Martin; Meyer-Arndt, Lil; Behrens, Janina Ruth; Wakonig, Katharina; Bellmann-Strobl, Judith; Ritter, Kerstin; Scheel, Michael; Brandt, Alexander U.; Labadie, Christian; Hetzer, Stefan; Gold, Stefan M.; Paul, Friedemann; Haynes, John-Dylan

2016-01-01

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone. PMID:27821732

Epstein-Barr virus in oral shedding of children with multiple sclerosis

PubMed Central

Yea, Carmen; Tellier, Raymond; Chong, Patrick; Westmacott, Garrett; Marrie, Ruth Ann; Bar-Or, Amit

2013-01-01

Objective: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with multiple sclerosis (MS). Methods: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry. Results: Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive patients with MS compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus–1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in patients with MS; however, no specific EBV genetic variant was preferentially associated with MS. Conclusion: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV. PMID:24014504

Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis

PubMed Central

Darlington, Peter J; Boivin, Marie-Noëlle; Bar-Or, Amit

2011-01-01

Phase I clinical trials exploring the use of autologous mesenchymal stem cell (MSC) therapy for the treatment of multiple sclerosis (MS) have begun in a number of centers across the world. MS is a complex and chronic immune-mediated and neurodegenerative disease influenced by genetic susceptibility and environmental risk factors. The ideal treatment for MS would involve both attenuation of detrimental inflammatory responses, and induction of a degree of tissue protection/regeneration within the CNS. Preclinical studies have demonstrated that both human-derived and murine-derived MSCs are able to improve outcomes in the animal model of MS, experimental autoimmune encephalomyelitis. How MSCs ameliorate experimental autoimmune encephalomyelitis is being intensely investigated. One of the major mechanisms of action of MSC therapy is to inhibit various components of the immune system that contribute to tissue destruction. Emerging evidence now supports the idea that MSCs can access the CNS where they can provide protection against tissue damage, and may facilitate tissue regeneration through the production of growth factors. The prospect of cell-based therapy using MSCs has several advantages, including the relative ease with which they can be extracted from autologous bone marrow or adipose tissue and expanded in vitro to reach the purity and numbers required for transplantation, and the fact that MSC therapy has already been used in other human disease settings, such as graft-versus-host and cardiac disease, with initial reports indicating a good safety profile. This article will focus on the theoretical and practical issues relevant to considerations of MSC therapy in the context of MS. PMID:21864075

Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

PubMed

Giovannoni, Gavin

2018-06-01

The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

Evaluation of genetic association between an ITGAM non-synonymous SNP (rs1143679) and multiple autoimmune diseases.

PubMed

Anaya, Juan-Manuel; Kim-Howard, Xana; Prahalad, Sampath; Cherñavsky, Alejandra; Cañas, Carlos; Rojas-Villarraga, Adriana; Bohnsack, John; Jonsson, Roland; Bolstad, Anne Isine; Brun, Johan G; Cobb, Beth; Moser, Kathy L; James, Judith A; Harley, John B; Nath, Swapan K

2012-02-01

Many autoimmune diseases (ADs) share similar underlying pathology and have a tendency to cluster within families, supporting the involvement of shared susceptibility genes. To date, most of the genetic variants associated with systemic lupus erythematosus (SLE) susceptibility also show association with others ADs. ITGAM and its associated 'predisposing' variant (rs1143679, Arg77His), predicted to alter the tertiary structures of the ligand-binding domain of ITGAM, may play a key role for SLE pathogenesis. The aim of this study is to examine whether the ITGAM variant is also associated with other ADs. We evaluated case-control association between rs1143679 and ADs (N=18,457) including primary Sjögren's syndrome, systemic sclerosis, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, celiac disease, and type-1 diabetes. We also performed meta-analyses using our data in addition to available published data. Although the risk allele 'A' is relatively more frequent among cases for each disease, it was not significantly associated with any other ADs tested in this study. However, the meta-analysis for systemic sclerosis was associated with rs1143679 (p(meta)=0.008). In summary, this study explored the role of ITGAM in general autoimmunity in seven non-lupus ADs, and only found association for systemic sclerosis when our results were combined with published results. Thus ITGAM may not be a general autoimmunity gene but this variant may be specifically associated with SLE and systemic sclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Coexistence of multiple sclerosis and ankylosing spondylitis: Report of four cases from Russia and review of the literature.

PubMed

Fominykh, Vera; Shevtsova, Tatyana; Arzumanian, Narine; Brylev, Lev

2017-10-01

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system. There are many cases of multiple sclerosis - like syndrome and demyelinating disorders in systemic lupus erythematosus, Sjogren disease, Behcet disease and other autoimmune conditions. Coexistence of ankylosing spondylitis and multiple sclerosis usually is rare but in this article we report 4 Russian patients with concomitant multiple sclerosis and ankylosing spondylitis diseases. None of these patients received anti-tumor necrosis factor alpha therapy prior to diagnosis of multiple sclerosis. Pathogenesis, diagnostic and treatment challenges are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuromuscular orthotics in the treatment of craniomandibular dysfunction and the effects on patients with multiple sclerosis: a pilot study.

PubMed

Heit, Tammarie

2011-01-01

The purpose of this pilot study was to identify, measure and document an effect on the subjective multiple sclerosis symptoms and compare it to any objective data changes in the neuromuscular system of the head and neck, following the correction of the jaw position using a neuromuscular orthotic. The hope is to provide clinical evidence of improvement in the disease long-term without relying on the subjective evidence of remissions and exacerbations reported by the patient. The evidence found in the current pilot study measured improvement of head position, jaw position, jaw function, and airway in the neuromuscular bite position, which correlated with the improvement of subjective symptoms of craniomandibular dysfunction and multiple sclerosis. Studies show that the bite affects blood flow in the brain, which may explain the improvement of the patients in the current study.

Longitudinal change in physical activity and its correlates in relapsing-remitting multiple sclerosis.

PubMed

Motl, Robert W; McAuley, Edward; Sandroff, Brian M

2013-08-01

Physical activity is beneficial for people with multiple sclerosis (MS), but this population is largely inactive. There is minimal information on change in physical activity and its correlates for informing the development of behavioral interventions. This study examined change in physical activity and its symptomatic, social-cognitive, and ambulatory or disability correlates over a 2.5-year period of time in people with relapsing-remitting multiple sclerosis. On 6 occasions, each separated by 6 months, people (N=269) with relapsing-remitting multiple sclerosis completed assessments of symptoms, self-efficacy, walking impairment, disability, and physical activity. The participants wore an accelerometer for 7 days. The change in study variables over 6 time points was examined with unconditional latent growth curve modeling. The association among changes in study variables over time was examined using conditional latent growth curve modeling, and the associations were expressed as standardized path coefficients (β). There were significant linear changes in self-reported and objectively measured physical activity, self-efficacy, walking impairment, and disability over the 2.5-year period; there were no changes in fatigue, depression, and pain. The changes in self-reported and objective physical activity were associated with change in self-efficacy (β=.49 and β=.61, respectively), after controlling for other variables and confounders. The primary limitations of the study were the generalizability of results among those with progressive multiple sclerosis and inclusion of a single variable from social-cognitive theory. Researchers should consider designing interventions that target self-efficacy for the promotion and maintenance of physical activity in this population.

Astrocyte uncoupling as a cause of human temporal lobe epilepsy

PubMed Central

Bedner, Peter; Dupper, Alexander; Hüttmann, Kerstin; Müller, Julia; Herde, Michel K.; Dublin, Pavel; Deshpande, Tushar; Schramm, Johannes; Häussler, Ute; Haas, Carola A.; Henneberger, Christian; Theis, Martin

2015-01-01

Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K+ concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K+ buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention. PMID:25765328

An Investigation of Perspectives of Respite Admission Among People Living With Amyotrophic Lateral Sclerosis and the Hospitals That Support Them.

PubMed

Nakai, Michiko; Narita, Yugo; Tomimoto, Hidekazu

2017-07-01

Amyotrophic lateral sclerosis is a progressive disease with rapid degeneration. Respite care is an essential service for improving the well-being of both patients with this disease and their family caregivers, but accessibility of respite services is limited. This study investigates perspectives on respite admission among people living with amyotrophic lateral sclerosis and the hospitals supporting them. We conducted semistructured interviews among 3 patients with amyotrophic lateral sclerosis and 12 family members, exploring demographic information and their awareness and experience of respite admission. We also interviewed 16 representatives from hospitals about awareness of and preparation for respite admission for patients with this disease, the role of regional networks for intractable diseases, and knowledge about communication support schemes. We found significant differences in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale between patients who had and had not received respite admission. Qualitative analysis of the data indicated that respite admission was a contributory factor in continuing and stabilizing home care. Limited provision of social services and hospital care quality were barriers to respite admission. Respite admission was essential to continued home care for patients with amyotrophic lateral sclerosis. Severe-stage patients were eligible for respite admission. Its accessibility, however, was limited, especially for patients living in rural areas. Supporting hospitals had limited capacity to respond to patients' needs. Individualized care and communication were internal barriers to respite admission.

Which symptoms contribute the most to patients' perception of health in multiple sclerosis?

PubMed

Green, Rivka; Cutter, Gary; Friendly, Michael; Kister, Ilya

2017-01-01

Multiple sclerosis is a polysymptomatic disease. Little is known about relative contributions of the different multiple sclerosis symptoms to self-perception of health. To investigate the relationship between symptom severity in 11 domains affected by multiple sclerosis and self-rated health. Multiple sclerosis patients in two multiple sclerosis centers assessed self-rated health with a validated instrument and symptom burden with symptoMScreen, a validated battery of Likert scales for 11 domains commonly affected by multiple sclerosis. Pearson correlations and multivariate linear regressions were used to investigate the relationship between symptoMScreen scores and self-rated health. Among 1865 multiple sclerosis outpatients (68% women, 78% with relapsing-remitting multiple sclerosis, mean age 46.38 ± 12.47 years, disease duration 13.43 ± 10.04 years), average self-rated health score was 2.30 ('moderate to good'). Symptom burden (composite symptoMScreen score) highly correlated with self-rated health ( r  = 0.68, P  < 0.0001) as did each of the symptoMScreen domain subscores. In regression analysis, pain ( t  = 7.00), ambulation ( t  = 6.91), and fatigue ( t  = 5.85) contributed the highest amount of variance in self-rated health ( P  < 0.001). Pain contributed the most to multiple sclerosis outpatients' perception of health, followed by gait dysfunction and fatigue. These findings suggest that 'invisible disability' may be more important to patients' sense of wellbeing than physical disability, and challenge the notion that physical disability should be the primary outcome measure in multiple sclerosis.

38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was not...

A discrete-choice experiment to determine patient preferences for injectable multiple sclerosis treatments in Germany.

PubMed

Poulos, Christine; Kinter, Elizabeth; Yang, Jui-Chen; Bridges, John F P; Posner, Joshua; Gleißner, Erika; Mühlbacher, Axel; Kieseier, Bernd

2016-03-01

The aim of this study was to assess the relative importance of features of a hypothetical injectable disease-modifying treatment for patients with multiple sclerosis using a discrete-choice experiment. German residents at least 18 years of age with a self-reported physician diagnosis of multiple sclerosis completed a 25-30 minute online discrete-choice experiment. Patients were asked to choose one of two hypothetical injectable treatments for multiple sclerosis, defined by different levels of six attributes (disability progression, the number of relapses in the next 4 years, injection time, frequency of injections, presence of flu-like symptoms, and presence of injection-site reactions). The data were analyzed using a random-parameters logit model. Of 202 adults who completed the survey, results from 189 were used in the analysis. Approximately 50% of all patients reported a diagnosis of relapsing-remitting multiple sclerosis, and 31% reported secondary progressive multiple sclerosis. Approximately 71% of patients had current or prior experience with injectable multiple sclerosis medication. Approximately 53% had experienced flu-like symptoms caused by their medication, and 47% had experienced mild injection-site reactions. At least one significant difference was seen between levels in all attributes, except injection time. The greatest change in relative importance between levels of an attribute was years until symptoms get worse from 1 to 4 years. The magnitude of this difference was about twice that of relapses in the next 4 years, frequency of injections, and flu-like symptoms. Most attributes examined in this experiment had an influence on patient preference. Patients placed a significant value on improvements in the frequency of dosing and disability progression. Results suggest that changes in injection frequency can be as important as changes in efficacy and safety attributes. Understanding which attributes of injectable therapies influence patient preference could potentially improve outcomes and adherence in patients with multiple sclerosis.

Supportive care needs of patients with amyotrophic lateral sclerosis/motor neuron disease and their caregivers: A scoping review.

PubMed

Oh, Juyeon; Kim, Jung A

2017-12-01

To identify the supportive care needs of amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers, categorise and summarise them into a Supportive Care Needs Framework and identify gaps in literature. Little is known about the supportive care needs of amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers, and this subject has not previously been systemically reviewed. Scoping review. We conducted a scoping review from the MEDLINE, EMBASE, CINAHL and Cochrane databases for the period January 2000-July 2016, using the following inclusion criteria: (i) written in English only, (ii) published in peer-reviewed journals, (iii) at least part of the research considered the supportive care needs perspective of amyotrophic lateral sclerosis/motor neuron disease patients or their caregivers and (iv) the population sample included patients of amyotrophic lateral sclerosis/motor neuron disease or their caregivers. Thirty-seven articles were included. Our review shows that amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers' supportive care needs were mentioned across all seven domains of the Supportive Care Needs Framework. Most common were practical needs (n = 24), followed by Informational needs (n = 19), Social needs (n = 18), Psychological needs (n = 16), Physical needs (n = 15), Emotional needs (n = 13) and Spiritual needs (n = 8). From the perspectives of amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers, there is a significant need for more practical, social, informational, psychological, physical, emotional and spiritual support. The Supportive Care Needs Framework has potential utility in the development of patient-centred support services or healthcare policies and serves as an important base for further studies; especially, specific examples of each supportive care needs domain can guide in clinical settings when healthcare professionals provide multidisciplinary care to amyotrophic lateral sclerosis/motor neuron disease patients and individualised care. © 2017 John Wiley & Sons Ltd.

Effects on Cognition of Stereotactic Lesional Surgery For the Treatment of Tremor in Multiple Sclerosis

PubMed Central

Jahanshahi, Marjan; Pieter, Socorro; Alusi, Sundus H.; Jones, Catherine R. G.; Glickman, Scott; Stein, John; Aziz, Tipu; Bain, Peter G.

2008-01-01

Objective: To assess the effect of stereotactic lesional surgery for treatment of tremor in multiple sclerosis on cognition. Methods: Eleven patients (3 males, 8 females) with multiple sclerosis participated in the study. Six subjects comprised the surgical group and five the matched control group. All patients were assessed at baseline and three months using a neuropsychological test battery that included measures of intellectual ability, memory, language, perception and executive function. Results: There were no significant differences between the surgical and control groups and no change from pre to post testing except for a decline in scores on the Mini-Mental State Examination (MMSE), WAIS-R Digit Span and Verbal Fluency in the surgical group. Conclusions: The results indicate that stereotactic lesional surgery does not result in major cognitive impairment in multiple sclerosis. However, the decline in MMSE scores, digit span and verbal fluency require further investigation in a larger sample. PMID:19491469

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps.

PubMed

Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2015-09-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. © The Author(s) 2014.

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

PubMed Central

Casper, T. Charles; Rose, John W.; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E.; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2014-01-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. PMID:25270659

Co2/Erbium:YAG/Dye laser combination: an effective and successful treatment for angiofibromas in tuberous sclerosis.

PubMed

Fioramonti, Paolo; De Santo, Liliana; Ruggieri, Martina; Carella, Sara; Federico, Lo Torto; Onesti, Maria Giuseppina; Scuderi, Nicolò

2014-02-01

Tuberous sclerosis, an autosomal dominant neurocutaneous syndrome seen in approximately 1 in 6,000 people worldwide, is characterized by the appearance of hamartomas in multiple organs. The classic clinical triad consists of angiofibromas, epilepsy, and developmental delay. Dermatologic disorder is one of the main characteristics. Angiofibromas, a common form of presentation, causes significant cosmetic and medical problems. The current treatment for skin lesions is laser therapy. The carbon dioxide (CO2) laser has been used satisfactorily in treating these lesions, but several studies have demonstrated a high percentage of recurrences. Erbium:yttrium-aluminum-garnet (YAG) laser treatment has been used to resurface skin abnormalities in patients with dermatologic conditions. The dye laser as an alternative uses the principles of selective photothermolysis and is very effective in treating the vascular component of tuberous sclerosis. The use of all these lasers to treat skin lesions in patients affected by tuberous sclerosis has never been described in the literature. A retrospective study, conducted from 2007 to May 2013, investigated 13 patients who had tuberous sclerosis treated with an erbium:YAG/CO2/dye laser combination. All the patients showed great improvement of their skin lesions. The results were evident immediately after the first treatment. No patient experienced complications or recurrence. The combined use of the erbium:YAG/Dye/CO2 laser is a safe and effective treatment for skin lesions in patients affected by tuberous sclerosis. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The effectiveness of behaviour change interventions to increase physical activity participation in people with multiple sclerosis: a systematic review and meta-analysis.

PubMed

Sangelaji, Bahram; Smith, Catherin M; Paul, Lorna; Sampath, Kesava Kovanur; Treharne, Gareth J; Hale, Leigh Anne

2016-06-01

A systematic review and meta-analysis was conducted to illustrate whether people with multiple sclerosis engage in more physical activity following behaviour change interventions. MEDLINE, CINAHL, PubMed, Web of Sciences, Cochrane Library, SCOPUS, EMBASE and PEDro were searched from their inception till 30 April 2015. Randomized and clinical controlled trials that used behaviour change interventions to increase physical activity in people with multiple sclerosis were selected, regardless of type or duration of multiple sclerosis or disability severity. Data extraction was conducted by two independent reviewers and the Cochrane Collaboration's recommended method was used to assess the risk of bias of each included study. A total of 19 out of 573 studies were included. Focusing on trials without risk of bias, meta-analysis showed that behaviour change interventions can significantly increase physical activity participation (z = 2.20, p = 0.03, standardised main difference 0.65, 95% confidence interval 0.07 to 1.22, 3 trials, I(2) = 68%) (eight to 12 weeks' duration). Behaviour change interventions did not significantly impact on the physical components of quality of life or fatigue. Behaviour change interventions provided for relatively short duration (eight to 12 weeks) may increase the amount of physical activity people with multiple sclerosis engage in, but appear to have no effect on the physical components of quality of life and fatigue. Further high quality investigations of the efficacy of behaviour change interventions to increase physical activity participation that focus on dose, long-term impact and method of delivery are warranted for people with multiple sclerosis. © The Author(s) 2015.

Speech Deterioration in Amyotrophic Lateral Sclerosis (ALS) after Manifestation of Bulbar Symptoms

ERIC Educational Resources Information Center

Makkonen, Tanja; Ruottinen, Hanna; Puhto, Riitta; Helminen, Mika; Palmio, Johanna

2018-01-01

Background: The symptoms and their progression in amyotrophic lateral sclerosis (ALS) are typically studied after the diagnosis has been confirmed. However, many people with ALS already have severe dysarthria and loss of adequate speech at the time of diagnosis. Speech-and-language therapy interventions should be targeted timely based on…

Exercise and Quality of Life in Women with Multiple Sclerosis

ERIC Educational Resources Information Center

Giacobbi, Peter R., Jr.; Dietrich, Frederick; Larson, Rebecca; White, Lesley J.

2012-01-01

The purpose of this study was to evaluate perceptions of quality of life after a 4-month progressive resistance training program for individuals with multiple sclerosis (MS). A second purpose was to examine participants' views about factors that facilitated or impeded exercise behavior. Qualitative interviews were conducted with eight females…

Comparison of Intelligibility Measures for Adults with Parkinson's Disease, Adults with Multiple Sclerosis, and Healthy Controls

ERIC Educational Resources Information Center

Stipancic, Kaila L.; Tjaden, Kris; Wilding, Gregory

2016-01-01

Purpose: This study obtained judgments of sentence intelligibility using orthographic transcription for comparison with previously reported intelligibility judgments obtained using a visual analog scale (VAS) for individuals with Parkinson's disease and multiple sclerosis and healthy controls (K. Tjaden, J. E. Sussman, & G. E. Wilding, 2014).…

Preliminary Evidence that Self-Efficacy Predicts Physical Activity in Multiple Sclerosis

ERIC Educational Resources Information Center

Motl, Robert W.; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S.

2009-01-01

Individuals with multiple sclerosis (MS) are less physically active than nondiseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and…

Evaluating Functional Decline in Patients with Multiple Sclerosis

ERIC Educational Resources Information Center

Rosenblum, Sara; Weiss, Patrice L.

2010-01-01

Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

2009-01-01

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

Characteristics of Speaking Rate in the Dysarthria Associated with Amyotrophic Lateral Sclerosis.

ERIC Educational Resources Information Center

Turner, Greg S.; Weismer, Gary

1993-01-01

The ability to alter speaking rate was studied in nine adult subjects with amyotrophic lateral sclerosis and nine control subjects. Results suggest that the relationship between speaking rate, articulation rate, pause duration, and pause frequency remained largely intact for the dysarthric speakers. Data showed greater dependence on pausing by the…

Central nervous system remyelination in culture--a tool for multiple sclerosis research.

PubMed

Zhang, Hui; Jarjour, Andrew A; Boyd, Amanda; Williams, Anna

2011-07-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. Copyright © 2011 Elsevier Inc. All rights reserved.

Central nervous system remyelination in culture — A tool for multiple sclerosis research

PubMed Central

Zhang, Hui; Jarjour, Andrew A.; Boyd, Amanda; Williams, Anna

2011-01-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. PMID:21515259

The effect of saponification on the mucopolysaccharides of the ground substance of the human brain: the relation to focal edema and multiple sclerosis.

PubMed

Feigin, I

1981-03-01

The acid mucopolysaccharides of brain tissues are disclosed by their metachromatic staining with toluidine blue following saponification with potassium hydroxide, presumably as a result of the liberation of acid groups previously esterified. Earlier histochemical studies had disclosed the presence of neutral mucopolysaccharides by staining with the periodic acid-Schiff technique, and such staining is intensified by prior saponification. Many biochemical studies have reported the presence of both acid and neutral mucopolysaccharides in brain tissues. Within the white matter following brain edema, the quantity of stained mucopolysaccharides is decreased in the plaques of multiple sclerosis and pontine myelinolysis, and in the lesions of diffuse sclerosis. All of these are characterized by myelin loss with relative preservation of axons. The known physiological effects of the mucopolysaccharides on the water content of normal tissues, and on the properties and diffusability of the increments of fluid that constitute edema, lead to the suggestion that edema may play a major role in the pathogenesis of the demyelinating diseases, including multiple sclerosis.

Diagnostic support for selected neuromuscular diseases using answer-pattern recognition and data mining techniques: a proof of concept multicenter prospective trial.

PubMed

Grigull, Lorenz; Lechner, Werner; Petri, Susanne; Kollewe, Katja; Dengler, Reinhard; Mehmecke, Sandra; Schumacher, Ulrike; Lücke, Thomas; Schneider-Gold, Christiane; Köhler, Cornelia; Güttsches, Anne-Katrin; Kortum, Xiaowei; Klawonn, Frank

2016-03-08

Diagnosis of neuromuscular diseases in primary care is often challenging. Rare diseases such as Pompe disease are easily overlooked by the general practitioner. We therefore aimed to develop a diagnostic support tool using patient-oriented questions and combined data mining algorithms recognizing answer patterns in individuals with selected neuromuscular diseases. A multicenter prospective study for the proof of concept was conducted thereafter. First, 16 interviews with patients were conducted focusing on their pre-diagnostic observations and experiences. From these interviews, we developed a questionnaire with 46 items. Then, patients with diagnosed neuromuscular diseases as well as patients without such a disease answered the questionnaire to establish a database for data mining. For proof of concept, initially only six diagnoses were chosen (myotonic dystrophy and myotonia (MdMy), Pompe disease (MP), amyotrophic lateral sclerosis (ALS), polyneuropathy (PNP), spinal muscular atrophy (SMA), other neuromuscular diseases, and no neuromuscular disease (NND). A prospective study was performed to validate the automated malleable system, which included six different classification methods combined in a fusion algorithm proposing a final diagnosis. Finally, new diagnoses were incorporated into the system. In total, questionnaires from 210 individuals were used to train the system. 89.5 % correct diagnoses were achieved during cross-validation. The sensitivity of the system was 93-97 % for individuals with MP, with MdMy and without neuromuscular diseases, but only 69 % in SMA and 81 % in ALS patients. In the prospective trial, 57/64 (89 %) diagnoses were predicted correctly by the computerized system. All questions, or rather all answers, increased the diagnostic accuracy of the system, with the best results reached by the fusion of different classifier methods. Receiver operating curve (ROC) and p-value analyses confirmed the results. A questionnaire-based diagnostic support tool using data mining methods exhibited good results in predicting selected neuromuscular diseases. Due to the variety of neuromuscular diseases, additional studies are required to measure beneficial effects in the clinical setting.

Multiple Sclerosis and Catastrophic Health Expenditure in Iran.

PubMed

Juyani, Yaser; Hamedi, Dorsa; Hosseini Jebeli, Seyede Sedighe; Qasham, Maryam

2016-09-01

There are many disabling medical conditions which can result in catastrophic health expenditure. Multiple Sclerosis is one of the most costly medical conditions through the world which encounter families to the catastrophic health expenditures. This study aims to investigate on what extent Multiple sclerosis patients face catastrophic costs. This study was carried out in Ahvaz, Iran (2014). The study population included households that at least one of their members suffers from MS. To analyze data, Logit regression model was employed by using the default software STATA12. 3.37% of families were encountered with catastrophic costs. Important variables including brand of drug, housing, income and health insurance were significantly correlated with catastrophic expenditure. This study suggests that although a small proportion of MS patients met the catastrophic health expenditure, mechanisms that pool risk and cost (e.g. health insurance) are required to protect them and improve financial and access equity in health care.

Reliability and validity of the DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis (Greek version) and proposed modification.

PubMed

Printza, Athanasia; Kalaitzi, Maria; Bakirtzis, Christos; Nikolaidis, Ioannis; Proios, Hariklia; Grigoriadis, Nikolaos

2018-05-10

Recent research confirmed that at least a third of people with multiple sclerosis (MS) are suffering from swallowing difficulties. Dysphagia is associated with significant morbidity and mortality, and has profound impact on physical ability and quality of life. Dysphagia related complications can be prevented through an effective screening protocol. The Dysphagia in Multiple Sclerosis (DYMUS) questionnaire is the first dysphagia questionnaire developed specifically for patients with MS. The aim of the present study was the cultural adaptation of DYMUS for the Greek population, evaluation of the questionnaire's reliability and validity and normative data generation for DYMUS, which has not been published before. DYMUS was completed by 200 participants: 108 MS patients and 92 asymptomatic subjects (60 male and 140 female). Patients with MS were consecutively recruited from the Multiple Sclerosis Centre during regular visits. Asymptomatic participants were community-dwelling healthy persons. All data were collected prospectively. MS patients were invited to complete DYMUS and the Greek versions of the Eating Assessment Tool-10 (EAT-10), and the Swallowing-Quality of Life (SWAL-QoL) questionnaires. Healthy subjects completed DYMUS and the Greek EAT-10. The study consisted of item generation for the Greek DYMUS, internal consistency and reliability analysis, normative data generation, and validity analysis. Criterion validity was assessed by comparing scores between groups with expected differences: MS patients and healthy participants. Construct validity was assessed by comparison of DYMUS scores of dysphagic and non dysphagic patients. DYMUS was also validated against EAT-10, and SWAL-QoL to assess its convergent validity. DYMUS was completed by all participants in less than 3 min. The internal consistency was excellent (Cronbach's alpha was 0.866). Test-retest reliability was good (Pearson's correlation coefficient was 0.637). The mean DYMUS score for the healthy cohort was 0.23 ± 0.471. The upper limit of normal was 1.172. MS patients had statistically significantly higher score than controls (Mann Whitney test, p < 0.001). DYMUS mean score was statistically significantly higher in the dysphagic compared to the non dysphagic MS patients (Mann Whitney test, p < 0.001). There was a strong positive and statistically significant correlation between DYMUS and EAT-10 (Pearson's Correlation coefficient, r = 0.754, p = 0). In the MS patients cohort 25.9% reported themselves as dysphagic, 34.3% were classified as dysphagic according to EAT-10 and 44.4% according to DYMUS. The DYMUS score had a statistically significant positive correlation with the EDSS score, (Mann Whitney, p < 0.001) whereas age, sex, type of MS and disease duration were not significantly correlated. Based on our data analysis we propose the modification of DYMUS to a 9-items tool eliminating the question about weight loss. A DYMUS score of 2 or higher is indicating dysphagia for both the original DYMUS and the modified DYMUS. The Greek version of DYMUS was found to be a valid, reliable and practical for clinical use questionnaire for the detection of dysphagia in Multiple Sclerosis. The first reported normative data for DYMUS suggest a cut-off for the diagnosis of dysphagia at 2 and our findings support a modification of DYMUS eliminating the question about weight loss. Copyright © 2018 Elsevier B.V. All rights reserved.

Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study.

PubMed

Saggar, Rajeev; Khanna, D; Shapiro, S; Furst, D E; Maranian, P; Clements, P; Abtin, F; Dua, Shiv; Belperio, J; Saggar, Rajan

2012-12-01

Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum-associated ePH treated with open-label daily ambrisentan. Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and cardiopulmonary hemodynamics. Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm(5) ; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (-4.1 mm Hg; P = 0.02), and total pulmonary resistance (-93.0 dynes × seconds/cm(5) ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. Exercise hemodynamics and exercise capacity in patients with SSc spectrum-associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH. Copyright © 2012 by the American College of Rheumatology.

MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

PubMed

Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

2017-03-15

Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

Factors affecting reorganisation of memory encoding networks in temporal lobe epilepsy

PubMed Central

Sidhu, M.K.; Stretton, J.; Winston, G.P.; Symms, M.; Thompson, P.J.; Koepp, M.J.; Duncan, J.S.

2015-01-01

Summary Aims In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. Methods We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. Results Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. Conclusion Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst longer duration and higher seizure frequency were associated with greater, inefficient, extra-temporal reorganisation. PMID:25616449

Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation

PubMed Central

Soto, Lilian; Ferrier, Ashley; Aravena, Octavio; Fonseca, Elianet; Berendsen, Jorge; Biere, Andrea; Bueno, Daniel; Ramos, Verónica; Aguillón, Juan Carlos; Catalán, Diego

2015-01-01

The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis. PMID:26483788

High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis.

PubMed

Hoffmann-Vold, Anna-Maria; Tennøe, Anders Heiervang; Garen, Torhild; Midtvedt, Øyvind; Abraityte, Aurelija; Aaløkken, Trond Mogens; Lund, May Britt; Brunborg, Cathrine; Aukrust, Pål; Ueland, Thor; Molberg, Øyvind

2016-08-01

Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis. Sera from the Oslo University Hospital SSc cohort (n = 298) and healthy control subjects (n = 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff. High serum CCL18 was identified in 35% (105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3% and 4.7%; P = .016), as did the annual progression rate of lung fibrosis (0.9% [SD, 2.9] and 0.2% [SD, 1.9]). Highest rates of annual FVC decline > 10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10% (OR, 1.1; 95% CI, 1.01-1.11) and FVC < 70% at follow-up (OR, 3.1; 95% CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85% and 74%, compared with 97% and 89%, respectively; P = .001). The results from this prospective cohort reinforce the notion that high CCL18 may serve as a marker for early identification of progressive ILD in SSc. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Multiple sclerosis patients' experiences in relation to the impact of the kinect virtual home-exercise programme: a qualitative study.

PubMed

Palacios-Ceña, Domingo; Ortiz-Gutierrez, Rosa M; Buesa-Estellez, Almudena; Galán-Del-Río, Fernando; Cachon Perez, José M; Martínez-Piedrola, Rosa; Velarde-Garcia, Juan F; Cano-DE-LA-Cuerda, Roberto

2016-06-01

Neurorehabilitation programs are among the most popular therapies aimed at reducing the disabilities that result from multiple sclerosis. Video games have recently gained importance in the rehabilitation of patients with motor neurological dysfunctions. Currently, the studies describing the perspective of patients with multiple sclerosis who have participated in rehabilitation programmes via home-based video games are almost inexistent. The aim of this paper was to explore the experiences of multiple sclerosis patients who performed a virtual home-exercise programme using Kinect. A qualitative research enquiry was conducted as part of a study that examined postural control and balance after a 10-week Kinect home-exercise programme in adults with multiple sclerosis. Patients were recruited from a Neurology Unit of a University Hospital. The inclusion criteria were: subjects aged between 20 and 60 years, diagnosed with multiple sclerosis for over 2 years based on the McDonald Criteria; with an EDSS score ranging from 3 to 5. Purposeful sampling method was implemented. The data collection consisted of unstructured interviews, using open questions, and thematic analysis was conducted. Guidelines for conducting qualitative studies established by the Consolidated Criteria for Reporting Qualitative Research were followed. Twenty-four patients with a mean age of 36.69 were included. Four main themes emerged from the data: 1) regaining previous capacity and abilities. The patients described how, after the treatment with Kinect they felt more independent; 2) sharing the disease. The patients sharing the experience of living with MS with their family, thanks to the use of Kinect; 3) adapting to the new treatment. This refers to how the use of the videogame console incorporated novelties to their rehabilitation programme; and 4) comparing oneself. This refers to the appearance of factors that motivate the patient during KVHEP. The patients' experiences gathered in this study highlight perceptions of unexpected improvement, an eagerness to improve, and the positive opportunity of sharing treatment with their social entourage thanks to the games. These results can be applied to future research using video consoles, by individualizing and adapting the games to the patient's abilities, and by developing a new field in rehabilitation.

Neural Correlates of Alerting and Orienting Impairment in Multiple Sclerosis Patients

PubMed Central

Vázquez-Marrufo, Manuel; Galvao-Carmona, Alejandro; González-Rosa, Javier J.; Hidalgo-Muñoz, Antonio R.; Borges, Mónica; Ruiz-Peña, Juan Luis; Izquierdo, Guillermo

2014-01-01

Background A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test. Results After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (p<0.05). ANOVAs showed for the patient group a significant latency delay for P1 and N1 components (p<0.05) and a decrease of P3 amplitude for congruent and incongruent stimuli (p<0.01). With regard to correlation analysis, PASAT-3s and SDMT showed significant correlations with behavioral measures of the Attention Network Test (p<0.01) and an ERP parameter (CNV amplitude). Conclusions Behavioral data are highly correlated with the neuropsychological scores and show that the alerting and orienting mechanisms in the patient group were impaired. Reduced amplitude for the Contingent Negative Variation in the patient group suggests that this component could be a physiological marker related to the alerting and orienting impairment in relapsing-remitting multiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients. PMID:24820333

Neural correlates of alerting and orienting impairment in multiple sclerosis patients.

PubMed

Vázquez-Marrufo, Manuel; Galvao-Carmona, Alejandro; González-Rosa, Javier J; Hidalgo-Muñoz, Antonio R; Borges, Mónica; Ruiz-Peña, Juan Luis; Izquierdo, Guillermo

2014-01-01

A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test. After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (p<0.05). ANOVAs showed for the patient group a significant latency delay for P1 and N1 components (p<0.05) and a decrease of P3 amplitude for congruent and incongruent stimuli (p<0.01). With regard to correlation analysis, PASAT-3s and SDMT showed significant correlations with behavioral measures of the Attention Network Test (p<0.01) and an ERP parameter (CNV amplitude). Behavioral data are highly correlated with the neuropsychological scores and show that the alerting and orienting mechanisms in the patient group were impaired. Reduced amplitude for the Contingent Negative Variation in the patient group suggests that this component could be a physiological marker related to the alerting and orienting impairment in relapsing-remitting multiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients.

Abnormal sudomotor function in the hypomelanotic macules of tuberous sclerosis complex.

PubMed

Chudnow, R S; Wolfe, G I; Sparagana, S P; Delgado, M R; Batchelor, L; Roach, E S

2000-08-01

To investigate the integrity of sympathetic innervation in the hypomelanotic macules of tuberous sclerosis complex, we studied sudomotor function in nine patients with tuberous sclerosis complex. Postganglionic sudomotor function was assessed using the Silastic imprint test in nine patients with tuberous sclerosis complex who have at least one hypomelanotic macule greater than 2 cm in diameter. Sweating was induced by iontophoresis with 0.5% pilocarpine nitrate and sweat droplets were counted under a microscope using a 1 x 1 cm grid. Silastic imprint testing of an analogous skin area contralateral to the hypomelanotic macule was measured as a control. Sweat volume quantitation using sweat collectors was performed in five of the subjects. The sweat volume collected from the hypomelanotic macule was reduced compared to the control skin in four of the five subjects. Sweat droplet counts from the hypomelanotic macule were significantly reduced in only one of nine subjects. These data suggest that, although there is no difference in the number of functioning sweat glands in most hypomelanotic macules, the sweat glands produce less sweat (ie, decreased sweat volume) than in normal skin. We hypothesize that focal abnormalities of sympathetic innervation might be responsible for the hypomelanotic macules of tuberous sclerosis complex.

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis

PubMed Central

Motta, Caterina; Palermo, Eduardo; Studer, Valeria; Germanotta, Marco; Germani, Giorgio; Centonze, Diego; Cappa, Paolo

2016-01-01

Background The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. Objective To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. Methods A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. Results We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Conclusions Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis. PMID:26863109

Loss of Peristaltic Reserve, Determined by Multiple Rapid Swallows, Is the Most Frequent Esophageal Motility Abnormality in Patients With Systemic Sclerosis.

PubMed

Carlson, Dustin A; Crowell, Michael D; Kimmel, Jessica N; Patel, Amit; Gyawali, C Prakash; Hinchcliff, Monique; Griffing, W Leroy; Pandolfino, John E; Vela, Marcelo F

2016-10-01

We assessed peristaltic reserve using multiple rapid swallows (MRS) during esophageal high-resolution manometry (HRM) of 111 patients with systemic sclerosis (89 women; ages, 42-64 y). We performed a retrospective analysis of HRM studies that included MRS in patients with systemic sclerosis, performed at 2 tertiary referral centers, and compared data with those from 18 healthy volunteers (controls). HRM findings were analyzed according to the Chicago Classification to provide an esophageal motility diagnosis. Response to MRS was evaluated for the presence of contraction and for augmentation, defined as the distal contractile integral after MRS greater than the median distal contractile integral of 10 supine swallows. Esophageal motility diagnoses included 41% with absent contractility, 31% with normal motility, 23% with ineffective esophageal motility, and 5% that met the criteria for other esophageal motility disorders. Contraction (37%) and peristaltic augmentation (18%) after MRS were observed less frequently in patients with systemic sclerosis than in controls (83% and 100%, respectively). Impaired peristaltic reserve, as assessed with MRS during HRM, is therefore the most common esophageal motility finding among patients with systemic sclerosis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature.

PubMed

Ighodaro, Eseosa T; Jicha, Gregory A; Schmitt, Frederick A; Neltner, Janna H; Abner, Erin L; Kryscio, Richard J; Smith, Charles D; Duplessis, Taylor; Anderson, Sonya; Patel, Ela; Bachstetter, Adam; Van Eldik, Linda J; Nelson, Peter T

2015-07-01

Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with "hippocampal sclerosis" pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of "segmental" HS-Aging in which "sclerosis" in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of "hippocampal sclerosis" and TDP-43 pathologies in aged subjects.

Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.

PubMed

Panitch, Hillel S; Thisted, Ronald A; Smith, Richard A; Wynn, Daniel R; Wymer, James P; Achiron, Anat; Vollmer, Timothy L; Mandler, Raul N; Dietrich, Dennis W; Fletcher, Malcolm; Pope, Laura E; Berg, James E; Miller, Ariel

2006-05-01

To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients. A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess pseudobulbar affect with the validated Center for Neurologic Study-Lability Scale. Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale. Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85). All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p

[Scleroderma cluster among type-setters].

PubMed

Magnavita, N

2007-01-01

The etiology of systemic sclerosis, probably multifactorial, is not yet well defined. Among the many endogenous and exogenous factors probably involved, occupational elements may play an essential role. Here we report a cluster of local scleroderma and systemic sclerosis, which occurred in a small group of typography workers exposed to polyvinyl-acetate glues, containing up to 1% of vinyl-acetate. Vinyl acetate exposure has been associated with acidification of the intracellular environment, which is thought to produce cytotoxic and/or mitogenic responses that are the sentinel pharmacodynamic steps toward cancer. Autoantibody production in systemic sclerosis depends upon intracellular acidification. More studies are needed to clarify the relationship between vinyl acetate exposure and scleroderma.

ALS - resources

MedlinePlus

Resources - ALS ... The following organizations are good resources for information on amyotrophic lateral sclerosis : Muscular Dystrophy Association -- www.mda.org/disease/amyotrophic-lateral-sclerosis National Amyotrophic Lateral Sclerosis (ALS) ...

High-Fat and Ketogenic Diets in Amyotrophic Lateral Sclerosis

PubMed Central

Paganoni, Sabrina; Wills, Anne-Marie

2015-01-01

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials. PMID:23666040

Systemic sclerosis: a world wide global analysis.

PubMed

Coral-Alvarado, Paola; Pardo, Aryce L; Castaño-Rodriguez, Natalia; Rojas-Villarraga, Adriana; Anaya, Juan-Manuel

2009-07-01

The objective of this study was to analyze epidemiological tendencies of systemic sclerosis (SSc) around the world in order to identify possible local variations in the presentation and occurrence of the disease. A systematic review of the literature was performed through electronic databases using the keywords "Systemic Sclerosis" and "Clinical Characteristics." Out of a total of 167 articles, 41 were included in the analysis. Significant differences in the mean age at the time of diagnosis, subsets of SSc, clinical characteristics, and presence of antibodies were found between different regions of the word. Because variations in both additive and nonadditive genetic factors and the environmental variance are specific to the investigated population, ethnicity and geography are important characteristics to be considered in the study of SSc and other autoimmune diseases.

Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect.

PubMed

Voldsgaard, A; Bager, P; Garde, E; Åkeson, P; Leffers, A M; Madsen, C G; Kapel, C; Roepstorff, A; Thamsborg, S M; Melbye, M; Siebner, H; Søndergaard, H B; Sellebjerg, F; Sørensen, P Soelberg

2015-11-01

An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. To evaluate the safety and efficacy on MRI activity of treatment with TSO in relapsing MS. The study was an open-label, magnetic resonance imaging assessor-blinded, baseline-to-treatment study including ten patients with relapsing forms of multiple sclerosis. Median (range) age was 41 (24-55) years, disease duration 9 (4-34) years, Expanded Disability Status Scale score 2.5 (1-5.0), and number of relapses within the last two years 3 (2-5). Four patients received no disease modifying therapy, while six patients received IFN-β. After an observational period of 8 weeks, patients received 2500 ova from the helminth Trichuris suis orally every second week for 12 weeks. Patients were followed with serial magnetic resonance imaging, neurological examinations, laboratory safety tests and expression of immunological biomarker genes. Treatment with Trichuris suis orally was well-tolerated apart from some gastrointestinal symptoms. Magnetic resonance imaging revealed 6 new or enlarged T2 lesions in the run-in period, 7 lesions in the early period and 21 lesions in the late treatment period. Two patients suffered a relapse before treatment and two during treatment. Eight patients developed eosinophilia. The expression of cytokines and transcription factors did not change. In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect. © The Author(s), 2015.

Epilepsy may be the major risk factor of mental retardation in children with tuberous sclerosis: A retrospective cohort study.

PubMed

Wang, Yang-Yang; Pang, Ling-Yu; Ma, Shu-Fang; Zhang, Meng-Na; Liu, Li-Ying; Zou, Li-Ping

2017-12-01

Mental retardation (MR) is one of the most common cognitive comorbidities in children with tuberous sclerosis, and there are enormous studies about its risk factors. The genetic difference and the severity of epilepsy are the two main factors, but their weight in the occurrence of MR is still unclear. Two hundred twenty-three patients with tuberous sclerosis who received intelligence assessment, genetic mutation analysis, and the epilepsy severity assessment were included in our study. Genotype-neurocognitive phenotype correlations and epilepsy-neurocognitive phenotype correlations were analyzed by binary logistic regression analysis. No statistical significant result was found on genotype-neurocognitive phenotype correlations, which contrasted the previous report. The prevalence of MR was 50.0% for the patients with tuberous sclerosis complex-1 (TSC1) mutation, 54.5% for TSC2 (p=0.561), 54.7% for patients with protein-truncating (PT) and 50.0% for patients with nontruncating (NT) (p=0.791), and 54.3% for patients with family history and 53.7% for patients without family history (p=0.748). Statistical significant results were found on epilepsy-neurocognitive phenotype correlations, both on E-chess score (p=0.01) and the occurrence of infantile spasms (p=0.014), which was consistent to the previous study. For children with tuberous sclerosis, instead of genetic factors, epilepsy may play the main role for the presence of mental retardation. Patients with mental retardation tend to have earlier seizure attack, take more AEDs, have more seizure types, and have higher seizure frequency. Among the four cognitive functions in Denver II, social ability and language ability are more vulnerable to be influenced than fine and gross motor ability. Copyright © 2017 Elsevier Inc. All rights reserved.

Is there an association between glaucoma and capillaroscopy in patients with systemic sclerosis?

PubMed

Gomes, Beatriz Fiuza; Souza, Rebeca; Valadão, Thiago; Kara-Junior, Newton; Moraes, Haroldo Vieira; Santhiago, Marcony R

2018-02-01

To evaluate the relationship between glaucoma diagnosis and the nailfold capillaroscopy pattern in patients with systemic sclerosis. An observational study in a cohort of patients with SSc was conducted. Patients with at least one nailfold videocapillaroscopy and one ophthalmology examination at the same year were included. Data collected were: age, sex; type of systemic sclerosis according to the degree of skin impairment, self-reported ethnicity, disease duration, current use and dosage of systemic corticosteroid, current use and dosage of bosentan ® , intraocular pressure, central corneal thickness, diagnosis of glaucoma and capillaroscopy pattern. Thirty-one patients with systemic sclerosis were enrolled, 23% had glaucoma. There was no statistically significant association between glaucoma diagnosis and the capillaroscopic pattern (p = 0.86). There was also no significant difference (p = 0.66) regarding intraocular pressure between patients with mild (13.9 ± 3.8 mmHg) and severe capillaroscopic pattern (14.4 ± 2.8 mmHg). The odds ratio of glaucoma for severe capillaroscopic pattern compared to mild was 1.6 (95% confidence interval: 0.3-9.5). Up to 23% of patients with SSc have glaucoma. The high prevalence of glaucoma in SSc suggests a possible systemic vascular disturbance as the cause. However, there seems to be no significant association between the capillaroscopy pattern and glaucoma in systemic sclerosis. Further research is required to improve the understanding of glaucoma in the context of systemic sclerosis.

Using normalisation process theory to understand barriers and facilitators to implementing mindfulness-based stress reduction for people with multiple sclerosis.

PubMed

Simpson, Robert; Simpson, Sharon; Wood, Karen; Mercer, Stewart W; Mair, Frances S

2018-01-01

Objectives To study barriers and facilitators to implementation of mindfulness-based stress reduction for people with multiple sclerosis. Methods Qualitative interviews were used to explore barriers and facilitators to implementation of mindfulness-based stress reduction, including 33 people with multiple sclerosis, 6 multiple sclerosis clinicians and 2 course instructors. Normalisation process theory provided the underpinning conceptual framework. Data were analysed deductively using normalisation process theory constructs (coherence, cognitive participation, collective action and reflexive monitoring). Results Key barriers included mismatched stakeholder expectations, lack of knowledge about mindfulness-based stress reduction, high levels of comorbidity and disability and skepticism about embedding mindfulness-based stress reduction in routine multiple sclerosis care. Facilitators to implementation included introducing a pre-course orientation session; adaptations to mindfulness-based stress reduction to accommodate comorbidity and disability and participants suggested smaller, shorter classes, shortened practices, exclusion of mindful-walking and more time with peers. Post-mindfulness-based stress reduction booster sessions may be required, and objective and subjective reports of benefit would increase clinician confidence in mindfulness-based stress reduction. Discussion Multiple sclerosis patients and clinicians know little about mindfulness-based stress reduction. Mismatched expectations are a barrier to participation, as is rigid application of mindfulness-based stress reduction in the context of disability. Course adaptations in response to patient needs would facilitate uptake and utilisation. Rendering access to mindfulness-based stress reduction rapid and flexible could facilitate implementation. Embedded outcome assessment is desirable.

Diagnostic value of conventional visual evoked potentials applied to patients with multiple sclerosis.

PubMed

Balnytė, Renata; Ulozienė, Ingrida; Rastenytė, Daiva; Vaitkus, Antanas; Malcienė, Lina; Laučkaitė, Kristina

2011-01-01

The aim of this study was to determine the sensitivity and specificity of this classical technique employed at the Hospital of Lithuanian University of Health Sciences for the patients with multiple sclerosis and to assess its possible correlations with affected neurological systems. Pattern shift visual evoked potentials were recorded in 63 patients with multiple sclerosis, 17 (27%) of whom had a history of optic neuritis, and in 63 control patients with other neurological diseases. The latencies and amplitudes of P100 were measured. In total, 126 patients were referred to the inpatient department of neurology for differential diagnosis of demyelinating disorders between January and December of 2007. Abnormalities of visual evoked potentials were observed by 73% more frequently in patients with multiple sclerosis than in control patients (α=0.05, β<0.01). The combined monocular/interocular test showed a specificity of 90.5% and a sensitivity of 82.5%. The probability of an affection of the pyramidal system was 5 times greater (95% CI, 2.2-11.0; P<0.01) and the probability of the optic pathways involvement was 4.8 times greater (95% CI, 1.9-11.9; P<0.01) in patients with multiple sclerosis than in controls. Conventional visual evoked potentials must be reappraised in light of their diagnostic value in multiple sclerosis given their high diagnostic efficiency, relatively easy, short, and cheap implementation, and easy availability in everyday clinical practice.

Validity and reliability of the multidimensional assessment of fatigue scale in Iranian patients with relapsing-remitting subtype of multiple sclerosis.

PubMed

Behrangrad, Shabnam; Kordi Yoosefinejad, Amin

2018-03-01

The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart. Construct validity of the MAFS was assessed with the Fatigue Impact Scale. The MAFS had high internal consistency (Cronbach's alpha >0.9) and 3-d test-retest reliability (intraclass correlation coefficient = 0.99). Correlation between the Fatigue Impact Scale and MAFS was high (r = 0.99). Correlation between MAFS scores and the Expanded Disability Status Scale was also strong (r = 0.85). Questionnaire items showed acceptable item-scale correlation (0.968-0.993). The Persian version of the MAFS appears to be a valid and reliable questionnaire. It is an appropriate short multidimensional instrument to assess fatigue in patients with multiple sclerosis in clinical practice and research. Implications for Rehabilitation The Persian version of Multidimensional Assessment of Fatigue is a valid and reliable instrument for the assessment and monitoring the fatigue in Persian-language patients with multiple sclerosis. It is very easy to administer and a time efficient scale in comparison to other instruments evaluating fatigue in patients with multiple sclerosis.

Pain and Cognition in Multiple Sclerosis.

PubMed

Scherder, R; Kant, N; Wolf, E; Pijnenburg, A C M; Scherder, E

2017-10-01

The goal of the present study was to examine the relationship between pain and cognition in patients with multiple sclerosis. Cross-sectional. Nursing home and personal environment of the investigators. Two groups of participants were included: 91 patients with multiple sclerosis and 80 matched control participants. The level of pain was measured by the following pain scales: Number of Words Chosen-Affective, Colored Analogue Scale for pain intensity and suffering from pain, and the Faces Pain Scale. Mood was tested by administering the Beck Depression Inventory and the Symptom Check List-90 anxiety and depression subscale. Global cognitive functioning was assessed by the Mini Mental State Examination. Memory and executive functions were assessed by several neuropsychological tests. Multiple sclerosis (MS) patients scored significantly lower than control participants on the majority of the neuropsychological tests. The MS patients experienced more pain compared with control participants, despite the fact that they were taking significantly more pain medication. No significant correlation was observed between cognition and pain in MS patients. Verbal working memory explained 10% of pain intensity (trend). Mood appeared to be a significant predictor of pain in patients with multiple sclerosis. The lack of a relationship between cognition and pain might be explained by the fact that, compared with control participants, patients with multiple sclerosis activate other non-pain-related areas to perform executive functions and memory tasks. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com