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

Pulmonary function and dysfunction in multiple sclerosis.

PubMed

Smeltzer, S C; Utell, M J; Rudick, R A; Herndon, R M

1988-11-01

Pulmonary function was studied in 25 patients with clinically definite multiple sclerosis with a range of motor impairment. Forced vital capacity (FVC), maximal voluntary ventilation (MVV), and maximal expiratory pressure (MEP) were normal in the ambulatory patients (mean greater than or equal to 80% predicted) but reduced in bedridden patients (mean, 38.5%, 31.6%, and 36.3% predicted; FCV, MVV, and MEP, respectively) and wheelchair-bound patients with upper extremity involvement (mean, 69.4%, 50.4%, and 62.6% predicted; FVC, MVV, and MEP, respectively). Forced vital capacity, MVV, and MEP correlated with Kurtzke Expanded Disability Status scores (tau = -0.72, -0.70, and -0.65) and expiratory muscle weakness occurred most frequently. These findings demonstrate that marked expiratory weakness develops in severely paraparetic patients with multiple sclerosis and the weakness increases as the upper extremities become increasingly involved.

Evidence for the efficacy and effectiveness of THC-CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis.

PubMed

Zettl, Uwe K; Rommer, Paulus; Hipp, Petra; Patejdl, Robert

2016-01-01

Spasticity, one of the main symptoms of multiple sclerosis (MS), can affect more than 80% of MS patients during the course of their disease and is often not treated adequately. δ-9-Tetrahydrocannabinol-cannabidiol (THC-CBD) oromucosal spray is a plant-derived, standardized cannabinoid-based oromucosal spray medicine for add-on treatment of moderate to severe, resistant multiple sclerosis-induced spasticity. This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity. Results from both randomized controlled phase III studies involving about,1600 MS patients or 1500 patient-years and recently published studies on everyday clinical practice involving more than 1000 patients or more than,1000 patient-years are presented.

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.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

PubMed

Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue

PubMed Central

Whitley, Corinna; Gunst, Karin; Müller, Hermann; Funk, Mathis; zur Hausen, Harald

2014-01-01

Epidemiological data point to the involvement of a cow milk factor in the etiology of multiple sclerosis (MS). Eleven circular DNA molecules closely related to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 1.76 were isolated from healthy cattle serum, cow milk, and serum and brain tissue from MS patients. PMID:25169859

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.

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.

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.

Evidence for the efficacy and effectiveness of THC-CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis

PubMed Central

Zettl, Uwe K.; Rommer, Paulus; Hipp, Petra; Patejdl, Robert

2016-01-01

Spasticity, one of the main symptoms of multiple sclerosis (MS), can affect more than 80% of MS patients during the course of their disease and is often not treated adequately. δ-9-Tetrahydrocannabinol-cannabidiol (THC-CBD) oromucosal spray is a plant-derived, standardized cannabinoid-based oromucosal spray medicine for add-on treatment of moderate to severe, resistant multiple sclerosis-induced spasticity. This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity. Results from both randomized controlled phase III studies involving about,1600 MS patients or 1500 patient-years and recently published studies on everyday clinical practice involving more than 1000 patients or more than,1000 patient-years are presented. PMID:26788128

[Current description of multiple sclerosis].

PubMed

Río, Jordi; Montalbán, Xavier

2014-12-01

Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Acute symptomatic sinus bradycardia in a woman treated with pulse dose steroids for multiple sclerosis: a case report.

PubMed

Kundu, Amartya; Fitzgibbons, Timothy P

2015-09-24

Sinus bradycardia has been reported after administration of pulse dose steroids, although most cases have occurred in children and are asymptomatic. We report a case of acute symptomatic sinus bradycardia due to pulse dose steroids in a woman with multiple sclerosis. Interestingly, this patient also suffered from inappropriate sinus tachycardia due to autonomic involvement of multiple sclerosis. A 48-year-old Caucasian woman with multiple sclerosis and chronic palpitations due to inappropriate sinus tachycardia was prescribed a 5-day course of intravenous methylprednisolone for treatment of an acute flare. Immediately following the fourth dose of intravenous methylprednisolone, she developed dyspnea, chest heaviness, and lightheadedness. She was referred to the emergency department where an electrocardiogram showed marked sinus bradycardia (40 beats per minute). Initial laboratory test results, including a complete blood count, basic metabolic profile and cardiac biomarkers, were normal. She was admitted for observation on telemetry monitoring. Her heart rate gradually increased and her symptoms resolved. Her outpatient dose of atenolol, taken for symptomatic inappropriate sinus tachycardia, was resumed. Our patient's acute symptoms were attributed to symptomatic sinus bradycardia due to pulse dose steroid treatment. Although several theories have been suggested to explain this phenomenon, the exact mechanism still remains unknown. It does not warrant any specific treatment, as it is a self-limiting side effect that resolves after discontinuing steroid infusion. Young patients who are free of any active cardiac conditions can safely be administered pulse dose steroids without monitoring. However, older patients with active cardiac conditions should have heart rate and blood pressure monitoring during infusion. Our patient also suffered from inappropriate sinus tachycardia, a manifestation of autonomic involvement of multiple sclerosis that has not been previously described. This case has implications for the pathogenesis and treatment of dysautonomia in patients with multiple sclerosis.

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

Multiple sclerosis: Pregnancy and women's health issues.

PubMed

Mendibe Bilbao, M; Boyero Durán, S; Bárcena Llona, J; Rodriguez-Antigüedad, A

2016-08-18

The course of multiple sclerosis (MS) is influenced by sex, pregnancy and hormonal factors. To analyse the influence of the above factors in order to clarify the aetiopathogenic mechanisms involved in the disease. We conducted a comprehensive review of scientific publications in the PubMed database using a keyword search for 'multiple sclerosis', 'MS', 'EAE', 'pregnancy', 'hormonal factors', 'treatment', and related terms. We reviewed the advances presented at the meeting held by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in March 2013 in London, as well as recommendations by international experts. We provide recommendations for counselling and treating women with MS prior to and during pregnancy and after delivery. Current findings on the effects of treatment on the mother, fetus, and newborn are also presented. We issue recommendations for future research in order to address knowledge gaps and clarify any inconsistencies in currently available data. Copyright © 2016 Sociedad Española de Neurología. 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

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.

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.

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.

Microcystic macular oedema in multiple sclerosis is associated with disease severity

PubMed Central

Gelfand, Jeffrey M.; Nolan, Rachel; Schwartz, Daniel M.; Graves, Jennifer

2012-01-01

Macular oedema typically results from blood–retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis. Despite a lack of myelin, the retina is a site of inflammation and microglial activation in multiple sclerosis and demonstrates significant neuronal and axonal loss. We unexpectedly observed microcystic macular oedema using spectral domain optical coherence tomography in patients with multiple sclerosis who did not have another reason for macular oedema. We therefore evaluated spectral domain optical coherence tomography images in consecutive patients with multiple sclerosis for microcystic macular oedema and examined correlations between macular oedema and visual and ambulatory disability in a cross-sectional analysis. Participants were excluded if there was a comorbidity that could account for the presence of macular oedema, such as uveitis, diabetes or other retinal disease. A microcystic pattern of macular oedema was observed on optical coherence tomography in 15 of 318 (4.7%) patients with multiple sclerosis. No macular oedema was identified in 52 healthy controls assessed over the same period. The microcystic oedema predominantly involved the inner nuclear layer of the retina and tended to occur in small, discrete patches. Patients with multiple sclerosis with microcystic macular oedema had significantly worse disability [median Expanded Disability Score Scale 4 (interquartile range 3–6)] than patients without macular oedema [median Expanded Disability Score Scale 2 (interquartile range 1.5–3.5)], P = 0.0002. Patients with multiple sclerosis with microcystic macular oedema also had higher Multiple Sclerosis Severity Scores, a measure of disease progression, than those without oedema [median of 6.47 (interquartile range 4.96–7.98) versus 3.65 (interquartile range 1.92–5.87), P = 0.0009]. Microcystic macular oedema occurred more commonly in eyes with prior optic neuritis than eyes without prior optic neuritis (50 versus 27%) and was associated with lower visual acuity (median logMAR acuity of 0.17 versus −0.1) and a thinner retinal nerve fibre layer. The presence of microcystic macular oedema in multiple sclerosis suggests that there may be breakdown of the blood–retinal barrier and tight junction integrity in a part of the nervous system that lacks myelin. Microcystic macular oedema may also contribute to visual dysfunction beyond that explained by nerve fibre layer loss. Microcystic changes need to be assessed, and potentially adjusted for, in clinical trials that evaluate macular volume as a marker of retinal ganglion cell survival. These findings also have implications for clinical monitoring in patients with multiple sclerosis on sphingosine 1-phosphate receptor modulating agents. PMID:22539259

Simultaneous, Bilateral Ophthalmoplegia as the Presenting Sign of Paediatric Multiple Sclerosis: Case Report and Discussion of the Differential Diagnosis

PubMed Central

Adam, Murtaza K.; Krespan, Kelly; Moster, Mark L.; Sergott, Robert C.

2014-01-01

Abstract An 11-year-old female developed bilateral oculomotor nerve palsies without pupillary involvement and bilateral optic neuropathy as the presenting signs of paediatric multiple sclerosis (MS). Although ocular mono-neuropathies have been reported, this is the first bilateral mono-neuropathy reported in a paediatric patient due to MS. The differential diagnosis and evaluation for bilateral ophthalmoplegia are discussed in detail. PMID:27928305

Primary Sjogren's syndrome with central nervous system involvement.

PubMed

Alhomoud, Iftetah A; Bohlega, Saeed A; Alkawi, Mohammed Z; Alsemari, Abdulaziz M; Omer, Saleh M; Alsenani, Fahmi M

2009-08-01

To describe the clinical, laboratory, and radiological features of Primary Sjogren's syndrome (PSS) with central nervous system (CNS) involvement. A retrospective case series of 12 female patients with PSS and CNS involvement at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia from 1991-2009. The diagnosis of PSS is defined by the American-European Diagnostic Criteria. We analyzed the clinical, radiological, and immunological features. The mean age was 40 years (range 16-58 years); all patient were females and presented with active neurological symptoms. The neurological involvement preceded the classic sicca symptoms (33%). Eight patients (66%) presented with myelopathy, 9 patients (75%) had optic neuritis, and the rest had variable neurological signs. Immunological tests (anti-Sjogren's syndrome A and anti-Sjogren's syndrome B) were high in 7 patients (58%). Minor salivary gland biopsy revealed inflammatory cell infiltrate in 11 patients (92%). Brain MRI showed scattered white matter changes in 7 patients (58%). Spine MRI showed multiple foci of hyperintensity in T2-weighted image in 6 patients (50%), and long segment of hyperintensity at the cervical spinal cord in 2 patients (16%). Our findings demonstrate that CNS involvements in PSS have great clinical variability and could precede the classic sicca symptoms by years. Primary Sjogren's syndrome can mimic multiple sclerosis (primary progressive multiple sclerosis or relapsing remitting multiple sclerosis), therefore a screening test for PSS should be considered in suspected cases. A well-defined management protocol awaits studies with larger case numbers.

A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging

PubMed Central

Louapre, Céline; Govindarajan, Sindhuja T.; Giannì, Costanza; Nielsen, A. Scott; Cohen-Adad, Julien; Sloane, Jacob; Kinkel, Revere P.

2015-01-01

We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients’ normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10−10 and P < 10−7), and mean cortical T2* in controls (P < 10−5 and P < 10−6). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface. PMID:25681411

[Multiple sclerosis, loss of functionality and gender].

PubMed

Bravo-González, Félix; Álvarez-Roldán, Arturo

2017-12-01

To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects the perception of these needs. Interpretative-phenomenological qualitative study. Granada (Spain). Year: 2014. Intentional sample: 30 patients and 20 family caregivers. Data were gathered from 26 interviews and 4 focus groups. The data were coded and analysed with the NVivo programme. The multiple sclerosis patients and family caregivers had different perceptions of the loss of capacity to undertake activities of daily living. Being able to self care was considered the last vestige of autonomy. The women with multiple sclerosis tried to take on the responsibility of housework, but the male caregivers became gradually involved in these tasks. Gender roles were redefined with respect to housekeeping. The multiple sclerosis patients showed a need for emotional support. Some of the men had abandoned the stereotype of the strong male as a result of the decline in their health. Adaptations in the home took place without planning them in advance. The use of mobility devices started on an occasional basis. A fear of stigma was an obstacle for regular use of assistive technology. Health care for people with multiple sclerosis should include family caregivers. Gender influences the perception that caregivers and patients have of the assistance they require to maximise their quality of life. This flags up several intervention areas for the follow-up and long-term care of these patients by the healthcare system. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Adaptive human immunity drives remyelination in a mouse model of demyelination

PubMed Central

El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand

2017-01-01

Abstract One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies. PMID:28334918

Adaptive human immunity drives remyelination in a mouse model of demyelination.

PubMed

El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand; Zujovic, Violetta

2017-04-01

One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Patient perspectives on physician conflict of interest in industry-sponsored clinical trials for multiple sclerosis therapeutics.

PubMed

Solomon, Andrew J; Klein, Eran P; Corboy, John R; Bernat, James L

2015-10-01

Pharmaceutical industry financial support of physicians, physician practices, and academic departments involved in multicenter industry-sponsored clinical trials of novel therapeutic agents is a relatively new and infrequently acknowledged source of potential physician conflict of interest. Detailed disclosure of these relationships to study participants is not uniformly a part of informed consent and documentation practices. To understand attitudes of patients with multiple sclerosis concerning disclosure of potential physician-industry conflicts of interest created by clinical trials and how such disclosures may influence study participation An anonymous online instrument was developed. 597 people with multiple sclerosis participated in the study. The study found that detailed disclosure of conflicts of interest is important to potential participants in industry-sponsored clinical trials for multiple sclerosis therapies and that the presence of these conflicts of interest may influence patients' decisions to participate in these studies. Findings from this study support a call for uniform guidelines regarding disclosure of physician-industry relationships to prospective research participants for industry-sponsored clinical trials. © The Author(s), 2015.

Can multiple sclerosis as a cognitive disorder influence patients’ dreams?

PubMed Central

Owji, Mahsa

2013-01-01

Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS) is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients’ dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease. PMID:24250908

Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

PubMed

Suneetha, A; Raja Rajeswari, K

2016-04-15

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via oxidative stress pathway. The rapid screening methods are also need to be developed to estimate DMF in biological samples to perform and proceed for further investigations. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Recommendations for the detection and therapeutic management of cognitive impairment in multiple sclerosis.

PubMed

Bensa, C; Bodiguel, E; Brassat, D; Laplaud, D; Magy, L; Ouallet, J-C; Zephir, H; De Seze, J; Blanc, F

2012-11-01

The aim of the Multiple Sclerosis Think Tank (Groupe de réflexion sur la sclérose en plaques [GRESEP]) is to prescribe recommendations following a systematic literature search and using a Rand Corporation and California University (RAND/UCLA) appropriateness derived method, in response to practical questions that are raised in the management of patients with multiple sclerosis (MS). The topics of this working program were chosen because they were not addressed in the French recommendations and because of the few data in the literature that enabled practices to be based on validated data. Following the theme on useful serum testing with suspected multiple sclerosis, the subjects of the present work concern the detection and management of cognitive impairment in the beginning stages of the disease course. Two clinical questions were asked: which complementary exams (besides physical examination and neuropsychological tests) would help in the screening of cognitive impairment at the beginning of the disease? What care management should the person with MS and cognitive impairment be offered (treatments and neurocognitive rehabilitation)? The recommendations are the result of a consensus amongst a working group, a rating group and a reading group comprised of hospital neurologists involved in the management of patients with multiple sclerosis. Each recommendation is presented with the degree of consensus that it was accorded. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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.

Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

PubMed

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

PubMed Central

Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis. PMID:25883816

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.

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

PubMed

Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C; Otto, Markus; Tumani, Hayrettin

2015-07-31

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

PubMed Central

Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C.; Otto, Markus; Tumani, Hayrettin

2015-01-01

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. PMID:26263977

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

PubMed

Swirsky-Sacchetti, T; Mitchell, D R; Seward, J; Gonzales, C; Lublin, F; Knobler, R; Field, H L

1992-07-01

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.

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.

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.

Nature plus nurture: the triggering of multiple sclerosis.

PubMed

Wekerle, Hartmut

2015-01-01

Recent clinical and experimental studies indicate that multiple sclerosis develops as consequence of a failed interplay between genetic ("nature") and environmental ("nurture") factors. A large number of risk genes favour an autoimmune response against the body's own brain matter. New experimental data indicate that the actual trigger of this attack is however provided by an interaction of brain-specific immune cells with components of the regular commensal gut flora, the intestinal microbiota. This concept opens the way for new therapeutic approaches involving modulation of the microbiota by dietary or antibiotic regimens.

[Consensus document on spasticity in patients with multiple sclerosis. Grupo de Enfermedades Desmielinizantes de la Sociedad Española de Neurología].

PubMed

Oreja-Guevara, Celia; Montalban, Xavier; de Andrés, Clara; Casanova-Estruch, Bonaventura; Muñoz-García, Delicias; García, Inmaculada; Fernández, Óscar

2013-10-16

Multiple sclerosis is a chronic neurological inflammatory demyelinating disease. Specialists involved in the symptomatic treatment of this disease tend to apply heterogeneous diagnostic and treatment criteria. To establish homogeneous criteria for treating spasticity based on available scientific knowledge, facilitating decision-making in regular clinical practice. A group of multiple sclerosis specialists from the Spanish Neurological Society demyelinating diseases working group met to review aspects related to spasticity in this disease and draw up the consensus. After an exhaustive bibliographic search and following a metaplan technique, a number of preliminary recommendations were established to incorporate into the document. Finally, each argument was classified depending on the degree of recommendation according to the SIGN (Scottish Intercollegiate Guidelines Network) system. The resulting text was submitted for review by the demyelinating disease group. An experts' consensus was reached regarding spasticity triggering factors, related symptoms, diagnostic criteria, assessment methods, quality of life and therapeutic management (drug and non-drug) criteria. The recommendations included in this consensus can be a useful tool for improving the quality of life of multiple sclerosis patients, as they enable improved diagnosis and treatment of spasticity.

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

May Diet and Dietary Supplements Improve the Wellness of Multiple Sclerosis Patients? A Molecular Approach

PubMed Central

Riccio, Paolo; Rossano, Rocco; Liuzzi, Grazia Maria

2010-01-01

Multiple sclerosis is a complex and multifactorial neurological disease, and nutrition is one of the environmental factors possibly involved in its pathogenesis. At present, the role of nutrition is unclear, and MS therapy is not associated to a particular diet. MS clinical trials based on specific diets or dietary supplements are very few and in some cases controversial. To understand how diet can influence the course of MS and improve the wellness of MS patients, it is necessary to identify the dietary molecules, their targets and the molecular mechanisms involved in the control of the disease. The aim of this paper is to provide a molecular basis for the nutritional intervention in MS by evaluating at molecular level the effect of dietary molecules on the inflammatory and autoimmune processes involved in the disease. PMID:21461338

[When thinking to scleroderma?].

PubMed

Cogan, E

2007-09-01

Scleroderma encompasses an heterogeneous group of autoimmune disorders characterized by an hidebound thickened skin involvement. When the changes are limited to the skin, localized scleroderma is suspected. Although the latter is most often a benign disease, it may be exceptionally associated with involvement of multiple organs, mainly the neurological system. At the opposite, systemic sclerosis is a serious disorder associated with high morbidity and even mortality and defined by an extended skin sclerosis, multiple organ involvement and general symptoms. Raynaud phenomena is nearly always present at the beginning of the disease. Identifying initial manifestations of the disease (Raynaud phenomena, diffuse non pitting edema, symmetrical polyarthritis with tendon friction rubs, dysphagia associated with mucosal telangiectasia) may allow the clinician to rapidly transfer the patient to a specialized reference center in order to organize a multidisciplinary approach and to prompt optimum therapy.

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

PubMed

Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

2017-04-01

Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experimental models of demyelination and remyelination.

PubMed

Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

2017-08-29

Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study.

PubMed

Filippi, Massimo; Preziosa, Paolo; Meani, Alessandro; Ciccarelli, Olga; Mesaros, Sarlota; Rovira, Alex; Frederiksen, Jette; Enzinger, Christian; Barkhof, Frederik; Gasperini, Claudio; Brownlee, Wallace; Drulovic, Jelena; Montalban, Xavier; Cramer, Stig P; Pichler, Alexander; Hagens, Marloes; Ruggieri, Serena; Martinelli, Vittorio; Miszkiel, Katherine; Tintorè, Mar; Comi, Giancarlo; Dekker, Iris; Uitdehaag, Bernard; Dujmovic-Basuroski, Irena; Rocca, Maria A

2018-02-01

In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). Changes to the DIS definition included removal of the distinction between symptomatic and asymptomatic lesions, increasing the number of lesions needed to define periventricular involvement to three, combining cortical and juxtacortical lesions, and inclusion of optic nerve evaluation. For DIT, removal of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic criteria. Brain and spinal cord MRI and optic nerve assessments from patients with typical CIS suggestive of multiple sclerosis done less than 3 months from clinical onset in eight European multiple sclerosis centres were included in this retrospective study. Eligible patients were 16-60 years, and had a first CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple sclerosis, a complete neurological examination, a baseline brain and spinal cord MRI scan obtained less than 3 months from clinical onset, and a follow-up brain scan obtained less than 12 months from CIS onset. We recorded occurrence of a second clinical attack (clinically definite multiple sclerosis) at months 36 and 60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a time-dependent receiver operating characteristic curve analysis. Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed clinically definite multiple sclerosis. At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0·91 [95% CI 0·85-0·94] and 2016 MAGNIMS 0·93 [0·88-0·96]), similar specificity (0·33 [0·25-0·42] and 0·32 [0·24-0·41]), and similar area under the curve values (AUC; 0·62 [0·57-0·67] and 0·63 [0·58-0·67]). Performance was not affected by inclusion of symptomatic lesions (sensitivity 0·92 [0·87-0·96], specificity 0·31 [0·23-0·40], AUC 0·62 [0·57-0·66]) or cortical lesions (sensitivity 0·92 [0·87-0·95], specificity 0·32 [0·24-0·41], AUC 0·62 [0·57-0·67]). Requirement of three periventricular lesions resulted in slightly lower sensitivity (0·85 [0·78-0·90], slightly higher specificity (0·40 [0·32-0·50], and similar AUC (0·63 [0·57-0·68]). Inclusion of optic nerve evaluation resulted in similar sensitivity (0·92 [0·87-0·96]), and slightly lower specificity (0·26 [0·18-0·34]) and AUC (0·59 [0·55-0·64]). AUC values were also similar for DIT (2010 McDonald 0·61 [0·55-0·67] and 2016 MAGNIMS 0·61 [0·55-0·66]) and DIS plus DIT (0·62 [0·56-0·67] and 0·64 [0·58-0·69]). The 2016 MAGNIMS criteria showed similar accuracy to the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis. Inclusion of symptomatic lesions is expected to simplify the clinical use of MRI criteria without reducing accuracy, and our findings suggest that needing three lesions to define periventricular involvement might slightly increase specificity, suggesting that these two factors could be considered during further revisions of multiple sclerosis diagnostic criteria. UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre, Dutch MS Research Foundation. Copyright © 2018 Elsevier Ltd. All rights reserved.

The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells.

PubMed

Machado-Santos, Joana; Saji, Etsuji; Tröscher, Anna R; Paunovic, Manuela; Liblau, Roland; Gabriely, Galina; Bien, Christian G; Bauer, Jan; Lassmann, Hans

2018-06-04

Multiple sclerosis is an inflammatory demyelinating disease in which active demyelination and neurodegeneration are associated with lymphocyte infiltrates in the brain. However, so far little is known regarding the phenotype and function of these infiltrating lymphocyte populations. In this study, we performed an in-depth phenotypic characterization of T and B cell infiltrates in a large set of multiple sclerosis cases with different disease and lesion stages and compared the findings with those seen in inflammatory, non-inflammatory and normal human controls. In multiple sclerosis lesions, we found a dominance of CD8+ T cells and a prominent contribution of CD20+ B cells in all disease courses and lesion stages, including acute multiple sclerosis cases with very short disease duration, while CD4+ T cells were sparse. A dominance of CD8+ T cells was also seen in other inflammatory controls, such as Rasmussen's encephalitis and viral encephalitis, but the contribution of B cells in these diseases was modest. Phenotypic analysis of the CD8+ T cells suggested that part of the infiltrating cells in active lesions proliferate, show an activated cytotoxic phenotype and are in part destroyed by apoptosis. Further characterization of the remaining cells suggest that CD8+ T cells acquire features of tissue-resident memory cells, which may be focally reactivated in active lesions of acute, relapsing and progressive multiple sclerosis, while B cells, at least in part, gradually transform into plasma cells. The loss of surface molecules involved in the egress of leucocytes from inflamed tissue, such as S1P1 or CCR7, and the upregulation of CD103 expression may be responsible for the compartmentalization of the inflammatory response in established lesions. Similar phenotypic changes of tissue-infiltrating CD8+ T cells were also seen in Rasmussen's encephalitis. Our data underline the potential importance of CD8+ T lymphocytes and B cells in the inflammatory response in established multiple sclerosis lesions. Tissue-resident T and B cells may represent guardians of previous inflammatory brain disease, which can be reactivated and sustain the inflammatory response, when they are re-exposed to their specific antigen.

Deciphering amyotrophic lateral sclerosis: what phenotype, neuropathology and genetics are telling us about pathogenesis.

PubMed

Ravits, John; Appel, Stanley; Baloh, Robert H; Barohn, Richard; Brooks, Benjamin Rix; Elman, Lauren; Floeter, Mary Kay; Henderson, Christopher; Lomen-Hoerth, Catherine; Macklis, Jeffrey D; McCluskey, Leo; Mitsumoto, Hiroshi; Przedborski, Serge; Rothstein, Jeffrey; Trojanowski, John Q; van den Berg, Leonard H; Ringel, Steven

2013-05-01

Amyotrophic lateral sclerosis (ALS) is characterized phenotypically by progressive weakness and neuropathologically by loss of motor neurons. Phenotypically, there is marked heterogeneity. Typical ALS has mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Primary lateral sclerosis has predominant UMN involvement. Progressive muscular atrophy has predominant LMN involvement. Bulbar and limb ALS have predominant regional involvement. Frontotemporal dementia has significant cognitive and behavioral involvement. These phenotypes can be so distinctive that they would seem to have differing biology. However, they cannot be distinguished, at least neuropathologically or genetically. In sporadic ALS (SALS), they are mostly characterized by ubiquitinated cytoplasmic inclusions of TDP-43. In familial ALS (FALS), where phenotypes are indistinguishable from SALS and similarly heterogeneous, each mutated gene has its own genetic and molecular signature. Overall, since the same phenotypes can have multiple causes including different gene mutations, there must be multiple molecular mechanisms causing ALS - and ALS is a syndrome. Since, however, multiple phenotypes can be caused by one single gene mutation, a single molecular mechanism can cause heterogeneity. What the mechanisms are remain unknown, but active propagation of the pathology neuroanatomically seems to be a principal component. Leading candidate mechanisms include RNA processing, cell-cell interactions between neurons and non-neuronal neighbors, focal seeding from a misfolded protein that has prion-like propagation, and fatal errors introduced during neurodevelopment of the motor system. If fundamental mechanisms could be identified and understood, ALS therapy could rationally target progression and stop the disease - a goal that seems increasingly achievable.

Gray Matter Is Targeted in First-Attack Multiple Sclerosis

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

Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao

The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We foundmore » that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.« less

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.

Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

PubMed

Vidal-Jordana, Angela; Montalban, Xavier

2017-05-01

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive assessment in multiple sclerosis-an Italian consensus.

PubMed

Amato, Maria Pia; Morra, Vincenzo Brescia; Falautano, Monica; Ghezzi, Angelo; Goretti, Benedetta; Patti, Francesco; Riccardi, Alice; Mattioli, Flavia

2018-05-15

The aim of this consensus paper was to define the state of the art on cognitive assessment of persons with multiple sclerosis (PwMS), with the purpose of providing recommendations for the Italian centers involved in MS management. While there are no formal guidelines published regarding the assessment of cognitive function in MS, on the basis of an expert opinion meeting, held in Milan (Italy) on July 4, 2016, we report the recommendations of a panel of Italian experts including MS neurologists and neuropsychologists for the assessment and follow-up of cognitive function in adult MS subjects.

Genetic variation in the myeloperoxidase gene and cognitive impairment in Multiple Sclerosis

PubMed Central

Manna, I; Valentino, P; La Russa, A; Condino, F; Nisticò, R; Liguori, M; Clodomiro, A; Andreoli, V; Pirritano, D; Cittadella, R; Quattrone, A

2006-01-01

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to β-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS. PMID:16504169

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.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

PubMed

Prokopova, Barbora; Hlavacova, Natasa; Vlcek, Miroslav; Penesova, Adela; Grunnerova, Lucia; Garafova, Alexandra; Turcani, Peter; Kollar, Branislav; Jezova, Daniela

2017-01-15

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients. Copyright © 2016. Published by Elsevier B.V.

Vestibular evoked myogenic potential findings in multiple sclerosis.

PubMed

Escorihuela García, Vicente; Llópez Carratalá, Ignacio; Orts Alborch, Miguel; Marco Algarra, Jaime

2013-01-01

Multiple sclerosis is an inflammatory disease involving the occurrence of demyelinating, chronic neurodegenerative lesions in the central nervous system. We studied vestibular evoked myogenic potentials (VEMPs) in this pathology, to allow us to evaluate the saccule, inferior vestibular nerve and vestibular-spinal pathway non-invasively. There were 23 patients diagnosed with multiple sclerosis who underwent VEMP recordings, comparing our results with a control group consisting of 35 healthy subjects. We registered p13 and n23 wave latencies, interaural amplitude difference and asymmetry ratio between both ears. Subjects also underwent an otoscopy and audiometric examination. The prolongation of p13 and n23 wave latencies was the most notable characteristic, with a mean p13 wave latency of 19.53 milliseconds and a mean latency of 30.06 milliseconds for n23. In contrast, the asymmetry index showed no significant differences with our control group. In case of multiple sclerosis, the prolongation of the p13 and n23 VEMP wave latencies is a feature that has been attributed to slowing of conduction by demyelination of the vestibular-spinal pathway. In this regard, alteration of the response or lack thereof in these potentials has a locator value of injury to the lower brainstem. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Effects of Rhythmic Auditory Cueing in Gait Rehabilitation for Multiple Sclerosis: A Mini Systematic Review and Meta-Analysis

PubMed Central

Ghai, Shashank; Ghai, Ishan

2018-01-01

Rhythmic auditory cueing has been shown to enhance gait performance in several movement disorders. The “entrainment effect” generated by the stimulations can enhance auditory motor coupling and instigate plasticity. However, a consensus as to its influence over gait training among patients with multiple sclerosis is still warranted. A systematic review and meta-analysis was carried out to analyze the effects of rhythmic auditory cueing in studies gait performance in patients with multiple sclerosis. This systematic identification of published literature was performed according to PRISMA guidelines, from inception until Dec 2017, on online databases: Web of science, PEDro, EBSCO, MEDLINE, Cochrane, EMBASE, and PROQUEST. Studies were critically appraised using PEDro scale. Of 602 records, five studies (PEDro score: 5.7 ± 1.3) involving 188 participants (144 females/40 males) met our inclusion criteria. The meta-analysis revealed enhancements in spatiotemporal parameters of gait i.e., velocity (Hedge's g: 0.67), stride length (0.70), and cadence (1.0), and reduction in timed 25 feet walking test (−0.17). Underlying neurophysiological mechanisms, and clinical implications are discussed. This present review bridges the gaps in literature by suggesting application of rhythmic auditory cueing in conventional rehabilitation approaches to enhance gait performance in the multiple sclerosis community. PMID:29942278

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.

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.

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…

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.

Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

PubMed

Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

2017-04-01

Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

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.

Pseudobulbar affect in multiple sclerosis: toward the development of innovative therapeutic strategies.

PubMed

Miller, Ariel

2006-06-15

Pseudobulbar affect (PBA), a condition involving involuntary and uncontrollable episodes of crying and/or laughing, occurs frequently in patients with a variety of neurological disorders, including amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, dementia including Alzheimer's disease, and multiple sclerosis (MS). Although PBA results in considerable distress for patients and caretakers, it is underrecognized and undertreated. Agents used to treat psychiatric disorders--particularly tricyclic antidepressants and selective serotonin reuptake inhibitors--are useful in alleviating PBA, but act on diffuse neural networks rather than targeting those involved in emotional motor expression. As a result of their nonspecific activity, these agents are associated with a range of unwanted effects that preclude many patients from using them. Dextromethorphan, a common cough suppressant, specifically targets sigma(1) receptors concentrated in the brainstem and cerebellum, thus providing the possibility of targeting regions implicated in emotional expression. When administered in a fixed combination with quinidine, dextromethorphan is effective in treating PBA in patients with ALS, and preliminary results suggest that this therapy also is effective in treating MS-related PBA.

TEAMS (Tele-Exercise and Multiple Sclerosis), a Tailored Telerehabilitation mHealth App: Participant-Centered Development and Usability Study

PubMed Central

Rimmer, James H; Johnson, George; Wilroy, Jereme; Young, Hui-Ju; Mehta, Tapan; Lai, Byron

2018-01-01

Background People with multiple sclerosis face varying levels of disability and symptoms, thus requiring highly trained therapists and/or exercise trainers to design personalized exercise programs. However, for people living in geographically isolated communities, access to such trained professionals can be challenging due to a number of barriers associated with cost, access to transportation, and travel distance. Generic mobile health exercise apps often fall short of what people with multiple sclerosis need to become physically active (ie, exercise content that has been adapted to accommodate a wide range of functional limitations). Objective This usability study describes the development process of the TEAMS (Tele-Exercise and Multiple Sclerosis) app, which is being used by people with multiple sclerosis in a large randomized controlled trial to engage in home-based telerehabilitation. Methods Twenty-one participants with disabilities (10 people with multiple sclerosis) were involved in the double iterative design, which included the simultaneous development of the app features and exercise content (exercise videos and articles). Framed within a user-centered design approach, the development process included 2 stages: ground-level creation (focus group followed by early stage evaluations and developments), and proof of concept through 2 usability tests. Usability (effectiveness, usefulness, and satisfaction) was evaluated using a mixed-methods approach. Results During testing of the app’s effectiveness, the second usability test resulted in an average of 1 problem per participant, a decrease of 53% compared to the initial usability test. Five themes were constructed from the qualitative data that related to app usefulness and satisfaction, namely: high perceived confidence for app usability, positive perceptions of exercise videos, viable exercise option at home, orientation and familiarity required for successful participation, and app issues. Participants acknowledged that the final app was ready to be delivered to the public after minor revisions. After including these revisions, the project team released the final app that is being used in the randomized controlled trial. Conclusions A multi-level user-centered development process resulted in the development of an inclusive exercise program for people with multiple sclerosis operated through an easy-to-use app. The promotion of exercise through self-regulated mHealth programs requires a stakeholder-driven approach to app development. This ensures that app and content match the preferences and functional abilities of the end user (ie, people with varying levels of multiple sclerosis). PMID:29798832

TEAMS (Tele-Exercise and Multiple Sclerosis), a Tailored Telerehabilitation mHealth App: Participant-Centered Development and Usability Study.

PubMed

Thirumalai, Mohanraj; Rimmer, James H; Johnson, George; Wilroy, Jereme; Young, Hui-Ju; Mehta, Tapan; Lai, Byron

2018-05-24

People with multiple sclerosis face varying levels of disability and symptoms, thus requiring highly trained therapists and/or exercise trainers to design personalized exercise programs. However, for people living in geographically isolated communities, access to such trained professionals can be challenging due to a number of barriers associated with cost, access to transportation, and travel distance. Generic mobile health exercise apps often fall short of what people with multiple sclerosis need to become physically active (ie, exercise content that has been adapted to accommodate a wide range of functional limitations). This usability study describes the development process of the TEAMS (Tele-Exercise and Multiple Sclerosis) app, which is being used by people with multiple sclerosis in a large randomized controlled trial to engage in home-based telerehabilitation. Twenty-one participants with disabilities (10 people with multiple sclerosis) were involved in the double iterative design, which included the simultaneous development of the app features and exercise content (exercise videos and articles). Framed within a user-centered design approach, the development process included 2 stages: ground-level creation (focus group followed by early stage evaluations and developments), and proof of concept through 2 usability tests. Usability (effectiveness, usefulness, and satisfaction) was evaluated using a mixed-methods approach. During testing of the app's effectiveness, the second usability test resulted in an average of 1 problem per participant, a decrease of 53% compared to the initial usability test. Five themes were constructed from the qualitative data that related to app usefulness and satisfaction, namely: high perceived confidence for app usability, positive perceptions of exercise videos, viable exercise option at home, orientation and familiarity required for successful participation, and app issues. Participants acknowledged that the final app was ready to be delivered to the public after minor revisions. After including these revisions, the project team released the final app that is being used in the randomized controlled trial. A multi-level user-centered development process resulted in the development of an inclusive exercise program for people with multiple sclerosis operated through an easy-to-use app. The promotion of exercise through self-regulated mHealth programs requires a stakeholder-driven approach to app development. This ensures that app and content match the preferences and functional abilities of the end user (ie, people with varying levels of multiple sclerosis). ©Mohanraj Thirumalai, James H Rimmer, George Johnson, Jereme Wilroy, Hui-Ju Young, Tapan Mehta, Byron Lai. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 24.05.2018.

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.

Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols

PubMed Central

Vejux, Anne; Namsi, Amira; Nury, Thomas; Moreau, Thibault; Lizard, Gérard

2018-01-01

Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease in adults with motor disorders. Two forms exist: a sporadic form (90% of cases) and a family form due to mutations in more than 20 genes including the Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9 open reading frame 72 and VAPB genes. The mechanisms associated with this pathology are beginning to be known: oxidative stress, glutamate excitotoxicity, protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration of RNA metabolism. In various neurodegenerative diseases, such as Alzheimer’s disease or multiple sclerosis, the involvement of lipids is increasingly suggested based on lipid metabolism modifications. With regard to ALS, research has also focused on the possible involvement of lipids. Lipid involvement was suggested for clinical arguments where changes in cholesterol and LDL/HDL levels were reported with, however, differences in positivity between studies. Since lipids are involved in the membrane structure and certain signaling pathways, it may be considered to look for oxysterols, mainly 25-hydroxycholesterol and its metabolites involved in immune response, or phytosterols to find suitable biomarkers for this pathology. PMID:29445325

Anti-inflammatory genes associated with multiple sclerosis: a gene expression study.

PubMed

Perga, S; Montarolo, F; Martire, S; Berchialla, P; Malucchi, S; Bertolotto, A

2015-02-15

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system caused by a complex interaction between multiple genes and environmental factors. HLA region is the strongest susceptibility locus, but recent huge genome-wide association studies identified new susceptibility genes. Among these, BACH2, PTGER4, RGS1 and ZFP36L1 were highlighted. Here, a gene expression analysis revealed that three of them, namely BACH2, PTGER4 and ZFP36L1, are down-regulated in MS patients' blood cells compared to healthy subjects. Interestingly, all these genes are involved in the immune system regulation with predominant anti-inflammatory role and their reduction could predispose to MS development. Copyright © 2015 Elsevier B.V. All rights reserved.

Positive or negative involvement of heat shock proteins in multiple sclerosis pathogenesis: an overview.

PubMed

Turturici, Giuseppina; Tinnirello, Rosaria; Sconzo, Gabriella; Asea, Alexzander; Savettieri, Giovanni; Ragonese, Paolo; Geraci, Fabiana

2014-12-01

Multiple sclerosis (MS) is the most diffuse chronic inflammatory disease of the central nervous system. Both immune-mediated and neurodegenerative processes apparently play roles in the pathogenesis of this disease. Heat shock proteins (HSPs) are a family of highly evolutionarily conserved proteins; their expression in the nervous system is induced in a variety of pathologic states, including cerebral ischemia, neurodegenerative diseases, epilepsy, and trauma. To date, investigators have observed protective effects of HSPs in a variety of brain disease models (e.g. of Alzheimer disease and Parkinson disease). In contrast, unequivocal data have been obtained for their roles in MS that depend on the HSP family and particularly on their localization (i.e. intracellular or extracellular). This article reviews our current understanding of the involvement of the principal HSP families in MS.

Parental Involvement of Mothers with Chronic Illness and Children's Academic Achievement

ERIC Educational Resources Information Center

Chen, Yung-Chi; Fish, Marian C.

2013-01-01

This study examined how maternal chronic illnesses may affect children's academic achievement through parental involvement. A total of 189 mothers diagnosed with chronic illnesses, such as multiple sclerosis, diabetes, cancer, HIV/AIDS, chronic pain, asthma, myelodysplasic syndrome, and fibromyalgia, and with a child in middle school or high…

Multiple sclerosis pathogenesis: missing pieces of an old puzzle.

PubMed

Rahmanzadeh, Reza; Brück, Wolfgang; Minagar, Alireza; Sahraian, Mohammad Ali

2018-06-08

Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.

Nature, nurture, and microbes: The development of multiple sclerosis.

PubMed

Wekerle, H

2017-11-01

This paper argues that multiple sclerosis (MS) is the result of an autoimmune attack against components of the central nervous system (CNS). The effector cells involved in the pathogenic process are CNS-autoreactive T cells present in the healthy immune system in a resting state. Upon activation, these cells cross the blood-brain barrier and attack the CNS target tissue. Recent evidence indicates that autoimmune activation may happen in the intestine, following an interaction of bacterial components of the gut flora with local CNS autoreactive T cells. The consequences of this concept are discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Notes on the Epidemiology of Multiple Sclerosis, with Special Reference to Dietary Habits

PubMed Central

Lauer, Klaus

2014-01-01

A hypothesis, based primarily on the occurrence of multiple sclerosis (MS) in the Faroe Islands and supported by numerous analytical epidemiological studies, is described. It proposes that MS is caused by the interaction of a virus disease with intestinal pathology, e.g., infectious mononucleosis, and application of smoked and nitrate/nitrite-cured meat products in the diet during circumscribed time intervals. The biological mechanisms might involve a break of tolerance by an alteration of self within the central nervous system, by nitrophenylated compounds conjugated to animal tissue, in particular to proteins occurring in the central nervous system. Further research is needed. PMID:24577315

[The influence of high-tone power therapy on the functional status of patients with multiple sclerosis].

PubMed

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

2014-07-01

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, which is characterized by diverse symptomatology. Most often affects people at a young age gradually leading to their disability. Looking for new therapies to alleviate neurological deficits caused by the disease. One of the alternative methods of therapy is high - tone power therapy. The article is a comparison of high-tone power therapy and kinesis in improving patients with multiple sclerosis. The aim of this study was to evaluate the effectiveness of high-tone power therapy and exercises in kinesis on the functional status of patients with multiple sclerosis. The study involved 20 patients with multiple sclerosis, both sexes, treated at the Department of Rehabilitation and Physical Medicine in Lodz. Patients were randomly divided into two groups studied. In group high-tone power therapy applied for 60 minutes, while in group II were used exercises for kinesis. Treatment time for both groups of patients was 15 days. To assess the functional status scale was used: Expanded Disability Status Scale of Kurtzke (EDSS), as well as by Barthel ADL Index. Assessment of quality of life were made using MSQOL Questionnaire-54. For the evaluation of gait and balance using Tinetti scale, and pain VAS rated, and Laitinen. Changes in muscle tone was assessed on the basis of the Ashworth scale. Both group I and II improved on scales conducted before and after therapy. In group I, in which the applied high-tone power therapy, reported statistically significant results in 9 out of 10 tested parameters, while in group II, which was used in the exercises in kinesis an improvement in 6 out of 10 tested parameters. Correlating the results of both the test groups in relation to each other did not show statistically significant differences. High-Tone Power Therapy beneficial effect on the functional status of patients with multiple sclerosis. Obtaining results in terms of number of tested parameters allows for the use of this therapy in the comprehensive improvement of patients with multiple sclerosis. Exercises from the scheme kinesis favorable impact on the functional status of patients with MS and are essential in the rehabilitation of these patients. In any group, no adverse effects were observed.

Multiple sclerosis

MedlinePlus

... this page: //medlineplus.gov/ency/article/000737.htm Multiple sclerosis To use the sharing features on this page, please enable JavaScript. Multiple sclerosis (MS) is an autoimmune disease that affects the ...

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.

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.

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

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.

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.

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

Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

PubMed

Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

2010-11-01

Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

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 ...

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, ...

Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis.

PubMed

Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

2015-12-01

Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis.

PubMed

Cohen, Jeffrey A; Imrey, Peter B; Planchon, Sarah M; Bermel, Robert A; Fisher, Elizabeth; Fox, Robert J; Bar-Or, Amit; Sharp, Susan L; Skaramagas, Thomai T; Jagodnik, Patricia; Karafa, Matt; Morrison, Shannon; Reese Koc, Jane; Gerson, Stanton L; Lazarus, Hillard M

2018-04-01

Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest. To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 10 6 MSCs/kg were thawed and administered IV. In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 10 6 MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation. Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

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

MedlinePlus

Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

Episodic Mood Changes Preceding an Exacerbation of Multiple Sclerosis

PubMed Central

Sharma, Priya; Morrow, Sarah A.; Owen, Richard J.

2015-01-01

Multiple sclerosis is a neurologic inflammatory disease that can manifest with psychiatric symptoms. Although depression is the most common psychiatric diagnosis in patients with multiple sclerosis, how depression develops is not fully understood. We present the case of an individual who displayed episodic mood changes preceding an exacerbation of multiple sclerosis symptoms. The clinical and research implications of this association are discussed. PMID:26835163

Mobilization of Neural Precursors in the Circulating Blood of Patients with Multiple Sclerosis

DTIC Science & Technology

2012-07-01

circulating blood of patients with multiple sclerosis PRINCIPAL INVESTIGATOR: Ernesto R. Bongarzone, Ph.D... multiple sclerosis 5b. GRANT NUMBER W81XWH-09-1-0427 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Ernesto R. Bongarzone...NOTES 14. ABSTRACT Relapsing remitting multiple sclerosis (RRMS) is demyelinating disease that affects both men and women and is characterized by

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.

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.

Development and validation of a patient self-assessed questionnaire on satisfaction with communication of the multiple sclerosis diagnosis.

PubMed

Solari, A; Mattarozzi, K; Vignatelli, L; Giordano, A; Russo, P M; Uccelli, M Messmer; D'Alessandro, R

2010-10-01

We describe the development and clinical validation of a patient self-administered tool assessing the quality of multiple sclerosis diagnosis disclosure. A multiple sclerosis expert panel generated questionnaire items from the Doctor's Interpersonal Skills Questionnaire, literature review, and interviews with neurology inpatients. The resulting 19-item Comunicazione medico-paziente nella Sclerosi Multipla (COSM) was pilot tested/debriefed on seven patients with multiple sclerosis and administered to 80 patients newly diagnosed with multiple sclerosis. The resulting revised 20-item version (COSM-R) was debriefed on five patients with multiple sclerosis, field tested/debriefed on multiple sclerosis patients, and field tested on 105 patients newly diagnosed with multiple sclerosis participating in a clinical trial on an information aid. The hypothesized monofactorial structure of COSM-R section 2 was tested on the latter two groups. The questionnaire was well accepted. Scaling assumptions were satisfactory in terms of score distributions, item-total correlations and internal consistency. Factor analysis confirmed section 2's monofactorial structure, which was also test-retest reliable (intraclass correlation coefficient [ICC] 0.73; 95% CI 0.54-0.85). Section 1 had only fair test-retest reliability (ICC 0.45; 95% CI 0.12-0.69), and three items had 8-21% missed responses. COSM-R is a brief, easy-to-interpret MS-specific questionnaire for use as a health care indicator.

[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.

Multiple sclerosis - discharge

MedlinePlus

... this page: //medlineplus.gov/ency/patientinstructions/000129.htm Multiple sclerosis - discharge To use the sharing features on this ... Your doctor has told you that you have multiple sclerosis (MS). This disease affects the brain and spinal ...

Multiple Sclerosis: Can It Cause Seizures?

MedlinePlus

... Is there any connection between multiple sclerosis and epilepsy? Answers from B Mark Keegan, M.D. Epileptic ... E, et al. The prevalence and characteristics of epilepsy in patients with multiple sclerosis in Nordland County, ...

Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

DTIC Science & Technology

2015-10-01

Page | 2 AWARD NUMBER: W81XWH-13-1-0464 TITLE: Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI...Sep 2014 – 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional...findings include: 1) detection of brain organization in a cohort of 24 pediatric onset multiple sclerosis patients (POMS) and 25 healthy controls

Plasma Endothelial Microparticles in Multiple Sclerosis: A Novel Metric Assay of Disease Activity and Response to Treatment

DTIC Science & Technology

2011-09-01

direct link to a source of increased tissue iron deposition which is characteristic for multiple sclerosis . The results of these data and their... Multiple Sclerosis : A Novel Metric Assay of Disease Activity and Response to Treatment PRINCIPAL INVESTIGATOR: Jonathan Steven...SUBTITLE 5a. CONTRACT NUMBER Plasma Endothelial Microparticles in Multiple Sclerosis : A Novel Metric Assay of Disease Activity and Response to

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.

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.

Accelerated Cure Project for Multiple Sclerosis

MedlinePlus

... main content Accelerating research toward a cure for multiple sclerosis Toggle navigation Search form Search Connect Volunteer Donate ... is to accelerate efforts toward a cure for multiple sclerosis by rapidly advancing research that determines its causes ...

Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis.

PubMed

Koff, Matthew D; Cohen, Jeffrey A; McIntyre, John J; Carr, Charles F; Sites, Brian D

2008-02-01

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.

New biological agents in the treatment of multiple sclerosis.

PubMed

Buc, M

2018-01-01

Multiple sclerosis (MS) is an inflammatory disease induced by autoimmune processes. Their understanding has resulted in an introduction of biological agents to its treatment. Interferon beta and glatiramer acetate have been in clinical practice for more than 20 years. Nowadays, novel biologics, which target molecules involved in immunopathological processes more specifically have entered the scene. They are represented by monoclonal antibodies binding to molecules VLA4 (natalizumab), CD20 (ocrelizumab), CD52 (alemtuzumab) or alpha subunit of IL-2 receptor (daclizumab) or by small molecules such as those modulating the receptors involved in regulation of lymphocyte migration (fingolimod, ozanimod) or in induction of lymphopenia by apoptosis (dimethyl fumarate, cladribine). In the article, we shortly describe their efficacies, adverse reactions and perspectives of a future development in MS biologics. A treatment of neuromyelitis optica by monoclonal antibodies (rituximab, aquaporumab) is given too (Tab. 1, Fig. 2, Ref. 71).

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.

Relaxation and health-related quality of life in multiple sclerosis: the example of autogenic training.

PubMed

Sutherland, Georgina; Andersen, Mark B; Morris, Tony

2005-06-01

This study was a pilot project to explore the effect of an autogenic training program (AT; a relaxation intervention) on the health-related quality of life (HRQOL) and well-being for people with multiple sclerosis. Participants either met weekly for sessions in AT for 10 weeks (n = 11) or were assigned to the control group (n = 11). The AT group was also asked to practice the technique daily at home. Scales designed to measure HRQOL and aspects of well-being (mood and depressed affect) were taken preintervention and at week 8 of the 10-week program. ANCOVAs using a measure of social support and pretest scores as covariates revealed that at the posttest the AT group reported more energy and vigor than the control group and were less limited in their roles due to physical and emotional problems. Future research should involve studies conducted over an extended period, together with sufficiently sized samples to explore the effect of frequency of practice of relaxation training on HRQOL and well-being for people with multiple sclerosis.

78 FR 17613 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... Multiple Sclerosis Event Type: Regatta and Sailboat Regatta. Race Sponsor: Maine Chapter, Multiple...]13'51'' W 8.7 Multiple Sclerosis Event Type: Power Boat Race Harborfest Lobster Boat/ Sponsor: Maine Chapter, National Tugboat Races. Multiple Sclerosis Society [[Page 17619

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

PubMed Central

Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

2015-01-01

Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

Segmentation And Quantification Of Black Holes In Multiple Sclerosis

PubMed Central

Datta, Sushmita; Sajja, Balasrinivasa Rao; He, Renjie; Wolinsky, Jerry S.; Gupta, Rakesh K.; Narayana, Ponnada A.

2006-01-01

A technique that involves minimal operator intervention was developed and implemented for identification and quantification of black holes on T1- weighted magnetic resonance images (T1 images) in multiple sclerosis (MS). Black holes were segmented on T1 images based on grayscale morphological operations. False classification of black holes was minimized by masking the segmented images with images obtained from the orthogonalization of T2-weighted and T1 images. Enhancing lesion voxels on postcontrast images were automatically identified and eliminated from being included in the black hole volume. Fuzzy connectivity was used for the delineation of black holes. The performance of this algorithm was quantitatively evaluated on 14 MS patients. PMID:16126416

Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and treatment response biomarkers.

PubMed

Pravica, Vera; Popadic, Dusan; Savic, Emina; Markovic, Milos; Drulovic, Jelena; Mostarica-Stojkovic, Marija

2012-04-01

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by unpredictable and variable clinical course. Etiology of MS involves both genetic and environmental factors. New technologies identified genetic polymorphisms associated with MS susceptibility among which immunologically relevant genes are significantly overrepresented. Although individual genes contribute only a small part to MS susceptibility, they might be used as biomarkers, thus helping to identify accurate diagnosis, predict clinical disease course and response to therapy. This review focuses on recent progress in research on MS genetics with special emphasis on the possibility to use single nucleotide polymorphism of candidate genes as biomarkers of susceptibility to disease and response to therapy.

Connected health and multiple sclerosis.

PubMed

Cohen, M

2018-06-01

There is as yet no consensual definition of "connected health". In general, the term refers to the growing use of technology and, in particular, mobile technology in medicine. Over the past 10 years, there have been an increasing number of published reports on the wide-ranging and heterogeneous fields involving the application of technology in medicine, ranging from telemedicine to tools to improve patients' evaluation and monitoring by physicians, as well as a multitude of patient-centered applications. They also represent promising tools in the field of clinical research. This report is a review of the importance of using this technology in the management of multiple sclerosis patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Dysregulated MicroRNA Involvement in Multiple Sclerosis by Induction of T Helper 17 Cell Differentiation

PubMed Central

Chen, Chen; Zhou, Yifan; Wang, Jingqi; Yan, Yaping; Peng, Lisheng; Qiu, Wei

2018-01-01

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Growing evidence has proven that T helper 17 (Th17) cells are one of the regulators of neuroinflammation mechanisms in MS disease. Researchers have demonstrated that some microRNAs (miRNAs) are associated with disease activity and duration, even with different MS patterns. miRNAs regulate CD4+ T cells to differentiate toward various T cell subtypes including Th17 cells. In this review, we discuss the possible mechanisms of miRNAs in MS pathophysiology by regulating CD4+ T cell differentiation into Th17 cells, and potential miRNA targets for current disease-modifying treatments.

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

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 ...

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.

Brain-derived neurotrophic factor levels under chronic natalizumab treatment in multiple sclerosis. A preliminary report.

PubMed

Văcăraş, Vitalie; Major, Zoltán Zsigmond; Buzoianu, Anca Dana

Our main purpose was to investigate if the chronic treatment with the disease-modifying drug natalizumab shows quantifiable effect on BDNF levels in multiple sclerosis patients. BDNF plasma concentration was evaluated using enzyme-linked immunosorbent assay in healthy individuals, not treated multiple sclerosis patients and patients treated with natalizumab. Multiple sclerosis patients have a significantly lower amount of peripheral BDNF than healthy individuals. Patients treated with natalizumab have significantly higher BDNF levels than not treated patients. Chronic natalizumab treatment is associated with significantly increased plasma BDNF concentration in multiple sclerosis. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

[Coincidence of juvenile idiopathic arthritis and multiple sclerosis: case report].

PubMed

Puszczewicz, Mariusz J; Tuchocka-Piotrowska, Aleksandra; Majewski, Dominik; Kołczewska, Aleksandra

2006-01-01

Juvenile idiopathic arthritis is a systemic pathology of connective tissue characterized by a chronic inflammatory process with an autoimmune background whereas multiple sclerosis is a demyelination disease with an important role of immune disorders in its pathogenesis. The etiology in both cases remains unknown. The coincidence of juvenile idiopathic arthritis and multiple sclerosis was described a just a few patients. We now report on a 31-year-old woman with juvenile idiopathic arthritis and multiple sclerosis. In the present case, the main problem was to find the right proper medication for a very, aggressive course of multiple sclerosis and for arthritis. Treatment with interferon-beta and methylprednisolone led to remission with just minor side-effects.

Will PEDF Therapy Reverse Chronic Demyelination and Prevent Axon Loss in a Murine Model of Progressive Multiple Sclerosis

DTIC Science & Technology

2015-12-01

Multiple Sclerosis ? PRINCIPAL INVESTIGATOR: David Pleasure MD CONTRACTING ORGANIZATION: University of California Davis, CA 95618 REPORT DATE...Murine Model of Progressive Multiple Sclerosis ? 5b. GRANT NUMBER W81XWH-12-1-0566 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Pleasure MD 5d...enhance central nervous system (CNS) remyelination and preserve CNS axons in mouse models of multiple sclerosis models. After determining the dosage of

Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

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.

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.

Safinamide and flecainide protect axons and reduce microglial activation in models of multiple sclerosis.

PubMed

Morsali, Damineh; Bechtold, David; Lee, Woojin; Chauhdry, Summen; Palchaudhuri, Upayan; Hassoon, Paula; Snell, Daniel M; Malpass, Katy; Piers, Thomas; Pocock, Jennifer; Roach, Arthur; Smith, Kenneth J

2013-04-01

Axonal degeneration is a major cause of permanent disability in the inflammatory demyelinating disease multiple sclerosis, but no therapies are known to be effective in axonal protection. Sodium channel blocking agents can provide effective protection of axons in the white matter in experimental models of multiple sclerosis, but the mechanism of action (directly on axons or indirectly via immune modulation) remains uncertain. Here we have examined the efficacy of two sodium channel blocking agents to protect white matter axons in two forms of experimental autoimmune encephalomyelitis, a common model of multiple sclerosis. Safinamide is currently in phase III development for use in Parkinson's disease based on its inhibition of monoamine oxidase B, but the drug is also a potent state-dependent inhibitor of sodium channels. Safinamide provided significant protection against neurological deficit and axonal degeneration in experimental autoimmune encephalomyelitis, even when administration was delayed until after the onset of neurological deficit. Protection of axons was associated with a significant reduction in the activation of microglia/macrophages within the central nervous system. To clarify which property of safinamide was likely to be involved in the suppression of the innate immune cells, the action of safinamide on microglia/macrophages was compared with that of the classical sodium channel blocking agent, flecainide, which has no recognized monoamine oxidase B activity, and which has previously been shown to protect the white matter in experimental autoimmune encephalomyelitis. Flecainide was also potent in suppressing microglial activation in experimental autoimmune encephalomyelitis. To distinguish whether the suppression of microglia was an indirect consequence of the reduction in axonal damage, or possibly instrumental in the axonal protection, the action of safinamide was examined in separate experiments in vitro. In cultured primary rat microglial cells activated by lipopolysaccharide, safinamide potently suppressed microglial superoxide production and enhanced the production of the anti-oxidant glutathione. The findings show that safinamide is effective in protecting axons from degeneration in experimental autoimmune encephalomyelitis, and that this effect is likely to involve a direct effect on microglia that can result in a less activated phenotype. Together, this work highlights the potential of safinamide as an effective neuroprotective agent in multiple sclerosis, and implicates microglia in the protective mechanism.

Health status and costs of ambulatory patients with multiple sclerosis in Hungary.

PubMed

Péntek, Márta; Gulácsi, László; Rózsa, Csilla; Simó, Magdolna; Iljicsov, Anna; Komoly, Sámuel; Brodszky, Valentin

2012-09-30

Data on disease burden of multiple sclerosis from Eastern-Central Europe are very limited. Our aim was to explore the quality of life, resource utilisation and costs of ambulating patients with multiple sclerosis in Hungary. Cross-sectional questionnaire survey was performed in two outpatient neurology centres in 2009. Clinical history, health care utilisation in the past 12 months were surveyed, the Expanded Disability Status Scale and the EQ-5D questionnaires were applied. Cost calculation was conducted from the societal perspective. Sixty-eight patients (female 70.6%) aged 38.0 (SD 9.1) with disease duration of 7.8 (SD 6.7) years were involved. Fifty-five (80.9%) had relapsing-remitting form and 52 (76.5%) were taking immunomodulatory drug. The average scores were: Expanded Disability Status Scale 1.9 (SD 1.7), EQ-5D 0.67 (SD 0.28). Mean total cost amounted to 10 902 Euros/patient/year (direct medical 67%, direct nonmedical 13%, indirect costs 20%). Drugs, disability pension and informal care were the highest cost items. Costs of mild (Expanded Disability Status Scale 0-3.5) and moderate (Expanded Disability Status Scale 4.0-6.5) disease were 9 218 and 17 634 Euros/patient/year respectively (p<0.01), that is lower than results from Western European countries. Our study provides current inputs for policy making and contributes to understanding variation of cost-of-illness of multiple sclerosis in Europe.

An investigation of multidisciplinary complex health care interventions - steps towards an integrative treatment model in the rehabilitation of People with Multiple Sclerosis

PubMed Central

2012-01-01

Background The Danish Multiple Sclerosis Society initiated a large-scale bridge building and integrative treatment project to take place from 2004–2010 at a specialized Multiple Sclerosis (MS) hospital. In this project, a team of five conventional health care practitioners and five alternative practitioners was set up to work together in developing and offering individualized treatments to 200 people with MS. The purpose of this paper is to present results from the six year treatment collaboration process regarding the development of an integrative treatment model. Discussion The collaborative work towards an integrative treatment model for people with MS, involved six steps: 1) Working with an initial model 2) Unfolding the different treatment philosophies 3) Discussing the elements of the Intervention-Mechanism-Context-Outcome-scheme (the IMCO-scheme) 4) Phrasing the common assumptions for an integrative MS program theory 5) Developing the integrative MS program theory 6) Building the integrative MS treatment model. The model includes important elements of the different treatment philosophies represented in the team and thereby describes a common understanding of the complexity of the courses of treatment. Summary An integrative team of practitioners has developed an integrative model for combined treatments of People with Multiple Sclerosis. The model unites different treatment philosophies and focuses on process-oriented factors and the strengthening of the patients’ resources and competences on a physical, an emotional and a cognitive level. PMID:22524586

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

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis.

PubMed

Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

2017-08-01

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc . Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g. , oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g. , ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

Gait Characteristics in Adolescents With Multiple Sclerosis.

PubMed

Kalron, Alon; Frid, Lior; Menascu, Shay

2017-03-01

Multiple sclerosis is a progressive autoimmune disease of the central nervous system. A presentation of multiple sclerosis before age18 years has traditionally been thought to be rare. However, during the past decade, more cases have been reported. We examined gait characteristics in 24 adolescents with multiple sclerosis (12 girls, 12 boys). Mean disease duration was 20.4 (S.D. = 24.9) months and mean age was 15.5 (S.D. = 1.1) years. The mean expanded disability status scale score was 1.7 (S.D. = 0.7) indicating minimal disability. Outcomes were compared with gait and the gait variability index value of healthy age-matched adolescents. Adolescents with multiple sclerosis walked slower with a wider base of support compared with age-matched healthy control subjects. Moreover, the gait variability index was lower in the multiple sclerosis group compared with the values in the healthy adolescents: 85.4 (S.D. = 8.1) versus 96.5 (S.D. = 7.4). We present gait parameters of adolescents with multiple sclerosis. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

A multigenerational family with multiple sclerosis.

PubMed

Dyment, D A; Cader, M Z; Willer, C J; Risch, N; Sadovnick, A D; Ebers, G C

2002-07-01

We report a family with 15 individuals affected with multiple sclerosis present in three and possibly four generations. The segregation of multiple sclerosis within this pedigree is consistent with an autosomal dominant mode of inheritance with reduced penetrance. The clinical characteristics of the affected individuals are indistinguishable from those seen in sporadic multiple sclerosis with respect to sex ratio, age at onset, onset symptom, MRI and clinical course. Eleven of 14 cases (78.6%) were positive for the known multiple sclerosis-associated major histocompatibility complex (MHC) Class II HLA DRB1*15 allele. Parametric linkage analysis gave a non-significant LOD score of 0.31 (theta; = 0.33) for the DRB1 gene. However, among 11 affected children with at least one DRB1*15 bearing parent, all 11 out of 11 received at least one copy of this known susceptibility allele. A transmission disequilibrium test analysis was significant for the DRB1*15 allele within this single family; P = 0.0054. The inheritance pattern in this family suggests the presence of a single major locus responsible for multiple sclerosis susceptibility, with DRB1 acting as an important modifier. This family could be an important resource for the identification of a multiple sclerosis susceptibility gene.

77 FR 23601 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... Multiple Sclerosis Regatta......... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple...'' W. 8.7 Multiple Sclerosis Harborfest Event Type: Power Boat Tugboat Race. Race. Sponsor: Maine Chapter, National Multiple Sclerosis Society. Date: A one day event on Sunday during the third week of...

Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated Encephalomyelitis From Multiple Sclerosis at First Demyelination.

PubMed

Aung, Wint Yan; Massoumzadeh, Parinaz; Najmi, Safa; Salter, Amber; Heaps, Jodi; Benzinger, Tammie L S; Mar, Soe

2018-01-01

There are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disability. Therefore, we intend to explore neuroimaging biomarkers that can reliably distinguish between the two diagnoses. We reviewed prospectively collected clinical, standard MRI and diffusion tensor imaging data from 12 pediatric patients who presented with acute demyelination with and without encephalopathy. Patients were followed for an average of 6.5 years to determine the accuracy of final diagnosis. Final diagnosis was determined using 2013 International Pediatric MS Study Group criteria. Control subjects consisted of four age-matched healthy individuals for each patient. The study population consisted of six patients with central nervous system demyelination with encephalopathy with a presumed diagnosis of acute disseminated encephalomyelitis and six without encephalopathy with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome at high risk for multiple sclerosis. During follow-up, two patients with initial diagnosis of acute disseminated encephalomyelitis were later diagnosed with multiple sclerosis. Diffusion tensor imaging region of interest analysis of baseline scans showed differences between final diagnosis of multiple sclerosis and acute disseminated encephalomyelitis patients, whereby low fractional anisotropy and high radial diffusivity occurred in multiple sclerosis patients compared with acute disseminated encephalomyelitis patients and the age-matched controls. Fractional anisotropy and radial diffusivity measures may have the potential to serve as biomarkers for distinguishing acute disseminated encephalomyelitis from multiple sclerosis at the onset. Copyright © 2017 Elsevier Inc. All rights reserved.

Physical Activity and Its Correlates in Youth with Multiple Sclerosis.

PubMed

Grover, Stephanie A; Sawicki, Carolyn P; Kinnett-Hopkins, Dominique; Finlayson, Marcia; Schneiderman, Jane E; Banwell, Brenda; Till, Christine; Motl, Robert W; Yeh, E Ann

2016-12-01

To investigate physical activity levels in youth with multiple sclerosis and monophasic acquired demyelinating syndromes ([mono-ADS], ie, children without relapsing disease) compared with healthy controls and to determine factors that contribute to engagement in physical activity. We hypothesized that greater physical activity goal setting and physical activity self-efficacy would be associated with greater levels of vigorous physical activity in youth with multiple sclerosis. A total of 68 consecutive patients (27 multiple sclerosis, 41 mono-ADS) and 37 healthy controls completed fatigue, depression, Physical Activity Self-Efficacy Scale, perceived disability, Exercise Goal-Setting scale, and physical activity questionnaires, and wore an accelerometer for 7 days. All patients had no ambulatory limitations (Expanded Disability Status Scale, scores all <4). Youth with multiple sclerosis engaged in fewer minutes per day of vigorous (P = .009) and moderate and vigorous physical activity (P = .048) than did patients with mono-ADS and healthy controls. A lower proportion of the group with multiple sclerosis (63%) reported participating in any strenuous physical activity than the mono-ADS (85%) and healthy control (89%) groups (P = .020). When we adjusted for age and sex, the Physical Activity Self-Efficacy Scale and Exercise Goal-Setting scale were associated positively with vigorous physical activity in the group with multiple sclerosis. Fatigue and depression did not predict physical activity or accelerometry metrics. Youth with multiple sclerosis participate in less physical activity than their counterparts with mono-ADS and healthy controls. Physical activity self-efficacy and exercise goal setting serve as potentially modifiable correlates of physical activity, and are measures suited to future interventions aimed to increase physical activity in youth with multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

PubMed Central

Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

2015-01-01

Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

[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.

Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - Feasibility testing, pilot randomised controlled trial and mixed methods process evaluation.

PubMed

Rahn, A C; Köpke, S; Backhus, I; Kasper, J; Anger, K; Untiedt, B; Alegiani, A; Kleiter, I; Mühlhauser, I; Heesen, C

2018-02-01

Treatment decision-making is complex for people with multiple sclerosis. Profound information on available options is virtually not possible in regular neurologist encounters. The "nurse decision coach model" was developed to redistribute health professionals' tasks in supporting immunotreatment decision-making following the principles of informed shared decision-making. To test the feasibility of a decision coaching programme and recruitment strategies to inform the main trial. Feasibility testing and parallel pilot randomised controlled trial, accompanied by a mixed methods process evaluation. Two German multiple sclerosis university centres. People with suspected or relapsing-remitting multiple sclerosis facing immunotreatment decisions on first line drugs were recruited. Randomisation to the intervention (n = 38) or control group (n = 35) was performed on a daily basis. Quantitative and qualitative process data were collected from people with multiple sclerosis, nurses and physicians. We report on the development and piloting of the decision coaching programme. It comprises a training course for multiple sclerosis nurses and the coaching intervention. The intervention consists of up to three structured nurse-led decision coaching sessions, access to an evidence-based online information platform (DECIMS-Wiki) and a final physician consultation. After feasibility testing, a pilot randomised controlled trial was performed. People with multiple sclerosis were randomised to the intervention or control group. The latter had also access to the DECIMS-Wiki, but received otherwise care as usual. Nurses were not blinded to group assignment, while people with multiple sclerosis and physicians were. The primary outcome was 'informed choice' after six months including the sub-dimensions' risk knowledge (after 14 days), attitude concerning immunotreatment (after physician consultation), and treatment uptake (after six months). Quantitative process evaluation data were collected via questionnaires. Qualitative interviews were performed with all nurses and a convenience sample of nine people with multiple sclerosis. 116 people with multiple sclerosis fulfilled the inclusion criteria and 73 (63%) were included. Groups were comparable at baseline. Data of 51 people with multiple sclerosis (70%) were available for the primary endpoint. In the intervention group 15 of 31 (48%) people with multiple sclerosis achieved an informed choice after six months and 6 of 20 (30%) in the control group. Process evaluation data illustrated a positive response towards the coaching programme as well as good acceptance. The pilot-phase showed promising results concerning acceptability and feasibility of the intervention, which was well perceived by people with multiple sclerosis, most nurses and physicians. Delegating parts of the immunotreatment decision-making process to trained nurses has the potential to increase informed choice and participation as well as effectiveness of patient-physician consultations. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

[Effect of preventive treatment on cognitive performance in patients with multiple sclerosis].

PubMed

Shorobura, Maria S

2018-01-01

Introduction: cognitive, emotional and psychopathological changes play a significant role in the clinical picture of multiple sclerosis and influence the effectiveness of drug therapy, working capacity, quality of life, and the process of rehabilitation of patients with multiple sclerosis. The aim: investigate the changes in cognitive function in patients with multiple sclerosis, such as information processing speed and working memory of patients before and after treatment with immunomodulating drug. Materials and methods:33 patients examined reliably diagnosed with multiple sclerosis who were treated with preventive examinations and treatment from 2012 to 2016. For all patients with multiple sclerosis had clinical-neurological examination (neurological status using the EDSS scale) and the cognitive status was evaluated using the PASAT auditory test. Patient screening was performed before, during and after the therapy. Statistical analysis of the results was performed in the system Statistica 8.0. We used Student's t-test (t), Mann-Whitney test (Z). Person evaluated the correlation coefficients and Spearman (r, R), Wilcoxon criterion (T), Chi-square (X²). Results: The age of patients with multiple sclerosis affects the growth and EDSS scale score decrease PASAT to treatment. Duration of illness affects the EDSS scale score and performance PASAT. Indicators PASAT not significantly decreased throughout the treatment. Conclusions: glatiramer acetate has a positive effect on cognitive function, information processing speed and working memory patients with multiple sclerosis, which is one of the important components of the therapeutic effect of this drug.

Topical moringin cream relieves neuropathic pain by suppression of inflammatory pathway and voltage-gated ion channels in murine model of multiple sclerosis

PubMed Central

Giacoppo, Sabrina; Iori, Renato; Bramanti, Placido

2017-01-01

Background Neuropathic pain represents the major public health burden with a strong impact on quality life in multiple sclerosis patients. Although some advances have been obtained in the last years, the conventional therapies remain poorly effective. Thus, the discovery of innovative approaches to improve the outcomes for multiple sclerosis patients is a goal of primary importance. With this aim, we investigated the efficacy of the 4-(α−L-rhamnopyranosyloxy)benzyl isothiocyanate (moringin), purified from Moringa oleifera seeds and ready-to-use as topical treatment in experimental autoimmune encephalomyelitis, murine model of multiple sclerosis. Female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG35–55) were topically treated with 2% moringin cream twice daily from the onset of the symptoms until the sacrifice occurred about 21 days after experimental autoimmune encephalomyelitis induction. Results Our observations showed the efficacy of 2% moringin cream treatment in reducing clinical and histological disease score, as well as in alleviating neuropathic pain with consequent recovering of the hind limbs and response to mechanical stimuli. In particular, Western blot analysis and immunohistochemical evaluations revealed that 2% moringin cream was able to counteract the inflammatory cascade by reducing the production of pro-inflammatory cytokines (interleukin-17 and interferon-γ) and in parallel by increasing the expression of anti-inflammatory cytokine (interleukin-10). Interestingly, 2% moringin cream treatment was found to modulate the expression of voltage-gated ion channels (results focused on P2X7, Nav 1.7, Nav 1.8 KV4.2, and α2δ-1) as well as metabotropic glutamate receptors (mGluR5 and xCT) involved in neuropathic pain initiation and maintenance. Conclusions Finally, our evidences suggest 2% moringin cream as a new pharmacological trend in the management of multiple sclerosis-induced neuropathic pain. PMID:28741431

A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

PubMed Central

Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

2012-01-01

Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies. PMID:23065787

Hypothalamic demyelination causing panhypopituitarism.

PubMed

Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

2018-05-01

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

The potential of mesenchymal stromal cells as a novel cellular therapy for multiple sclerosis

PubMed Central

Auletta, Jeffery J; Bartholomew, Amelia M; Maziarz, Richard T; Deans, Robert J; Miller, Robert H; Lazarus, Hillard M; Cohen, Jeffrey A

2012-01-01

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the CNS for which only partially effective therapies exist. Intense research defining the underlying immune pathophysiology is advancing both the understanding of MS as well as revealing potential targets for disease intervention. Mesenchymal stromal cell (MSC) therapy has the potential to modulate aberrant immune responses causing demyelination and axonal injury associated with MS, as well as to repair and restore damaged CNS tissue and cells. This article reviews the pathophysiology underlying MS, as well as providing a cutting-edge perspective into the field of MSC therapy based upon the experience of authors intrinsically involved in MS and MSC basic and translational science research. PMID:22642335

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

PubMed Central

Miljković, Djordje; Spasojević, Ivan

2013-01-01

Abstract The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286–2334. PMID:23473637

Multiple sclerosis and human T-cell lymphotropic retroviruses

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Defreitas, Elaine C.; Harper, Mary E.; Sandberg-Wollheim, Magnhild; Sheremata, William A.; Robert-Guroff, Marjorie; Saxinger, Carl W.; Feinberg, Mark B.; Wong-Staal, Flossie; Gallo, Robert C.

1985-11-01

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

ERIC Educational Resources Information Center

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Demyelination of subcortical nuclei in multiple sclerosis

NASA Astrophysics Data System (ADS)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

Multiple Sclerosis and the Family Physician

PubMed Central

Sky, Ruth

1977-01-01

Multiple sclerosis is difficult to diagnose since it develops over a period of time and the symptoms and signs are scattered throughout the central nervous system. Because there is no specific treatment, the problems of management are especially challenging. Case histories are presented to support the concept that multiple sclerosis is a family and community concern. Family physicians are urged to maintain a supportive role and an interested attitude towards patients with multiple sclerosis. These patients and their families have urgent and continuing needs for their doctors' skills. PMID:21304869

Novel Insights and Therapeutics in Multiple Sclerosis.

PubMed

Wagner, Catriona A; Goverman, Joan M

2015-01-01

The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.

[Future challenges in multiple sclerosis].

PubMed

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

'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.

[Physical rehabilitation in multiple sclerosis: general principles and high-tech approaches].

PubMed

Peresedova, A V; Chernikova, L A; Zavalishin, I A

2013-01-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation programs are of major importance for the preservation of physical, physiological, social and professional functioning and improvement of quality of life. Currently, it is generally assumed that physical activity is an important component of non-pharmacological rehabilitation in multiple sclerosis. Properly organized exercise is a safe and efficient way to induce improvements in a number of physiological functions. A multidisciplinary rehabilitative approach should be recommended. The main recommendations for the use of exercise for patients with multiple sclerosis have been listed. An important aspect of the modern physical rehabilitation in multiple sclerosis is the usage of high-tech methods. The published results of robot-assisted training to improve the hand function and walking impairment have been represented. An important trend in the rehabilitation of patients with multiple sclerosis is the reduction of postural disorders through training balance coordination. The role of transcranial magnetic stimulation in spasticity reducing is being investigated. The use of telemedicine capabilities is quite promising. Due to the fact that the decline in physical activity can lead to the deterioration of many aspects of physiological functions and, ultimately, to mobility decrease, further research of the role of physical rehabilitation as an important therapeutic approach in preventing the progression of disability in multiple sclerosis is required.

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

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

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.

Cognitive status in patients with multiple sclerosis in Lanzarote.

PubMed

Pérez-Martín, María Yaiza; Eguia-Del Río, Pablo; González-Platas, Montserrat; Jiménez-Sosa, Alejandro

2016-01-01

Cognitive impairment is a common feature in multiple sclerosis affecting ~43%-72% of patients, which involves cognitive functions such as memory, processing speed, attention, and executive function. The aim of this study was to describe the extent and pattern of the involvement of cognitive impairment and psychological status in all patients with multiple sclerosis on a small Spanish island. In all, 70 patients and 56 healthy controls were included in the study between February 2013 and May 2013. All participants were assessed using the Brief Repeatable Battery of Neuropsychological Test. The patients also completed instruments to evaluate the presence of fatigue, perceived cognitive dysfunction, and symptoms of anxiety and depression. All procedures were performed in a single session. Cognitive impairment, defined as a score <1.5 standard deviation on two subtests of the battery, was present in 35% of the participants. The most frequently affected domain was working memory, followed by verbal memory and processing speed. Disease duration showed a moderate correlation with visuospatial memory and processing speed. The Expanded Disability Status Scale score correlated with verbal and processing speed. Verbal memory was correlated with depression symptoms and fatigue. Cognitive impairment was present in 35% of the study population. The most affected domains were working memory and verbal memory. Working memory and verbal fluency deficit are independent factors of disease evolution. Cognitive decline is related to clinical variables and psychological measures such as fatigue or depression but not to anxiety.

Cognitive status in patients with multiple sclerosis in Lanzarote

PubMed Central

Pérez-Martín, María Yaiza; Eguia-del Río, Pablo; González-Platas, Montserrat; Jiménez-Sosa, Alejandro

2016-01-01

Objectives Cognitive impairment is a common feature in multiple sclerosis affecting ~43%–72% of patients, which involves cognitive functions such as memory, processing speed, attention, and executive function. The aim of this study was to describe the extent and pattern of the involvement of cognitive impairment and psychological status in all patients with multiple sclerosis on a small Spanish island. Patients and methods In all, 70 patients and 56 healthy controls were included in the study between February 2013 and May 2013. All participants were assessed using the Brief Repeatable Battery of Neuropsychological Test. The patients also completed instruments to evaluate the presence of fatigue, perceived cognitive dysfunction, and symptoms of anxiety and depression. All procedures were performed in a single session. Results Cognitive impairment, defined as a score <1.5 standard deviation on two subtests of the battery, was present in 35% of the participants. The most frequently affected domain was working memory, followed by verbal memory and processing speed. Disease duration showed a moderate correlation with visuospatial memory and processing speed. The Expanded Disability Status Scale score correlated with verbal and processing speed. Verbal memory was correlated with depression symptoms and fatigue. Conclusion Cognitive impairment was present in 35% of the study population. The most affected domains were working memory and verbal memory. Working memory and verbal fluency deficit are independent factors of disease evolution. Cognitive decline is related to clinical variables and psychological measures such as fatigue or depression but not to anxiety. PMID:27418825

Effects of dextromethorphan/quinidine on auditory event-related potentials in multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2009-10-01

The purpose of this study was to characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of laughing and/or crying in patients with multiple sclerosis before and after treatment with dextromethorphan/quinidine (DM/Q). Behavioral responses and event-related potentials (ERPs) in response to subjectively significant and neutral verbal stimuli were recorded from 2 groups: 6 multiple sclerosis patients with PBA before (PBA-preTx) and after (PBA-DM/Q) treatment with DM/Q and 6 healthy control (HC) subjects. Statistical nonparametric mapping comparisons of ERP source current density distributions between groups were conducted for subjectively significant and neutral stimuli separately before and after treatment with DM/Q. Treatment with DM/Q had a normalizing effect on the behavioral responses of PBA patients. Event-related potential waveform comparisons of PBA-preTx and PBA-DM/Q with HC, for both neutral and subjectively significant stimuli, revealed effects on early ERP components. Comparisons between PBA-preTx and HC, in response to subjectively significant stimuli, revealed both early and late effects. Source analysis comparisons between PBA-preTx and PBA-DM/Q indicated distinct activations in areas involved in emotional processing and high-level and associative visual processing in response to neutral stimuli and in areas involved in emotional, somatosensory, primary, and premotor processing in response to subjectively significant stimuli. In most cases, stimuli evoked higher current density in PBA-DM/Q compared with the other groups. In conclusion, differences in brain activity were observed before and after medication. Also, DM/Q administration resulted in normalization of behavioral and electrophysiological measures.

Systemic and localized scleroderma in children: current and future treatment options.

PubMed

Rosenkranz, Margalit E; Agle, Lucila M A; Efthimiou, Petros; Lehman, Thomas J A

2006-01-01

Scleroderma is a group of rare and complex diseases with varied clinical manifestations. The most obvious manifestation of the diseases is skin hardening and sclerosis. Scleroderma can be divided into two main subgroups: systemic and localized. The systemic form, also known as systemic sclerosis, involves diffuse skin involvement and potentially severe visceral involvement. Localized scleroderma on the other hand is more common in children and usually confined to a specific region of the body with no internal organ involvement. The juvenile forms of systemic sclerosis and localized scleroderma are important conditions in children because of the clinical severity and substantial mortality of systemic scleroderma and the major growth defects associated with childhood-onset localized disease even if the active disease itself is self-limited. The pathogenic pathways of the various forms of scleroderma are only partially defined, but the main defect in scleroderma is abnormal collagen deposition leading to eventual fibrosis in the skin as well as multiple organ systems such as the heart and lungs in juvenile systemic sclerosis. Therapeutics are divided into three main subgroups for systemic sclerosis: antifibrotics, anti-inflammatories, and vasodilators. For localized disease, anti-inflammatories, vitamin D analogs, and UV irradiation have been investigated. However, the infrequency of scleroderma in the pediatric population plus the fact that this disease is very often self-limiting makes randomized controlled trials very difficult. It is for this reason that most data on treatment modalities for this disease have been extrapolated from studies in adult patients. There is no one therapy for systemic sclerosis or localized scleroderma that has proven to be very effective or significantly disease modifying. However, current therapeutic strategies must be initiated early in the disease course for maximum beneficial clinical effects. New interventions such as autologous stem cell transplant and cytokine-directed therapies are under investigation as potential treatments for this complex disease.

Urea cycle disorder misdiagnosed as multiple sclerosis: a case report and review of the literature.

PubMed

Algahtani, Hussein; Alameer, Seham; Marzouk, Yousef; Shirah, Bader

2018-04-01

Urea cycle disorders are a group of inborn errors of metabolism caused by dysfunction of any of the six enzymes or two transport proteins involved in urea biosynthesis. In this paper, we report a patient who presented with neurological dysfunction and coma in the immediate postpartum period. She was misdiagnosed for many years as a case of multiple sclerosis. The importance of reporting this case is to illustrate that the wrong diagnosis of patients as being affected with multiple sclerosis for many years due to magnetic resonance imaging abnormalities rather than the classic relapsing-remitting nature of the disease may lead to catastrophic consequences. The patient was treated with intravenous steroids several times, which is contraindicated in patients with urea cycle disorders as it may precipitate acute hyperammonemic attacks. In addition, the management of urea cycle disorder could have started earlier and avoided multiple admissions to the intensive care unit. We believe that the presence of symmetric hyperintense insular cortical changes are seen in multiple hyperammonemic processes, and in the context of the clinical presentation and high ammonia levels can be suggestive of a urea cycle disorder. For any patient presenting with atypical clinical features, images should be reviewed and discussed in detail with an experienced neuroradiologist. In addition, the ammonia levels should be checked if a urea cycle disorder is suspected.

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.

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.

Striving for balance between caring and restraint: young adults' experiences with parental multiple sclerosis.

PubMed

Moberg, Julie Y; Larsen, Dorte; Brødsgaard, Anne

2017-05-01

To explore and describe how young adults between 18-25 years of age experienced growing up with a parent with multiple sclerosis and how these experiences continue to influence their daily lives. Chronic parental illness is occurring in about 10% of families worldwide, but little is known about how the children experience growing up with a parent with multiple sclerosis during their childhood and into young adulthood. We chose a qualitative design using a phenomenological approach based on Giorgi. Exploratory and open-ended interviews with 14 young adults were conducted. The essence of the phenomenon of having a parent with multiple sclerosis was synthesized into 'Striving for balance between caring and restraint' from two themes 'caring' and 'restraint' and eight subthemes. Participants' experiences of caring for parents with multiple sclerosis continued influencing their other close relationships, in which they tended to assume responsibility while concealing some of their feelings and desires. Most participants showed restraint among parents with and without multiple sclerosis, friends and partners. It seems that one of the greatest challenges of having a parent with multiple sclerosis is achieving a balance between caring for others and asserting one's own desires. Healthcare professionals can support the family by encouraging family members to participate in consultations and to assist the parents in providing information about multiple sclerosis and its symptoms to the children. Parents might need assistance in applying for help with domestic chores or referrals to support groups for their children or other family members. © 2016 John Wiley & Sons Ltd.

Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

PubMed

Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

2014-01-01

Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

Vitamin D and remyelination in multiple sclerosis.

PubMed

Matías-Guíu, J; Oreja-Guevara, C; Matias-Guiu, J A; Gomez-Pinedo, U

2018-04-01

Several studies have found an association between multiple sclerosis and vitamin D (VD) deficiency, which suggests that VD may play a role in the immune response. However, few studies have addressed its role in remyelination. The VD receptor and the enzymes transforming VD into metabolites which activate the VD receptor are expressed in central nervous system (CNS) cells, which suggests a potential effect of VD on the CNS. Both in vitro and animal model studies have shown that VD may play a role in myelination by acting on factors that influence the microenvironment which promotes both proliferation and differentiation of neural stem cells into oligodendrocyte progenitor cells and oligodendrocytes. It remains unknown whether the mechanisms of internalisation of VD in the CNS are synergistic with or antagonistic to the mechanisms that facilitate the entry of VD metabolites into immune cells. VD seems to play a role in the CNS and our hypothesis is that VD is involved in remyelination. Understanding the basic mechanisms of VD in myelination is necessary to manage multiple sclerosis patients with VD deficiency. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Optical coherence tomography angiography retinal vascular network assessment in multiple sclerosis.

PubMed

Lanzillo, Roberta; Cennamo, Gilda; Criscuolo, Chiara; Carotenuto, Antonio; Velotti, Nunzio; Sparnelli, Federica; Cianflone, Alessandra; Moccia, Marcello; Brescia Morra, Vincenzo

2017-09-01

Optical coherence tomography (OCT) angiography is a new method to assess the density of the vascular networks. Vascular abnormalities are considered involved in multiple sclerosis (MS) pathology. To assess the presence of vascular abnormalities in MS and to evaluate their correlation to disease features. A total of 50 MS patients with and without history of optic neuritis (ON) and 46 healthy subjects were included. All underwent spectral domain (SD)-OCT and OCT angiography. Clinical history, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS) and disease duration were collected. Angio-OCT showed a vessel density reduction in eyes of MS patients when compared to controls. A statistically significant reduction in all SD-OCT and OCT angiography parameters was noticed both in eyes with and without ON when compared with control eyes. We found an inverse correlation between SD-OCT parameters and MSSS ( p = 0.003) and between vessel density parameters and EDSS ( p = 0.007). We report a vessel density reduction in retina of MS patients. We highlight the clinical correlation between vessel density and EDSS, suggesting that angio-OCT could be a good marker of disease and of disability in MS.

Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.

PubMed

Vercellino, Marco; Fenoglio, Chiara; Galimberti, Daniela; Mattioda, Alessandra; Chiavazza, Carlotta; Binello, Eleonora; Pinessi, Lorenzo; Giobbe, Dario; Scarpini, Elio; Cavalla, Paola

2016-07-01

Progranulin (GRN) is a multifunctional protein involved in inflammation and repair, and also a neurotrophic factor critical for neuronal survival. Progranulin is strongly expressed in multiple sclerosis (MS) brains by macrophages and microglia. In this study we evaluated GRN genetic variability in 400 MS patients, in correlation with clinical variables such as disease severity and relapse recovery. We also evaluated serum progranulin levels in the different groups of GRN variants carriers. We found that incomplete recovery after a relapse is correlated with an increased frequency of the rs9897526 A allele (odds ratio (OR) 4.367, p = 0.005). A more severe disease course (Multiple Sclerosis Severity Score > 5) is correlated with an increased frequency of the rs9897526 A allele (OR 1.886, p = 0.002) and of the rs5848 T allele (OR 1.580, p = 0.019). Carriers of the variants associated with a more severe disease course (rs9897526 A, rs5848 T) have significantly lower levels of circulating progranulin (80.5 ± 9.1 ng/mL vs. 165.7 ng/mL, p = 0.01). GRN genetic polymorphisms likely influence disease course and relapse recovery in MS. © The Author(s), 2015.

Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

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

Habib, A.C.; Zheng, W.; Haacke, E.M.

To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximalmore » to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.« less

Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

NASA Astrophysics Data System (ADS)

Habib, Charbel A.; Zheng, Weili; Mark Haacke, E.; Webb, Sam; Nichol, Helen

2010-07-01

Aim: To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Material and Methods: Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Conclusion: Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.

Symptomatic therapy in multiple sclerosis

PubMed Central

Frohman, Teresa C.; Castro, Wanda; Shah, Anjali; Courtney, Ardith; Ortstadt, Jeffrey; Davis, Scott L.; Logan, Diana; Abraham, Thomas; Abraham, Jaspreet; Remington, Gina; Treadaway, Katherine; Graves, Donna; Hart, John; Stuve, Olaf; Lemack, Gary; Greenberg, Benjamin; Frohman, Elliot M.

2011-01-01

Multiple sclerosis is the most common disabling neurological disease of young adults. The ability to impact the quality of life of patients with multiple sclerosis should not only incorporate therapies that are disease modifying, but should also include a course of action for the global multidisciplinary management focused on quality of life and functional capabilities. PMID:21694806

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…

78 FR 40632 - Drawbridge Operation Regulation; Trent River, New Bern, NC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... navigation position for one hour on two consecutive days to accommodate the annual Bike Multiple Sclerosis... INFORMATION: The Event Director for the Bike Multiple Sclerosis: Historic New Bern Bike Ride, with approval... safe passage for cyclists during the Bike Multiple Sclerosis: Historic New Bern Bike Ride. The US 70...

Self care programs and multiple sclerosis: physical therapeutics treatment - literature review.

PubMed

Demaille-Wlodyka, S; Donze, C; Givron, P; Gallien, P

2011-03-01

To clarify the therapeutic education program impact with multiple sclerosis patients, literature review. Highlight contents and efficacy. A non-systematic review on Medline, PubMed and Cochrane library databases from 1966 to 2010 using the following keywords: "multiple sclerosis", "self-care", "self-management" and specific symptoms keywords. Clinical trials and randomized clinical trials, as well as literature reviews published in English, French and German will be analyzed. Counseling is a part of the non-pharmacological management of chronic illnesses such as multiple sclerosis. Symptoms' diversity and the different clinical forms limit standardized programs of self-care management, applicable to patients. In the literature review, counseling programs have often low metrology. A behavior change with patients and medical staff could exist. To empower the patient, to reduce symptoms' impact and to improve treatment access are the aims of educational therapy. Therapeutic education program for multiple sclerosis patients could progress with their standardization and assessment, for each sign. To promote the educational therapy of multiple sclerosis patients, a specific training for medical staff, as specific financing are necessary. 2011 Elsevier Masson SAS. All rights reserved.

Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.

PubMed

Negahban, Hossein; Rezaie, Solmaz; Goharpey, Shahin

2013-12-01

The primary aim was to investigate the comparative effects of massage therapy and exercise therapy on patients with multiple sclerosis. The secondary aim was to investigate whether combination of both massage and exercise has an additive effect. Randomized controlled pilot trial with repeated measurements and blinded assessments. Local Multiple Sclerosis Society. A total of 48 patients with multiple sclerosis were randomly assigned to four equal subgroups labelled as massage therapy, exercise therapy, combined massage-exercise therapy and control group. The treatment group received 15 sessions of supervised intervention for five weeks. The massage therapy group received a standard Swedish massage. The exercise therapy group was given a combined set of strength, stretch, endurance and balance exercises. Patients in the massage-exercise therapy received a combined set of massage and exercise treatments. Patients in the control group were asked to continue their standard medical care. Pain, fatigue, spasticity, balance, gait and quality of life were assessed before and after intervention. Massage therapy resulted in significantly larger improvement in pain reduction (mean change 2.75 points, P = 0.001), dynamic balance (mean change, 3.69 seconds, P = 0.009) and walking speed (mean change, 7.84 seconds, P = 0.007) than exercise therapy. Patients involved in the combined massage-exercise therapy showed significantly larger improvement in pain reduction than those in the exercise therapy (mean change, 1.67 points, P = 0.001). Massage therapy could be more effective than exercise therapy. Moreover, the combination of massage and exercise therapy may be a little more effective than exercise therapy alone.

Evaluating walking in patients with multiple sclerosis: which assessment tools are useful in clinical practice?

PubMed

Bethoux, Francois; Bennett, Susan

2011-01-01

Walking limitations are among the most visible manifestations of multiple sclerosis (MS). Regular walking assessments should be a component of patient management and require instruments that are appropriate from the clinician's and the patient's perspectives. This article reviews frequently used instruments to assess walking in patients with MS, with emphasis on their validity, reliability, and practicality in the clinical setting. Relevant articles were identified based on PubMed searches using the following terms: "multiple sclerosis AND (walking OR gait OR mobility OR physical activity) AND (disability evaluation)"; references of relevant articles were also searched. Although many clinician- and patient-driven instruments are available, not all have been validated in MS, and some are not sensitive enough to detect small but clinically important changes. Choosing among these depends on what needs to be measured, psychometric properties, the clinical relevance of results, and practicality with respect to space, time, and patient burden. Of the instruments available, the clinician-observed Timed 25-Foot Walk and patient self-report 12-Item Multiple Sclerosis Walking Scale have properties that make them suitable for routine evaluation of walking performance. The Dynamic Gait Index and the Timed Up and Go test involve other aspects of mobility, including balance. Tests of endurance, such as the 2- or 6-Minute Walk, may provide information on motor fatigue not captured by other tests. Quantitative measurement of gait kinetics and kinematics, and recordings of mobility in the patient's environment via accelerometry or Global Positioning System odometry, are currently not routinely used in the clinical setting.

Evaluating Walking in Patients with Multiple Sclerosis

PubMed Central

Bennett, Susan

2011-01-01

Walking limitations are among the most visible manifestations of multiple sclerosis (MS). Regular walking assessments should be a component of patient management and require instruments that are appropriate from the clinician's and the patient's perspectives. This article reviews frequently used instruments to assess walking in patients with MS, with emphasis on their validity, reliability, and practicality in the clinical setting. Relevant articles were identified based on PubMed searches using the following terms: “multiple sclerosis AND (walking OR gait OR mobility OR physical activity) AND (disability evaluation)”; references of relevant articles were also searched. Although many clinician- and patient-driven instruments are available, not all have been validated in MS, and some are not sensitive enough to detect small but clinically important changes. Choosing among these depends on what needs to be measured, psychometric properties, the clinical relevance of results, and practicality with respect to space, time, and patient burden. Of the instruments available, the clinician-observed Timed 25-Foot Walk and patient self-report 12-Item Multiple Sclerosis Walking Scale have properties that make them suitable for routine evaluation of walking performance. The Dynamic Gait Index and the Timed Up and Go test involve other aspects of mobility, including balance. Tests of endurance, such as the 2- or 6-Minute Walk, may provide information on motor fatigue not captured by other tests. Quantitative measurement of gait kinetics and kinematics, and recordings of mobility in the patient's environment via accelerometry or Global Positioning System odometry, are currently not routinely used in the clinical setting. PMID:24453700

The Effect of Orem’s Self-Care Model on Fatigue in Patients With Multiple Sclerosis: A Single Blind Randomized Clinical Trial Study

PubMed Central

Afrasiabifar, Ardashir; Mehri, Zahra; Javad Sadat, Saied; Ghaffarian Shirazi, Hamid Reza

2016-01-01

Background Orem’s self-care model is a nursing model that was introduced with the purpose of improving the self-care of individuals, especially patients suffering from chronic diseases. Objectives To determining the effect of Orem’s self-care model on fatigue in multiple sclerosis patients. Patients and Methods This research involved a clinical trial. Sixty-three multiple sclerosis patients at the vice-chancellor in treatment affairs of Yasuj University of Medical Sciences were selected based on nonrandom sampling, but they were allocated to the two groups based on random allocation. In the intervention group, Orem’s model was applied during six sessions of 45 - 60 minutes in length, and the process continued for 1 month. The data were collected 1 week before and 7 weeks after the end of the intervention using the Orem’s self-care model-based assessment form and fatigue severity scale, the validity and reliability of which have been Results Before the intervention, 11.11% of the participants had a good knowledge of self-care. In addition, self-care willingness and skills were observed in 76.19% and 4.76% of participants, respectively. The mean difference in fatigue reduced significantly in the intervention group after the intervention (P < 0.05). After the intervention, a statistically significant difference was observed in the mean difference of fatigue between the two groups (P < 0.05). Conclusions Orem’s self-care model is significantly effective in reducing the fatigue of multiple sclerosis patients. PMID:27781119

Epigenetic changes in neurology: DNA methylation in multiple sclerosis.

PubMed

Iridoy Zulet, M; Pulido Fontes, L; Ayuso Blanco, T; Lacruz Bescos, F; Mendioroz Iriarte, M

2017-09-01

Epigenetics is defined as the study of the mechanisms that regulate gene expression without altering the underlying DNA sequence. The best known is DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known etiology, in which it is stated that the involvement of environmental factors on people with a genetic predisposition, may be key to the development of the disease. It is at this intersection between genetic predisposition and environmental factors where DNA methylation may play a pathogenic role. A literature review of the effects of environmental risk factors for the development of MS can have on the different epigenetic mechanisms as well as the implication that such changes have on the development of the disease. Knowledge of epigenetic modifications involved in the pathogenesis of MS, opens a new avenue of research for identification of potential biomarkers, as well as finding new therapeutic targets. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

PubMed Central

Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

2009-01-01

Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

Nutraceuticals against Neurodegeneration: A Mechanistic Insight.

PubMed

Dadhania, Vivekkumar P; Trivedi, Priyanka P; Vikram, Ajit; Tripathi, Durga Nand

2016-01-01

The mechanisms underlying neurodegenerative disorders are complex and multifactorial; however, accumulating evidences suggest few common shared pathways. These common pathways include mitochondrial dysfunction, intracellular Ca2+ overload, oxidative stress and inflammation. Often multiple pathways co-exist, and therefore limit the benefits of therapeutic interventions. Nutraceuticals have recently gained importance owing to their multifaceted effects. These food-based approaches are believed to target multiple pathways in a slow but more physiological manner without causing severe adverse effects. Available information strongly supports the notion that apart from preventing the onset of neuronal damage, nutraceuticals can potentially attenuate the continued progression of neuronal destruction. In this article, we i) review the common pathways involved in the pathogenesis of the toxicants-induced neurotoxicity and neurodegenerative disorders with special emphasis on Alzheimer`s disease (AD), Parkinson`s disease (PD), Huntington`s disease (HD), Multiple sclerosis (MS) and Amyotrophic lateral sclerosis (ALS), and ii) summarize current research advancements on the effects of nutraceuticals against these detrimental pathways.

Nutraceuticals against Neurodegeneration: A Mechanistic Insight

PubMed Central

Dadhania, Vivekkumar P.; Trivedi, Priyanka P.; Vikram, Ajit; Tripathi, Durga Nand

2016-01-01

The mechanisms underlying neurodegenerative disorders are complex and multifactorial; however, accumulating evidences suggest few common shared pathways. These common pathways include mitochondrial dysfunction, intracellular Ca2+ overload, oxidative stress and inflammation. Often multiple pathways co-exist, and therefore limit the benefits of therapeutic interventions. Nutraceuticals have recently gained importance owing to their multifaceted effects. These food-based approaches are believed to target multiple pathways in a slow but more physiological manner without causing severe adverse effects. Available information strongly supports the notion that apart from preventing the onset of neuronal damage, nutraceuticals can potentially attenuate the continued progression of neuronal destruction. In this article, we i) review the common pathways involved in the pathogenesis of the toxicants-induced neurotoxicity and neurodegenerative disorders with special emphasis on Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS) and Amyotrophic lateral sclerosis (ALS), and ii) summarize current research advancements on the effects of nutraceuticals against these detrimental pathways. PMID:26725888

The Role of Microglial Subsets in Regulating Traumatic Brain Injury

DTIC Science & Technology

2013-07-01

CCR)2. J. Exp. Med. 2000. 192: 1075–1080. 9 Mahad, D. J. and Ransohoff, R. M., The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and...at multiple timepoints in vivo and establish the function of these microglial subtypes ex vivo. 2. Skew the microglial response to TBI towards... multiple aspects, most notably in their chemokine repertoires. Thus, the macrophage response to TBI ini- tially involves heterogeneous polarization

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.

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.

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.

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.

Therapeutics for multiple sclerosis symptoms.

PubMed

Ben-Zacharia, Aliza Bitton

2011-01-01

Symptoms management in multiple sclerosis is an integral part of its care. Accurate assessment and addressing the different symptoms provides increased quality of life among patients with multiple sclerosis. Multiple sclerosis symptoms may be identified as primary, secondary, or tertiary symptoms. Primary symptoms, such as weakness, sensory loss, and ataxia, are directly related to demyelination and axonal loss. Secondary symptoms, such as urinary tract infections as a result of urinary retention, are a result of the primary symptoms. Tertiary symptoms, such as reactive depression or social isolation, are a result of the social and psychological consequences of the disease. Common multiple sclerosis symptoms include fatigue and weakness; decreased balance, spasticity and gait problems; depression and cognitive issues; bladder, bowel, and sexual deficits; visual and sensory loss; and neuropathic pain. Less-common symptoms include dysarthria and dysphagia, vertigo, and tremors. Rare symptoms in multiple sclerosis include seizures, hearing loss, and paralysis. Symptom management includes nonpharmacological methods, such as rehabilitation and psychosocial support, and pharmacological methods, ie, medications and surgical procedures. The keys to symptom management are awareness, knowledge, and coordination of care. Symptoms have to be recognized and management needs to be individualized. Multiple sclerosis therapeutics include nonpharmacological strategies that consist of lifestyle modifications, rehabilitation, social support, counseling, and pharmacological agents or surgical procedures. The goal is vigilant management to improve quality of life and promote realistic expectations and hope. © 2011 Mount Sinai School of Medicine.

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.

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.

Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability.

PubMed

Dasenbrock, Hormuzdiyar H; Smith, Seth A; Ozturk, Arzu; Farrell, Sheena K; Calabresi, Peter A; Reich, Daniel S

2011-04-01

Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P=.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=.51, P=.003) and total-macular-volume reduction (r=.59, P=.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. Copyright © 2010 by the American Society of Neuroimaging.

Diffusion Tensor Imaging of the Optic Tracts in Multiple Sclerosis: Association with Retinal Thinning and Visual Disability

PubMed Central

Dasenbrock, Hormuzdiyar H.; Smith, Seth A.; Ozturk, Arzu; Farrell, Sheena K.; Calabresi, Peter A.; Reich, Daniel S.

2009-01-01

Background and purpose Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Methods Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. Results After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (p=0.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=0.51, p=0.003) and total-macular-volume reduction (r=0.59, p=0.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Conclusions Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. PMID:20331501

Clustering of multiple sclerosis in Galion, Ohio, 1982-1985

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

Ingalls, T.H.

1989-09-01

Epidemiologic evidence indicates that the outbreak of 30-40 cases of multiple sclerosis and other demyelinating syndromes in Galion, Ohio, USA, during 1982-1985 was related to an excess concentration of heavy-metal wastes, especially of cadmium and chromium in sewage and river water. Both multiple sclerosis and myasthenia gravis were diagnosed by board-certified neurologists.

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.

Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

DTIC Science & Technology

2017-10-01

Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive Function in Multiple Sclerosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...going to evaluate if intranasal insulin improves cognition in people with MS, as assessed by standardized cognitive assessment tests . 2. KEYWORDS...Multiple Sclerosis, Cognitive Impairment, Neurodegenerative diseases, Intranasal Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive

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…

76 FR 17530 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

...'' N 069[deg] 31'56'' W. 8.6 Multiple Sclerosis Regatta.... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: A one day event on Saturday during the third... 070[deg] 13'51'' W. 8.7 Multiple Sclerosis Harborfest Event Type: Power Boat Tugboat Race. Race...

75 FR 32280 - Safety Zones; Marine Events Within the Captain of the Port Sector Northern New England Area of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

.... Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: August 21, 2010. Time: 11 am to 2 pm. Location... Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: August 21, 2010. Time: 10 am to 4... Tugboat Muster. Event Type: Power Boat Race. Sponsor: Maine Chapter, National Multiple Sclerosis Society...

Is Hypovitaminosis D One of the Environmental Risk Factors for Multiple Sclerosis?

ERIC Educational Resources Information Center

Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

2010-01-01

The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical…

Epstein Barr Virus and Blood Brain Barrier in Multiple Sclerosis

DTIC Science & Technology

2013-07-01

Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease . Epstein - Barr ...of EBV in MS disease . 15. SUBJECT TERMS Blood-brain-barrier, Epstein - Barr virus ; EBV; BBB; MS, Multiple sclerosis 16. SECURITY CLASSIFICATION OF...AD_________________ Award Number: W81XWH-12-1-0225 TITLE: Epstein Barr virus and blood brain

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.

[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.

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.

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.

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.

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.

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.

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.

Metabolic Dysfunction and Peroxisome Proliferator-Activated Receptors (PPAR) in Multiple Sclerosis.

PubMed

Ferret-Sena, Véronique; Capela, Carlos; Sena, Armando

2018-06-01

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) probably caused, in most cases, by the interaction of genetic and environmental factors. This review first summarizes some clinical, epidemiological and pathological characteristics of MS. Then, the involvement of biochemical pathways is discussed in the development and repair of the CNS lesions and the immune dysfunction in the disease. Finally, the potential roles of peroxisome proliferator-activated receptors (PPAR) in MS are discussed. It is suggested that metabolic mechanisms modulated by PPAR provide a window to integrate the systemic and neurological events underlying the pathogenesis of the disease. In conclusion, the reviewed data highlight molecular avenues of understanding MS that may open new targets for improved therapies and preventive strategies for the disease.

[C-ANCA positive necrotising scleritis and multiple sclerosis compatible with ocular Wegener: treatment with rituximab].

PubMed

Aldasoro-Cáceres, V; Aldasoro-Cáceres, I; Pérez-Moreiras, J V; Murié-Fernández, M; Ibáñez-Bosch, R

2014-01-01

A patient diagnosed with necrotizing scleritis, c-ANCA+ an orbital pseudotumour, and possible multiple sclerosis in 2003 was treated with oral cyclophosphamide and steroids with partial response. Between 2005-2010 she suffered self-limited episodes. In 2010 a first scleral transplant was performed with poor outcome. She was treated with rituximab, and a second graft was performed with good results. At 12 months there was no change in magnetic resonance and the second graft healed. Wegener's disease with limited involvement of the orbit and/or the eye is a rare condition. The histopathology, blood analysis, symptoms and good response to treatment are the key to its diagnosis. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis - A case report.

PubMed

Dalbjerg, Sara Maria; Tsakiri, Anna; Frederiksen, Jette Lautrup

2016-07-01

Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis associated with Interferon-beta treatment. We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved. Clinicians should be aware of the possibility of rhabdomyolysis occurring during Interferon-beta-1-alpha therapy. In cases where patients complain of severe myalgia, and in particular if weakness is reported, creatine kinase activity should be measured to prevent irreversible rhabdomyolysis during Interferon-beta-1-alpha therapy in patients with multiple sclerosis. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Latin American algorithm for treatment of relapsing-remitting multiple sclerosis using disease-modifying agents.

PubMed

Finkelsztejn, Alessandro; Gabbai, Alberto Alain; Fragoso, Yara Dadalti; Carrá, Adriana; Macías-Islas, Miguel Angel; Arcega-Revilla, Raul; García-Bonitto, Juan; Oehninger-Gatti, Carlos Luis; Orozco-Escobar, Geraldine; Tarulla, Adriana; Vergara, Fernando; Vizcarra, Darwin

2012-10-01

It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North-American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

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.

Grey matter damage in progressive multiple sclerosis versus amyotrophic lateral sclerosis: a voxel-based morphometry MRI study.

PubMed

Tavazzi, Eleonora; Laganà, Maria Marcella; Bergsland, Niels; Tortorella, Paola; Pinardi, Giovanna; Lunetta, Christian; Corbo, Massimo; Rovaris, Marco

2015-03-01

Primary progressive multiple sclerosis (PPMS) and amyotrophic lateral sclerosis (ALS) seem to share some clinical and pathological features. MRI studies revealed the presence of grey matter (GM) atrophy in both diseases, but no comparative data are available. The objective was to compare the regional patterns of GM tissue loss in PPMS and ALS with voxel-based morphometry (VBM). Eighteen PPMS patients, 20 ALS patients, and 31 healthy controls (HC) were studied with a 1.5 Tesla scanner. VBM was performed to assess volumetric GM differences with age and sex as covariates. Threshold-free cluster enhancement analysis was used to obtain significant clusters. Group comparisons were tested with family-wise error correction for multiple comparisons (p < 0.05) except for HC versus MND which was tested at a level of p < 0.001 uncorrected and a cluster threshold of 20 contiguous voxels. Compared to HC, ALS patients showed GM tissue reduction in selected frontal and temporal areas, while PPMS patients showed a widespread bilateral GM volume decrease, involving both deep and cortical regions. Compared to ALS, PPMS patients showed tissue volume reductions in both deep and cortical GM areas. This preliminary study confirms that PPMS is characterized by a more diffuse cortical and subcortical GM atrophy than ALS and that, in the latter condition, brain damage is present outside the motor system. These results suggest that PPMS and ALS may share pathological features leading to GM tissue loss.

The Role of Microglia and Matrix Metalloproteinases Involvement in Neuroinflammation and Gliomas

PubMed Central

Könnecke, Helen; Bechmann, Ingo

2013-01-01

Matrix metalloproteinases (MMPs) are involved in the pathogenesis of neuroinflammatory diseases (such as multiple sclerosis) as well as in the expansion of malignant gliomas because they facilitate penetration of anatomical barriers (such as the glia limitans) and migration within the neuropil. This review elucidates pathomechanisms and summarizes the current knowledge of the involvement of MMPs in neuroinflammation and glioma, invasion highlighting microglia as major sources of MMPs. The induction of expression, suppression, and multiple pathways of function of MMPs in these scenarios will also be discussed. Understanding the induction and action of MMPs might provide valuable information and reveal attractive targets for future therapeutic strategies. PMID:24023566

76 FR 1568 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

..., 069[deg]31[min]29[sec] W;43[deg]52[min]09[sec] N, 069[deg]31[min]56[sec] W. 8.6 Multiple Sclerosis Event Type: Regatta and Sailboat Regatta. Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date...]51[sec] W. 8.7 Multiple Sclerosis Event Type: Power Boat Race. Harborfest Tugboat Race. Sponsor...

76 FR 80850 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

...[deg]31'29'' W. 43[deg]52'09'' N, 069[deg]31'56'' W. 8.6 Multiple Sclerosis Regatta......... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: A one day event on..., 070[deg]13'51'' W. 8.7 Multiple Sclerosis Harborfest Event Type: Power Boat Tugboat Race. Race...

78 FR 47555 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

...]52'35'' N, 069[deg]31'29'' W. 43[deg]52'09'' N, 069[deg]31'56'' W. 8.6 Multiple Sclerosis Regatta......... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: A one..., National Multiple Sclerosis Society. Date: A one day event on the third Sunday of August.* Time...

Multiple sclerosis - etiology and diagnostic potential.

PubMed

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

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.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress.

PubMed

Briones-Buixassa, Laia; Milà, Raimon; Mª Aragonès, Josep; Bufill, Enric; Olaya, Beatriz; Arrufat, Francesc Xavier

2015-07-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms "stress*" AND "multiple sclerosis." Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset ( n  = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression ( n  = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress

PubMed Central

Briones-Buixassa, Laia; Milà, Raimon; Mª Aragonès, Josep; Bufill, Enric; Olaya, Beatriz; Arrufat, Francesc Xavier

2015-01-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms “stress*” AND “multiple sclerosis.” Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset (n = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression (n = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis. PMID:28070374

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

PubMed Central

2013-01-01

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis. PMID:23356351

Subclinical visual involvement in multiple sclerosis: a study by MRI, VEPs, frequency-doubling perimetry, standard perimetry, and contrast sensitivity.

PubMed

Sisto, Dario; Trojano, Maria; Vetrugno, Michele; Trabucco, Tiziana; Iliceto, Giovanni; Sborgia, Carlo

2005-04-01

To evaluate the effectiveness of visual evoked potentials (VEPs), frequency-doubling perimetry (FDP), standard achromatic perimetry (SAP), contrast sensitivity (CS) test, and magnetic resonance imaging (MRI), isolated or in combination, in detecting subclinical impairment of visual function in multiple sclerosis (MS). Twenty-two eyes of 11 patients affected by clinically definite MS, without a history of optic neuritis and asymptomatic for visual disturbances, underwent full ophthalmic examination and, in addition, VEPs, FDP, SAP, CS, and MRI. Abnormal results were taken to be as follows: for VEPs, a P100 latency >115 ms; for FDP, abnormal mean deviation (MD) or pattern SD (PSD); for SAP, abnormal MD or PSD; for CS, abnormal CS at one spatial frequency, at least; and for MRI, evidence of at least one demyelinating plaque along the visual pathway. VEPs showed abnormal results in 12 eyes (54.4%), FDP in 11 (50%), SAP in 14 (63.6%), CS in 17 (77.1%), and MRI in 16 (72.7%). In only two (9.1%) eyes of the same patient was no abnormality found. No single test detected all the abnormal eyes. Four (18.2%) eyes had pure optic nerve involvement and the remaining 16 (72.7%) had both pre- and postchiasmal involvement. In patients affected by clinically definite MS without history of optic neuritis and no visual symptoms, there is a large prevalence of visual pathway involvement that can be diagnosed only by performing multiple tests. The comparison of the tests is also useful to detect the presence of multiple lesions in the same patient.

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.

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

[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.

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.

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients.

PubMed

Han, Xue-Mei; Tian, Hong-Ji; Han, Zheng; Zhang, Ce; Liu, Ying; Gu, Jie-Bing; Bakshi, Rohit; Cao, Xia

2017-05-01

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe (postcentral and inferior parietal gyri), right temporal lobe (caudate nucleus), right occipital lobe (middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

The "Yin" and "Yang" of Cell Cycle Progression and Differentiation in the Oligodendroglial Lineage

ERIC Educational Resources Information Center

Nguyen, Laurent; Borgs, Laurence; Vandenbosch, Renaud; Mangin, Jean-Marie; Beukelaers, Pierre; Moonen, Gustave; Gallo, Vittorio; Malgrange, Brigitte; Belachew, Shibeshih

2006-01-01

In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor cells involves errors in the sequence of events that normally occur during development when progenitors proliferate, migrate through the white…

The Latest Innovations in the Drug Pipeline for Multiple Sclerosis.

PubMed

Radick, Lea; Mehr, Stanton R

2015-11-01

Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of fingolimod. Ocrelizumab is a CD20-positive B-cell-targeting monoclonal antibody with a promising new mechanism of action. Ofatumumab is also a CD20 inhibitor. Daclizumab, an interleukin-2 inhibitor, has evidence of good efficacy but is associated with unfavorable side effects. Masitinib is a mast-cell inhibitor that also has shown efficacy in Alzheimer's disease and amyotrophic lateral sclerosis. Phase 3 trials for some of these agents will conclude in the next 12 months, and their manufacturers are expected to apply for US Food and Drug Administration approval soon thereafter. This review article summarizes data for newly approved and late-phase investigational agents for the treatment of patients with MS.

The Latest Innovations in the Drug Pipeline for Multiple Sclerosis

PubMed Central

Radick, Lea; Mehr, Stanton R.

2015-01-01

Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of fingolimod. Ocrelizumab is a CD20-positive B-cell–targeting monoclonal antibody with a promising new mechanism of action. Ofatumumab is also a CD20 inhibitor. Daclizumab, an interleukin-2 inhibitor, has evidence of good efficacy but is associated with unfavorable side effects. Masitinib is a mast-cell inhibitor that also has shown efficacy in Alzheimer's disease and amyotrophic lateral sclerosis. Phase 3 trials for some of these agents will conclude in the next 12 months, and their manufacturers are expected to apply for US Food and Drug Administration approval soon thereafter. This review article summarizes data for newly approved and late-phase investigational agents for the treatment of patients with MS. PMID:26702336

Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial.

PubMed

Rosche, Berit; Wernecke, Klaus-Dieter; Ohlraun, Stephanie; Dörr, Jan-Markus; Paul, Friedemann

2013-04-25

Trichuris suis ova is a probiotic treatment based on the hygiene hypothesis. It has been demonstrated as safe and effective in autoimmune inflammatory bowel diseases and clinical trials indicate that helminth infections also have an immunomodulatory effect in multiple sclerosis.We hypothesize that administering 2,500 Trichuris suis ova eggs orally every two weeks for 12 months is--due to its immunomodulatory and anti-inflammatory effect--significantly more effective than oral placebo in preventing new T2 and Gd+ lesions, as quantified by cerebral MRI and clinical examination, in relapsing-remitting multiple sclerosis and clinically isolated syndrome. Fifty patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome with clinical activity, not undergoing any standard therapies, will be randomized 1:1 to Trichuris suis ova 2,500 eggs every two weeks or matching placebo. The safety, tolerability and effect on disease activity and in vivo mechanisms of action of Trichuris suis ova in MS will be assessed by neurological, laboratory and immunological exams and magnetic resonance imaging throughout the 12-month treatment period and over a follow-up period of 6 months. Various immunological analyses will be used to assess the overall patient immune response prior to and at varying time points following treatment with Trichuris suis ova. We anticipate that Trichuris suis ova will be well tolerated and more effective than the placebo in preventing new T2 and Gd+ lesions, as quantified by MRI. We also expect the Th1/Th17 proinflammatory response to shift towards the more anti-inflammatory Th2 response. This study has important clinical implications and will involve extensive research on the immunology of helminth therapy. ClinicalTrials.gov: NCT01413243.

Epidemiological and clinical characteristics of multiple sclerosis in paediatric population in Slovenia: A descriptive nation-wide study.

PubMed

Bizjak, Neli; Osredkar, Damjan; Perković Benedik, Mirjana; Šega Jazbec, Saša

2017-11-01

Although multiple sclerosis usually affects young adults, paediatric-onset multiple sclerosis (pMS) is increasingly recognized in the past ten years. The aim of the present study was to evaluate the incidence of pMS in Slovenia and to characterize the clinical, laboratory and neuroradiological characteristics of pMS at the disease onset. We performed a national retrospective descriptive study including all patients diagnosed with pMS between January 1992 and June 2017. We reviewed data of all patients younger than 18 years at the first demyelinating event. The estimated incidence of pMS was 0.66/100,000 children per year. We included 61 patients (77% were female) with a median age at diagnosis of 16.3 years. In 4 patients, onset of pMS was before the age of 12 years old (childhood-onset pMS). Relapsing-remitting multiple sclerosis was most prevalent, with only 2 patients presenting a primary progressive pMS. Polysymptomatic pMS was found at onset in 59% of patients and monosymptomatic in 41%. In the cerebrospinal fluid study, 88% of patients had positive oligoclonal bands. Brain magnetic resonance imaging studies showed a predominant supratentorial involvement (100% of patients). The clinical pattern of pMS in our cohort of patients was characterized by polysymptomatic presentation and predominantly sensory symptoms at onset, developing a relapsing-remitting pMS pattern. It is important to gather more information about the incidence of pMS and its initial presentation and clinical course to improve early recognition and appropriate initiation of immunomodulatory treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

[The overall assessment of the quality of the physical health of patients with multiple sclerosis after the application of physical therapy. Part 1].

PubMed

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

2016-01-01

Multiple sclerosis is one of the demyelinating diseases of the central nervous system. The biggest problem of patients affected by this disease are physical limitations which force many times to changes in employment and dependent on their families.The progressive disability significantly reduces the quality of life of patients with MS. The study involved 120 patients with multiple sclerosis at the age of 21 - 81 years. Patients were divided into four groups, and the test was performed three times. In the first group was used laser therapy, group II laser and magnetostimulation, in the third group kinesiotherapy in the fourth group magnetostimulation. In all patients MSQOL (Quality of Life Questionnaire-54) was carried out, this survey analyzed overall assessment of physical health. In all test groups was observed tends to decrease as a result of a point in Quality of Life Questionnaire MSQOL-54 and continuation in this relationship even after cessation of use of these therapies. The correlation between the two groups showed a statistically significant result at the level of p <0.001 in the group I and II in relation to group III and IV. Synergic action of laser radiation and magnetic stimulation, causing a plurality of changes at the cellular and tissue level, has a beneficial effect on improving functional status, and thereby improves the quality of life of patients with multiple sclerosis. Thanks to physical therapy, it is possible to achieve long-term effects of therapy, which proves the biological hysteresis phenomenon. Such results can not be achieved with using monotherapy only - by kinesiotherapy.

A survey of endogenous retrovirus (ERV) sequences in the vicinity of multiple sclerosis (MS)-associated single nucleotide polymorphisms (SNPs).

PubMed

Brütting, Christine; Emmer, Alexander; Kornhuber, Malte; Staege, Martin S

2016-08-01

Although multiple sclerosis (MS) is one of the most common central nervous system diseases in young adults, little is known about its etiology. Several human endogenous retroviruses (ERVs) are considered to play a role in MS. We are interested in which ERVs can be identified in the vicinity of MS associated genetic marker to find potential initiators of MS. We analysed the chromosomal regions surrounding 58 single nucleotide polymorphisms (SNPs) that are associated with MS identified in one of the last major genome wide association studies. We scanned these regions for putative endogenous retrovirus sequences with large open reading frames (ORFs). We observed that more retrovirus-related putative ORFs exist in the relatively close vicinity of SNP marker indices in multiple sclerosis compared to control SNPs. We found very high homologies to HERV-K, HCML-ARV, XMRV, Galidia ERV, HERV-H/env62 and XMRV-like mouse endogenous retrovirus mERV-XL. The associated genes (CYP27B1, CD6, CD58, MPV17L2, IL12RB1, CXCR5, PTGER4, TAGAP, TYK2, ICAM3, CD86, GALC, GPR65 as well as the HLA DRB1*1501) are mainly involved in the immune system, but also in vitamin D regulation. The most frequently detected ERV sequences are related to the multiple sclerosis-associated retrovirus, the human immunodeficiency virus 1, HERV-K, and the Simian foamy virus. Our data shows that there is a relation between MS associated SNPs and the number of retroviral elements compared to control. Our data identifies new ERV sequences that have not been associated with MS, so far.

Azathioprine therapy in a case of pediatric multiple sclerosis that was seropositive for MOG-IgG.

PubMed

Zhou, Yifan; Huang, Qiao; Lu, Tingting; Sun, Xiaobo; Fang, Ling; Lu, Zhengqi; Hu, Xueqiang; Kermode, Allan; Qiu, Wei

2017-04-01

There is a lack of evidence for treatment of pediatric multiple sclerosis (PedMS). Treatment using azathioprine for PedMS has not been reported. A 10-year-old boy with multiple sclerosis who was seropositive for antibodies against myelin oligodendrocyte glycoprotein (MOG)-IgG was treated with azathioprine plus oral methylprednisolone. The patient showed clinical and magnetic resonance imaging stability, with MOG-IgG seroconversion. There were no major side effects over a 5-year period. Azathioprine may be a treatment option, particularly in poor medical resource areas, for pediatric patients with multiple sclerosis who are seropositive for MOG-IgG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Review of the novelties from the 32nd ECTRIMS Congress, 2016, presented at the 9th Post-ECTRIMS Meeting (I).

PubMed

Fernandez, O; Oterino, A; Oreja-Guevara, C; Prieto, J M; Mendibe-Bilbao, M M; Garcia-Merino, J A; Ramio-Torrenta, Ll; Ginestal, R; Meca-Lallana, J E; Romero-Pinel, L; Munoz, D; Oliva-Nacarino, P; Calles-Hernandez, M C; Izquierdo, G; Martinez-Gines, M L; Saiz, A; Comabella, M; Casanova-Estruch, B; Brieva, Ll; Arroyo, R; Rodriguez-Antiguedad, A

2017-07-01

For the ninth year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain) with the aim of presenting and discussing the hottest issues debated at the ECTRIMS Congress by renowned specialists in multiple sclerosis in our country. One outcome of this scientific activity, endorsed by the Spanish Neurology Society, is this review article, which is published in two parts. This first part addresses family planning, pregnancy management and the role of breastfeeding in women with multiple sclerosis. Attention is drawn to the paediatric population, to magnetic resonance imaging features and to the genetic-environmental risk factors for developing the disease in children, without neglecting the risk factors for development in adults. The review updates the epidemiology of cognitive deterioration in patients with multiple sclerosis, the advantages and disadvantages of available assessment tools, and current management approaches, while also insisting on the importance of cognitive involvement during the course of the disease. Furthermore, the concept of individualised, precision medicine is introduced, from the diagnosis of the disease until its treatment, with the controversies that inevitably arise in patient management, above all with regard to the change of treatment and the handling of associated risks.

Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

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

Habib, Charbel A.; Zheng Weili; Mark Haacke, E.

Aim: To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Material and Methods: Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, theremore » were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Conclusion: Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.« less

Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes.

PubMed

Ruano, Luis; Portaccio, Emilio; Goretti, Benedetta; Niccolai, Claudia; Severo, Milton; Patti, Francesco; Cilia, Sabina; Gallo, Paolo; Grossi, Paola; Ghezzi, Angelo; Roscio, Marco; Mattioli, Flavia; Stampatori, Chiara; Trojano, Maria; Viterbo, Rosa Gemma; Amato, Maria Pia

2017-08-01

There is limited and inconsistent information on the clinical determinants of cognitive impairment (CI) in multiple sclerosis (MS). The aim of this study was to compare the prevalence and profile of CI across MS disease subtypes and assess its clinical determinants. Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop test in consecutive patients with MS referred to six Italian centers. CI was defined as impairment in ⩾ 2 cognitive domains. A total of 1040 patients were included, 167 with clinically isolated syndrome (CIS), 759 with relapsing remitting (RR), 74 with secondary progressive (SP), and 40 with primary progressive (PP) disease course. The overall prevalence of CI was 46.3%; 34.5% in CIS, 44.5% in RR, 79.4% in SP, and 91.3% in PP. The severity of impairment and the number of involved domains were significantly higher in SP and primary progressive multiple sclerosis (PPMS) than in CIS and RR. In multivariable logistic regression analysis, the presence of CI was significantly associated with higher Expanded Disability Status Scale (EDSS) and older age. CI is present in all MS subtypes since the clinical onset and its frequency is increased in the progressive forms, but these differences seem to be more associated with patient age and physical disability than to disease subtype per se.

Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells.

PubMed

Ceronie, Bryan; Jacobs, Benjamin M; Baker, David; Dubuisson, Nicolas; Mao, Zhifeng; Ammoscato, Francesca; Lock, Helen; Longhurst, Hilary J; Giovannoni, Gavin; Schmierer, Klaus

2018-05-01

The mechanism of action of oral cladribine, recently licensed for relapsing multiple sclerosis, is unknown. To determine whether cladribine depletes memory B cells consistent with our recent hypothesis that effective, disease-modifying treatments act by physical/functional depletion of memory B cells. A cross-sectional study examined 40 people with multiple sclerosis at the end of the first cycle of alemtuzumab or injectable cladribine. The relative proportions and absolute numbers of peripheral blood B lymphocyte subsets were measured using flow cytometry. Cell-subtype expression of genes involved in cladribine metabolism was examined from data in public repositories. Cladribine markedly depleted class-switched and unswitched memory B cells to levels comparable with alemtuzumab, but without the associated initial lymphopenia. CD3 + T cell depletion was modest. The mRNA expression of metabolism genes varied between lymphocyte subsets. A high ratio of deoxycytidine kinase to group I cytosolic 5' nucleotidase expression was present in B cells and was particularly high in mature, memory and notably germinal centre B cells, but not plasma cells. Selective B cell cytotoxicity coupled with slow repopulation kinetics results in long-term, memory B cell depletion by cladribine. These may offer a new target, possibly with potential biomarker activity, for future drug development.

Most Scottish neurologists do not apply the 2010 McDonald criteria when diagnosing multiple sclerosis.

PubMed

Lumley, R; Davenport, R; Williams, A

2015-03-01

The diagnostic criteria for multiple sclerosis have evolved over time and currently the 2010 McDonald criteria are the most widely accepted. These criteria allow the diagnosis of multiple sclerosis to be made at the clinically isolated syndrome stage provided certain criteria are met on a single magnetic resonance brain scan. Our hypothesis was that neurologists in Scotland did not use these criteria routinely. We sent a SurveyMonkey questionnaire to all Scottish neurologists (consultants and trainees) regarding the diagnosis of multiple sclerosis. Our questionnaire response rate was 65/99 (66%). Most Scottish neurologists were aware of the criteria and 31/58 (53%) felt that they were using these routinely. However, in a clinical vignette designed to test the application of these criteria, only 5/57 (9%) of neurologists appeared to use them. Scottish neurologists' use of the 2010 McDonald criteria for diagnosis of multiple sclerosis varies from practitioners' perception of their use of these criteria.

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

Determining the IgM and IgG antibody titer against CMV and helicobacter pylori in the serum of multiple sclerosis patients comparing to the control group in Hamadan.

PubMed

Salim, Masome Afiati; Eftekharian, Mohammad Mahdi; Taheri, Mohammad; Yousef Alikhani, Mohammad

2017-07-19

Multiple sclerosis (MS) is a chronic autoimmune disease that disables central nervous system (CNS) system. Cytomegalovirus (CMV) probably has an important role in the MS pathology. The infection with helicobacter pylori also is recognized as a protective agent against MS in female. Serum samples were isolated and frozen at -70∘C. The earlier mentioned anti-virus antibodies and antibacterial antibodies were quantified by Elisa kit. The results showed that IgG antibody average value against cytomegalovirus in the blood of multiple sclerosis patients not only decreased but also was significant statistically (p< 0.05). IgM and IgG antibodies average value in the blood of multiple sclerosis patients against helicobacter pylori shown a statistically significant decrease (p< 0.05). Therefore it may be considered that probably helicobacter pylori presence in the individuals especially in female can alleviate MS signs. CMV infection can intensify the symptoms in multiple sclerosis patients.

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.

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.

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.

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.

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.

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.

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

Heat Shock Protein 70: Roles in Multiple Sclerosis

PubMed Central

Mansilla, María José; Montalban, Xavier; Espejo, Carmen

2012-01-01

Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE. PMID:22669475

Evidence for the Role of B Cells and Immunoglobulins in the Pathogenesis of Multiple Sclerosis

PubMed Central

Wootla, Bharath; Denic, Aleksandar; Keegan, B. Mark; Winters, Jeffrey L.; Astapenko, David; Warrington, Arthur E.; Bieber, Allan J.; Rodriguez, Moses

2011-01-01

The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports advocate greater involvement of B cells and immunoglobulins in the initiation and propagation of MS lesions at different stages of their ontogeny. The key role of B cells and immunoglobulins in pathogenesis was initially identified by studies in which patients whose fulminant attacks of demyelination did not respond to steroids experienced remarkable functional improvement following plasma exchange. The positive response to Rituximab in Phase II clinical trials of relapsing-remitting MS confirms the role of B cells. The critical question is how B cells contribute to MS. In this paper, we discuss both the deleterious and the beneficial roles of B cells and immunoglobulins in MS lesions. We provide alternative hypotheses to explain both damaging and protective antibody responses. PMID:21961063

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

PubMed

Tobin, W O; Popescu, B F; Lowe, V; Pirko, I; Parisi, J E; Kantarci, K; Fields, J A; Bruns, M B; Boeve, B F; Lucchinetti, C F

2016-04-01

We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry. © The Author(s), 2015.

From the "little brain" gastrointestinal infection to the "big brain" neuroinflammation: a proposed fast axonal transport pathway involved in multiple sclerosis.

PubMed

Deretzi, Georgia; Kountouras, Jannis; Grigoriadis, Nikolaos; Zavos, Christos; Chatzigeorgiou, Stavros; Koutlas, Evangelos; Tsiptsios, Iakovos

2009-11-01

The human central nervous system (CNS) is targeted by different pathogens which, apart from pathogens' intranasal inoculation or trafficking into the brain through infected blood cells, may use a distinct pathway to bypass the blood-brain barrier by using the gastrointestinal tract (GIT) retrograde axonal transport through sensory or motor fibres. The recent findings regarding the enteric nervous system (often called the "little brain") similarities with CNS and GIT axonal transport of infections resulting in CNS neuroinflammation are mainly reviewed in this article. We herein propose that the GIT is the vulnerable area through which pathogens (such as Helicobacter pylori) may influence the brain and induce multiple sclerosis pathologies, mainly via the fast axonal transport by the afferent neurones connecting the GIT to brain.

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.

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.

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.

Potassium Channel KIR4.1 as an Immune Target in Multiple Sclerosis

PubMed Central

Srivastava, Rajneesh; Aslam, Muhammad; Kalluri, Sudhakar Reddy; Schirmer, Lucas; Buck, Dorothea; Tackenberg, Björn; Rothhammer, Veit; Chan, Andrew; Gold, Ralf; Berthele, Achim; Bennett, Jeffrey L.; Korn, Thomas; Hemmer, Bernhard

2016-01-01

BACKGROUND Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Many findings suggest that the disease has an autoimmune pathogenesis; the target of the immune response is not yet known. METHODS We screened serum IgG from persons with multiple sclerosis to identify antibodies that are capable of binding to brain tissue and observed specific binding of IgG to glial cells in a subgroup of patients. Using a proteomic approach focusing on membrane proteins, we identified the ATP-sensitive inward rectifying potassium channel KIR4.1 as the target of the IgG antibodies. We used a multifaceted validation strategy to confirm KIR4.1 as a target of the autoantibody response in multiple sclerosis and to show its potential pathogenicity in vivo. RESULTS Serum levels of antibodies to KIR4.1 were higher in persons with multiple sclerosis than in persons with other neurologic diseases and healthy donors (P<0.001 for both comparisons). We replicated this finding in two independent groups of persons with multiple sclerosis or other neurologic diseases (P<0.001 for both comparisons). Analysis of the combined data sets indicated the presence of serum antibodies to KIR4.1 in 186 of 397 persons with multiple sclerosis (46.9%), in 3 of 329 persons with other neurologic diseases (0.9%), and in none of the 59 healthy donors. These antibodies bound to the first extracellular loop of KIR4.1. Injection of KIR4.1 serum IgG into the cisternae magnae of mice led to a profound loss of KIR4.1 expression, altered expression of glial fibrillary acidic protein in astrocytes, and activation of the complement cascade at sites of KIR4.1 expression in the cerebellum. CONCLUSIONS KIR4.1 is a target of the autoantibody response in a subgroup of persons with multiple sclerosis. (Funded by the German Ministry for Education and Research and Deutsche Forschungsgemeinschaft.) PMID:22784115

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.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

PubMed

Metz, Luanne M; Li, David K B; Traboulsee, Anthony L; Duquette, Pierre; Eliasziw, Misha; Cerchiaro, Graziela; Greenfield, Jamie; Riddehough, Andrew; Yeung, Michael; Kremenchutzky, Marcelo; Vorobeychik, Galina; Freedman, Mark S; Bhan, Virender; Blevins, Gregg; Marriott, James J; Grand'Maison, Francois; Lee, Liesly; Thibault, Manon; Hill, Michael D; Yong, V Wee

2017-06-01

On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T 2 -weighted MRI, cumulative number of new lesions enhanced on T 1 -weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T 1 -weighted MRI plus new and newly enlarged lesions on T 2 -weighted MRI]). A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo. The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

What Is Leukodystrophy

MedlinePlus

... having the disease. Are the leukodystrophies related to Multiple Sclerosis? The leukodystrophies do share some common features with multiple sclerosis (MS). Like the leukodystrophies, MS is caused by ...

[Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

PubMed

Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

2016-01-01

The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

Disease Modifying Therapy in Multiple Sclerosis

PubMed Central

Williams, U. E.; Oparah, S. K.; Philip-Ephraim, E. E.

2014-01-01

Multiple sclerosis is an autoimmune disease of the central nervous system characterized by inflammatory demyelination and axonal degeneration. It is the commonest cause of permanent disability in young adults. Environmental and genetic factors have been suggested in its etiology. Currently available disease modifying drugs are only effective in controlling inflammation but not prevention of neurodegeneration or accumulation of disability. Search for an effective neuroprotective therapy is at the forefront of multiple sclerosis research. PMID:27355035

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

PubMed

Pryce, Gareth; Ahmed, Zubair; Hankey, Deborah J R; Jackson, Samuel J; Croxford, J Ludovic; Pocock, Jennifer M; Ledent, Catherine; Petzold, Axel; Thompson, Alan J; Giovannoni, Gavin; Cuzner, M Louise; Baker, David

2003-10-01

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

Design of Chemical Conjugate for Targeted Therapy of Multiple Sclerosis Based of Constant Fragment of Human Antibody Heavy Chain and Peptoid Analog of Autoantigen MOG35-55.

PubMed

Lomakin, Y A; Stepanov, A V; Balabashin, D S; Ponomarenko, N A; Smirnov, I V; Belogurov, A A

2017-04-01

Elimination of B cells producing autoantibodies to neuroantigens is considered as beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by pathological lymphocytes. We propose a structure of an innovative drug for targeted elimination of the pool of autoreactive B cells responsible for multiple sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc fragment of human immunoglobulin. The obtained Fc-PEG-AMogP3 conjugate effectively interact with autoreactive antibodies, which attests to their high therapeutic potential.

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis.

PubMed

Rogers, James A; Mishra, Manoj K; Hahn, Jennifer; Greene, Catherine J; Yates, Robin M; Metz, Luanne M; Yong, V Wee

2017-05-09

Environmental and hormonal factors are implicated in dysimmunity in multiple sclerosis. We investigated whether bisphenol-A, a prominent contaminant with endocrine-disrupting capabilities, altered susceptibility in an inflammatory model of multiple sclerosis. We found that gestational, but not adult, exposure to bisphenol-A increased the development of experimental autoimmune encephalomyelitis in adulthood in male, but not female, mice when a suboptimal disease-inducing immunization was used. Gestational bisphenol-A in male mice primed macrophages in adulthood and raised granulocyte-colony stimulating factor and neutrophil counts/activity postsuboptimal immunization. Neutralizing granulocyte-colony stimulating factor blocked susceptibility to disease in bisphenol-A mice. Early life exposure to bisphenol-A may represent an environmental consideration in multiple sclerosis.

Oligosaccharide modification by N-acetylglucosaminyltransferase-V in macrophages are involved in pathogenesis of bleomycin-induced scleroderma.

PubMed

Kato, Arisa; Yutani, Mizuki; Terao, Mika; Kimura, Akihiro; Itoi, Saori; Murota, Hiroyuki; Miyoshi, Eiji; Katayama, Ichiro

2015-08-01

Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), which catalyses the formation of β1,6 GlcNAc (N-acetylglucosamine) branches on N-glycans, is associated with various pathologies, such as cancer metastasis, multiple sclerosis and liver fibrosis. In this study, we demonstrated the involvement of GnT-V in the pathophysiology of scleroderma. High expression of GnT-V was observed in infiltrating cells in skin section samples from systemic and localized patients with scleroderma. Most of the infiltrating cells were T cells and macrophages, most of which were CD163(+) M2 macrophages. To determine the role of GnT-V in scleroderma, we next investigated skin sclerosis in GnT-V knockout (MGAT5(-/-) ) mice. Expression of GnT-V was also elevated in bleomycin (BLM)-injected sclerotic skin, and MGAT5(-/-) mice were resistant to BLM-induced skin sclerosis with reduced collagen type 1 α1 content, suggesting the biological significance of GnT-V in skin sclerosis. Furthermore, the number of CD163(+) M2 macrophages and CD3-positive T cells in BLM-induced skin sclerosis was significantly fewer in MGAT5(-/-) mice. In bone marrow-derived macrophages (BMDMs), IL-4-induced expressions of Fizz1 and Ym1 were significantly reduced in MGAT5(-/-) mice-derived BMDMs. Taken together, these results suggest the induction of GnT-V in skin sclerosis progression is possibly dependent on increased numbers of M2 macrophages in the skin, which are important for tissue fibrosis and remodelling. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey

PubMed Central

Turner, Martin R; Swash, Michael

2015-01-01

Recent advances in understanding amyotrophic lateral sclerosis (ALS) have delivered new questions. Disappointingly, the initial enthusiasm for transgenic mouse models of the disease has not been followed by rapid advances in therapy or prevention. Monogenic models may have inadvertently masked the true complexity of the human disease. ALS has evolved into a multisystem disorder, involving a final common pathway accessible via multiple upstream aetiological tributaries. Nonetheless, there is a common clinical core to ALS, as clear today as it was to Charcot and others. We stress the continuing relevance of clinical observations amid the increasing molecular complexity of ALS. PMID:25644224

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.

Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

PubMed

Matute-Blanch, Clara; Villar, Luisa M; Álvarez-Cermeño, José C; Rejdak, Konrad; Evdoshenko, Evgeniy; Makshakov, Gleb; Nazarov, Vladimir; Lapin, Sergey; Midaglia, Luciana; Vidal-Jordana, Angela; Drulovic, Jelena; García-Merino, Antonio; Sánchez-López, Antonio J; Havrdova, Eva; Saiz, Albert; Llufriu, Sara; Alvarez-Lafuente, Roberto; Schroeder, Ina; Zettl, Uwe K; Galimberti, Daniela; Ramió-Torrentà, Lluís; Robles, René; Quintana, Ester; Hegen, Harald; Deisenhammer, Florian; Río, Jordi; Tintoré, Mar; Sánchez, Alex; Montalban, Xavier; Comabella, Manuel

2018-04-01

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

Pediatric multiple sclerosis: current perspectives on health behaviors.

PubMed

Sikes, Elizabeth Morghen; Motl, Robert W; Ness, Jayne M

2018-01-01

Pediatric-onset multiple sclerosis (POMS) accounts for ~5% of all multiple sclerosis cases, and has a prevalence of ~10,000 children in the USA. POMS is associated with a higher relapse rate, and results in irreversible disability on average 10 years earlier than adult-onset multiple sclerosis. Other manifestations of POMS include mental and physical fatigue, cognitive impairment, and depression. We believe that the health behaviors of physical activity, diet, and sleep may have potential benefits in POMS, and present a scoping review of the existing literature. We identified papers by searching three electronic databases (PubMed, GoogleScholar, and CINAHL). Search terms included: pediatric multiple sclerosis OR pediatric onset multiple sclerosis OR POMS AND health behavior OR physical activity OR sleep OR diet OR nutrition OR obesity. Papers were included in this review if they were published in English, referenced nutrition, diet, obesity, sleep, exercise, or physical activity, and included pediatric-onset multiple sclerosis as a primary population. Twenty papers were identified via the literature search that addressed health-promoting behaviors in POMS, and 11, 8, and 3 papers focused on diet, activity, and sleep, respectively. Health-promoting behaviors were associated with markers of disease burden in POMS. Physical activity participation was associated with reduced relapse rate, disease burden, and sleep/rest fatigue symptoms. Nutritional factors, particularly vitamin D intake, may be associated with relapse rate. Obesity has been associated with increased risk of developing POMS. POMS is associated with better sleep hygiene, and this may benefit fatigue and quality of life. Participation in health behaviors, particularly physical activity, diet, and sleep, may have benefits for POMS. Nevertheless, there are currently no interventions targeting promotion of these behaviors and examining the benefits of managing the primary and secondary manifestations of POMS.

Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease.

PubMed

Kissoon, Narayan R; Watson, James C; Boes, Christopher J; Kantarci, Orhun H

2018-01-01

Background The association of trigeminal neuralgia with pontine lesions has been well documented in multiple sclerosis, and we tested the hypothesis that occipital neuralgia in multiple sclerosis is associated with high cervical spinal cord lesions. Methods We retrospectively reviewed the records of 29 patients diagnosed with both occipital neuralgia and demyelinating disease by a neurologist from January 2001 to December 2014. We collected data on demographics, clinical findings, presence of C2-3 demyelinating lesions, and treatment responses. Results The patients with both occipital neuralgia and multiple sclerosis were typically female (76%) and had a later onset (age > 40) of occipital neuralgia (72%). Eighteen patients (64%) had the presence of C2-3 lesions and the majority had unilateral symptoms (83%) or episodic pain (78%). All patients with documented sensory loss (3/3) had C2-3 lesions. Most patients with progressive multiple sclerosis (6/8) had C2-3 lesions. Of the eight patients with C2-3 lesions and imaging at onset of occipital neuralgia, five (62.5%) had evidence of active demyelination. None of the patients with progressive multiple sclerosis (3/3) responded to occipital nerve blocks or high dose intravenous steroids, whereas all of the other phenotypes with long term follow-up (eight patients) had good responses. Conclusions A cervical spine MRI should be considered in all patients presenting with occipital neuralgia. In patients with multiple sclerosis, clinical features in occipital neuralgia that were predictive of the presence of a C2-3 lesion were unilateral episodic symptoms, sensory loss, later onset of occipital neuralgia, and progressive multiple sclerosis phenotype. Clinical phenotype predicted response to treatment.

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.

[Current therapy of multiple sclerosis].

PubMed

Antonio García Merino, J

2014-12-01

Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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.

Characteristics of pediatric multiple sclerosis: The Turkish pediatric multiple sclerosis database.

PubMed

Yılmaz, Ünsal; Anlar, Banu; Gücüyener, Kıvılcım

2017-11-01

To document the clinical and paraclinical features of pediatric multiple sclerosis (MS) in Turkey. Data of MS patients with onset before age 18 years (n = 193) were collected from 27 pediatric neurology centers throughout Turkey. Earlier-onset (<12 years) and later-onset (≥12 years) groups were compared. There were 123 (63.7%) girls and 70 (36.3%) boys aged 4-17 years, median 14 years at disease onset. Family history of MS was 6.5%. The first presentation was polysymptomatic in 55.4% of patients, with brainstem syndromes (50.3%), sensory disturbances (44%), motor symptoms (33.2%), and optic neuritis (26.4%) as common initial manifestations. Nineteen children had facial paralysis and 10 had epileptic seizures at first attack; 21 (11%) were initially diagnosed with acute disseminated encephalomyelitis (ADEM). Oligoclonal bands were identified in 68% of patients. Magnetic resonance imaging revealed periventricular (96%), cortical/juxtacortical (64.2%), brainstem (63%), cerebellum (51.4%), and spinal cord (67%) involvement. Visual evoked potentials (VEP) were abnormal in 52%; serum 25-hydroxyvitamin D levels were low in 68.5% of patients. The earlier-onset group had a higher rate of infection/vaccination preceding initial attack, initial diagnosis of ADEM, longer interval between first 2 attacks, and more disability accumulating in the first 3 years of the disease. Brainstem and cerebellum are common sites of clinical and radiological involvement in pediatric-onset MS. VEP abnormalities are frequent even in patients without history of optic neuropathy. Vitamin D status does not appear to affect the course in early disease. MS beginning before 12 years of age has certain characteristics in history and course. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

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.

Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis

PubMed Central

Haider, Lukas

2015-01-01

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Different trigger pathologies have been suggested by the primary cytodegenerative “inside-out” and primary inflammation-driven “outside-in” hypotheses. Recent data indicate that mitochondrial injury and subsequent energy failure are key factors in the induction of demyelination and neurodegeneration. The brain weighs only a few percent of the body mass but accounts for approximately 20% of the total basal oxygen consumption of mitochondria. Oxidative stress induces mitochondrial injury in patients with multiple sclerosis and energy failure in the central nervous system of susceptible individuals. The interconnected mechanisms responsible for free radical production in patients with multiple sclerosis are as follows: (i) inflammation-induced production of free radicals by activated immune cells, (ii) liberation of iron from the myelin sheets during demyelination, and (iii) mitochondrial injury and thus energy failure-related free radical production. In the present review, the different sources of oxidative stress and their relationships to patients with multiple sclerosis considering tissue injury mechanisms and clinical aspects have been discussed. PMID:26106458

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.

A Case of Tuberous Sclerosis Without Multiorgan Involvement.

PubMed

Falsafi, Parisa; Taghavi-Zenouz, Ali; Khorshidi-Khiyavi, Reza; Nezami, Nariman; Estiar, Mehrdad Asghari

2015-02-24

Tuberous sclerosis or Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant and progressive neurocutaneous disorder involves multiple organs mainly brain, heart, kidney, lung, liver, skin and eye. The diagnosis is typically made clinically. Here, we are reporting a case of TSC presented mainly with dermatologic findings and only neurologic manifestations on MRI. A 15-year-old female with intellectual disability is followed up at neurology clinic for history of seizure. Intelligence evaluation showed that she has intellectual disability. She had wart like lesions distributed in form of butterfly over the face especially involving nose. She did not have any sign and symptom of heart, kidney, lung, bone and eye involvement. Also, her laboratory tests were normal. Despite the physical examination showed absolutely intact neurologic examination, but brain MRI and CT scan revealed several cortical and subcortical tubers, and subependymal glial nodules; no evidence of giant cell astrocytomas and aneurysm. Hypesignal foci are seen at subcortical white matter on long TR images. Fibers are involved. In this case, there is no evidence of giant cell astrocytomas and aneurysm. It seems that TSC could be the prevalent disorder and referring intellectual disability patients in birth with normal organs could be diagnosed as TSC. Therefore, there is necessary need to design genetic natal and post natal tests for diagnosis of TSC cases. Also, there is pivotal that similar cases must be reported; perhaps TSC is more prevalent than to be considered.

The Impact of Exercise Training on Living Quality in Multiple Sclerosis Individuals

ClinicalTrials.gov

2017-08-27

Multiple Sclerosis; Fatigue; Mental Status Change; Physical Disability; Physical Activity; Mental Impairment; Quality of Life; Disabilities Psychological; Disability Physical; Pain; Energy Supply; Deficiency; Motivation

Cell-based therapeutic strategies for multiple sclerosis

PubMed Central

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A; Atkins, Harold; Banwell, Brenda; Bar-Or, Amit; Bebo, Bruce; Bowen, James; Burt, Richard; Calabresi, Peter; Cohen, Jeffrey; Comi, Giancarlo; Connick, Peter; Cross, Anne; Cutter, Gary; Derfuss, Tobias; Ffrench-Constant, Charles; Freedman, Mark; Galipeau, Jacques; Goldman, Myla; Goldman, Steven; Goodman, Andrew; Green, Ari; Griffith, Linda; Hartung, Hans-Peter; Hemmer, Bernhard; Hyun, Insoo; Iacobaeus, Ellen; Inglese, Matilde; Jubelt, Burk; Karussis, Dimitrios; Küry, Patrick; Landsman, Douglas; Laule, Cornelia; Liblau, Roland; Mancardi, Giovanni; Ann Marrie, Ruth; Miller, Aaron; Miller, Robert; Miller, David; Mowry, Ellen; Muraro, Paolo; Nash, Richard; Ontaneda, Daniel; Pasquini, Marcelo; Pelletier, Daniel; Peruzzotti-Jametti, Luca; Pluchino, Stefano; Racke, Michael; Reingold, Stephen; Rice, Claire; Ringdén, Olle; Rovira, Alex; Saccardi, Riccardo; Sadiq, Saud; Sarantopoulos, Stefanie; Savitz, Sean; Scolding, Neil; Soelberg Sorensen, Per; Pia Sormani, Maria; Stuve, Olaf; Tesar, Paul; Thompson, Alan; Trojano, Maria; Uccelli, Antonio; Uitdehaag, Bernard; Utz, Ursula; Vukusic, Sandra; Waubant, Emmanuelle; Wilkins, Alastair

2017-01-01

Abstract The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. PMID:29053779

Social Identity in People with Multiple Sclerosis: An Examination of Family Identity and Mood.

PubMed

Barker, Alex B; Lincoln, Nadina B; Hunt, Nigel; dasNair, Roshan

2018-01-01

Mood disorders are highly prevalent in people with multiple sclerosis (MS). MS causes changes to a person's sense of self. The Social Identity Model of Identity Change posits that group membership can have a positive effect on mood during identity change. The family is a social group implicated in adjustment to MS. The objectives of this study were to investigate whether family identity can predict mood in people with MS and to test whether this prediction was mediated by social support and connectedness to others. This cross-sectional survey of 195 participants comprised measures of family identity, family social support, connectedness to others, and mood. Family identity predicted mood both directly and indirectly through parallel mediators of family social support and connectedness to others. Family identity predicted mood as posited by the Social Identity Model of Identity Change. Involving the family in adjustment to MS could reduce low mood.

Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives

PubMed Central

Lang, Yue

2018-01-01

The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS. PMID:29805314

Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis.

PubMed

Cramer, Stig P; Modvig, Signe; Simonsen, Helle J; Frederiksen, Jette L; Larsson, Henrik B W

2015-09-01

Optic neuritis is an acute inflammatory condition that is highly associated with multiple sclerosis. Currently, the best predictor of future development of multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging. Previous research has found abnormalities in the permeability of the blood-brain barrier in normal-appearing white matter of patients with multiple sclerosis and here, for the first time, we present a study on the capability of blood-brain barrier permeability in predicting conversion from optic neuritis to multiple sclerosis and a direct comparison with cerebrospinal fluid markers of inflammation, cellular trafficking and blood-brain barrier breakdown. To this end, we applied dynamic contrast-enhanced magnetic resonance imaging at 3 T to measure blood-brain barrier permeability in 39 patients with monosymptomatic optic neuritis, all referred for imaging as part of the diagnostic work-up at time of diagnosis. Eighteen healthy controls were included for comparison. Patients had magnetic resonance imaging and lumbar puncture performed within 4 weeks of onset of optic neuritis. Information on multiple sclerosis conversion was acquired from hospital records 2 years after optic neuritis onset. Logistic regression analysis showed that baseline permeability in normal-appearing white matter significantly improved prediction of multiple sclerosis conversion (according to the 2010 revised McDonald diagnostic criteria) within 2 years compared to T2 lesion count alone. There was no correlation between permeability and T2 lesion count. An increase in permeability in normal-appearing white matter of 0.1 ml/100 g/min increased the risk of multiple sclerosis 8.5 times whereas having more than nine T2 lesions increased the risk 52.6 times. Receiver operating characteristic curve analysis of permeability in normal-appearing white matter gave a cut-off of 0.13 ml/100 g/min, which predicted conversion to multiple sclerosis with a sensitivity of 88% and specificity of 72%. We found a significant correlation between permeability and the leucocyte count in cerebrospinal fluid as well as levels of CXCL10 and MMP9 in the cerebrospinal fluid. These findings suggest that blood-brain barrier permeability, as measured by magnetic resonance imaging, may provide novel pathological information as a marker of neuroinflammation related to multiple sclerosis, to some extent reflecting cellular permeability of the blood-brain barrier, whereas T2 lesion count may more reflect the length of the subclinical pre-relapse phase.See Naismith and Cross (doi:10.1093/brain/awv196) for a scientific commentary on this article. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Fingolimod

MedlinePlus

... symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do ... take your first dose.Fingolimod may help control multiple sclerosis but will not cure it. Do not stop ...

Riboflavin

MedlinePlus

... and nails, to slow aging, for canker sores, multiple sclerosis, memory loss including Alzheimer's disease, high blood pressure, ... the risk of liver cancer in older people. Multiple sclerosis. Early research shows that taking riboflavin by mouth ...

Teriflunomide

MedlinePlus

... symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do ... doctor.Teriflunomide may help control the symptoms of multiple sclerosis but does not cure it. Continue to take ...

Dalfampridine

MedlinePlus

... used to improve walking in people who have multiple sclerosis (MS; a disease in which the nerves do ... weakness back pain difficulty with balance worsening of multiple sclerosis symptoms burning, tingling, or itching of the skin ...

Cognitive Impairment in MS Linked to Structural and Functional Connectivity

DTIC Science & Technology

2016-10-01

AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple sclerosis (MS) is the most...9 9. Appendices……………………………………………………………9 Krupp MS130103  2  Abstract Multiple sclerosis (MS) is the most common progressive neurologic...This symptom represents a major concern for many individuals living with multiple sclerosis (MS). Unfortunately, no reliable treatments exist to

Two Approaches to the Synthesis of Dimethyl Fumarate That Demonstrate Fundamental Principles of Organic Chemistry

ERIC Educational Resources Information Center

Love, Brian E.; Bennett, Lisa J.

2017-01-01

Two experiments are described which lead to the preparation of dimethyl fumarate, a compound currently used in the treatment of multiple sclerosis. Preparation of a compound with "real-world" applications is believed to increase student interest in the experiment. One experiment involves the isomerization of dimethyl maleate to the…

Vestibular evoked myogenic potentials and MRI in early multiple sclerosis: Validation of the VEMP score.

PubMed

Crnošija, Luka; Krbot Skorić, Magdalena; Gabelić, Tereza; Adamec, Ivan; Habek, Mario

2017-01-15

To validate the VEMP score as a measure of brainstem dysfunction in patients with the first symptom of multiple sclerosis (MS) (clinically isolated syndrome (CIS)) and to investigate the correlation between VEMP and brainstem MRI results. 121 consecutive CIS patients were enrolled and brainstem functional system score (BSFS) was determined. Ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were analyzed for latencies, conduction block and amplitude asymmetry ratio and the VEMP score was calculated. MRI was analyzed for the presence of brainstem lesions as a whole and separately for the presence of pontine, midbrain and medulla oblongata lesions. Patients with signs of brainstem involvement during the neurological examination (with BSFS ≥1) had a higher oVEMP score compared to patients with no signs of brainstem involvement. A binary logistic regression model showed that patients with brainstem lesion on the MRI are 6.780 times more likely to have BSFS ≥1 (p=0.001); and also, a higher VEMP score is associated with BSFS ≥1 (p=0.042). Furthermore, significant correlations were found between clinical brainstem involvement and brainstem and pontine MRI lesions, and prolonged latencies and/or absent VEMP responses. The VEMP score is a valuable tool in evaluation of brainstem involvement in patients with early MS. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuromyelitis Optica

MedlinePlus

... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ...

Ocrelizumab Injection

MedlinePlus

... forms (symptoms gradually become worse over time) of multiple sclerosis (MS; a disease in which the nerves do ... or medical facility.Ocrelizumab may help to control multiple sclerosis symptoms, but does not cure it. Your doctor ...

Swallowing problems

MedlinePlus

... Read More Brain aneurysm repair Brain surgery Laryngectomy Multiple sclerosis Oral cancer Parkinson disease Stroke Throat or larynx ... Jejunostomy feeding tube Mouth and neck radiation - discharge Multiple sclerosis - discharge Stroke - discharge Review Date 5/11/2016 ...

Cerebellar Degeneration

MedlinePlus

... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ...

Glatiramer Injection

MedlinePlus

... symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do ... minutes, but do not rub it. Glatiramer controls multiple sclerosis but does not cure it. Continue to use ...

Foot Drop

MedlinePlus

... muscular problems, such as multiple sclerosis, stroke, and cerebral palsy; motor neuron disorders such as polio, some forms ... muscular problems, such as multiple sclerosis, stroke, and cerebral palsy; motor neuron disorders such as polio, some forms ...

Physical activity motivation and benefits in people with multiple sclerosis.

PubMed

Fasczewski, Kimberly S; Gill, Diane L; Rothberger, Sara M

2018-06-01

Multiple sclerosis is a degenerative neurological disease that affects 2.1 million people worldwide. There is no cure, but an expanding body of research supports the positive impact of physical activity and suggests physical activity has benefits for the individual's psychological and physical well-being. Using Self-Determination Theory as a framework, mixed methods with a focus on qualitative interviews were used to explore physical activity motivation and benefits with a sample of highly active people with multiple sclerosis (n = 15). Disability level ranged from not disabled to wheelchair bound with the majority of participants reporting minimal impact from multiple sclerosis. Survey data were collected using a number of open-ended questions along with measures of self-efficacy, self-determined motivation, physical activity, and quality of life. Additionally, eight individuals participated in semistructured telephone interviews focused on (a) motivation and strategies used to maintain physical activity and (b) the benefits and impact of physical activity in their lives. The main findings were consistent with Self-Determination Theory; participants described feelings of accomplishment and competence in both their physical activity and daily life, as well as a sense of independence and autonomy. Similarly, all participants cited benefits, and the main themes were enhanced satisfaction with life and an overall positive outlook on life. Results provide insight into the role of physical activity in a highly active sample and have implications for professionals working in physical activity settings with the multiple sclerosis population. Interventions aimed at increasing long-term physical activity adherence should focus on increasing autonomy and competence for physical activity in the individual and promoting potential increased quality of life outcomes from physical activity participation. Implications for Rehabilitation Multiple sclerosis is a chronic degenerative neurological disease that the individual lives with for a majority of the lifespan. Physical activity is one means that has been shown to aid is the control of multiple sclerosis symptoms. Increasing patient understanding of the benefits of using physical activity as a means to control multiple sclerosis symptoms may result in long-term physical activity adherence. Physical activity interventions that develop feelings of competence and independent choice in the patient may be more successful for long-term participation.

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.

PubMed

Gandolfi, Marialuisa; Munari, Daniele; Geroin, Christian; Gajofatto, Alberto; Benedetti, Maria Donata; Midiri, Alessandro; Carla, Fontana; Picelli, Alessandro; Waldner, Andreas; Smania, Nicola

2015-10-01

Impaired sensory integration contributes to balance disorders in patients with multiple sclerosis (MS). The objective of this paper is to compare the effects of sensory integration balance training against conventional rehabilitation on balance disorders, the level of balance confidence perceived, quality of life, fatigue, frequency of falls, and sensory integration processing on a large sample of patients with MS. This single-blind, randomized, controlled trial involved 80 outpatients with MS (EDSS: 1.5-6.0) and subjective symptoms of balance disorders. The experimental group (n = 39) received specific training to improve central integration of afferent sensory inputs; the control group (n = 41) received conventional rehabilitation (15 treatment sessions of 50 minutes each). Before, after treatment, and at one month post-treatment, patients were evaluated by a blinded rater using the Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), Multiple Sclerosis Quality of Life-54, Fatigue Severity Scale (FSS), number of falls and the Sensory Organization Balance Test (SOT). The experimental training program produced greater improvements than the control group training on the BBS (p < 0.001), the FSS (p < 0.002), number of falls (p = 0.002) and SOT (p < 0.05). Specific training to improve central integration of afferent sensory inputs may ameliorate balance disorders in patients with MS. Clinical Trial Registration (NCT01040117). © The Author(s), 2015.

CSF oligoclonal banding

MedlinePlus

... oligoclonal bands may point to a diagnosis of multiple sclerosis. How the Test is Performed A sample of ... Performed This test helps support the diagnosis of multiple sclerosis (MS). However, it does not confirm the diagnosis. ...

Central Pain Syndrome

MedlinePlus

... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ...

Thoracic Outlet Syndrome

MedlinePlus

... including rotator cuff injuries, cervical disc disorders, fibromyalgia, multiple sclerosis, complex regional pain syndrome, and tumors of the ... including rotator cuff injuries, cervical disc disorders, fibromyalgia, multiple sclerosis, complex regional pain syndrome, and tumors of the ...

Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis

PubMed Central

Abrahamsson, Sofia V.; Angelini, Daniela F.; Dubinsky, Amy N.; Morel, Esther; Oh, Unsong; Jones, Joanne L.; Carassiti, Daniele; Reynolds, Richard; Salvetti, Marco; Calabresi, Peter A.; Coles, Alasdair J.; Battistini, Luca; Martin, Roland; Burt, Richard K.

2013-01-01

Autologous haematopoietic stem cell transplantation has been tried as one experimental strategy for the treatment of patients with aggressive multiple sclerosis refractory to other immunotherapies. The procedure is aimed at ablating and repopulating the immune repertoire by sequentially mobilizing and harvesting haematopoietic stem cells, administering an immunosuppressive conditioning regimen, and re-infusing the autologous haematopoietic cell product. ‘Non-myeloablative’ conditioning regimens to achieve lymphocytic ablation without marrow suppression have been proposed to improve safety and tolerability. One trial with non-myeloablative autologous haematopoietic stem cell transplantation reported clinical improvement and inflammatory stabilization in treated patients with highly active multiple sclerosis. The aim of the present study was to understand the changes in the reconstituted immune repertoire bearing potential relevance to its mode of action. Peripheral blood was obtained from 12 patients with multiple sclerosis participating in the aforementioned trial and longitudinally followed for 2 years. We examined the phenotype and function of peripheral blood lymphocytes by cell surface or intracellular staining and multi-colour fluorescence activated cell sorting alone or in combination with proliferation assays. During immune reconstitution post-transplantation we observed significant though transient increases in the proportion of CD4+FoxP3+ T cells and CD56high natural killer cell subsets, which are cell subsets associated with immunoregulatory function. CD8+CD57+ cytotoxic T cells were persistently increased after therapy and were able to suppress CD4+ T cell proliferation with variable potency. In contrast, a CD161high proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161highCD8+ T cells were mucosal-associated invariant T cells, a novel cell population originating in the gut mucosa but expressing the central nervous system-homing receptor CCR6. Detection of mucosal-associated invariant T cells in post-mortem multiple sclerosis brain white matter active lesions confirmed their involvement in the disease pathology. Intracellular cytokine staining demonstrated interferon γ and interleukin 17 production and lack of interleukin 10 production, a pro-inflammatory profile. Mucosal-associated invariant T cell frequency did not change in patients treated with interferon β; and was more depleted after autologous haematopoietic stem cell transplantation than in patients who had received high-dose cyclophosphamide (n = 7) or alemtuzumab (n = 21) treatment alone, suggesting an additive or synergistic effect of the conditioning regime components. We propose that a favourably modified balance of regulatory and pro-inflammatory lymphocytes underlies the suppression of central nervous system inflammation in patients with multiple sclerosis following non-myeloablative autologous haematopoietic stem cell transplantation with a conditioning regimen consisting of cyclophosphamide and alemtuzumab. PMID:23864273

Stiff-Person Syndrome

MedlinePlus

... The disorder is often misdiagnosed as Parkinson’s disease, multiple sclerosis, fibromyalgia, psychosomatic illness, or anxiety and phobia. A ... The disorder is often misdiagnosed as Parkinson’s disease, multiple sclerosis, fibromyalgia, psychosomatic illness, or anxiety and phobia. A ...

CSF myelin basic protein

MedlinePlus

... done to see if myelin is breaking down. Multiple sclerosis is the most common cause for this, but ... tap) References Fabian MT, Krieger SC, Lublin FD. Multiple sclerosis and other inflammatory demyelinating diseases of the central ...

Technique Selectively Represses Immune System

MedlinePlus

... from attacking myelin in a mouse model of multiple sclerosis. Dr David Furness, Wellcome Images. All rights reserved ... devised a way to successfully treat symptoms resembling multiple sclerosis in a mouse model. With further development, the ...

Brown-Sequard Syndrome

MedlinePlus

... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. × Definition Brown-Sequard syndrome (BSS) is a rare ... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. View Full Definition Treatment Generally treatment for individuals ...

Daily bowel care program

MedlinePlus

... a brain or spinal cord injury. People with multiple sclerosis also have problems with their bowels. Those with ... PA: Elsevier Saunders; 2016:chap 18. Read More Multiple sclerosis Recovering after stroke Patient Instructions Constipation - self-care ...

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.

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.

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

Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis.

PubMed

Iparraguirre, Leire; Muñoz-Culla, Maider; Prada-Luengo, Iñigo; Castillo-Triviño, Tamara; Olascoaga, Javier; Otaegui, David

2017-09-15

Multiple sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice. Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a 'sponge system' and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers. Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered. Therefore, we carried out expression profiling of 13.617 circular RNAs in peripheral blood leucocytes from multiple sclerosis patients and healthy controls finding 406 differentially expressed (P-value < 0.05, Fold change > 1.5) and demonstrate after validation that, circ_0005402 and circ_0035560 are underexpressed in multiple sclerosis patients and could be used as biomarkers of the disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Smoking and multiple sclerosis: A systematic review and meta-analysis using the Bradford Hill criteria for causation.

PubMed

Degelman, Michelle L; Herman, Katya M

2017-10-01

Despite being one of the most common neurological disorders globally, the cause(s) of multiple sclerosis (MS) remain unknown. Cigarette smoking has been studied with regards to both the development and progression of MS. The Bradford Hill criteria for causation can contribute to a more comprehensive evaluation of a potentially causal risk factor-disease outcome relationship. The objective of this systematic review and meta-analysis was to assess the relationship between smoking and both MS risk and MS progression, subsequently applying Hill's criteria to further evaluate the likelihood of causal associations. The Medline, EMBASE, CINAHL, PsycInfo, and Cochrane Library databases were searched for relevant studies up until July 28, 2015. A random-effects meta-analysis was conducted for three outcomes: MS risk, conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS), and progression from relapsing-remitting multiple sclerosis (RRMS) to secondary-progressive multiple sclerosis (SPMS). Dose-response relationships and risk factor interactions, and discussions of mechanisms and analogous associations were noted. Hill's criteria were applied to assess causality of the relationships between smoking and each outcome. The effect of second-hand smoke exposure was also briefly reviewed. Smoking had a statistically significant association with both MS risk (conservative: OR/RR 1.54, 95% CI [1.46-1.63]) and SPMS risk (HR 1.80, 95% CI [1.04-3.10]), but the association with progression from CIS to CDMS was non-significant (HR 1.13, 95% CI [0.73-1.76]). Using Hill's criteria, there was strong evidence of a causal role of smoking in MS risk, but only moderate evidence of a causal association between smoking and MS progression. Heterogeneity in study designs and target populations, inconsistent results, and an overall scarcity of studies point to the need for more research on second-hand smoke exposure in relation to MS prior to conducting a detailed meta-analysis. This first review to supplement systematic review and meta-analytic methods with Hill's criteria to analyze the smoking-MS association provides evidence supporting the causal involvement of smoking in the development and progression of MS. Smoking prevention and cessation programs and policies should consider MS as an additional health risk when aiming to reduce smoking prevalence in the population. Copyright © 2017 Elsevier B.V. All rights reserved.

Aquatherapy for neurodegenerative disorders.

PubMed

Plecash, Alyson R; Leavitt, Blair R

2014-01-01

Aquatherapy is used for rehabilitation and exercise; water provides a challenging, yet safe exercise environment for many special populations. We have reviewed the use of aquatherapy programs in four neurodegenerative disorders: Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Results support the use of aquatherapy in Parkinson's disease and multiple sclerosis, however further evidence is required to make specific recommendations in all of the aforementioned disorders.

Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death

PubMed Central

Veto, Sara; Acs, Peter; Bauer, Jan; Lassmann, Hans; Berente, Zoltan; Setalo, Gyorgy; Borgulya, Gabor; Sumegi, Balazs; Komoly, Samuel; Gallyas, Ferenc; Illes, Zsolt

2010-01-01

Oligodendrocyte loss and demyelination are major pathological hallmarks of multiple sclerosis. In pattern III lesions, inflammation is minor in the early stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose) polymerase activation and apoptosis inducing factor nuclear translocation within apoptotic oligodendrocytes in such multiple sclerosis lesions. The same morphological and molecular pathology was observed in an experimental model of primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion and decreased demyelination. Poly(ADP-ribose) polymerase inhibition suppressed c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation, increased the activation of the cytoprotective phosphatidylinositol-3 kinase-Akt pathway and prevented caspase-independent apoptosis inducing factor-mediated apoptosis. Our data indicate that poly(ADP-ribose) polymerase activation plays a crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory model of multiple sclerosis, it may target all subtypes of multiple sclerosis, either by preventing oligodendrocyte death or attenuating inflammation. PMID:20157013

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.

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

Schilder's Disease

MedlinePlus

... Information from the National Library of Medicine’s MedlinePlus Multiple Sclerosis × What research is being done? The NINDS supports ... Information from the National Library of Medicine’s MedlinePlus Multiple Sclerosis See More About Research The NINDS supports and ...

Shaking Out Clues to Autoimmune Disease

MedlinePlus

... include type 1 diabetes, inflammatory bowel diseases and multiple sclerosis. Researchers have found many genetic variants that affect ... they examined a mouse disease that resembles human multiple sclerosis. Mice lacking SGK1 had less severe symptoms and ...

[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.

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

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.

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

CT and MR imaging findings of lymphangioleiomyomatosis involving the uterus and pelvic cavity.

PubMed

Kim, You Sung; Rha, Sung Eun; Byun, Jae Young; Lee, Ahwon; Park, Jong Sup

2011-01-01

Lymphangioleiomyomatosis (LAM) is a rare idiopathic disease and this is characterized by a proliferation of abnormal smooth muscle cells in the lungs and in the lymphatic system of the thorax and retroperitoneum. The female genital tract is rarely affected by LAM. We report here on the CT and MR imaging findings of extensive LAM involving the uterus and pelvic cavity, and this was seen as multiple cystic uterine and parauterine masses with internal hemorrhage in a young female with tuberous sclerosis complex.

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

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.

Axonal loss in the multiple sclerosis spinal cord revisited.

PubMed

Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

2018-05-01

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area, reduced by about 20%, appears to be a poor predictor of axonal density. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Comprehension of confidence intervals - development and piloting of patient information materials for people with multiple sclerosis: qualitative study and pilot randomised controlled trial.

PubMed

Rahn, Anne C; Backhus, Imke; Fuest, Franz; Riemann-Lorenz, Karin; Köpke, Sascha; van de Roemer, Adrianus; Mühlhauser, Ingrid; Heesen, Christoph

2016-09-20

Presentation of confidence intervals alongside information about treatment effects can support informed treatment choices in people with multiple sclerosis. We aimed to develop and pilot-test different written patient information materials explaining confidence intervals in people with relapsing-remitting multiple sclerosis. Further, a questionnaire on comprehension of confidence intervals was developed and piloted. We developed different patient information versions aiming to explain confidence intervals. We used an illustrative example to test three different approaches: (1) short version, (2) "average weight" version and (3) "worm prophylaxis" version. Interviews were conducted using think-aloud and teach-back approaches to test feasibility and analysed using qualitative content analysis. To assess comprehension of confidence intervals, a six-item multiple choice questionnaire was developed and tested in a pilot randomised controlled trial using the online survey software UNIPARK. Here, the average weight version (intervention group) was tested against a standard patient information version on confidence intervals (control group). People with multiple sclerosis were invited to take part using existing mailing-lists of people with multiple sclerosis in Germany and were randomised using the UNIPARK algorithm. Participants were blinded towards group allocation. Primary endpoint was comprehension of confidence intervals, assessed with the six-item multiple choice questionnaire with six points representing perfect knowledge. Feasibility of the patient information versions was tested with 16 people with multiple sclerosis. For the pilot randomised controlled trial, 64 people with multiple sclerosis were randomised (intervention group: n = 36; control group: n = 28). More questions were answered correctly in the intervention group compared to the control group (mean 4.8 vs 3.8, mean difference 1.1 (95 % CI 0.42-1.69), p = 0.002). The questionnaire's internal consistency was moderate (Cronbach's alpha = 0.56). The pilot-phase shows promising results concerning acceptability and feasibility. Pilot randomised controlled trial results indicate that the patient information is well understood and that knowledge gain on confidence intervals can be assessed with a set of six questions. German Clinical Trials Register: DRKS00008561 . Registered 8th of June 2015.

Involvement of the Warburg effect in non-tumor diseases processes.

PubMed

Chen, Zhe; Liu, Meiqing; Li, Lanfang; Chen, Linxi

2018-04-01

Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases. © 2017 Wiley Periodicals, Inc.

A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?

PubMed

Morris, Gerwyn; Berk, Michael; Puri, Basant K

2018-04-01

There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes. Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role. Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.

Multiple Sclerosis and Obesity: Possible Roles of Adipokines

PubMed Central

Guerrero-García, José de Jesús; Márquez-Aguirre, Ana Laura

2016-01-01

Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS. PMID:27721574

Modulation of B cell regulatory molecules CD22 and CD72 in myasthenia gravis and multiple sclerosis.

PubMed

Lu, Jiayin; Li, Jing; Zhu, Tai-qing; Zhang, Longbo; Wang, Yuzhong; Tian, Fa-fa; Yang, Huan

2013-06-01

B cell activation mediated by cluster of differentiation (CD) molecules plays an important role in B cell-related autoimmune diseases. CD22 and CD72 have been demonstrated to act as B cell inhibitory receptors in many autoimmune diseases. Activated B cells are involved in the pathogenesis of myasthenia gravis (MG) by secretion of anti-acetylcholine receptor (AchR) antibodies. However, the roles of CD22 and CD72 on B cells of MG are unknown. In this study, we detected the expression of CD22 and CD72 on B cells of MG, compared to multiple sclerosis (MS) patient controls and healthy controls by flow cytometry and quantitative real-time polymerase transcription chain reaction. Our data demonstrated that aberrant expression of CD72 exists on B cells of MG and MS patients and expression level of CD72 molecule has a significantly negative correlation with anti-AchR antibody levels in MG, which suggests that CD72 may be involved in the pathogenesis of MG and MS. There were no significant differences between study patients (MG, ocular MG, generalized MG, and MS) and healthy controls.

Overview and diagnosis of multiple sclerosis.

PubMed

Hunter, Samuel F

2016-06-01

Multiple sclerosis (MS), a chronic inflammatory disease of unknown etiology, involves an immunemediated attack of the central nervous system (CNS) that produces demyelination and axonal/neuronal damage, resulting in characteristic multifocal lesions apparent on magnetic resonance imaging and a variety of neurologic manifestations. The disease pathology is characterized by multifocal lesions within the CNS, in both the white matter and gray matter, with perivenular inflammatory cell infiltrates, demyelination, axonal transection, neuronal degeneration, and gliosis. MS pathogenesis is complex, as it involves both T- and B-cell mechanisms and is heterogeneous in presentation. Relatively recently, the historical 4 core clinical categories of MS were revised in an effort to improve characterization of the clinical course, better identify where a given patient is positioned in the disease spectrum, and to guide clinical studies. In young and middle-aged adults, MS is one of the most common contributors to neurologic disability, and it exerts detrimental effects on a patient's productivity and health-related quality of life. Typically, patients with MS have a long life span, although healthcare utilization increases over time. As a consequence, the disease places a substantial burden on patients and their caregivers/families, as well as employers, the healthcare system, and society.

Adaptive Personalized Training Games for Individual and Collaborative Rehabilitation of People with Multiple Sclerosis

PubMed Central

2014-01-01

Any rehabilitation involves people who are unique individuals with their own characteristics and rehabilitation needs, including patients suffering from Multiple Sclerosis (MS). The prominent variation of MS symptoms and the disease severity elevate a need to accommodate the patient diversity and support adaptive personalized training to meet every patient's rehabilitation needs. In this paper, we focus on integrating adaptivity and personalization in rehabilitation training for MS patients. We introduced the automatic adjustment of difficulty levels as an adaptation that can be provided in individual and collaborative rehabilitation training exercises for MS patients. Two user studies have been carried out with nine MS patients to investigate the outcome of this adaptation. The findings showed that adaptive personalized training trajectories have been successfully provided to MS patients according to their individual training progress, which was appreciated by the patients and the therapist. They considered the automatic adjustment of difficulty levels to provide more variety in the training and to minimize the therapists involvement in setting up the training. With regard to social interaction in the collaborative training exercise, we have observed some social behaviors between the patients and their training partner which indicated the development of social interaction during the training. PMID:24982862

Multiple Sclerosis: Hope Through Research | NIH MedlinePlus the Magazine

MedlinePlus

... turn Javascript on. Feature: Multiple Sclerosis Hope Through Research Past Issues / Spring 2012 Table of Contents Neil ... a champion for those with MS and for research to find the causes and cures for the ...

Postsecondary Education for Individuals with Multiple Sclerosis: Issues and Strategies.

ERIC Educational Resources Information Center

Yagodich, Nancy L.; Wolfe, Pamela S.; Boone, Rosalie S.

2000-01-01

Describes characteristics of multiple sclerosis and the implications of its manifestations for postsecondary education. Provides a checklist for students selecting a postsecondary institution regarding general considerations, academic accommodations, support and services, and self-assessment. (SK)

Multiple Sclerosis, Personal Stories | NIH MedlinePlus the Magazine

MedlinePlus

... please turn Javascript on. Feature: Multiple Sclerosis Personal Stories: Nicole Lemelle, Iris Young, Michael Anthony, John Cantú ... Better," an Internet video series that brings the story of MS to life through the eyes of ...

[Multiple sclerosis associated with antiphospholipid syndrome: diagnostic and therapeutic difficulties].

PubMed

Ahbeddou, N; Ait Ben Haddou, E; Hammi, S; Slimani, C; Regragui, W; Benomar, A; Yahyaoui, M

2012-01-01

Strokes are the main neurological manifestation of antiphospholipid syndrome. Other clinical presentations are possible and may mimic classic symptoms of multiple sclerosis (MS). A 46-year-old woman, with a history of two miscarriages, presented four subacute neurological episodes (optic neuritis, right facial paralysis, paraparesis of the thigh, and right brachial monoparesis). Using McDonald criteria, the diagnosis of multiple sclerosis was retained. Because of the occurrence of thrombocytopenia during a final relapse, we reconsidered the diagnosis of MS. Search for antiphospholipid antibodies was positive. All clinical manifestations and complementary tests were compatible with the diagnosis of antiphospholipid syndrome associated with multiple sclerosis. Given the great similarity of clinical, radiological and biological findings in the two diseases, non-thrombotic neurological manifestations of antiphospholipid syndrome can be difficult to distinguish from MS associated with antiphospholipid syndrome. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

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

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

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

PubMed

Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

2017-07-01

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

A rare condition of anorectal dysfunction in a patient with multiple sclerosis: Coexistence of faecal incontinence and mechanical constipation: Report of case

PubMed Central

Dandin, Özgür; Akpak, Yaşam Kemal; Karakaş, Dursun Özgür; Hazer, Batuhan; Ergin, Tuncer; Dandinoğlu, Taner; Teomete, Uygar

2014-01-01

INTRODUCTION Multiple sclerosis is a chronic demyelinating neurological disease and causing a variety of neurological symptoms, including discomfort of anorectal function. Constipation and faecal incontinence present as anorectal dysfunction in MS and anal manometry, colonic transit time, electromyography, and defecography can be used for assessment. PRESENTATION OF CASE We presented a thirty-three years old woman with rare condition of anorectal dysfunction in multiple sclerosis. Anal manometry, defecography were done, and synchronously anal incontinence and mechanical constipation due to rectocele and anismus were detected in this patient. DISCUSSION Although anal incontinence and constipation are seen often in patients with multiple sclerosis, in the literature, coexistence of animus, rectocele and anal incontinence are quite rare. CONCLUSION Defecography and anal manometry are useful diagnostic methods for demonstration of anorectal dysfuntions in patients with MS. PMID:25460483

A rare condition of anorectal dysfunction in a patient with multiple sclerosis: Coexistence of faecal incontinence and mechanical constipation: Report of case.

PubMed

Dandin, Özgür; Akpak, Yaşam Kemal; Karakaş, Dursun Özgür; Hazer, Batuhan; Ergin, Tuncer; Dandinoğlu, Taner; Teomete, Uygar

2014-01-01

Multiple sclerosis is a chronic demyelinating neurological disease and causing a variety of neurological symptoms, including discomfort of anorectal function. Constipation and faecal incontinence present as anorectal dysfunction in MS and anal manometry, colonic transit time, electromyography, and defecography can be used for assessment. We presented a thirty-three years old woman with rare condition of anorectal dysfunction in multiple sclerosis. Anal manometry, defecography were done, and synchronously anal incontinence and mechanical constipation due to rectocele and anismus were detected in this patient. Although anal incontinence and constipation are seen often in patients with multiple sclerosis, in the literature, coexistence of animus, rectocele and anal incontinence are quite rare. Defecography and anal manometry are useful diagnostic methods for demonstration of anorectal dysfuntions in patients with MS. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of craniosacral therapy on lower urinary tract signs and symptoms in multiple sclerosis.

PubMed

Raviv, Gil; Shefi, Shai; Nizani, Dalia; Achiron, Anat

2009-05-01

To examine whether craniosacral therapy improves lower urinary tract symptoms of multiple sclerosis (MS) patients. A prospective cohort study. Out-patient clinic of multiple sclerosis center in a referral medical center. Hands on craniosacral therapy (CST). Change in lower urinary tract symptoms, post voiding residual volume and quality of life. Patients from our multiple sclerosis clinic were assessed before and after craniosacral therapy. Evaluation included neurological examination, disability status determination, ultrasonographic post voiding residual volume estimation and questionnaires regarding lower urinary tract symptoms and quality of life. Twenty eight patients met eligibility criteria and were included in this study. Comparison of post voiding residual volume, lower urinary tract symptoms and quality of life before and after craniosacral therapy revealed a significant improvement (0.001>p>0.0001). CST was found to be an effective means for treating lower urinary tract symptoms and improving quality of life in MS patients.

Cell-based therapeutic strategies for multiple sclerosis.

PubMed

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Assessing interactions between HLA-DRB1*15 and infectious mononucleosis on the risk of multiple sclerosis.

PubMed

Disanto, Giulio; Hall, Carolina; Lucas, Robyn; Ponsonby, Anne-Louise; Berlanga-Taylor, Antonio J; Giovannoni, Gavin; Ramagopalan, Sreeram V

2013-09-01

Gene-environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). Individuals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92-10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79-2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59-2.59; excess risk due to interaction=3.30, 95%CI=0.47-6.12; attributable proportion due to interaction=45%, 95% CI=22-68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene-environment interactions on both a multiplicative and additive scale.

The comparison of socio-economic conditions and personal hygiene habits of neuro-Behçet's disease and multiple sclerosis patients.

PubMed

Pehlivan, Münevver; Kürtüncü, Murat; Tüzün, Erdem; Shugaiv, Erkingül; Mutlu, Melike; Eraksoy, Mefküre; Akman-Demir, Gülşen

2011-07-01

The "hygiene hypothesis" suggests that a reduction in the exposure to infectious agents due to improved health conditions has contributed to the increased incidence of autoimmune disorders in developed countries. In keeping with the hygiene hypothesis, many autoimmune disorders such as multiple sclerosis (MS) are more frequently observed in developed countries. To identify the relevance of hygiene hypothesis in neuro-Behçet's disease (NBD), another chronic inflammatory disease of the central nervous system, we developed and administered a multiple choice questionnaire to evaluate the hygiene conditions and practices of age and gender-matched NBD patients (n = 50) and control MS (n =5 0) and headache (n = 50) patients. Overall, MS patients had the highest socio-economic and hygiene features, whereas NBD patients displayed a lower socio-economic status group and showed poorer hygiene conditions than MS and headache controls. These poor hygiene conditions might be increasing the susceptibility of exposure to infectious agents that might, at least in part, trigger the inflammatory responses involved in NBD pathogenesis. Copyright © 2011 Elsevier GmbH. All rights reserved.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

PubMed

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C A; Patsopoulos, Nikolaos A; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E; Edkins, Sarah; Gray, Emma; Booth, David R; Potter, Simon C; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D'alfonso, Sandra; Blackburn, Hannah; Martinelli Boneschi, Filippo; Liddle, Jennifer; Harbo, Hanne F; Perez, Marc L; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J; Barcellos, Lisa F; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P; Brassat, David; Broadley, Simon A; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M; Cavalla, Paola; Celius, Elisabeth G; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B; Cozen, Wendy; Cree, Bruce A C; Cross, Anne H; Cusi, Daniele; Daly, Mark J; Davis, Emma; de Bakker, Paul I W; Debouverie, Marc; D'hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F A; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G; Kilpatrick, Trevor J; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S; Leone, Maurizio A; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R; Link, Jenny; Liu, Jianjun; Lorentzen, Aslaug R; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L; Ramsay, Patricia P; Reunanen, Mauri; Reynolds, Richard; Rioux, John D; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J; Sellebjerg, Finn; Selmaj, Krzysztof W; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M A; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A; Tronczynska, Ewa; Casas, Juan P; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S; Wang, Kai; Mathew, Christopher G; Wason, James; Palmer, Colin N A; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C; Yaouanq, Jacqueline; Viswanathan, Ananth C; Zhang, Haitao; Wood, Nicholas W; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R; Pericak-Vance, Margaret A; Haines, Jonathan L; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J; De Jager, Philip L; Peltonen, Leena; Stewart, Graeme J; Hafler, David A; Hauser, Stephen L; McVean, Gil; Donnelly, Peter; Compston, Alastair

2011-08-10

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

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.

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.

An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.

PubMed

Peruzzi, Agnese; Zarbo, Ignazio Roberto; Cereatti, Andrea; Della Croce, Ugo; Mirelman, Anat

2017-07-01

In this single blind randomized controlled trial, we examined the effect of a virtual reality-based training on gait of people with multiple sclerosis. Twenty-five individuals with multiple sclerosis with mild to moderate disability were randomly assigned to either the control group (n = 11) or the experimental group (n = 14). The subjects in the control group received treadmill training. Subjects in the experimental group received virtual reality based treadmill training. Clinical measures and gait parameters were evaluated. Subjects in both the groups significantly improved the walking endurance and speed, cadence and stride length, lower limb joint ranges of motion and powers, during single and dual task gait. Moreover, subjects in the experimental group also improved balance, as indicated by the results of the clinical motor tests (p < 0.05). Between-group comparisons revealed that the experimental group improved significantly more than control group in hip range of motion and hip generated power at terminal stance at post-training. Our results support the perceived benefits of training programs that incorporate virtual reality to improve gait measures in individuals with multiple sclerosis. Implication of rehabilitation Gait deficits are common in multiple sclerosis (85%) and worsen during dual task activities. Intensive and progressive treadmill training, with and without virtual reality, is effective on dual task gait in persons with multiple sclerosis. Virtual reality-based treadmill training requiring obstacle negotiation increases the range of motion and the power generated at the hip, consequently allowing longer stride length and, consequently, higher gait speed.

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

Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

PubMed

Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

2017-08-01

Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

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.

Structural disconnection is responsible for increased functional connectivity in multiple sclerosis.

PubMed

Patel, Kevin R; Tobyne, Sean; Porter, Daria; Bireley, John Daniel; Smith, Victoria; Klawiter, Eric

2018-06-01

Increased synchrony within neuroanatomical networks is often observed in neurophysiologic studies of human brain disease. Most often, this phenomenon is ascribed to a compensatory process in the face of injury, though evidence supporting such accounts is limited. Given the known dependence of resting-state functional connectivity (rsFC) on underlying structural connectivity (SC), we examine an alternative hypothesis: that topographical changes in SC, specifically particular patterns of disconnection, contribute to increased network rsFC. We obtain measures of rsFC using fMRI and SC using probabilistic tractography in 50 healthy and 28 multiple sclerosis subjects. Using a computational model of neuronal dynamics, we simulate BOLD using healthy subject SC to couple regions. We find that altering the model by introducing structural disconnection patterns observed in those multiple sclerosis subjects with high network rsFC generates simulations with high rsFC as well, suggesting that disconnection itself plays a role in producing high network functional connectivity. We then examine SC data in individuals. In multiple sclerosis subjects with high network rsFC, we find a preferential disconnection between the relevant network and wider system. We examine the significance of such network isolation by introducing random disconnection into the model. As observed empirically, simulated network rsFC increases with removal of connections bridging a community with the remainder of the brain. We thus show that structural disconnection known to occur in multiple sclerosis contributes to network rsFC changes in multiple sclerosis and further that community isolation is responsible for elevated network functional connectivity.

Variables Associated with Communicative Participation in People with Multiple Sclerosis: A Regression Analysis

ERIC Educational Resources Information Center

Baylor, Carolyn; Yorkston, Kathryn; Bamer, Alyssa; Britton, Deanna; Amtmann, Dagmar

2010-01-01

Purpose: To explore variables associated with self-reported communicative participation in a sample (n = 498) of community-dwelling adults with multiple sclerosis (MS). Method: A battery of questionnaires was administered online or on paper per participant preference. Data were analyzed using multiple linear backward stepwise regression. The…

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.

Demographic, socioeconomic and clinical correlates of self-management in multiple sclerosis.

PubMed

Wilski, Maciej; Tasiemski, Tomasz; Kocur, Piotr

2015-01-01

Our aim was to identify demographic, clinical and socioeconomic predictors of self-management in multiple sclerosis (MS). The study was performed on a group of 283 patients with multiple sclerosis who completed Multiple Sclerosis Self-Management Scale - Revised (MSSM-R), Multiple Sclerosis Impact Scale (MSIS-29), Actually Received Support Scale (part of Berlin Social Support Scale), Expanded Disability Status Scale (EDSS) and Socioeconomic resources scale. Patients were recruited through cooperation with Multiple Sclerosis Rehabilitation Centre in Borne Sulinowo and Polish Society of Multiple Sclerosis. Demographic and illness-related problems were determined with self-report survey. The group consisted of 185 women and 98 men, with a mean age of 48 years. The level of disability and disease severity varied, mean time elapsed since MS diagnosis was 13 years. The final predictive model of self-management in MS was based on two main predictors: received support and available socioeconomic resources. Patients with MS who received adequate support from the closest relatives (R(2 )= 0.07, F(1, 279) = 21.84, p ≤ 0.01) and had larger available socioeconomic resources (R(2) = 0.11, F(2, 278) = 17.06, p ≤ 0.01), turned out to be the most effective in self-management. Moreover, a relationship between self-management in MS and gender as well as monthly income attributable to one family member was documented. We identified a group of MS patients who are at an increased risk of poor self-management and therefore require more attention from medical staff. This group includes patients with low level of received support, low socioeconomic resources and to a lesser degree men, and also persons receiving low monthly income. Implications for Rehabilitation Self-management of chronic illness is a key component of active participation in rehabilitation process. Low self-management in multiple sclerosis (MS) is considered to be one of the most important factors contributing to low rehabilitation efficacy, more severe long-term complications and increase in healthcare costs. Knowledge on predictors of self-management should be used in clinical practice when providing treatment, support, education and rehabilitation for patients with MS. Increasing support and improving social conditions are potentially important targets for interventions aimed at optimization of self-management, and thereby reduction of health care costs and improvement of health.

Involving Members of the Public in Health Economics Research: Insights from Selecting Health States for Valuation to Estimate Quality-Adjusted Life-Year (QALY) Weights.

PubMed

Goodwin, Elizabeth; Boddy, Kate; Tatnell, Lynn; Hawton, Annie

2018-04-01

Over recent years, public involvement in health research has expanded considerably. However, public involvement in designing and conducting health economics research is seldom reported. Here we describe the development, delivery and assessment of an approach for involving people in a clearly defined piece of health economics research: selecting health states for valuation in estimating quality-adjusted life-years (QALYs). This involvement formed part of a study to develop a condition-specific preference-based measure of health-related quality of life, the Multiple Sclerosis Impact Scale (MSIS-8D), and the work reported here relates to the identification of plausible, or realistic, health states for valuation. An Expert Panel of three people with multiple sclerosis (MS) was recruited from a local involvement network, and two health economists designed an interactive task that enabled the Panel to identify health states that were implausible, or unlikely to be experienced. Following some initial confusion over terminology, which was resolved by discussion with the Panel, the task worked well and can be adapted to select health states for valuation in the development of any preference-based measure. As part of the involvement process, five themes were identified by the Panel members and the researchers which summarised our experiences of public involvement in this health economics research example: proportionality, task design, prior involvement, protectiveness and partnerships. These are described in the paper, along with their practical implications for involving members of the public in health economics research. Our experience demonstrates how members of the public and health economists can work together to improve the validity of health economics research. Plain Language Summary It has become commonplace to involve members of the public in health service research. However, published reports of involving people in designing health economics research are rare. We describe how we designed a way of involving people in a particular piece of health economics research.The aim of the work was to produce descriptions of different states of health experienced by people with multiple sclerosis (MS). These descriptions have since been rated in terms of how good or bad they are in a way that can be used by the National Institute for Health and Care Excellence (NICE) to make decisions about what services to fund on the NHS.We formed a panel of three people with MS, and designed a task to help the group produce health descriptions likely to be experienced by people with MS. After discussion about jargon, and working together to find more layman's terms, the task worked well, and can be adapted to produce health descriptions for any condition.We identified some key themes about working together that give insights into how members of the public can be involved in health economics research, and show the importance of their involvement in improving the relevance of this research.

The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations.

PubMed

Pardo, Gabriel; Jones, David E

2017-12-01

The treatment landscape for relapsing forms of multiple sclerosis (RMS) has expanded considerably over the last 10 years with the approval of multiple new disease-modifying therapies (DMTs), and others in late-stage clinical development. All DMTs for RMS are believed to reduce central nervous system immune-mediated inflammatory processes, which translate into demonstrable improvement in clinical and radiologic outcomes. However, some DMTs are associated with long-lasting effects on the immune system and/or serious adverse events, both of which may complicate the use of subsequent therapies. When customizing a treatment program, a benefit-risk assessment must consider multiple factors, including the efficacy of the DMT to reduce disease activity, the short- and long-term safety and immunologic profiles of each DMT, the criteria used to define switching treatment, and the risk tolerance of each patient. A comprehensive benefit-risk assessment can only be achieved by evaluating the immunologic, safety, and efficacy data for DMTs in the controlled clinical trial environment and the postmarketing clinical practice setting. This review is intended to help neurologists make informed decisions when treating RMS by summarizing the known data for each DMT and raising awareness of the multiple considerations involved in treating people with RMS throughout the entire course of their disease.

The potential role of subclinical Bordetella Pertussis colonization in the etiology of multiple sclerosis.

PubMed

Rubin, Keith; Glazer, Steven

2016-04-01

It is established that (1) subclinical Bordetella pertussis colonization of the nasopharynx persists in highly vaccinated populations, and (2) B. pertussis toxin is a potent adjuvant that, when co-administered with neural antigens, induces neuropathology in experimental autoimmune encephalomyelitis, the principle animal model of multiple sclerosis. Building on these observations with supporting epidemiologic and biologic evidence, we propose that, contrary to conventional wisdom that subclinical pertussis infections are innocuous to hosts, B. pertussis colonization is an important cause of multiple sclerosis. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

Cognitive Impairment in MS Linked to Structural and Functional Connectivity

DTIC Science & Technology

2015-10-01

DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple sclerosis (MS) is...Requirements………………………………… 9 9. Appendices……………………………………………………………9 Krupp MS130103  2    Abstract Multiple sclerosis (MS) is the most common progressive...information processing needed to learn and solve problems. This symptom represents a major concern for many individuals living with multiple sclerosis

Multiple sclerosis in the Orkney and Shetland Islands. II: The search for an exogenous aetiology.

PubMed Central

Poskanzer, D C; Sheridan, J L; Prenney, L B; Walker, A M

1980-01-01

In Orkney and Shetland, a survey of lifetime events was undertaken in multiple sclerosis patients and two control groups to define shared exposure to an exogenous agent or environmental insult. Analyses of demographic factors, diet, social class and occupation, housing and environment, animal exposure, schooling, travel, infectious disease, and medical history disclosed a remarkable similarity in responses between patients and controls for a majority of questions. However, differences were noted for sanitation, place of residence at onset, and animal exposure. The data give additional support for an exogenous aetiology of multiple sclerosis. PMID:7241023

Superparamagnetic Iron Oxide Nanoparticles: Promises for Diagnosis and Treatment of Multiple Sclerosis

PubMed Central

2011-01-01

Smart superparamagnetic iron oxide nanoparticles (SPIONs) are the most promising candidate for theragnosis (i.e., diagnosis and treatment) of multiple sclerosis. A deep understanding of the dynamics of the in vivo neuropathology of multiple sclerosis can be achieved by improving the efficiency of various medical techniques (e.g., positron emission tomography and magnetic resonance imaging) using multimodal SPIONs. In this Review, recent advances and challenges in the development of smart SPIONs for theragnostic applications are comprehensively described. In addition, critical outlines of emerging developments are provided from the points of view of both clinicians and nanotechnologists. PMID:22778862

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.

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.

The effects of pranayama, hatha and raja yoga on physical pain and the quality of life of women with multiple sclerosis.

PubMed

Doulatabad, Shahla Najafi; Nooreyan, Khirollah; Doulatabad, Ardavan Najafi; Noubandegani, Zinat Mohebbi

2012-01-01

In a clinical trial carried out on 60 women with multiple sclerosis, the researchers obtained data using survey questionnaires. In addition to demographic data, the Multiple Sclerosis Quality of Life-54 (MSQoL-54) instrument was used to determine how multiple sclerosis influences the quality of life of the studied women. Within the frame of this randomized controlled trial, the participants were divided into two equally sized groups (the case and the control group) in which the level of pain and the quality of life were evaluated. The case group exercised pain-managing Yoga methods for three months, keeping the pace of eight 90-minute sessions per month. The control participants were subjected to no intervention. One month after the Yoga therapy, the level of pain and the quality of life were evaluated in both groups and compared to the baseline data. Data were analyzed using SPSS software and paired t-tests. After the Yoga therapy, the case group showed a significant improvement in physical pain management (P=0.007) and the quality of life (P=0.001) as compared to the control group. The results showed that Yoga techniques can alleviate physical pain and improve the quality of life of multiple sclerosis patients.

Intensity ratio to improve black hole assessment in multiple sclerosis.

PubMed

Adusumilli, Gautam; Trinkaus, Kathryn; Sun, Peng; Lancia, Samantha; Viox, Jeffrey D; Wen, Jie; Naismith, Robert T; Cross, Anne H

2018-01-01

Improved imaging methods are critical to assess neurodegeneration and remyelination in multiple sclerosis. Chronic hypointensities observed on T1-weighted brain MRI, "persistent black holes," reflect severe focal tissue damage. Present measures consist of determining persistent black holes numbers and volumes, but do not quantitate severity of individual lesions. Develop a method to differentiate black and gray holes and estimate the severity of individual multiple sclerosis lesions using standard magnetic resonance imaging. 38 multiple sclerosis patients contributed images. Intensities of lesions on T1-weighted scans were assessed relative to cerebrospinal fluid intensity using commercial software. Magnetization transfer imaging, diffusion tensor imaging and clinical testing were performed to assess associations with T1w intensity-based measures. Intensity-based assessments of T1w hypointensities were reproducible and achieved > 90% concordance with expert rater determinations of "black" and "gray" holes. Intensity ratio values correlated with magnetization transfer ratios (R = 0.473) and diffusion tensor imaging metrics (R values ranging from 0.283 to -0.531) that have been associated with demyelination and axon loss. Intensity ratio values incorporated into T1w hypointensity volumes correlated with clinical measures of cognition. This method of determining the degree of hypointensity within multiple sclerosis lesions can add information to conventional imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Impact of a 10-Week Individualized Exercise Program on Physical Function and Fatigue of People with Multiple Sclerosis

PubMed Central

Elgelid, Staffan; Bolger, Shannon; Parsons, Caroline; Quashnoc, Rachel; Raymor, Johanna

2011-01-01

Research has found that people with multiple sclerosis (MS) who engage in exercise programs experience improvements in physical and psychological health, resulting in enhanced quality of life. These studies have involved structured exercise protocols, but few have examined the effects of an individualized exercise program allowing for peer socialization. The purpose of this study was to investigate the effects of a 10-week individualized exercise program offering opportunities to socialize with peers on fatigue and physical functioning in people with MS. Thirteen individuals with a physician diagnosis of MS were enrolled in a 10-week exercise program at Nazareth College in Rochester, New York. Eleven participants (9 female, 2 male; mean ± SD age, 55.0 ± 7.06 years) completed the study. The following qualitative and quantitative measures were used for evaluation before and after the exercise program: Multiple Sclerosis Quality of Life–54 (MSQOL-54), Activities-specific Balance Confidence (ABC) scale, Modified Fatigue Impact Scale (MFIS), Timed Up and Go (TUG) test, Timed 10-Meter Walk (T10MW) test, functional reach test, and single-leg stance (SLS) test. Statistically significant differences were found for the TUG (P = .005), T10MW (P = .014), and MFIS physical functioning subscore (P = .039). The results showed significant increases in gait speed and mobility as well as decreased impact of fatigue on physical functioning after the 10-week exercise program. PMID:24453715

Neuroanatomy of pseudobulbar affect : a quantitative MRI study in multiple sclerosis.

PubMed

Ghaffar, Omar; Chamelian, Laury; Feinstein, Anthony

2008-03-01

Pseudobulbar affect (PBA) is defined as episodes of involuntary crying, laughing, or both in the absence of a matching subjective mood state. This neuropsychiatric syndrome can be found in a number of neurological disorders including multiple sclerosis (MS). The aim of this study was to identify neuroanatomical correlates of PBA in multiple sclerosis (MS) using a case-control 1.5T MRI study. MS patients with (n = 14) and without (n = 14) PBA were matched on demographic, disease course, and disability variables. Comorbid psychiatric disorders including depressive and anxiety disorders were absent. Hypo- and hyperintense lesion volumes plus measurements of atrophy were obtained and localized anatomically according to parcellated brain regions. Between-group statistical comparisons were undertaken with alpha set at 0.01 for the primary analysis. Discrete differences in lesion volume were noted in six regions: Brainstem hypointense lesions, bilateral inferior parietal and medial inferior frontal hyperintense lesions, and right medial superior frontal hyperintense lesions were all significantly higher in the PBA group. A logistic regression model identified four of these variables (brainstem hypointense, left inferior parietal hyperintense, and left and right medial inferior frontal hyperintense lesion volumes) that accounted for 70% of the variance when it came to explaining the presence of PBA. In conclusion, MS patients with PBA have a distinct distribution of brain lesions when compared to a matched MS sample without PBA. The lesion data support a widely-dispersed neural network involving frontal, parietal, and brainstem regions in the pathophysiology of PBA.

Electromagnetic hypersensitivity: biological effects of dirty electricity with emphasis on diabetes and multiple sclerosis.

PubMed

Havas, Magda

2006-01-01

Dirty electricity is a ubiquitous pollutant. It flows along wires and radiates from them and involves both extremely low frequency electromagnetic fields and radio frequency radiation. Until recently, dirty electricity has been largely ignored by the scientific community. Recent inventions of metering and filter equipment provide scientists with the tools to measure and reduce dirty electricity on electrical wires. Several case studies and anecdotal reports are presented. Graham/Stetzer (GS) filters have been installed in schools with sick building syndrome and both staff and students reported improved health and more energy. The number of students needing inhalers for asthma was reduced in one school and student behavior associated with ADD/ADHD improved in another school. Blood sugar levels for some diabetics respond to the amount of dirty electricity in their environment. Type 1 diabetics require less insulin and Type 2 diabetics have lower blood sugar levels in an electromagnetically clean environment. Individuals diagnosed with multiple sclerosis have better balance and fewer tremors. Those requiring a cane walked unassisted within a few days to weeks after GS filters were installed in their home. Several disorders, including asthma, ADD/ADHD, diabetes, multiple sclerosis, chronic fatigue, fibromyalgia, are increasing at an alarming rate, as is electromagnetic pollution in the form of dirty electricity, ground current, and radio frequency radiation from wireless devices. The connection between electromagnetic pollution and these disorders needs to be investigated and the percentage of people sensitive to this form of energy needs to be determined.

The thalamus and multiple sclerosis

PubMed Central

Minagar, Alireza; Barnett, Michael H.; Benedict, Ralph H.B.; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott

2013-01-01

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. PMID:23296131

The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects.

PubMed

Minagar, Alireza; Barnett, Michael H; Benedict, Ralph H B; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott; Zivadinov, Robert

2013-01-08

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process.

Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2008-08-15

To characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups. PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of pseudobulbar affect.

Multiple Sclerosis.

ERIC Educational Resources Information Center

Plummer, Nancy; Michael, Nancy, Ed.

This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

Women with Multiple Sclerosis and Employment Issues: A Focus on Social and Institutional Environment.

ERIC Educational Resources Information Center

Dyck, Isabel; Jongbloed, Lyn

2000-01-01

Examines employment issues for women with multiple sclerosis. Focuses on experiences of women managing their disability and demonstrates the importance of the social and institutional dimensions of environment in shaping occupational performance. (Contains 27 references.) (JOW)

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.

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

Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

PubMed Central

Viswanathan, S.; Rose, N.; Masita, A.; Dhaliwal, J. S.; Puvanarajah, S. D.; Rafia, M. H.; Muda, S.

2013-01-01

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. PMID:24455266

Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis.

PubMed

Broggi, G; Ferroli, P; Franzini, A; Servello, D; Dones, I

2000-01-01

To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24 months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits.

Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis

PubMed Central

Broggi, G.; Ferroli, P.; Franzini, A.; Servello, D.; Dones, I.

2000-01-01

OBJECTIVE—To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment.
METHODS—Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis.
RESULTS—Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients.
CONCLUSIONS—Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits. 

 PMID:10601403

A Specific Reduction in Aβ1-42 vs. a Universal Loss of Aβ Peptides in CSF Differentiates Alzheimer's Disease From Meningitis and Multiple Sclerosis.

PubMed

Spitzer, Philipp; Lang, Roland; Oberstein, Timo J; Lewczuk, Piotr; Ermann, Natalia; Huttner, Hagen B; Masouris, Ilias; Kornhuber, Johannes; Ködel, Uwe; Maler, Juan M

2018-01-01

A reduced concentration of Aβ 1-42 in CSF is one of the established biomarkers of Alzheimer's disease. Reduced CSF concentrations of Aβ 1-42 have also been shown in multiple sclerosis, viral encephalitis and bacterial meningitis. As neuroinflammation is one of the neuropathological hallmarks of Alzheimer's disease, an infectious origin of the disease has been proposed. According to this hypothesis, amyloid pathology is a consequence of a microbial infection and the resulting immune defense. Accordingly, changes in CSF levels of amyloid-β peptides should be similar in AD and inflammatory brain diseases. Aβ 1-42 and Aβ 1-40 levels were measured in cerebrospinal fluid by ELISA and Western blotting in 34 patients with bacterial meningitis ( n = 9), multiple sclerosis ( n = 5) or Alzheimer's disease ( n = 9) and in suitable controls ( n = 11). Reduced concentrations of Aβ 1-42 were detected in patients with bacterial meningitis, multiple sclerosis and Alzheimer's disease. However, due to a concurrent reduction in Aβ 1-40 in multiple sclerosis and meningitis patients, the ratio of Aβ 1-42 /Aβ 1-40 was reduced only in the CSF of Alzheimer's disease patients. Urea-SDS-PAGE followed by Western blotting revealed that all Aβ peptide variants are reduced in bacterial meningitis, whereas in Alzheimer's disease, only Aβ 1-42 is reduced. These results have two implications. First, they confirm the discriminatory diagnostic power of the Aβ 1-42 /Aβ 1-40 ratio. Second, the differential pattern of Aβ peptide reductions suggests that the amyloid pathology in meningitis and multiple sclerosis differs from that in AD and does not support the notion of AD as an infection-triggered immunopathology.

Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.

PubMed

Kalron, Alon; Rosenblum, Uri; Frid, Lior; Achiron, Anat

2017-03-01

Evaluate the effects of a Pilates exercise programme on walking and balance in people with multiple sclerosis and compare this exercise approach to conventional physical therapy sessions. Randomized controlled trial. Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel. Forty-five people with multiple sclerosis, 29 females, mean age (SD) was 43.2 (11.6) years; mean Expanded Disability Status Scale (S.D) was 4.3 (1.3). Participants received 12 weekly training sessions of either Pilates ( n=22) or standardized physical therapy ( n=23) in an outpatient basis. Spatio-temporal parameters of walking and posturography parameters during static stance. Functional tests included the Time Up and Go Test, 2 and 6-minute walk test, Functional Reach Test, Berg Balance Scale and the Four Square Step Test. In addition, the following self-report forms included the Multiple Sclerosis Walking Scale and Modified Fatigue Impact Scale. At the termination, both groups had significantly increased their walking speed ( P=0.021) and mean step length ( P=0.023). According to the 2-minute and 6-minute walking tests, both groups at the end of the intervention program had increased their walking speed. Mean (SD) increase in the Pilates and physical therapy groups were 39.1 (78.3) and 25.3 (67.2) meters, respectively. There was no effect of group X time in all instrumented and clinical balance and gait measures. Pilates is a possible treatment option for people with multiple sclerosis in order to improve their walking and balance capabilities. However, this approach does not have any significant advantage over standardized physical therapy.

Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

PubMed

Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

2017-07-01

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

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.

Crying and suicidal, but not depressed. Pseudobulbar affect in multiple sclerosis successfully treated with valproic acid: Case report and literature review.

PubMed

Johnson, Bridgette; Nichols, Scott

2015-12-01

Pseudobulbar affect/emotional incontinence is a potentially disabling condition characterized by expressions of affect or emotions out of context from the normal emotional basis for those expressions. This condition can result in diagnostic confusion and unrelieved suffering when clinicians interpret the emotional expressions at face value. In addition, the nomenclature, etiology, and treatment for this condition remain unclear in the medical literature. We report the case of a 60-year-old woman with multiple sclerosis who was referred to an inpatient psychiatry unit with complaints of worsening depression along with hopelessness, characterized by unrelenting crying. Our investigation showed that her symptoms were caused by pseudobulbar affect/emotional incontinence stemming from multiple sclerosis. The patient's history of multiple sclerosis and the fact that she identified herself as depressed only because of her incessant crying suggested that her symptoms might be due to the multiple sclerosis rather than to a depressive disorder. Magnetic resonance imaging demonstrated a new plaque consistent with multiple sclerosis lateral to her corpus callosum. Her symptoms resolved completely within three days on valproic acid but returned after she was cross-tapered to dextromethorphan plus quinidine, which is the FDA-approved treatment for this condition. This case provides important additional information to the current literature on pseudobulbar affect/emotional incontinence. The existing literature suggests a selective serotonin reuptake inhibitor (SSRI) and dextromethorphan/quinidine (Nuedexta) as first-line treatments; however, our patient was taking an SSRI at the time of presentation without appreciable benefit, and her symptoms responded to valproic acid but not to the dextromethorphan/quinidine. In addition, the case and the literature review suggest that the current nomenclature for this constellation of symptoms can be misleading.

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.

Conflicting Role of Mycobacterium Species in Multiple Sclerosis

PubMed Central

Cossu, Davide; Yokoyama, Kazumasa; Hattori, Nobutaka

2017-01-01

Mycobacterium is a genus of aerobic and acid-fast bacteria, which include several pathogenic organisms that cause serious diseases in mammals. Previous studies have associated the immune response against mycobacteria with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system with unknown etiology. The role of mycobacteria in the pathological process has been controversial and often conflicting. We provide a detailed review of the mycobacteria that have been linked to MS over the last three decades, with a focus on Mycobacterium bovis bacille Calmette–Guérin vaccine for human and oral exposure to Mycobacterium avium subsp. paratuberculosis. We will also discuss the exposure and genetic susceptibility to mycobacterial infection, the protective role of vaccination, as well as the possible mechanisms involved in initiating or worsening MS symptoms, with particular emphasis on the molecular mimicry between mycobacterial and human proteins. Finally, we will introduce topics such as heat shock proteins and recognition by innate immunity, and toll-like receptor signaling-mediated responses to Mycobacterium exposure. PMID:28579973

[Recommendations for the clinical use of motor evoked potentials in multiple sclerosis].

PubMed

Fernández, V; Valls-Sole, J; Relova, J L; Raguer, N; Miralles, F; Dinca, L; Taramundi, S; Costa-Frossard, L; Ferrandiz, M; Ramió-Torrentà, Ll; Villoslada, P; Saiz, A; Calles, C; Antigüedad, A; Alvarez-Cermeño, J C; Prieto, J M; Izquierdo, G; Montalbán, X; Fernández, O

2013-09-01

To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Achievements and obstacles of remyelinating therapies in multiple sclerosis.

PubMed

Stangel, Martin; Kuhlmann, Tanja; Matthews, Paul M; Kilpatrick, Trevor J

2017-12-01

Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials. However, trial design faces several obstacles: optimal clinical or paraclinical outcome measures to assess remyelination remain ill-defined, and identification of the ideal timing of therapy is also a crucial issue. In addition, realistic expectations are needed concerning the probable benefits of such therapies. Nevertheless, approaches that enhance remyelination are likely to be protective for axons and so could prevent long-term neurodegeneration. Future MS treatment paradigms, therefore, are likely to comprise a combinatorial approach that involves both immunomodulatory and regenerative treatments.

The analysis of correlation between IL-1B gene expression and genotyping in multiple sclerosis patients.

PubMed

Heidary, Masoumeh; Rakhshi, Nahid; Pahlevan Kakhki, Majid; Behmanesh, Mehrdad; Sanati, Mohammad Hossein; Sanadgol, Nima; Kamaladini, Hossein; Nikravesh, Abbas

2014-08-15

IL-1B is released by monocytes, astrocytes and brain endothelial cells and seems to be involved in inflammatory reactions of the central nervous system (CNS) in multiple sclerosis (MS). This study aims to evaluate the expression level of IL-1B mRNA in peripheral blood mononuclear cells (PBMCs), genotype the rs16944 SNP and find out the role of this SNP on the expression level of IL-1B in MS patients. We found that the expression level of IL-1B in MS patients increased 3.336 times more than controls in PBMCs but the rs16944 SNP in the promoter region of IL-1B did not affect the expression level of this gene and there was not association of this SNP with MS in the examined population. Also, our data did not reveal any correlation between normalized expressions of IL-1B gene with age of participants, age of onset, and disease duration. Copyright © 2014 Elsevier B.V. All rights reserved.

G protein-coupled receptors as therapeutic targets for multiple sclerosis

PubMed Central

Du, Changsheng; Xie, Xin

2012-01-01

G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. They are considered as the most successful therapeutic targets for a broad spectrum of diseases. Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). It is the leading cause of non-traumatic disability in young adults. Great progress has been made over the past few decades in understanding the pathogenesis of MS. Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis, including antigen presentation, cytokine production, T-cell differentiation, T-cell proliferation, T-cell invasion, etc. In this review, we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models, and the influences of GPCRs on disease severity upon genetic or pharmacological manipulations. Hopefully some of these findings will lead to the development of novel therapies for MS in the near future. PMID:22664908

Ambulatory rehabilitation in multiple sclerosis.

PubMed

Kelleher, Kevin John; Spence, William; Solomonidis, Stephan; Apatsidis, Dimitrios

2009-01-01

Multiple sclerosis (MS) is an autoimmunogenic disease involving demyelination within the central nervous system. Many of the typical impairments associated with MS can affect gait patterns. With walking ability being one of the most decisive factors when assessing quality of life and independent living, this review focuses on matters, which are considered of significance for maintaining and supporting ambulation. This article is an attempt to describe current research and available interventions that the caring healthcare professional can avail of and to review the present trends in research to further these available options. Evidence-based rehabilitation techniques are of interest in the care of patients with MS, given the various existing modalities of treatment. In this review, we summarise the primary factors affecting ambulation and highlight available treatment methods. We review studies that have attempted to characterise gait deficits within this patient population. Finally, as ambulatory rehabilitation requires multidisciplinary interventions, we examine approaches, which may serve to support and maintain ambulation within this patient group for as long as possible.

Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy.

PubMed

Forte, Giovanni; Bocca, Beatrice; Oggiano, Riccardo; Clemente, Simonetta; Asara, Yolande; Sotgiu, Maria Alessandra; Farace, Cristiano; Montella, Andrea; Fois, Alessandro Giuseppe; Malaguarnera, Michele; Pirina, Pietro; Madeddu, Roberto

2017-09-01

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration.

Failure to detect genomic material of HTLV-I or HTLV-II in mononuclear cells of Italian patients with multiple sclerosis and chronic progressive myelopathy.

PubMed

Merelli, E; Sola, P; Marasca, R; Salati, R; Torelli, G

1993-01-01

To contribute to the undecided question if a retrovirus of the human T-cell lymphotropic virus (HTLV) family may be involved in the development of multiple sclerosis (MS), we investigated by the polymerase chain reaction (PCR) the presence of HTLV-I and HTLV-II sequences in the peripheral blood mononuclear cell DNAs from 30 patients affected by MS and 15 by chronic progressive myelopathy. Moreover a control group of 14 blood donors was examined. All these patients were devoid of anti-HTLV-I antibody in the serum and cerebrospinal fluid at ELISA. For the PCR, primers and probes specific for the tax region common to HTLV-I and HTLV-II, for the pol region of HTLV-I, and for the pol region of HTLV-II were used. In spite of the high sensitivity of the technique used, the three groups of subjects were negative for HTLV-I and HTLV-II genomic sequences.

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

Localized scleroderma and systemic sclerosis: is there a connection?

PubMed

Gupta, Rajnish A; Fiorentino, David

2007-12-01

Excess fibrosis of the skin is a clinical hallmark of both localized scleroderma and systemic sclerosis. Localized scleroderma is generally thought to be a skin-limited disease whereas systemic sclerosis can have a wide range of internal organ involvement. Recent data suggest that a subset of patients with juvenile localized scleroderma can go on to develop systemic involvement of their disease. This raises the question of what the connection is, if any, between localized scleroderma and systemic sclerosis.

The effectiveness of music as a mnemonic device on recognition memory for people with multiple sclerosis.

PubMed

Moore, Kimberly Sena; Peterson, David A; O'Shea, Geoffrey; McIntosh, Gerald C; Thaut, Michael H

2008-01-01

Research shows that people with multiple sclerosis exhibit learning and memory difficulties and that music can be used successfully as a mnemonic device to aid in learning and memory. However, there is currently no research investigating the effectiveness of music mnemonics as a compensatory learning strategy for people with multiple sclerosis. Participants with clinically definitive multiple sclerosis (N = 38) were given a verbal learning and memory test. Results from a recognition memory task were analyzed that compared learning through music (n = 20) versus learning through speech (n = 18). Preliminary baseline neuropsychological data were collected that measured executive functioning skills, learning and memory abilities, sustained attention, and level of disability. An independent samples t test showed no significant difference between groups on baseline neuropsychological functioning or on recognition task measures. Correlation analyses suggest that music mnemonics may facilitate learning for people who are less impaired by the disease. Implications for future research are discussed.

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.

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

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.

Motivational and Volitional Variables Associated with Stages of Change for Exercise in Multiple Sclerosis: A Multiple Discriminant Analysis

ERIC Educational Resources Information Center

Chiu, Chung-Yi; Fitzgerald, Sandra D.; Strand, David M.; Muller, Veronica; Brooks, Jessica; Chan, Fong

2012-01-01

The main objective of this study was to determine whether motivational and volitional variables identified in the health action process approach (HAPA) model can be used to successfully differentiate people with multiple sclerosis (MS) in different stages of change for exercise and physical activity. Ex-post-facto design using multiple…

Cognitive Rehabilitation for Attention and Memory in people with Multiple Sclerosis: study protocol for a randomised controlled trial (CRAMMS).

PubMed

Lincoln, Nadina B; das Nair, Roshan; Bradshaw, Lucy; Constantinescu, Cris S; Drummond, Avril E R; Erven, Alexandra; Evans, Amy L; Fitzsimmons, Deborah; Montgomery, Alan A; Morgan, Miriam

2015-12-08

People with multiple sclerosis have problems with memory and attention. Cognitive rehabilitation is a structured set of therapeutic activities designed to retrain an individual's memory and other cognitive functions. Cognitive rehabilitation may be provided to teach people strategies to cope with these problems, in order to reduce the impact on everyday life. The effectiveness of cognitive rehabilitation for people with multiple sclerosis has not been established. This is a multi-centre, randomised controlled trial investigating the clinical and cost-effectiveness of a group-based cognitive rehabilitation programme for attention and memory problems for people with multiple sclerosis. Four hundred people with multiple sclerosis will be randomised from at least four centres. Participants will be eligible if they have memory problems, are 18 to 69 years of age, are able to travel to attend group sessions and give informed consent. Participants will be randomised in a ratio of 6:5 to the group rehabilitation intervention plus usual care or usual care alone. Intervention groups will receive 10 weekly sessions of a manualised cognitive rehabilitation programme. The intervention will include both restitution strategies to retrain impaired attention and memory functions and compensation strategies to enable participants to cope with their cognitive problems. All participants will receive a follow-up questionnaire and an assessment by a research assistant at 6 and 12 months after randomisation. The primary outcome is the Multiple Sclerosis Impact Scale (MSIS) Psychological subscale at 12 months. Secondary outcomes include the Everyday Memory Questionnaire, General Health Questionnaire-30, EQ-5D and a service use questionnaire from participants, and the Everyday Memory Questionnaire-relative version and Carer Strain Index from a relative or friend. The primary analysis will be based on intention to treat. A mixed-model regression analysis of the MSIS Psychological subscale at 12 months will be used to estimate the effect of the group cognitive rehabilitation programme. The study will provide evidence regarding the clinical and cost-effectiveness of a group-based cognitive rehabilitation programme for attention and memory problems in people with multiple sclerosis. ISRCTN09697576 . Registered 14 August 2014.

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

Uhthoff`s phenomenon 125 years later - what do we know today?

PubMed Central

Opara, JA; Brola, W; Wylegala, AA; Wylegala, E

2016-01-01

125 years have passed since Wilhelm Uhthoff reported the symptoms he observed after an increased body temperature from physical exertion. Those symptoms, which might have led to the transient impairment of vision in patients with Multiple Sclerosis and also observed in optic neuritis, were later named after him "Uhthoff's phenomenon". This has defined the strategy of rehabilitation procedures in Multiple Sclerosis for more than 100 years, restricting the use of thermal treatments and the possibility of aerobic exercises. The current state of knowledge concerning the Uhthoff's phenomenon and its influence on comprehensive rehabilitation in Multiple Sclerosis were presented in the current review report. PMID:27974923

Management of Fatigue in Persons with Multiple Sclerosis

PubMed Central

Khan, Fary; Amatya, Bhasker; Galea, Mary

2014-01-01

Fatigue is one of the most common symptoms of multiple sclerosis. Despite advances in pharmacological and non-pharmacological treatment, fatigue continues to be the disabling symptom in persons with MS (pwMS), affecting almost 80% of pwMS. In current practice, both pharmacological and non-pharmacological interventions are used in combination, encompassing a multi-disciplinary approach. The body of research investigating the effect of these interventions is growing. This review systematically evaluated the existing evidence on the effectiveness and safety of different interventions currently applied for the management of fatigue in person with multiple sclerosis in improving patient outcomes, to guide treating clinicians. PMID:25309504

Multiple Sclerosis in the Contemporary Age: Understanding the Millennial Patient with Multiple Sclerosis to Create Next-Generation Care.

PubMed

Hansen, Madison R; Okuda, Darin T

2018-02-01

The average age of onset of multiple sclerosis (MS) is between 20 and 40 years of age. Therefore, most new patients diagnosed with MS within the next 10 to 15 years will be from the millennial generation, representing those born between 1982 and 2000. Certain preferences and trends of this contemporary generation will present new challenges to the MS physician and effective MS care. By first understanding these challenges, relevant and successful solutions can be created to craft a system of care that best benefits the millennial patient with MS. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

Prevalence of multiple sclerosis in Lanzarote (Canary Islands)

PubMed

Garcia, J R; Rodriguez, S; Sosa Henriquez, M; Batista, E; Corujo, E; Font de Mora Turon, A; Hernandez Hernandez, D; Betancor Leon, P

1989-02-01

In the island of Lanzarote of the Province of Las Palmas, which is part of the Spanish archipelago of the Canary Islands, the prevalence of multiple sclerosis is 15 per 100,000. The prevalence of MS in Lanzarote seems related more to ethnic conditions than to geography.

Clinical Practice Improvement Approach in Multiple Sclerosis Rehabilitation: A Pilot Study

ERIC Educational Resources Information Center

Khan, Fary

2010-01-01

The objective of this study was to explore methods examining patient complexity and therapy interventions in relation to functional outcomes from an inpatient multiple sclerosis (MS) rehabilitation program. Retrospective and prospective data for 24 consecutive inpatients at a tertiary rehabilitation facility assessed (i)…

Determinants of Employment Status among People with Multiple Sclerosis.

ERIC Educational Resources Information Center

Roessler, Richard T.; Fitzgerald, Shawn M.; Rumrill, Phillip D.; Koch, Lynn C.

2001-01-01

Identifies factors predicting employment or lack thereof among adults with multiple sclerosis (MS). Results included the following variables as the best predictors of employment: symptom persistence, severity of symptoms, educational attainment, and presence of cognitive limitations. The relevance of the findings for rehabilitation assessment and…

An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis.

PubMed

Brown, J William L; Pardini, Matteo; Brownlee, Wallace J; Fernando, Kryshani; Samson, Rebecca S; Prados Carrasco, Ferran; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2017-02-01

In established multiple sclerosis, tissue abnormality-as assessed using magnetization transfer ratio-increases close to the lateral ventricles. We aimed to determine whether or not (i) these changes are present from the earliest clinical stages of multiple sclerosis; (ii) they occur independent of white matter lesions; and (iii) they are associated with subsequent conversion to clinically definite multiple sclerosis and disability. Seventy-one subjects had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (49 females, mean age 33.5 years) and were followed up clinically 2 and 5 years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter, magnetization transfer ratio gradients were measured 1-5 mm and 6-10 mm from the lateral ventricles. In control subjects, magnetization transfer ratio was highest adjacent to the ventricles and decreased with distance from them; in optic neuritis, normal-appearing white matter magnetization transfer ratio was lowest adjacent to the ventricles, increased over the first 5 mm, and then paralleled control values. The magnetization transfer ratio gradient over 1-5 mm differed significantly between the optic neuritis and control groups [+0.059 percentage units/mm (pu/mm) versus -0.033 pu/mm, P = 0.010], and was significantly steeper in those developing clinically definite multiple sclerosis within 2 years compared to those who did not (0.132 pu/mm versus 0.016 pu/mm, P = 0.020). In multivariate binary logistic regression the magnetization transfer ratio gradient was independently associated with the development of clinically definite multiple sclerosis within 2 years (magnetization transfer ratio gradient odds ratio 61.708, P = 0.023; presence of T 2 lesions odds ratio 8.500, P = 0.071). At 5 years, lesional measures overtook magnetization transfer ratio gradients as significant predictors of conversion to multiple sclerosis. The magnetization transfer ratio gradient was not significantly affected by the presence of brain lesions [T 2 lesions (P = 0.918), periventricular T 2 lesions (P = 0.580) or gadolinium-enhancing T 1 lesions (P = 0.724)]. The magnetization transfer ratio gradient also correlated with Expanded Disability Status Scale score 5 years later (Spearman r = 0.313, P = 0.027). An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis, is clinically relevant, and may arise from one or more mechanisms that are at least partly independent of lesion formation. © 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.

An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis

PubMed Central

Brown, J William L; Pardini, Matteo; Brownlee, Wallace J; Fernando, Kryshani; Samson, Rebecca S; Prados Carrasco, Ferran; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2017-01-01

Abstract In established multiple sclerosis, tissue abnormality—as assessed using magnetization transfer ratio—increases close to the lateral ventricles. We aimed to determine whether or not (i) these changes are present from the earliest clinical stages of multiple sclerosis; (ii) they occur independent of white matter lesions; and (iii) they are associated with subsequent conversion to clinically definite multiple sclerosis and disability. Seventy-one subjects had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (49 females, mean age 33.5 years) and were followed up clinically 2 and 5 years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter, magnetization transfer ratio gradients were measured 1–5 mm and 6–10 mm from the lateral ventricles. In control subjects, magnetization transfer ratio was highest adjacent to the ventricles and decreased with distance from them; in optic neuritis, normal-appearing white matter magnetization transfer ratio was lowest adjacent to the ventricles, increased over the first 5 mm, and then paralleled control values. The magnetization transfer ratio gradient over 1–5 mm differed significantly between the optic neuritis and control groups [+0.059 percentage units/mm (pu/mm) versus −0.033 pu/mm, P = 0.010], and was significantly steeper in those developing clinically definite multiple sclerosis within 2 years compared to those who did not (0.132 pu/mm versus 0.016 pu/mm, P = 0.020). In multivariate binary logistic regression the magnetization transfer ratio gradient was independently associated with the development of clinically definite multiple sclerosis within 2 years (magnetization transfer ratio gradient odds ratio 61.708, P = 0.023; presence of T2 lesions odds ratio 8.500, P = 0.071). At 5 years, lesional measures overtook magnetization transfer ratio gradients as significant predictors of conversion to multiple sclerosis. The magnetization transfer ratio gradient was not significantly affected by the presence of brain lesions [T2 lesions (P = 0.918), periventricular T2 lesions (P = 0.580) or gadolinium-enhancing T1 lesions (P = 0.724)]. The magnetization transfer ratio gradient also correlated with Expanded Disability Status Scale score 5 years later (Spearman r = 0.313, P = 0.027). An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis, is clinically relevant, and may arise from one or more mechanisms that are at least partly independent of lesion formation. PMID:28043954

The Swedish version of the Acceptance of Chronic Health Conditions Scale for people with multiple sclerosis: Translation, cultural adaptation and psychometric properties.

PubMed

Forslin, Mia; Kottorp, Anders; Kierkegaard, Marie; Johansson, Sverker

2016-11-11

To translate and culturally adapt the Acceptance of Chronic Health Conditions (ACHC) Scale for people with multiple sclerosis into Swedish, and to analyse the psychometric properties of the Swedish version. Ten people with multiple sclerosis participated in translation and cultural adaptation of the ACHC Scale; 148 people with multiple sclerosis were included in evaluation of the psychometric properties of the scale. Translation and cultural adaptation were carried out through translation and back-translation, by expert committee evaluation and pre-test with cognitive interviews in people with multiple sclerosis. The psychometric properties of the Swedish version were evaluated using Rasch analysis. The Swedish version of the ACHC Scale was an acceptable equivalent to the original version. Seven of the original 10 items fitted the Rasch model and demonstrated ability to separate between groups. A 5-item version, including 2 items and 3 super-items, demonstrated better psychometric properties, but lower ability to separate between groups. The Swedish version of the ACHC Scale with the original 10 items did not fit the Rasch model. Two solutions, either with 7 items (ACHC-7) or with 2 items and 3 super-items (ACHC-5), demonstrated acceptable psychometric properties. Use of the ACHC-5 Scale with super-items is recommended, since this solution adjusts for local dependency among items.

Systematic framework to evaluate the status of physical activity research for persons with multiple sclerosis.

PubMed

Dixon-Ibarra, Alicia; Vanderbom, Kerri; Dugala, Anisia; Driver, Simon

2014-04-01

Exploring the current state of health behavior research for individuals with multiple sclerosis is essential to understanding the next steps required to reducing preventable disability. A way to link research to translational health promotion programs is by utilizing the Behavioral Epidemiological Framework, which describes a sequence of phases used to categorize health-related behavioral research. This critical audit of the literature examines the current state of physical activity research for persons with multiple sclerosis by utilizing the proposed Behavioral Epidemiological Framework. After searching MEDLINE, PUBMED, PsycINFO, Google Scholar and several major areas within EBSCOHOST (2000 to present), retrieved articles were categorized according to the framework phases and coding rules. Of 139 articles, 49% were in phase 1 (establishing links between behavior and health), 18% phase 2 (developing methods for measuring behavior), 24% phase 3 (identifying factors influencing behavior and implications for theory), and 9% phase 4 and 5 (evaluating interventions to change behavior and translating research into practice). Emphasis on phase 1 research indicates the field is in its early stages of development. Providing those with multiple sclerosis with necessary tools through health promotion programs is needed to reduce secondary conditions and co-morbidities. Reassessment of the field of physical activity and multiple sclerosis in the future could provide insight into whether the field is evolving over time or remaining stagnant. Published by Elsevier Inc.

The development of an observational screening tool to assess safe, effective and appropriate walking aid use in people with multiple sclerosis.

PubMed

Eitzen, Abby; Finlayson, Marcia; Carolan-Laing, Leanne; Nacionales, Arthur Junn; Walker, Christie; O'Connor, Josephine; Asano, Miho; Coote, Susan

2017-08-01

The purpose of this study was to identify potential items for an observational screening tool to assess safe, effective and appropriate walking aid use among people with multiple sclerosis (MS). Such a tool is needed because of the association between fall risk and mobility aid use in this population. Four individuals with MS were videotaped using a one or two straight canes, crutches or a rollator in different settings. Seventeen health care professionals from Canada, Ireland and the United States were recruited, and viewed the videos, and were then interviewed about the use of the devices by the individuals in the videos. Interview questions addressed safety, effectiveness and appropriateness of the device in the setting. Data were analyzed qualitatively. Coding consistency across raters was evaluated and confirmed. Nineteen codes were identified as possible items for the screening tool. The most frequent issues raised regardless of setting and device were "device used for duration/abandoned", "appropriate device", "balance and stability", "device technique", "environmental modification" and "hands free." With the identification of a number of potential tool items, researchers can now move forward with the development of the tool. This will involve consultation with both healthcare professionals and people with MS. Implications for rehabilitation Falls among people with multiple sclerosis are associated with mobility device use and use of multiple devices is associated with greater falls risk. The ability to assess for safe, effective and efficient use of walking aids is therefore important, no tools currently exist for this purpose. The codes arising from this study will be used to develop a screening tool for safe, effective and efficient walking aid use with the aim of reducing falls risk.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

PubMed Central

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

2011-01-01

Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

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.

Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone.

PubMed

Ludwig, Michael D; Zagon, Ian S; McLaughlin, Patricia J

2017-09-01

Low-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met 5 ]-enkephalin) facilitating interactions between opioid growth factor and opioid growth factor receptor that ultimately, result in inhibited cell proliferation. Preclinical studies have reported that enkephalin levels are deficient in animal models of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our hypothesis is that serum enkephalin levels are diminished in humans with multiple sclerosis and experimental autoimmune encephalomyelitis mice, and that change in serum opioid growth factor levels may serve as a reasonable candidate biomarker for the onset of experimental autoimmune encephalomyelitis and response to therapy. To address this, we designed a two-part study to measure endogenous opioids in multiple sclerosis patients, and to investigate the temporal pattern of decline in serum enkephalin concentrations in mice with chronic progressive experimental autoimmune encephalomyelitis and treated with low-dose naltrexone. For comparison, we investigated whether low-dose naltrexone exposure in normal mice also resulted in altered enkephalin levels. In both animal models, we monitored tactile and heat sensitivity, as well as differential white blood cell counts as indicators of inflammation. Serum [Met 5 ]-enkephalin levels were lower in humans with multiple sclerosis relative to non-multiple sclerosis patients, and low-dose naltrexone restored their levels. In experimental autoimmune encephalomyelitis mice, [Met 5 ]-enkephalin levels were depressed prior to the appearance of clinical disease, and were restored with low-dose naltrexone treatment. Low-dose naltrexone therapy had no effect on serum [Met 5 ]-enkephalin or β-endorphin in normal mice. Thus, [Met 5 ]-enkephalin (i.e. opioid growth factor) may be a reasonable candidate biomarker for multiple sclerosis, and may signal new pathways for treatment of autoimmune disorders. Impact statement This report presents human and animal data identifying a novel biomarker for the onset and progression of multiple sclerosis (MS). Humans diagnosed with MS have reduced serum levels of OGF (i.e. [Met 5 ]-enkephalin) relative to non-MS neurologic patients, and low-dose naltrexone (LDN) therapy restored their enkephalin levels. Serum OGF levels were reduced in mice immunized with MOG 35-55 prior to any clinical behavioral sign of experimental autoimmune encephalomyelitis, and LDN therapy restored their serum OGF levels. β-endorphin concentrations were not altered by LDN in humans or mice. Thus, blood levels of OGF may serve as a new, selective biomarker for the progression of MS, as well as response to therapy.

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement In systemic sclerosis

PubMed Central

Kumar, Sumit; Singh, Jagmohan; Rattan, Satish; DiMarino, Anthony J; Cohen, Sidney; Jimenez, Sergio A.

2017-01-01

SUMMARY Background Gastrointestinal tract involvement is a common cause of debilitating symptoms in patients with systemic sclerosis. There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. Aim To investigate novel aspects of the pathogenesis of gastrointestinal involvement in systemic sclerosis To summarize existing knowledge regarding the cardinal clinical gastrointestinal manifestations of systemic sclerosis and its pathogenesis, emphasizing recent investigations that may be valuable in identifying potentially novel therapeutic targets. Methods Electronic (Pubmed/Medline) and manual Google search Results The gastrointestinal tract is the most common internal organ involved in systemic sclerosis. Any part of the gastrointestinal tract from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are non-specific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the in the absence of cutaneous disease. Up to 8% of systemic sclerosis patients develop severe gastrointestinal tract symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the gastrointestinal tract causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of gastrointestinal tract dysmotility mediated by functional anti-muscarinic receptor autoantibodies. Conclusion Despite extensive investigation the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions. PMID:28185291

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.

Cytokines in Alzheimer's disease and multiple sclerosis.

PubMed

Patterson, P H

1995-10-01

Cytokines are well known as mediators of inflammation, and recent work has highlighted the role of these agents and inflammatory events in Alzheimer's disease and multiple sclerosis. The discovery of subclasses of T-helper cells has provided a critical framework to aid in understanding how the cytokine network regulates these diseases.

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)

Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

ERIC Educational Resources Information Center

Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

2002-01-01

Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

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…

Childhood Multiple Sclerosis: A Review

ERIC Educational Resources Information Center

Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan

2006-01-01

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when…

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders

DTIC Science & Technology

2004-01-01

phosphorylation was found mainly in microvessels and astrocytes.. B. Dysfunction 1. Multiple Sclerosis, Canine Distemper and EAE In order to initiate the...astrocytes is seen in canine distemper encephalitis, a demyelinating disease in dogs that closely resembles multiple sclerosis and is caused by a virus

Role of Snf5 Mutations in Schwannomatosis Pain

DTIC Science & Technology

2016-10-01

National Multiple Sclerosis Society • Name: • Fatima Banine • Project Role: • Staff Scientist • Researcher Identifier (e.g. ORCID ID...and the subsequent data analysis and validation assays (e.g. qPCR) • Funding Support: • National Multiple Sclerosis Society • Name: • Scott...40,000 individuals worldwide. The disease is characterized by multiple peripheral nerve tumors, called schwannomas, and a predisposition to other

Melorheostosis with bilateral involvement in a black African patient.

PubMed

Biaou, Olivier; Avimadje, Martin; Guira, Oumar; Adjagba, Alex; Zannou, Marcel; Hauzeur, Jean-Philippe

2004-01-01

Melorheostosis is a rare chronic bone disease of unknown etiology that often affects a single limb. Onset usually occurs in childhood or early adolescence. A flowing wax appearance along the surface of the bone and multiple areas of bone sclerosis produce a typical radiographic picture. We describe the first case reported in a black African, in whom an exceedingly rare feature was a bilateral distribution of the lesions.

Robot training of upper limb in multiple sclerosis: comparing protocols with or without manipulative task components.

PubMed

Carpinella, Ilaria; Cattaneo, Davide; Bertoni, Rita; Ferrarin, Maurizio

2012-05-01

In this pilot study, we compared two protocols for robot-based rehabilitation of upper limb in multiple sclerosis (MS): a protocol involving reaching tasks (RT) requiring arm transport only and a protocol requiring both objects' reaching and manipulation (RMT). Twenty-two MS subjects were assigned to RT or RMT group. Both protocols consisted of eight sessions. During RT training, subjects moved the handle of a planar robotic manipulandum toward circular targets displayed on a screen. RMT protocol required patients to reach and manipulate real objects, by moving the robotic arm equipped with a handle which left the hand free for distal tasks. In both trainings, the robot generated resistive and perturbing forces. Subjects were evaluated with clinical and instrumental tests. The results confirmed that MS patients maintained the ability to adapt to the robot-generated forces and that the rate of motor learning increased across sessions. Robot-therapy significantly reduced arm tremor and improved arm kinematics and functional ability. Compared to RT, RMT protocol induced a significantly larger improvement in movements involving grasp (improvement in Grasp ARAT sub-score: RMT 77.4%, RT 29.5%, p=0.035) but not precision grip. Future studies are needed to evaluate if longer trainings and the use of robotic handles would significantly improve also fine manipulation.

SncRNA (microRNA & snoRNA) opposite expression pattern found in multiple sclerosis relapse and remission is sex dependent

PubMed Central

Muñoz-Culla, Maider; Irizar, Haritz; Sáenz-Cuesta, Matías; Castillo-Triviño, Tamara; Osorio-Querejeta, Iñaki; Sepúlveda, Lucía; López de Munain, Adolfo; Olascoaga, Javier; Otaegui, David

2016-01-01

Multiple sclerosis (MS) is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes of neurological disability (relapses) followed by a recovery phase (remission). Recently, non-coding RNAs have emerged as new players in transcriptome regulation, and in turn, they could have a significant role in MS pathogenesis. In this context, our aim was to investigate the involvement of microRNAs and snoRNAs in the relapse-remission dynamics of MS in peripheral blood leucocytes, to shed light on the molecular and regulatory mechanisms that underlie this complex process. With this approach, we found that a subset of small non-coding RNAs (sncRNA) is altered in relapse and remission, revealing unexpected opposite changes that are sex dependent. Furthermore, we found that a relapse-related miRNA signature regulated general metabolism processes in leucocytes, and miRNA altered in remission are involved in the regulation of innate immunity. We observed that sncRNA dysregulation is different in relapse and remission leading to differences in transcriptome regulation, and that this process is sex dependent. In conclusion, relapse and remission have a different molecular background in men and women. PMID:26831009

Class II HLA interactions modulate genetic risk for multiple sclerosis

PubMed Central

Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

2016-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

PubMed Central

Volpe, Elisabetta; Sambucci, Manolo; Battistini, Luca; Borsellino, Giovanna

2016-01-01

Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas–FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas–FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas–FasL in regulating Th17 and Treg cells’ functions, in the context of MS. PMID:27729910

Fas-Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis.

PubMed

Volpe, Elisabetta; Sambucci, Manolo; Battistini, Luca; Borsellino, Giovanna

2016-01-01

Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas-FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas-FasL in regulating Th17 and Treg cells' functions, in the context of MS.

Multiple sclerosis patients need and want information on exercise promotion from healthcare providers: a qualitative study.

PubMed

Learmonth, Yvonne C; Adamson, Brynn C; Balto, Julia M; Chiu, Chung-Yi; Molina-Guzman, Isabel; Finlayson, Marcia; Riskin, Barry J; Motl, Robert W

2017-08-01

There is growing recognition of the benefits and safety of exercise and its importance in the comprehensive care of persons with multiple sclerosis (MS), yet uptake is low. We explored the needs and wants of patients with MS regarding exercise promotion through healthcare providers. Participants were adults with MS who had mild-or-moderate disability and a range of exercise levels. All participants lived in the Midwest of the United States. Fifty semi-structured interviews were conducted and analysed using thematic analysis. Two themes emerged, namely interactions between patients and healthcare providers and needs and wants of patients. Analysis of participant accounts illustrate that current exercise promotion by healthcare providers does not meet patient needs and wants. The identified needs and wants of persons with MS involved (i) information and knowledge on the benefits of exercise and exercise prescription, (ii) materials to allow home and community exercise and (iii) tools for initiating and maintaining exercise behaviour. Patients with MS frequently interact with healthcare providers and are generally unsatisfied with exercise promotion during interactions. Healthcare providers can address the low uptake of exercise among persons with MS by acting upon the identified unmet needs involving materials, knowledge and behaviour change strategies for exercise. © 2016 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Metabolomics: A potential way to know the role of vitamin D on multiple sclerosis.

PubMed

Luque-Córdoba, Diego; Luque de Castro, María D

2017-03-20

The literature about the influence of vitamin D on multiple sclerosis (MS) is very controversial, possibly as a result of the way through which the research on the subject has been conducted. The studies developed so far have been focused exclusively on gene expression: the effect of a given vitamin D metabolite on target receptors. The influence of the vitamin D status (either natural or after supplementation) on MS has been studied by measurement of the 25 monohydroxylated metabolite (also known as circulating form), despite the 1,25 dihydroxylated metabolite is considered the active form. In the light of the multiple metabolic pathways in which both forms of vitamin D (D 2 and D 3 ) are involved, monitoring of the metabolites is crucial to know the activity of the target enzymes as a function of both the state of the MS patient and the clinical treatment applied. The study of metabolomics aspects is here proposed to clarify the present controversy. In "omics" terms, our proposal is to take profit from up-stream information-thus is, from metabolomics to genomics-with a potential subsequent step to systems biology, if required. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

PubMed Central

Ortiz, Genaro G.; Pacheco-Moisés, Fermín P.; Bitzer-Quintero, Oscar K.; Ramírez-Anguiano, Ana C.; Flores-Alvarado, Luis J.; Ramírez-Ramírez, Viridiana; Macias-Islas, Miguel A.; Torres-Sánchez, Erandis D.

2013-01-01

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle. PMID:24174971

Symptomatic Therapy and Rehabilitation in Primary Progressive Multiple Sclerosis

PubMed Central

Khan, Fary; Amatya, Bhasker; Turner-Stokes, Lynne

2011-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system and a major cause of chronic neurological disability in young adults. Primary progressive MS (PPMS) constitutes about 10% of cases, and is characterized by a steady decline in function with no acute attacks. The rate of deterioration from disease onset is more rapid than relapsing remitting and secondary progressive MS types. Multiple system involvement at onset and rapid early progression have a worse prognosis. PPMS can cause significant disability and impact on quality of life. Recent studies are biased in favour of relapsing remitting patients as treatment is now available for them and they are more likely to be seen at MS clinics. Since prognosis for PPMS is worse than other types of MS, the focus of rehabilitation is on managing disability and enhancing participation, and application of a “neuropalliative” approach as the disease progresses. This chapter presents the symptomatic treatment and rehabilitation for persons with MS, including PPMS. A multidisciplinary approach optimizes the intermediate and long-term medical, psychological and social outcomes in this population. Restoration and maintenance of functional independence and societal reintegration, and issues relating to quality of life are addressed in rehabilitation processes. PMID:22013521

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

PubMed Central

Mahe, Julien; Meurette, Aurélie; Moreau, Anne; Vercel, Caroline; Jolliet, Pascale

2013-01-01

Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. PMID:23950639

Anxiety Levels Are Independently Associated With Cognitive Performance in an Australian Multiple Sclerosis Patient Cohort.

PubMed

Ribbons, Karen; Lea, Rodney; Schofield, Peter W; Lechner-Scott, Jeannette

2017-01-01

Neurological and psychological symptoms in multiple sclerosis can affect cognitive function. The objective of this study was to explore the relationship between psychological measures and cognitive performance in a patient cohort. In 322 multiple sclerosis patients, psychological symptoms were measured using the Depression Anxiety and Stress Scale, and cognitive function was evaluated using Audio Recorded Cognitive Screen. Multifactor linear regression analysis, accounting for all clinical covariates, found that anxiety was the only psychological measure to remain a significant predictor of cognitive performance (p<0.001), particularly memory function (p<0.001). Further prospective studies are required to determine whether treatment of anxiety improves cognitive impairment.

Construct validity and frequency of euphoria sclerotica in multiple sclerosis.

PubMed

Fishman, Inna; Benedict, Ralph H B; Bakshi, Rohit; Priore, Roger; Weinstock-Guttman, Bianca

2004-01-01

Using the Neuropsychiatric Inventory (NPI), we studied euphoria and other behavioral changes in 75 consecutive, unselected multiple sclerosis (MS) patients and 25 healthy controls. We also assessed disease duration, clinical course, physical disability, personality, depression, insight, cognition, and caregiver distress. Factor analysis identified a cluster of symptoms--labeled euphoria/disinhibition--similar to the euphoria sclerotica syndrome originally described by Charcot and others. The euphoria/disinhibition factor score was elevated in 9% of patients and associated with secondary-progressive course, low agreeableness, poor insight, impaired cognition, and high caregiver distress. Thus, we used the NPI to validate the euphoria syndrome in multiple sclerosis (MS) and determined its frequency, and its neurological and psychological correlates.

Exploring Wellness Interventions in Progressive Multiple Sclerosis: an Evidence-Based Review.

PubMed

Venasse, Myriam; Edwards, Thomas; Pilutti, Lara A

2018-04-10

There has been recent interest in the role of lifestyle and wellness-based approaches in the treatment and management of multiple sclerosis (MS). These approaches may be particularly relevant for patients with progressive MS, considering limited therapeutic options currently available. The purpose of this review is to examine the role of wellness-based interventions including exercise training, emotional well-being therapies, and dietary modification in patients with progressive MS. We conducted a literature search on the efficacy of wellness-based interventions in patients with progressive MS published between 1985 and July 2017. The level of evidence for each trial was evaluated using the American Academy of Neurology criteria. Overall, 21 articles reporting on 16 wellness-based interventions were identified: ten trials involved exercise training, three involved emotional wellness therapies, two involved dietary modification, and one was a combined wellness intervention. There is level C evidence (possibly effective; one class II study) for the efficacy of aerobic exercise training on cardiorespiratory fitness in patients with progressive MS. There is level B evidence (probably effective; one class I study) for the efficacy of mindfulness training on psychological distress, depression, anxiety, pain, and quality of life in patients with progressive MS. There is inadequate evidence (level U) for efficacy of dietary modification (one class III study and one class IV study) and combined wellness interventions involving exercise training, meditation, and dietary modification (one class IV study). High-quality research is needed to provide evidence-based recommendations for wellness behaviors and lifestyle change in patients with progressive MS.

Evaluation of lithium serum level in multiple sclerosis patients: A neuroprotective element.

PubMed

Karimi, Atieh; Bahrampour, Kobra; Momeni Moghaddam, Mohammad Amin; Asadikaram, Gholamreza; Ebrahimi, Ghasem; Torkzadeh-Mahani, Masoud; Esmaeili Tarzi, Mojdeh; Nematollahi, Mohammad Hadi

2017-10-01

It has been claimed that continuous and high production of nitric oxide (NO) and its metabolites may be involved in the pathogenesis of several neurological disorders such as multiple sclerosis. A number of studies have demonstrated that lithium regulates NO levels in disorders of the central nervous system. The aim of this study was to investigate whether NO as a marker of disease activity is correlated with lithium deficiency in relapsing remitting multiple sclerosis (RR-MS). This case-controlled study comprised 44 patients with RR-MS and 43 healthy subjects matched by age, gender, smoking status, and body mass index. The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in serum. In addition serum lithium levels were measured using atomic absorption spectrometry method. The mean serum NO concentrations in the groups RR-MS and the control were 18.5 ± 3.1µM and 15.5 ± 2.9µM, respectively. Data analysis showed a statistically significant difference between subjects with RR-MS and the control group (p < 0.05). Furthermore, serum lithium concentrations in RR-MS (0.57 ± 0.2) were remarkably lower in RR-MS patients than the controls (2.29 ± 0.7) (p < 0.05). The present findings suggest that lithium deficiency may upregulates NO production in RR-MS. Further studies with larger samples are needed to confirm the effects of lithium treatment on NO pathway and its association with synaptic plasticity in RR-MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Achieving patient engagement in multiple sclerosis: A perspective from the multiple sclerosis in the 21st Century Steering Group.

PubMed

Rieckmann, Peter; Boyko, Alexey; Centonze, Diego; Elovaara, Irina; Giovannoni, Gavin; Havrdová, Eva; Hommes, Otto; Kesselring, Jurg; Kobelt, Gisela; Langdon, Dawn; LeLorier, Jacques; Morrow, Sarah A; Oreja-Guevara, Celia; Schippling, Sven; Thalheim, Christoph; Thompson, Heidi; Vermersch, Patrick

2015-05-01

While advances in medicine, technology and healthcare services offer promises of longevity and improved quality of life (QoL), there is also increasing reliance on a patient׳s skills and motivation to optimize all the benefits available. Patient engagement in their own healthcare has been described as the 'blockbuster drug of the century'. In multiple sclerosis (MS), patient engagement is vital if outcomes for the patient, society and healthcare systems are to be optimized. The MS in the 21st Century Steering Group devised a set of themes that require action with regard to patient engagement in MS, namely: 1) setting and facilitating engagement by education and confidence-building; 2) increasing the importance placed on QoL and patient concerns through patient-reported outcomes (PROs); 3) providing credible sources of accurate information; 4) encouraging treatment adherence through engagement; and 5) empowering through a sense of responsibility. Group members independently researched and contributed examples of patient engagement strategies from several countries and examined interventions that have worked well in areas of patient engagement in MS, and other chronic illnesses. The group presents their perspective on these programs, discusses the barriers to achieving patient engagement, and suggests practical strategies for overcoming these barriers. With an understanding of the issues that influence patient engagement in MS, we can start to investigate ways to enhance engagement and subsequent health outcomes. Engaging patients involves a broad, multidisciplinary approach. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis

PubMed Central

Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Tabatabaei, Seyyed Mohammad; Namaki, Saeed

2016-01-01

Background The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein–protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease. Methods Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MS vs. control) and PBMCs (relapse vs. remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression. Results The networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapse vs. remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MS vs. control) and CDC37, MAP3K3, MYC genes in PBMCs (relapse vs. remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways. Discussion This study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets. PMID:28028462

Dextromethorphan/quinidine: in pseudobulbar affect.

PubMed

Garnock-Jones, Karly P

2011-05-01

Pseudobulbar affect is characterized by uncontrollable, inappropriate laughing and/or crying that is either unrelated or out of proportion to the emotions felt by the patient and occurs in patients with neurological disorders, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis or traumatic brain injury. Dextromethorphan/quinidine is indicated in the US for the treatment of pseudobulbar affect. Dextromethorphan, when its metabolism is inhibited by the coadministration of quinidine, has been shown to have a positive effect on the symptoms of pseudobulbar affect. Dextromethorphan/quinidine 20 mg/10 mg twice daily was associated with a significantly greater decrease in the rate of pseudobulbar affect episodes per day (primary endpoint) than placebo in the 12-week, randomized, double-blind, placebo-controlled, multicentre STAR trial (Safety, Tolerability, And efficacy Results trial of AVP-923 in PBA [pseudobulbar affect]) involving patients with pseudobulbar affect and ALS or multiple sclerosis. Moreover, the mean change from baseline in Center for Neurologic Study-Lability Scale score at 12 weeks was significantly greater among recipients of dextromethorphan/quinidine 20 mg/10 mg twice daily than those receiving placebo. Dextromethorphan/quinidine 20 mg/10 mg twice daily was generally well tolerated. The drug has been shown to cause dosage-dependent corrected QT interval (QTc) prolongation; however, in the STAR trial, dextromethorphan/quinidine 20 mg/10 mg twice daily appeared to be well tolerated with regard to QTc prolongation.

Effect of intermittent versus daily calorie restriction on changes in weight and patient reported outcomes in people with multiple sclerosis

USDA-ARS?s Scientific Manuscript database

An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding stud...

Content Validity of the Comprehensive ICF Core Set for Multiple Sclerosis from the Perspective of Speech and Language Therapists

ERIC Educational Resources Information Center

Renom, Marta; Conrad, Andrea; Bascuñana, Helena; Cieza, Alarcos; Galán, Ingrid; Kesselring, Jürg; Coenen, Michaela

2014-01-01

Background: The Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for Multiple Sclerosis (MS) is a comprehensive framework to structure the information obtained in multidisciplinary clinical settings according to the biopsychosocial perspective of the International Classification of Functioning,…

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…

Women Confronting the Reality of Multiple Sclerosis: A Qualitative Model of Self-Healing

ERIC Educational Resources Information Center

Romagosa, Carol J.

2010-01-01

Multiple sclerosis (MS) is a chronic debilitating disease that has an uncertain course. Although uncertainty is a universal experience in chronic illness, uncertainty in MS is especially threatening to psychological well-being. Chronic illness, including conditions of disability, is one of our greatest health care problems as society ages. Never…

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).…

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…