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.

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.

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

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

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…

Multiple sclerosis: Left advantage for auditory laterality in dichotic tests of central auditory processing and relationship of psychoacoustic tests with the Multiple Sclerosis Disability Scale-EDSS.

PubMed

Peñaloza López, Yolanda Rebeca; Orozco Peña, Xóchitl Daisy; Pérez Ruiz, Santiago Jesús

2018-04-03

To evaluate the central auditory processing disorders in patients with multiple sclerosis, emphasizing auditory laterality by applying psychoacoustic tests and to identify their relationship with the Multiple Sclerosis Disability Scale (EDSS) functions. Depression scales (HADS), EDSS, and 9 psychoacoustic tests to study CAPD were applied to 26 individuals with multiple sclerosis and 26 controls. Correlation tests were performed between the EDSS and psychoacoustic tests. Seven out of 9 psychoacoustic tests were significantly different (P<.05); right or left (14/19 explorations) with respect to control. In dichotic digits there was a left-ear advantage compared to the usual predominance of RDD. There was significant correlation in five psychoacoustic tests and the specific functions of EDSS. The left-ear advantage detected and interpreted as an expression of deficient influences of the corpus callosum and attention in multiple sclerosis should be investigated. There was a correlation between psychoacoustic tests and specific EDSS functions. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

Vision and vision-related outcome measures in multiple sclerosis

PubMed Central

Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

Prognostic factors for early severity in a childhood multiple sclerosis cohort.

PubMed

Mikaeloff, Yann; Caridade, Guillaume; Assi, Saada; Suissa, Samy; Tardieu, Marc

2006-09-01

The goal was to identify prognostic factors for an early severe course in a cohort of patients with childhood-onset multiple sclerosis, for the construction of a predictive tool. The cohort consisted of 197 children from the French Kid Sclérose en Plaques neuropediatric cohort with relapsing/remitting multiple sclerosis beginning before the age of 16 years. Patients were included from 1990 to 2003. We used multivariate survival analysis (Cox model) to evaluate the prognostic value of clinical, MRI, and biological covariates at onset for the occurrence of a third attack or severe disability ("severity" outcome). The cohort was monitored for a mean of 5.5 +/- 3.6 years. The "severity" outcome was recorded for 144 patients (73%). The risk of severity was higher for girls, for a time between the first and second attacks of < 1 year, for childhood-onset multiple sclerosis MRI criteria at onset, for an absence of severe mental state changes at onset, and for a progressive course. A derived childhood-onset multiple sclerosis potential index for early severity was found to have a positive predictive value for severity of > 35% for the upper 2 quartiles. The clinical and MRI prognostic factors for early severity that were identified were used as the basis of a predictive tool, which will be validated in another cohort. This tool should make it possible to identify subgroups at risk of early severe disease and should facilitate therapeutic studies.

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.

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…

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.

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

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.

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.

An ImmunoChip study of multiple sclerosis risk in African Americans

PubMed Central

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

2015-01-01

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

An ImmunoChip study of multiple sclerosis risk in African Americans.

PubMed

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

2015-06-01

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

The 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.

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

PubMed

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

2003-07-01

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

A 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.

Predictors of Employment Status for People with Multiple Sclerosis

ERIC Educational Resources Information Center

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

2004-01-01

This study examined the relevance of the disease-and-demographics model for explaining the employment outcomes of adults with multiple sclerosis (MS). Participating in a national survey of their employment concerns, 1,310 adults with MS provided data for the study (274 men, 21%; 1,020 women, 78%; 16 participants did not identify their gender).…

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

PubMed

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

2016-06-01

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

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.

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.

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.

Employment among Working-Age Adults with Multiple Sclerosis: A Data-Mining Approach to Identifying Employment Interventions

ERIC Educational Resources Information Center

Bishop, Malachy; Chan, Fong; Rumrill, Phillip D., Jr.; Frain, Michael P.; Tansey, Timothy N.; Chiu, Chung-Yi; Strauser, David; Umeasiegbu, Veronica I.

2015-01-01

Purpose: To examine demographic, functional, and clinical multiple sclerosis (MS) variables affecting employment status in a national sample of adults with MS in the United States. Method: The sample included 4,142 working-age (20-65 years) Americans with MS (79.1% female) who participated in a national survey. The mean age of participants was…

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.

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

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.

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.

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.

Dysregulation of NRXN1 by mutant MIR8485 leads to calcium overload in pre-synapses inducing neurodegeneration in Multiple sclerosis.

PubMed

Kattimani, Yogita; Veerappa, Avinash M

2018-04-09

To identify Damaging mutations in microRNAs (miRNAs) and 3' untranslated regions (UTRs) of target genes to establish Multiple sclerosis (MS) disease pathway. Female aged 16, with Relapsing Remitting Multiple sclerosis (RRMS) was reported with initial symptoms of blurred vision, severe immobility, upper and lower limb numbness and backache. Whole Exome Sequencing (WES) and disease pathway analysis was performed to identify mutations in miRNAs and UTRs. We identified Deleterious/Damaging multibase mutations in MIR8485 and NRXN1. miR-8485 was found carrying frameshift homozygous deletion of bases CA, while NRXN1 was found carrying nonframeshift homozygous substitution of bases CT to TC in exon 8 replacing Serine with Leucine. Mutations in miR-8485 and NRXN1 was found to alter calcium homeostasis and NRXN1/NLGN1 cell adhesion molecule binding affinities. The miR-8485 mutation leads to overexpression of NRXN1 altering pre-synaptic Ca 2+ homeostasis, inducing neurodegeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Evoked potentials in multiple sclerosis.

PubMed

Kraft, George H

2013-11-01

Before the development of magnetic resonance imaging (MRI), evoked potentials (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem auditory evoked responses-were commonly used to determine a second site of disease in patients being evaluated for possible multiple sclerosis (MS). The identification of an area of the central nervous system showing abnormal conduction was used to supplement the abnormal signs identified on the physical examination-thus identifying the "multiple" in MS. This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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

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.

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

PubMed

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

1999-04-01

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

[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.

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.

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

Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems

PubMed Central

Herrando-Grabulosa, Mireia; Mulet, Roger; Pujol, Albert; Mas, José Manuel; Navarro, Xavier; Aloy, Patrick; Coma, Mireia; Casas, Caty

2016-01-01

Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology), we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis. PMID:26807587

The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS).

PubMed

Alwan, Sura; Chambers, Christina D; Armenti, Vincent T; Sadovnick, A Dessa

2015-01-01

Multiple sclerosis (MS) is the most commonly acquired neurological disorder affecting young adults of reproductive age with an approximately 3:1 female to male ratio. Although pregnancy is not contraindicated in MS, data are limited regarding pregnancy outcome among MS patients, and the safety or risk to the fetus associated with most maternal MS treatments, such as disease modifying therapies (DMTs), during pregnancy is unknown. We review available epidemiological and registry data on MS and pregnancy and discuss the need to initiate a North American Multiple Sclerosis Pregnancy Registry that will prospectively identify pregnancies in women with MS, obtain information on the disease, and its treatment during gestation and lactation and follow the children to determine their health status. Copyright © 2014 Elsevier B.V. All rights reserved.

An update on MS Nurse PROfessional, an ongoing project of the European Multiple Sclerosis Platform.

PubMed

Winslow, Anne

2016-12-01

Within the multidisciplinary team required to manage people with multiple sclerosis (MS) effectively, the nurse is the central component of coordinated care and support. A 2009 survey led by the European Multiple Sclerosis Platform, an umbrella organization of national MS associations, identified variance and disparity across Europe in the nursing care of MS patients. This led to development of MS Nurse PROfessional, a continuing medical education-accredited modular online learning program endorsed and approved by leading international nursing and professional groups, and people with MS, as a tool to support the evolving role of the European MS nurse. Analysis of participant experience and nurse practice to date has been overwhelmingly positive. Expansion of MS Nurse PRO is underway or planned for future.

What multiple sclerosis could bring to cognitive neuroscience?

PubMed

Naccache, L

2009-01-01

The relevance of multiple sclerosis for cognitive neuroscience has evolved significantly during the last decades. After a relative and enduring disinterest, the 1980's has been marked by a first wave of studies aiming at characterizing the cognitive dysfunctions associated with this disease. Once identified, and grouped under the relatively vague and nonspecific concept of "subcorticofrontal syndrome", these cognitive symptoms had to wait until the end of the 1990's to give rise to a new and vigorous resurgence of attention. Interestingly, this genuine contemporary revival of interest originates in the promotion of the very same arguments that served until there to explain the weak investment of multiple sclerosis by neuropsychology and cognitive neuroscience. The early disseminated nature of brain lesions, their dynamic and unstable nature, the prevalence of white-matter lesions, and the alteration of non-modular aspects of cognition: all these arguments have discouraged neuropsychologists for a long time. Today, these very same specific properties of multiple sclerosis offer an extremely relevant model to explore cognitive dimensions of brain plasticity, to revivify the concept of disconnection in neuropsychology, and to evaluate some neuroscientific models of consciousness.

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.

Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla

PubMed Central

Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

2011-01-01

Previous authors have shown that the transverse relaxivity R2* and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a multiplicity of pathological processes. Hence, iron may have the unique potential to serve as an in vivo magnetic resonance imaging tracer of disease pathology. To investigate the ability of iron in tracking multiple sclerosis-induced pathology by magnetic resonance imaging, we performed qualitative histopathological analysis of white matter lesions and normal-appearing white matter regions with variable appearance on gradient echo magnetic resonance imaging at 7 Tesla. The samples used for this study derive from two patients with multiple sclerosis and one non-multiple sclerosis donor. Magnetic resonance images were acquired using a whole body 7 Tesla magnetic resonance imaging scanner equipped with a 24-channel receive-only array designed for tissue imaging. A 3D multi-gradient echo sequence was obtained and quantitative R2* and phase maps were reconstructed. Immunohistochemical stainings for myelin and oligodendrocytes, microglia and macrophages, ferritin and ferritin light polypeptide were performed on 3- to 5-µm thick paraffin sections. Iron was detected with Perl's staining and 3,3′-diaminobenzidine-tetrahydrochloride enhanced Turnbull blue staining. In multiple sclerosis tissue, iron presence invariably matched with an increase in R2*. Conversely, R2* increase was not always associated with the presence of iron on histochemical staining. We interpret this finding as the effect of embedding, sectioning and staining procedures. These processes likely affected the histopathological analysis results but not the magnetic resonance imaging that was obtained before tissue manipulations. Several cellular sources of iron were identified. These sources included oligodendrocytes in normal-appearing white matter and activated macrophages/microglia at the edges of white matter lesions. Additionally, in white matter lesions, iron precipitation in aggregates typical of microbleeds was shown by the Perl's staining. Our combined imaging and pathological study shows that multi-gradient echo magnetic resonance imaging is a sensitive technique for the identification of iron in the brain tissue of patients with multiple sclerosis. However, magnetic resonance imaging-identified iron does not necessarily reflect pathology and may also be seen in apparently normal tissue. Iron identification by multi-gradient echo magnetic resonance imaging in diseased tissues can shed light on the pathological processes when coupled with topographical information and patient disease history. PMID:22171355

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.

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.

Clustering Multiple Sclerosis Subgroups with Multifractal Methods and Self-Organizing Map Algorithm

NASA Astrophysics Data System (ADS)

Karaca, Yeliz; Cattani, Carlo

Magnetic resonance imaging (MRI) is the most sensitive method to detect chronic nervous system diseases such as multiple sclerosis (MS). In this paper, Brownian motion Hölder regularity functions (polynomial, periodic (sine), exponential) for 2D image, such as multifractal methods were applied to MR brain images, aiming to easily identify distressed regions, in MS patients. With these regions, we have proposed an MS classification based on the multifractal method by using the Self-Organizing Map (SOM) algorithm. Thus, we obtained a cluster analysis by identifying pixels from distressed regions in MR images through multifractal methods and by diagnosing subgroups of MS patients through artificial neural networks.

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

PubMed Central

Pauwels, Ine; Gustavsen, Marte W.; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D.; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D’Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A.; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H.; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G.; Gourraud, Pierre-Antoine; Sawcer, Stephen J.; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F.

2015-01-01

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants. PMID:25616667

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.

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.

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.

A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Gender as a prognostic factor and its impact on the incidence of multiple sclerosis in Lorraine, France.

PubMed

Debouverie, M

2009-11-15

We sought to identify (a) the change of incidence rates among gender from 1990 to 2002 from the LORSEP (Lorraine Multiple Sclerosis) population-based cohort, and (b) the role of gender as a predictive demographic factor of disability during the initial course of the disease among multiple sclerosis (MS) patients. The incidence rates of multiple sclerosis (MS) in Lorraine, France, have significantly increased in women, but not in men, from 1990 to 2002 but this increase in incidence of MS was not related to a better ascertainment of patients with mild disability. A total of 2871 MS patients were analyzed. For relapsing-remitting (RR) patients, a multivariate analysis showed that a shorter time to the assignment of an EDSS score of 3 and 4 was associated with the late onset MS, incomplete recovery from the first relapse and a high number of relapses during the first 5 years after the MS onset. Median times were not influenced by gender or by time between the first two relapses. The data were very different for the time between the assignment of scores of 4 and 6, since the median times were not influenced by any of the predicting variables.

Epstein–Barr virus in the multiple sclerosis brain: a controversial issue—report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria

PubMed Central

Niedobitek, Gerald; Aloisi, Francesca; Middeldorp, Jaap M.

2011-01-01

Recent epidemiological and immunological studies provide evidence for an association between Epstein–Barr virus infection and multiple sclerosis, suggesting a role of Epstein–Barr virus infection in disease induction and pathogenesis. A key question in this context is whether Epstein–Barr virus-infected B lymphocytes are present within the central nervous system and the lesions of patients with multiple sclerosis. Previous studies on this topic provided highly controversial results, showing Epstein–Barr virus reactivity in B cells in the vast majority of multiple sclerosis cases and lesions, or only exceptional Epstein–Barr virus-positive B cells in rare cases. In an attempt to explain the reasons for these divergent results, a workshop was organized under the umbrella of the European Union FP6 NeuroproMiSe project, the outcome of which is presented here. This report summarizes the current knowledge of Epstein–Barr virus biology and shows that Epstein–Barr virus infection is highly complex. There are still major controversies, how to unequivocally identify Epstein–Barr virus infection in pathological tissues, particularly in situations other than Epstein–Barr virus-driven lymphomas or acute Epstein–Barr virus infections. It further highlights that unequivocal proof of Epstein–Barr virus infection in multiple sclerosis lesions is still lacking, due to issues related to the sensitivity and specificity of the detection methods. PMID:21846731

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.

Overexpression of the Cytokine BAFF and Autoimmunity Risk.

PubMed

Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco

2017-04-27

Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).

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.

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.

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.

Time trends in the incidence and prevalence of multiple sclerosis in Norway during eight decades

PubMed Central

Grytten, N; Torkildsen, Ø; Myhr, K-M

2015-01-01

Norway has been subjected to numerous epidemiological investigations on the prevalence and incidence of multiple sclerosis (MS), dating back to 1935. The objective of this study was to review the studies on the prevalence and incidence of MS in Norway, provide an update on the prevalence of MS in Norway, and describe the time trends in the prevalence and incidence of MS in relation to risk factors, case ascertainment, and data. We performed a systematic search on PubMed and MEDLINE up to November 2014 using the search string ‘multiple sclerosis prevalence in Norway’ or ‘multiple sclerosis incidence in Norway’. In addition, we scrutinized the reference lists of the publications identified for relevant citations. We retrieved data on the distribution of MS in Norway on December 31, 2013 from the Norwegian Multiple Sclerosis Registry and Biobank and the Norwegian Patient Registry. We identified 29 articles. From 1961 to 2014, the reported prevalence of MS increased from 20 to 203 per 100,000 inhabitants, and the incidence increased from 1.9 to 8.0 per 100,000. The nationwide crude prevalence in Norway, based on the Norwegian Patient Registry, was 208 per 100,000 on December 31, 2013. The reported prevalence of MS in Norway has increased 10-fold, with several possible causes. During eight decades, neurological health services have generally become more accessible to the population, and transforming diagnostic criteria has made the diagnosis of MS more precise and valid. There have also been changes in lifestyle behavior and known risk factors, such as vitamin D and smoking, that might have contributed to the increased incidence of MS. A possible role of increased survival in MS needs to be examined further. This article is commented on by Berg-Hansen et al, published in 132: 364–367 (DOI: 10.1111/ane.12489). PMID:26046556

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

PubMed

Nielsen, Suzanne; Germanos, Rada; Weier, Megan; Pollard, John; Degenhardt, Louisa; Hall, Wayne; Buckley, Nicholas; Farrell, Michael

2018-02-13

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Neuromuscular orthotics in the treatment of craniomandibular dysfunction and the effects on patients with multiple sclerosis: a pilot study.

PubMed

Heit, Tammarie

2011-01-01

The purpose of this pilot study was to identify, measure and document an effect on the subjective multiple sclerosis symptoms and compare it to any objective data changes in the neuromuscular system of the head and neck, following the correction of the jaw position using a neuromuscular orthotic. The hope is to provide clinical evidence of improvement in the disease long-term without relying on the subjective evidence of remissions and exacerbations reported by the patient. The evidence found in the current pilot study measured improvement of head position, jaw position, jaw function, and airway in the neuromuscular bite position, which correlated with the improvement of subjective symptoms of craniomandibular dysfunction and multiple sclerosis. Studies show that the bite affects blood flow in the brain, which may explain the improvement of the patients in the current study.

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.

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, ...

Progression of regional grey matter atrophy in multiple sclerosis

PubMed Central

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

2018-01-01

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

Progression of regional grey matter atrophy in multiple sclerosis.

PubMed

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

2018-06-01

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

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

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 ...

GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis.

PubMed

Nantes, Julia C; Proulx, Sébastien; Zhong, Jidan; Holmes, Scott A; Narayanan, Sridar; Brown, Robert A; Hoge, Richard D; Koski, Lisa

2017-08-15

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting optimal response to B-cell depletion with rituximab in multiple sclerosis using CXCL13 index, magnetic resonance imaging and clinical measures

PubMed Central

Alvarez, Enrique; Piccio, Laura; Mikesell, Robert J; Trinkaus, Kathryn; Parks, Becky J; Naismith, Robert T

2015-01-01

Background B-cell depleting drugs show promise for treating multiple sclerosis. Objective We sought predictors of optimal response to rituximab, a B-cell depleting antibody, to help guide therapy selection. Methods We performed a post hoc study of 30 relapsing multiple sclerosis patients with breakthrough disease while on beta-interferon or glatiramer acetate who were treated with add-on rituximab. Standardized neurologic examinations, brain magnetic resonance imaging, and cerebrospinal fluid were obtained before and after rituximab. Tissue biomarkers were measured. Optimal responders were defined as having no evidence of disease activity. Results At baseline, optimal responders with no evidence of disease activity had higher IgG indices (P = 0.041), and higher CXCL13 indices ((cerebrospinal fluid CXCL13/serum CXCL13)/albumin index; P = 0.024), more contrast enhancing lesions (P = 0.002), better 25 foot timed walk (P = 0.001), and Expanded Disability Status Scale (P = 0.002). Rituximab treatment led to reduced cerebrospinal fluid biomarkers of tissue destruction: myelin basic protein (P = 0.046), neurofilament light chain (P < 0.001), and of inflammation (CXCL13 index; P = 0.042). Conclusions Multiple sclerosis patients with optimal response to rituximab had higher cerebrospinal fluid IgG and CXCL13 indices, more gadolinium-enhancing lesions, and less disability at baseline. Rituximab treatment led to decreased markers of inflammation and tissue damage. If validated, these results will help identify multiple sclerosis patients who will respond optimally to B-cell depletion. PMID:28607711

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

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

PubMed Central

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

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.

Exploring the facilitators and barriers to engagement in physical activity for people with multiple sclerosis.

PubMed

Kayes, Nicola M; McPherson, Kathryn M; Schluter, Philip; Taylor, Denise; Leete, Marta; Kolt, Gregory S

2011-01-01

To explore the relationship that cognitive behavioural and other previously identified variables have with physical activity engagement in people with multiple sclerosis (MS). This study adopted a cross-sectional questionnaire design. Participants were 282 individuals with MS. Outcome measures included the Physical Activity Disability Survey--Revised, Cognitive and Behavioural Responses to Symptoms Questionnaire, Barriers to Health Promoting Activities for Disabled Persons Scale, Multiple Sclerosis Self-efficacy Scale, Self-Efficacy for Chronic Diseases Scales and Chalder Fatigue Questionnaire. Multivariable stepwise regression analyses found that greater self-efficacy, greater reported mental fatigue and lower number of perceived barriers to physical activity accounted for a significant proportion of variance in physical activity behaviour, over that accounted for by illness-related variables. Although fear-avoidance beliefs accounted for a significant proportion of variance in the initial analyses, its effect was explained by other factors in the final multivariable analyses. Self-efficacy, mental fatigue and perceived barriers to physical activity are potentially modifiable variables which could be incorporated into interventions designed to improve physical activity engagement. Future research should explore whether a measurement tool tailored to capture beliefs about physical activity identified by people with MS would better predict participation in physical activity.

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain

PubMed Central

Haider, Lukas; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang

2016-01-01

Abstract Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. PMID:26912645

Physiotherapy Rehabilitation for People With Progressive Multiple Sclerosis: A Systematic Review.

PubMed

Campbell, Evan; Coulter, Elaine H; Mattison, Paul G; Miller, Linda; McFadyen, Angus; Paul, Lorna

2016-01-01

To assess the efficacy of physiotherapy interventions, including exercise therapy, for the rehabilitation of people with progressive multiple sclerosis. Five databases (Cochrane Library, Physiotherapy Evidence Database [PEDro], Web of Science Core Collections, MEDLINE, Embase) and reference lists of relevant articles were searched. Randomized experimental trials, including participants with progressive multiple sclerosis and investigating a physiotherapy intervention or an intervention containing a physiotherapy element, were included. Data were independently extracted using a standardized form, and methodologic quality was assessed using the PEDro scale. Thirteen studies (described by 15 articles) were identified and scored between 5 and 9 out of 10 on the PEDro scale. Eight interventions were assessed: exercise therapy, multidisciplinary rehabilitation, functional electrical stimulation, botulinum toxin type A injections and manual stretches, inspiratory muscle training, therapeutic standing, acupuncture, and body weight-supported treadmill training. All studies, apart from 1, produced positive results in at least 1 outcome measure; however, only 1 article used a power calculation to determine the sample size and because of dropouts the results were subsequently underpowered. This review suggests that physiotherapy may be effective for the rehabilitation of people with progressive multiple sclerosis. However, further appropriately powered studies are required. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.

PubMed

Planche, Vincent; Panatier, Aude; Hiba, Bassem; Ducourneau, Eva-Gunnel; Raffard, Gerard; Dubourdieu, Nadège; Maitre, Marlène; Lesté-Lasserre, Thierry; Brochet, Bruno; Dousset, Vincent; Desmedt, Aline; Oliet, Stéphane H; Tourdias, Thomas

2017-02-01

Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality of life and patient preferences: identification of subgroups of multiple sclerosis patients.

PubMed

Rosato, Rosalba; Testa, Silvia; Oggero, Alessandra; Molinengo, Giorgia; Bertolotto, Antonio

2015-09-01

The aim of this study was to estimate preferences related to quality of life attributes in people with multiple sclerosis, by keeping heterogeneity of patient preference in mind, using the latent class approach. A discrete choice experiment survey was developed using the following attributes: activities of daily living, instrumental activities of daily living, pain/fatigue, anxiety/depression and attention/concentration. Choice sets were presented as pairs of hypothetical health status, based upon a fractional factorial design. The latent class logit model estimated on 152 patients identified three subpopulations, which, respectively, attached more importance to: (1) the physical dimension; (2) pain/fatigue and anxiety/depression; and (3) instrumental activities of daily living impairments, anxiety/depression and attention/concentration. A posterior analysis suggests that the latent class membership may be related to an individual's age to some extent, or to diagnosis and treatment, while apart from energy dimension, no significant difference exists between latent groups, with regard to Multiple Sclerosis Quality of Life-54 scales. A quality of life preference-based utility measure for people with multiple sclerosis was developed. These utility values allow identification of a hierarchic priority among different aspects of quality of life and may allow physicians to develop a care programme tailored to patient needs.

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 ...

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.

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

Measuring outcomes for neurological disorders: a review of disease-specific health status instruments for three degenerative neurological conditions.

PubMed

Heffernan, Catherine; Jenkinson, Crispin

2005-06-01

Health-related quality-of-life measures have been increasingly used in research into neurological disorders in recent years. The aim of this paper is to provide an objective appraisal of the evidence in regard to disease-specific quality-of-life measures used in research on health interventions for three degenerative neurological disorders: multiple sclerosis, motor neurone disease/amyotrophic lateral sclerosis and Parkinson's disease. A comprehensive search strategy was developed to include nine relevant electronic databases. Only studies pertaining to patient-based outcome measurements in multiple sclerosis, motor neurone disease and Parkinson's disease were included. We identified 76 eligible studies. As studies consisted of descriptive and cross-sectional survey study designs, results were reported qualitatively rather than in the form of a meta-analysis. Four disease-specific measures were found for Parkinson's disease, 11 for multiple sclerosis and one for motor neurone disease. We conclude that health-related quality-of-life measures are useful in assessing the impact of treatments and interventions for neurological disorders. However, further research is needed on the development of instruments using psychometric methods and on the validation, utilization and responsiveness of instruments to change.

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.

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

PubMed

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

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.

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.

Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis.

PubMed

Mei, Feng; Fancy, Stephen P J; Shen, Yun-An A; Niu, Jianqin; Zhao, Chao; Presley, Bryan; Miao, Edna; Lee, Seonok; Mayoral, Sonia R; Redmond, Stephanie A; Etxeberria, Ainhoa; Xiao, Lan; Franklin, Robin J M; Green, Ari; Hauser, Stephen L; Chan, Jonah R

2014-08-01

Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as 'rings' of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.

The relationship between walking, manual dexterity, cognition and activity/participation in persons with multiple sclerosis.

PubMed

Kierkegaard, Marie; Einarsson, Ulrika; Gottberg, Kristina; von Koch, Lena; Holmqvist, Lotta Widén

2012-05-01

Multiple sclerosis has a vast impact on health, but the relationship between walking, manual dexterity, cognition and activity/participation is unclear. The specific aims were to explore the discriminative ability of measures of walking, manual dexterity and cognition, and to identify cut-off values in these measures, for prediction of independence in personal and instrumental activities of daily living (ADL) and activity/participation in social and lifestyle activities. Data from 164 persons with multiple sclerosis were collected during home visits with the following measures: the 2 × 5 m walk test, the Nine-hole Peg Test, the Symbol Digit Modalities Test, the Katz Personal and Instrumental ADL Indexes, and the Frenchay Activities Index (measuring frequency in social and lifestyle activities). The 2 × 5 m walk test and the Nine-hole Peg Test had high and better discriminative and predictive ability than the Symbol Digit Modalities Test. Cut-off values were identified. The accuracy of predictions was increased above all by combining the 2 × 5 m walk test and the Nine-hole Peg Test. The proposed cut-off values in the 2 × 5 m walk test and the Nine-hole Peg Test may be used as indicators of functioning and to identify persons risking activity limitations and participation restrictions. However, further studies are needed to confirm the usefulness in clinical practice.

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.

Barriers to the Accessibility and Continuity of Health-Care Services in People with Multiple Sclerosis

PubMed Central

Bishop, Malachy; Pionke, J.J.; Strauser, David; Santens, Ryan L.

2017-01-01

Background: Individuals with multiple sclerosis (MS) face a range of barriers to accessing and using health-care services. The aim of this review was to identify specific barriers to accessing and using health-care services based on a continuum of the health-care delivery system. Methods: Literature searches were conducted in the PubMed, PsycINFO, CINAHL, and Web of Science databases. The following terms were searched as subject headings, key words, or abstracts: health care, access, barriers, physical disability, and multiple sclerosis. The literature search produced 361 potentially relevant citations. After screening titles, abstracts, and citations, eight citations were selected for full-text review. Results: Health-care barriers were divided into three continuous phases of receiving health care. In the before-visit phase, the most commonly identified barrier was transportation. In the during-visit phase, communication quality was the major concern. In the after-visit phase, discontinued referral was the major barrier encountered. Conclusions: There are multiple interrelated barriers to accessing and using health-care services along the health-care delivery continuum for people with MS and its associated physical disabilities, ranging from complex and long-recognized barriers that will likely require extended advocacy to create policy changes to issues that can and should be addressed through relatively minor changes in health-care delivery practices, improved care coordination, and increased provider awareness, education, and responsiveness to patients' needs. PMID:29270089

MS in self-identified Hispanic/Latino individuals living in the US

PubMed Central

Amezcua, Lilyana; Oksenberg, Jorge R; McCauley, Jacob L

2017-01-01

Self-identified Hispanic/Latino individuals living with multiple sclerosis (MS) in the continental United States (US) are a diverse group that represents different cultural and ancestral backgrounds. A marked variability in the way MS affects various subgroups of Hispanics in the US has been observed. We reviewed and synthesized available data about MS in Hispanics in the US. There are likely a host of multifactorial elements contributing to these observations that could be explained by genetic, environmental, and social underpinnings. Barriers to adequate MS care in Hispanics are likely to include delivery of culturally competent care and social and economic disadvantages. Considerable efforts, including the formation of a national consortium known as the Alliance for Research in Hispanic Multiple Sclerosis (ARHMS), are underway to help further explore these various factors. PMID:28979795

[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.

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

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

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

PubMed

Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

2016-03-01

Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Autoantigen cross-reactive environmental antigen can trigger multiple sclerosis-like disease.

PubMed

Reynolds, Catherine J; Sim, Malcolm J W; Quigley, Kathryn J; Altmann, Daniel M; Boyton, Rosemary J

2015-05-13

Multiple sclerosis is generally considered an autoimmune disease resulting from interaction between predisposing genes and environmental factors, together allowing immunological self-tolerance to be compromised. The precise nature of the environmental inputs has been elusive, infectious agents having received considerable attention. A recent study generated an algorithm predicting naturally occurring T cell receptor (TCR) ligands from the proteome database. Taking the example of a multiple sclerosis patient-derived anti-myelin TCR, the study identified a number of stimulatory, cross-reactive peptide sequences from environmental and human antigens. Having previously generated a spontaneous multiple sclerosis (MS) model through expression of this TCR, we asked whether any of these could indeed function in vivo to trigger CNS disease by cross-reactive activation. A number of myelin epitope cross-reactive epitopes could stimulate T cell immunity in this MS anti-myelin TCR transgenic model. Two of the most stimulatory of these 'environmental' epitopes, from Dictyostyelium slime mold and from Emiliania huxleyi, were tested for the ability to induce MS-like disease in the transgenics. We found that immunization with cross-reactive peptide from Dictyostyelium slime mold (but not from E. huxleyi) induces severe disease. These specific environmental epitopes are unlikely to be common triggers of MS, but this study suggests that our search for the cross-reactivity triggers of autoimmune activation leading to MS should encompass epitopes not just from the 'infectome' but also from the full environmental 'exposome.'

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

PubMed

Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

2017-11-01

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor-somatosensory cortex was associated with increased Expanded Disability Status Scale scores in surface-based general linear modelling (P < 0.05). Microstructural pathology was frequent in early multiple sclerosis, and present mainly focally in cortical lesions, whereas more diffusely in white matter. These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions. © 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.

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.

Multiple sclerosis and employment: Associations of psychological factors and work instability.

PubMed

Wicks, Charlotte Rose; Ward, Karl; Stroud, Amanda; Tennant, Alan; Ford, Helen L

2016-10-12

People with multiple sclerosis often stop working earlier than expected. Psychological factors may have an impact on job retention. Investigation may inform interventions to help people stay in work. To investigate the associations between psychological factors and work instability in people with multiple sclerosis. A multi-method, 2-phased study. Focus groups were held to identify key themes. Questionnaire packs using validated scales of the key themes were completed at baseline and at 8-month follow-up. Four key psychological themes emerged. Out of 208 study subjects 57.2% reported medium/high risk of job loss, with marginal changes at 8 months. Some psychological variables fluctuated significantly, e.g. depression fell from 24.6% to 14.5%. Work instability and anxiety and depression were strongly correlated (χ2 p < 0.001). Those with probable depression at baseline had 7.1 times increased odds of medium/high work instability, and baseline depression levels also predicted later work instability (Hosmer-Lemeshow test 0.899; Nagelkerke R Square 0.579). Psychological factors fluctuated over the 8-month follow-up period. Some psychological variables, including anxiety and depression, were significantly associated with, and predictive of, work instability. Longitudinal analysis should further identify how these psychological attributes impact on work instability and potential job loss in the longer term.

Responder definition of the Multiple Sclerosis Impact Scale physical impact subscale for patients with physical worsening.

PubMed

Phillips, Glenn A; Wyrwich, Kathleen W; Guo, Shien; Medori, Rossella; Altincatal, Arman; Wagner, Linda; Elkins, Jacob

2014-11-01

The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective. To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing-remitting MS (RRMS) participating in a clinical trial. Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29. Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest). These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS. © The Author(s), 2014.

Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1

PubMed Central

Sanna, Serena; Gayán, Javier; Urcelay, Elena; Zara, Ilenia; Pitzalis, Maristella; Cavanillas, María L.; Arroyo, Rafael; Zoledziewska, Magdalena; Marrosu, Marisa; Fernández, Oscar; Leyva, Laura; Alcina, Antonio; Fedetz, Maria; Moreno-Rey, Concha; Velasco, Juan; Real, Luis M.; Ruiz-Peña, Juan Luis; Cucca, Francesco

2012-01-01

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80–0.89; p = 1.36×10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS. PMID:22570697

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.

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.

MR Imaging in Monitoring and Predicting Treatment Response in Multiple Sclerosis.

PubMed

Río, Jordi; Auger, Cristina; Rovira, Àlex

2017-05-01

MR imaging is the most sensitive tool for identifying lesions in patients with multiple sclerosis (MS). MR imaging has also acquired an essential role in the detection of complications arising from these treatments and in the assessment and prediction of efficacy. In the future, other radiological measures that have shown prognostic value may be incorporated within the models for predicting treatment response. This article examines the role of MR imaging as a prognostic tool in patients with MS and the recommendations that have been proposed in recent years to monitor patients who are treated with disease-modifying drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

GEMS Project: A Platform to Investigate Multiple Sclerosis Risk

PubMed Central

Xia, Zongqi; White, Charles C.; Owen, Emily K.; Von Korff, Alina; Clarkson, Sarah R.; McCabe, Cristin A.; Cimpean, Maria; Winn, Phoebe A.; Hoesing, Ashley; Steele, Sonya U.; Cortese, Irene C. M.; Chitnis, Tanuja; Weiner, Howard L.; Reich, Daniel S.; Chibnik, Lori B.; De Jager, Philip L.

2015-01-01

The Genes and Environment in Multiple Sclerosis (GEMS) project establishes a platform to investigate the events leading to MS in at-risk individuals. It has recruited 2,632 first-degree relatives from across the USA. Using an integrated genetic and environmental risk score, we identified subjects with twice the MS risk when compared to the average family member, and we report an initial incidence rate in these subjects that is 30 times greater than that of sporadic MS. We discuss the feasibility of large-scale studies of asymptomatic at-risk subjects that leverage modern tools of subject recruitment to execute collaborative projects. PMID:26583565

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.

Communicative participation restrictions in multiple sclerosis: associated variables and correlation with social functioning.

PubMed

Yorkston, Kathryn M; Baylor, Carolyn; Amtmann, Dagmar

2014-01-01

Individuals with multiple sclerosis (MS) are at risk for communication problems that may restrict their ability to take participation in important life roles such as maintenance of relationships, work, or household management. The aim of this project is to examine selected demographic and symptom-related variables that may contribute to participation restrictions. This examination is intended to aid clinicians in predicting who might be at risk for such restrictions and what variables may be targeted in interventions. Community-dwelling adults with MS (n=216) completed a survey either online or using paper forms. The survey included the 46-item version of the Communicative Participation Item Bank, demographics (age, sex, living situation, employment status, education, and time since onset of diagnosis of MS), and self-reported symptom-related variables (physical activity, emotional problems, fatigue, pain, speech severity, and cognitive/communication skills). In order to identify predictors of restrictions in communicative participation, these variables were entered into a backwards stepwise multiple linear regression analysis. Five variables (cognitive/communication skills, speech severity, speech usage, physical activity, and education) were statistically significant predictors of communication participation. In order to examine the relationship of communicative participation and social role variables, bivariate Spearman correlations were conducted. Results suggest only a fair to moderate relationship between communicative participation and measures of social roles. Communicative participation is a complex construct associated with a number of self-reported variables. Clinicians should be alert to risk factors for reduced communicative participation including reduced cognitive and speech skills, lower levels of speech usage, limitations in physical activities and higher levels of education. The reader will be able to: (a) describe the factors that may restrict participation in individuals with multiple sclerosis; (b) list measures of social functioning that may be pertinent in adults with multiple sclerosis; (c) discuss factors that can be used to predict communicative participation in multiple sclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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.

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

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.

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.

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

[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.

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.

Childhood infections and risk of multiple sclerosis.

PubMed

Bager, Peter; Nielsen, Nete Munk; Bihrmann, Kristine; Frisch, Morten; Hjalgrim, Henrik; Wohlfart, Jan; Koch-Henriksen, Nils; Melbye, Mads; Westergaard, Tine

2004-11-01

Multiple sclerosis has been hypothesized to be the result from an aberrant immune response possibly triggered by delayed exposure to a common childhood infection. Because the vast majority of previous studies testing this hypothesis have been based on a history of childhood infections recalled years to decades later in adulthood, we investigated whether age at six common childhood infections was associated with risk of multiple sclerosis, using information recalled in the childhood of a historical cohort of school children in Denmark. Cases included all individuals with multiple sclerosis in the country born between 1940 and 1975, who had attended school in the capital, Copenhagen. Controls were age- and sex-matched peers. School health records were obtained for all subjects. The records contained information on measles, pertussis, scarlet fever, birth order, sibship size, social class of the father, school years, and name of school and attended school classes for children born since 1940 (n(cases) = 455, n(controls) = 1801). For children born since 1950, the records also contained information on rubella, varicella and mumps (n(cases) = 182, n(controls) = 690). Neither age at infection with measles, rubella, varicella, mumps, pertussis and scarlet fever (upper age limit, 14 years) nor the cumulative number of these infections between the ages of 10 and 14 years was associated with the risk of multiple sclerosis. In addition, the risk of multiple sclerosis was not associated with birth order or social class. No clustering of multiple sclerosis in school classes was observed. Our findings suggest that measles, rubella, mumps, varicella, pertussis and scarlet fever, even if acquired late in childhood, are not associated with increased risk of multiple sclerosis later in life.

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

PubMed

Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

2013-01-01

Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Impaired heel to toe progression during gait is related to reduced ankle range of motion in people with Multiple Sclerosis.

PubMed

Psarakis, Michael; Greene, David; Moresi, Mark; Baker, Michael; Stubbs, Peter; Brodie, Matthew; Lord, Stephen; Hoang, Phu

2017-11-01

Gait impairment in people with Multiple Sclerosis results from neurological impairment, muscle weakness and reduced range of motion. Restrictions in passive ankle range of motion can result in abnormal heel-to-toe progression (weight transfer) and inefficient gait patterns in people with Multiple Sclerosis. The purpose of this study was to determine the associations between gait impairment, heel-to-toe progression and ankle range of motion in people with Multiple Sclerosis. Twelve participants with Multiple Sclerosis and twelve healthy age-matched participants were assessed. Spatiotemporal parameters of gait and individual footprint data were used to investigate group differences. A pressure sensitive walkway was used to divide each footprint into three phases (contact, mid-stance, propulsive) and calculate the heel-to-toe progression during the stance phase of gait. Compared to healthy controls, people with Multiple Sclerosis spent relatively less time in contact phase (7.8% vs 25.1%) and more time in the mid stance phase of gait (57.3% vs 33.7%). Inter-limb differences were observed in people with Multiple Sclerosis between the affected and non-affected sides for contact (7.8% vs 15.3%) and mid stance (57.3% and 47.1%) phases. Differences in heel-to-toe progression remained significant after adjusting for walking speed and were correlated with walking distance and ankle range of motion. Impaired heel-to-toe progression was related to poor ankle range of motion in people with Multiple Sclerosis. Heel-to-toe progression provided a sensitive measure for assessing gait impairments that were not detectable using standard spatiotemporal gait parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Always looking for a new balance": toward an understanding of what it takes to continue working while being diagnosed with relapsing-remitting multiple sclerosis.

PubMed

Meide, Hanneke van der; Gorp, Dennis van; van der Hiele, Karin; Visser, Leo

2017-06-22

The aim of this study was to gain insight into the meaning of work in the everyday lives of people with relapsing-remitting multiple sclerosis, and the barriers and facilitators to staying in work. Nineteen employed adults diagnosed with relapsing-remitting multiple sclerosis participated in narrative interviews. All interviews were transcribed and coded for thematic analysis. For people with relapsing-remitting multiple sclerosis, continuing to work was a precarious balancing act. Five themes influenced this balance: becoming familiar with the disease, adjusting expectations, having an understanding and realistic line manager, seeing work as meaningful life activity and strategic considerations. People receiving a diagnosis of relapsing-remitting multiple sclerosis have to refamiliarize themselves with their own body in a meaningful way to be able to continue their work. Rehabilitation professionals can support them herein by taking into account not merely functional capabilities but also identity aspects of the body. Medication that stabilizes symptoms supports making the necessary adjustments. A trusting relationship with the line manager is vital for this adaptation process. Additionally, a match between being adequately challenged by work, while still having the capacity to meet those work demands, is needed, as is long-term financial stability. Implications for rehabilitation Rehabilitation professionals can support employees with relapsing-remitting multiple sclerosis by taking into account not merely functional capabilities but also identity aspects of the body. A trusting relationship with the line manager, including a timely disclosure of the diagnosis, is vital for people with relapsing-remitting multiple sclerosis to remain at work. For people with relapsing-remitting multiple sclerosis, there is a delicate balance between being adequately challenged by work while still having the capacity to meet work demands.

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.

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.

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.

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.

Treatment of multiple sclerosis with interferon β: an appraisal of cost-effectiveness and quality of life

PubMed Central

Parkin, D.; Jacoby, A.; McNamee, P.; Miller, P.; Thomas, S.; Bates, D.

2000-01-01

OBJECTIVE—To evaluate the cost-effectiveness of interferon beta-1b (IFβ-1b) for relapsing-remitting multiple sclerosis (RRMS).
METHODS—Construction of a cost-effectiveness model using published data on IFβ-1b effectiveness and the natural history of RRMS, and new data on costs and quality of life (QoL) from a sample of 102patients with RRMS and resident in northern England.
RESULTS—Poorer QoL was found for patients with multiple sclerosis compared with the general population; those who had had a relapse; those with worse states identified by a clinical measure (expanded disability status scale (EDSS)). Relapses have effects over several months. Health state valuations were higher than in the general population. Costs were higher in relapse than remission and for worse EDSS states. IFβ-1b costs were larger than cost savings. The best cost-effectiveness estimate was £28 700 per relapse avoided, which is £809 900 per QALY gained; or £328 300 per QALY gained allowing for effects of progression over 5 years. Estimates were robust to changes in assumptions.
CONCLUSIONS—The impact of multiple sclerosis on QoL is substantial. Future trials should base outcomes measurement on QoL and be better linked to natural history and cost data. IFβ-1b produces important occasional short term QoL gains, but small gains in QALYs overall and large additional costs.

 PMID:10644777

Measuring the impact of multiple sclerosis: Enhancing the measurement performance of the Multiple Sclerosis Impact Scale (MSIS-29) using Rasch Measurement Theory (RMT)

PubMed Central

Cleanthous, Sophie; Kinter, Elizabeth; Marquis, Patrick; Petrillo, Jennifer; You, Xiaojun; Wakeford, Craig; Sabatella, Guido

2017-01-01

Background Study objectives were to evaluate the Multiple Sclerosis Impact Scale (MSIS-29) and explore an optimized scoring structure based on empirical post-hoc analyses of data from the Phase III ADVANCE clinical trial. Methods ADVANCE MSIS-29 data from six time-points were analyzed in a sample of patients with relapsing–remitting multiple sclerosis (RRMS). Rasch Measurement Theory (RMT) analysis was undertaken to examine three broad areas: sample-to-scale targeting, measurement scale properties, and sample measurement validity. Interpretation of results led to an alternative MSIS-29 scoring structure, further evaluated alongside responsiveness of the original and revised scales at Week 48. Results RMT analysis provided mixed evidence for Physical and Psychological Impact scales that were sub-optimally targeted at the lower functioning end of the scales. Their conceptual basis could also stand to improve based on item fit results. The revised MSIS-29 rescored scales improved but did not resolve the measurement scale properties and targeting of the MSIS-29. In two out of three revised scales, responsiveness analysis indicated strengthened ability to detect change. Conclusion The revised MSIS-29 provides an initial evidence-based improved patient-reported outcome (PRO) instrument for evaluating the impact of MS. Revised scoring improves conceptual clarity and interpretation of scores by refining scale structure to include Symptoms, Psychological Impact, and General Limitations. Clinical trial ADVANCE (ClinicalTrials.gov identifier NCT00906399). PMID:29104758

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

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

Ratiometric analysis of in vivo retinal layer thicknesses in multiple sclerosis

NASA Astrophysics Data System (ADS)

Bhaduri, Basanta; Nolan, Ryan M.; Shelton, Ryan L.; Pilutti, Lara A.; Motl, Robert W.; Boppart, Stephen A.

2016-09-01

We performed ratiometric analysis of retinal optical coherence tomography images for the first time in multiple sclerosis (MS) patients. The ratiometric analysis identified differences in several retinal layer thickness ratios in the cohort of MS subjects without a history of optic neuritis (ON) compared to healthy control (HC) subjects, and there was no difference in standard retinal nerve fiber layer thickness (RNFLT). The difference in such ratios between HC subjects and those with mild MS-disability, without a difference in RNFLT, further suggests the possibility of using layer ratiometric analysis for detecting early retinal changes in MS. Ratiometric analysis may be useful and potentially more sensitive for detecting disease changes in MS.

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.

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

Participant perceptions of a novel physiotherapy approach ("Blue Prescription") for increasing levels of physical activity in people with multiple sclerosis: a qualitative study following intervention.

PubMed

Smith, Catherine M; Hale, Leigh A; Mulligan, Hilda F; Treharne, Gareth J

2013-07-01

The aim of this study was to investigate experiences of participating in a feasibility trial of a novel physiotherapy intervention (Blue Prescription). The trial was designed to increase participation in physical activity for people with multiple sclerosis living in the community. We individually interviewed 27 volunteers from two New Zealand metropolitan areas at the conclusion of their participation in Blue Prescription. We asked volunteers about what participation in Blue Prescription had meant to them; how participants intended to continue with their physical activity; how the approach differed from previous experiences of physiotherapy encounters; and how Blue Prescription could be improved. Interviews were semi-structured, audio-recorded, transcribed verbatim, and analysed using a General Inductive Approach. 'Support' was identified as a key theme with three sub-themes: 'The therapeutic relationship'; 'The Blue Prescription approach'; and 'Supporting themselves'. We identified two additional themes 'Motivation to participate' and 'Improving the Blue Prescription approach'. A novel approach (Blue Prescription) which facilitates engagement in higher levels of desirable physical activity was perceived by participants to be supportive, motivating and enabling. This approach might be particularly useful for people with multiple sclerosis ready to adopt new health-related behaviours. For future studies, this approach requires further refinement, particularly with regards to methods of communication and evaluation.

Responder definition of the Multiple Sclerosis Impact Scale physical impact subscale for patients with physical worsening

PubMed Central

Wyrwich, Kathleen W; Guo, Shien; Medori, Rossella; Altincatal, Arman; Wagner, Linda; Elkins, Jacob

2014-01-01

Background: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient’s perspective. Objective: To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing–remitting MS (RRMS) participating in a clinical trial. Methods: Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29. Results: Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest). Conclusion: These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS. PMID:24740371

[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.

The Relational Impact of Multiple Sclerosis: An Integrative Review of the Literature Using a Cognitive Analytic Framework.

PubMed

Blundell Jones, Joanna; Walsh, Sue; Isaac, Claire

2017-12-01

This integrative literature review uses cognitive analytic therapy (CAT) theory to examine the impact of a chronic illness, multiple sclerosis (MS), on relationships and mental health. Electronic searches were conducted in six medical and social science databases. Thirty-eight articles met inclusion criteria, and also satisfied quality criteria. Articles revealed that MS-related demands change care needs and alter relationships. Using a CAT framework, the MS literature was analysed, and five key patterns of relating to oneself and to others were identified. A diagrammatic formulation is proposed that interconnects these patterns with wellbeing and suggests potential "exits" to improve mental health, for example, assisting families to minimise overprotection. Application of CAT analysis to the literature clarifies relational processes that may affect mental health among individuals with MS, which hopefully will inform how services assist in reducing unhelpful patterns and improve coping. Further investigation of the identified patterns is needed.

Breaking down the gut microbiome composition in multiple sclerosis.

PubMed

Budhram, Adrian; Parvathy, Seema; Kremenchutzky, Marcelo; Silverman, Michael

2017-04-01

The gut microbiome, which consists of a highly diverse ecologic community of micro-organisms, has increasingly been studied regarding its role in multiple sclerosis (MS) immunopathogenesis. This review critically examines the literature investigating the gut microbiome in MS. A comprehensive search was performed of PubMed databases and ECTRIMS meeting abstracts for literature relating to the gut microbiome in MS. Controlled studies examining the gut microbiome in patients with MS were included for review. Identified studies were predominantly case-control in their design and consistently found differences in the gut microbiome of MS patients compared to controls. We examine plausible mechanistic links between these differences and MS immunopathogenesis, and discuss the therapeutic implications of these findings. Review of the available literature reveals potential immunopathogenic links between the gut microbiome and MS, identifies avenues for therapeutic advancement, and emphasizes the need for further systematic study in this emerging field.

Seven-Tesla Magnetization Transfer Imaging to Detect Multiple Sclerosis White Matter Lesions.

PubMed

Chou, I-Jun; Lim, Su-Yin; Tanasescu, Radu; Al-Radaideh, Ali; Mougin, Olivier E; Tench, Christopher R; Whitehouse, William P; Gowland, Penny A; Constantinescu, Cris S

2018-03-01

Fluid-attenuated inversion recovery (FLAIR) imaging at 3 Tesla (T) field strength is the most sensitive modality for detecting white matter lesions in multiple sclerosis. While 7T FLAIR is effective in detecting cortical lesions, it has not been fully optimized for visualization of white matter lesions and thus has not been used for delineating lesions in quantitative magnetic resonance imaging (MRI) studies of the normal appearing white matter in multiple sclerosis. Therefore, we aimed to evaluate the sensitivity of 7T magnetization-transfer-weighted (MT w ) images in the detection of white matter lesions compared with 3T-FLAIR. Fifteen patients with clinically isolated syndrome, 6 with multiple sclerosis, and 10 healthy participants were scanned with 7T 3-dimensional (D) MT w and 3T-2D-FLAIR sequences on the same day. White matter lesions visible on either sequence were delineated. Of 662 lesions identified on 3T-2D-FLAIR images, 652 were detected on 7T-3D-MT w images (sensitivity, 98%; 95% confidence interval, 97% to 99%). The Spearman correlation coefficient between lesion loads estimated by the two sequences was .910. The intrarater and interrater reliability for 7T-3D-MT w images was good with an intraclass correlation coefficient (ICC) of 98.4% and 81.8%, which is similar to that for 3T-2D-FLAIR images (ICC 96.1% and 96.7%). Seven-Tesla MT w sequences detected most of the white matter lesions identified by FLAIR at 3T. This suggests that 7T-MT w imaging is a robust alternative for detecting demyelinating lesions in addition to 3T-FLAIR. Future studies need to compare the roles of optimized 7T-FLAIR and of 7T-MT w imaging. © 2017 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

Genetic variation influences glutamate concentrations in brains of patients with multiple sclerosis.

PubMed

Baranzini, Sergio E; Srinivasan, Radhika; Khankhanian, Pouya; Okuda, Darin T; Nelson, Sarah J; Matthews, Paul M; Hauser, Stephen L; Oksenberg, Jorge R; Pelletier, Daniel

2010-09-01

Glutamate is the main excitatory neurotransmitter in the mammalian brain. Appropriate transmission of nerve impulses through glutamatergic synapses is required throughout the brain and forms the basis of many processes including learning and memory. However, abnormally high levels of extracellular brain glutamate can lead to neuroaxonal cell death. We have previously reported elevated glutamate levels in the brains of patients suffering from multiple sclerosis. Here two complementary analyses to assess the extent of genomic control over glutamate levels were used. First, a genome-wide association analysis in 382 patients with multiple sclerosis using brain glutamate concentration as a quantitative trait was conducted. In a second approach, a protein interaction network was used to find associated genes within the same pathway. The top associated marker was rs794185 (P < 6.44 x 10(-7)), a non-coding single nucleotide polymorphism within the gene sulphatase modifying factor 1. Our pathway approach identified a module composed of 70 genes with high relevance to glutamate biology. Individuals carrying a higher number of associated alleles from genes in this module showed the highest levels of glutamate. These individuals also showed greater decreases in N-acetylaspartate and in brain volume over 1 year of follow-up. Patients were then stratified by the amount of annual brain volume loss and the same approach was performed in the 'high' (n = 250) and 'low' (n = 132) neurodegeneration groups. The association with rs794185 was highly significant in the group with high neurodegeneration. Further, results from the network-based pathway analysis remained largely unchanged even after stratification. Results from these analyses indicated that variance in the activity of neurochemical pathways implicated in neurodegeneration is explained, at least in part, by the inheritance of common genetic polymorphisms. Spectroscopy-based imaging provides a novel quantitative endophenotype for genetic association studies directed towards identifying new factors that contribute to the heterogeneity of clinical expression of multiple sclerosis.

Physical disability, life stress, and psychosocial adjustment in multiple sclerosis.

PubMed

Zeldow, P B; Pavlou, M

1984-02-01

Eighty-one outpatients with diagnosed multiple sclerosis were studied in an effort to examine the relative contributions of physical health status, life stress, duration of illness, age, sex, marital status, and social class on various aspects of personal and interpersonal functioning. Stepwise multiple regression analyses were performed to identify the most significant discriminators of the seven psychosocial measures. Physical health status exerted the broadest influence, affecting personal efficiency and well-being, capacity for independent thought and action, self-confidence, self-reliance, and number of meaningful social contacts. Life stress was associated with lowered personal efficiency and sense of well-being. Duration of illness and the demographic variables had few or no effects on psychosocial adjustment. Discussion contrasts the present findings with others in the rehabilitation literature and specifies certain limitations of the study's design.

Comparisons of Latinos, African Americans, and Caucasians with multiple sclerosis.

PubMed

Buchanan, Robert J; Zuniga, Miguel A; Carrillo-Zuniga, Genny; Chakravorty, Bonnie J; Tyry, Tuula; Moreau, Rachel L; Huang, Chunfeng; Vollmer, Timothy

2010-01-01

Identify racial/ethnic differences among people with multiple sclerosis (MS) in demographics, MS disease characteristics, and health services received. We analyzed enrollment data from the Registry of the North American Research Committee on Multiple Sclerosis (NARCOMS) Project to compare 26,967 Caucasians, 715 Latinos, and 1,313 African Americans with MS. Racial/ethnic analyses of NARCOMS data focused on descriptive characteristics, using ANOVA and chi-square tests to identify significant differences in means and frequencies among Caucasians, Latinos, and African Americans. We identified significant racial/ethnic differences in demographics, MS disease characteristics, and treatments. Caucasians were older when first MS symptoms were experienced (30.1 years) and at MS diagnosis (37.4 years) than Latinos (28.6 years and 34.5 years) or African Americans (29.8 years and 35.8 years). Larger proportions of Latinos reported normal function for mobility and bladder/bowel function compared to Caucasians. Larger proportions of Latinos (44.2 percent) and African Americans (45.8 percent) reported at least mild depression compared to only 38.7 percent of Caucasians. Larger proportions of Latinos never received mental health care or care from rehabilitation specialists than Caucasians or African Americans. A larger proportion of African Americans had never been treated by a neurologist specializing in MS and a smaller proportion of African Americans received care at a MS clinic than Caucasians or Latinos. Our findings highlight the need for future analyses to determine if age, disease duration, MS symptoms, and disability levels provide additional insights into racial/ethic differences in the use of MS-related providers.

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

PubMed

Feinstein, Anthony; Rector, Neil; Motl, Robert

2013-12-01

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

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.

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.

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.

Interleukin 35 and Hepatocyte Growth Factor; as a novel combined immune gene therapy for Multiple Sclerosis disease.

PubMed

Moghadam, Samira; Erfanmanesh, Maryam; Esmaeilzadeh, Abdolreza

2017-11-01

An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration. The authors propose a novel combined immune gene therapy for Multiple Sclerosis treatment using anti-inflammatory and remyelination of Interleukine-35 and Hepatocyte Growth Factor properties, respectively. In this hypothesis Interleukine-35 and Hepatocyte Growth Factor introduce to Mesenchymal Stem Cells of EAE mouse model via an adenovirus based vector. It is expected that Interleukine-35 and Hepatocyte Growth Factor genes expressed from MSCs could effectively perform in immunotherapy of Multiple Sclerosis. Copyright © 2017. Published by Elsevier Ltd.

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…

Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

PubMed

Liu, Mingyuan; Hou, Xiaojun; Zhang, Ping; Hao, Yong; Yang, Yiting; Wu, Xiongfeng; Zhu, Desheng; Guan, Yangtai

2013-05-01

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

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.

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

PubMed

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

2016-07-01

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

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

Immune Tolerance in Multiple Sclerosis

PubMed Central

Goverman, Joan M.

2011-01-01

Summary Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T-cell tolerance to myelin antigens and to understand how some myelin-specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin-specific T cells, as most myelin-specific T cells are eliminated by clonal deletion in the thymus. Self-reactive T cells that escape central tolerance are generally capable only of low-avidity interactions with antigen-presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin-specific T cells have been indentified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4+ myelin-specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8+ myelin-specific T cells. PMID:21488900

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.

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

PubMed

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

2017-09-28

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

Identification of treatment responders based on multiple longitudinal outcomes with applications to multiple sclerosis patients.

PubMed

Kondo, Yumi; Zhao, Yinshan; Petkau, John

2017-05-30

Identification of treatment responders is a challenge in comparative studies where treatment efficacy is measured by multiple longitudinally collected continuous and count outcomes. Existing procedures often identify responders on the basis of only a single outcome. We propose a novel multiple longitudinal outcome mixture model that assumes that, conditionally on a cluster label, each longitudinal outcome is from a generalized linear mixed effect model. We utilize a Monte Carlo expectation-maximization algorithm to obtain the maximum likelihood estimates of our high-dimensional model and classify patients according to their estimated posterior probability of being a responder. We demonstrate the flexibility of our novel procedure on two multiple sclerosis clinical trial datasets with distinct data structures. Our simulation study shows that incorporating multiple outcomes improves the responder identification performance; this can occur even if some of the outcomes are ineffective. Our general procedure facilitates the identification of responders who are comprehensively defined by multiple outcomes from various distributions. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

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.

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 .).

Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.

PubMed

Kremenchutzky, Marcelo; O'Connor, Paul; Hohlfeld, Reinhard; Zhang-Auberson, Lixin; von Rosenstiel, Philipp; Meng, Xiangyi; Grinspan, Augusto; Hashmonay, Ron; Kappos, Ludwig

2014-05-01

Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis. This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history. Annualized relapse rate and safety profile of treatment with fingolimod 0.5mg, 1.25mg, or placebo once-daily for 24 months were analyzed in 1272 relapsing multiple sclerosis patients, by subgroups based on disease-modifying therapy history (treatment-naive; prior interferon-β or glatiramer acetate), reason for discontinuation of prior disease-modifying therapy (unsatisfactory therapeutic response or adverse events), and prior disease-modifying therapy duration. Both fingolimod doses significantly reduced annualized relapse rate in patients that received prior interferon-β or glatiramer acetate, discontinued prior disease-modifying therapy owing to unsatisfactory therapeutic effect, were treatment-naive, or had prior disease-modifying therapy duration of >1-3 years (P≤0.0301 for all comparisons vs placebo). Fingolimod 1.25mg resulted in greater reductions in annualized relapse rate in patients that discontinued prior disease-modifying therapy for adverse events or had prior disease-modifying therapy duration of ≤1 year or >3 years (P≤0.0194 vs placebo). Fingolimod demonstrated similar efficacy in relapsing multiple sclerosis patients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Cost-effectiveness of an adjustment group for people with multiple sclerosis and low mood: a randomized trial.

PubMed

Humphreys, Ioan; Drummond, Avril E R; Phillips, Ceri; Lincoln, Nadina B

2013-11-01

To evaluate the cost effectiveness of a psychological adjustment group shown to be clinically effective in comparison with usual care for people with multiple sclerosis. Randomized controlled trial with comparison of costs and calculation of incremental cost effectiveness ratio. Community. People with multiple sclerosis were screened on the General Health Questionnaire 12 and Hospital Anxiety and Depression Scale, and those with low mood were recruited. Participants randomly allocated to the adjustment group received six group treatment sessions. The control group received usual care, which did not include psychological interventions. Outcomes were assessed four and eight months after randomization, blind to group allocation. The costs were assessed from a service use questionnaire and information provided on medication. Quality of life was assessed using the EQ-5D. Of the 311 patients identified, 221 (71%) met the criteria for having low mood. Of these, 72 were randomly allocated to receive treatment and 79 to usual care. Over eight months follow-up there was a decrease in the combined average costs of £378 per intervention respondent and an increase in the costs of £297 per patient in the control group, which was a significant difference (p=0.03). The incremental cost-effectiveness ratio indicated that the cost per point reduction on the Beck depression inventory-II was £118. In the short term, the adjustment group programme was cost effective when compared with usual care, for people with multiple sclerosis presenting with low mood. The longer-term costs need to be assessed.

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

Iron accumulation in multiple sclerosis: an early pathogenic event.

PubMed

LeVine, Steven M; Bilgen, Mehmet; Lynch, Sharon G

2013-03-01

Iron has been shown to accumulate in deep gray matter structures in many forms of multiple sclerosis (MS), but detecting its presence early in the disease course (e.g., clinically isolated syndrome [CIS]) has been less clear. Here, we review a recent study where MRI scanning at 7 T together with susceptibility mapping was performed to assess iron deposition in CIS and control subjects. Susceptibility indicative of iron deposition was found to be increased in the globus pallidus, caudate, putamen and pulvinar of CIS patients compared with controls. The findings suggest that iron deposition is a pathological change that occurs early in the development of MS. Identifying the mechanisms of iron accumulation and determining whether iron promotes pathogenesis in MS are important areas of future research.

Satisfaction with communicative participation as defined by adults with multiple sclerosis: a qualitative study.

PubMed

Yorkston, Kathryn M; Baylor, Carolyn R; Klasner, Estelle R; Deitz, Jean; Dudgeon, Brian J; Eadie, Tanya; Miller, Robert M; Amtmann, Dagmar

2007-01-01

This study examined satisfaction with communicative participation as reported by adults with multiple sclerosis (MS). Eight community-dwelling adults with MS participated in semi-structured interviews. They were asked to discuss their satisfaction with their communication in a variety of situations. Interviews were analyzed using a constant comparative method of qualitative description. Themes derived included: Comfort, consisting of Ease and Confidence; Success of the Outcome, including Function is Achieved and A Connection is Made; and Personal Meaning of Participation, including Personal Preferences, Comparison with the Past, and Thinking about One's Own Communication. Participants described multiple facets of satisfaction with communicative participation. Some of the dimensions were similar to those in existing assessment instruments such as levels of ease or difficulty with performance. Participants did not talk about frequency of activities as a key part of their satisfaction. Implications for identifying intervention targets and treatment outcome measurements are provided. The reader should be able to: 1) define communicative participation and identify key elements of this construct; 2) identify the issues that were most relevant to satisfaction with communicative participation with participants with MS; and 3) identify reasons for greater emphasis on the subjective viewpoint of people with communication disorders in measurement of treatment outcomes.

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

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 ...

Demographics and clinical characteristics of episodic hypothermia in multiple sclerosis.

PubMed

Toledano, Michel; Weinshenker, Brian G; Kaufmann, Timothy J; Parisi, Joseph E; Paz Soldán, M Mateo

2018-03-01

Episodic hypothermia (EH) can occur in multiple sclerosis (MS). The putative mechanism is impairment of thermoregulation due to a presumed demyelinating hypothalamic lesion. To describe a cohort of patients with MS, who developed EH. Patients were identified through review of the Mayo Clinic electronic medical record (1996 to July 2015). Search terms were [multiple sclerosis] or [MS] within the diagnoses field and [hypothermia] within any field. We reviewed records for accuracy of diagnoses and abstracted relevant data. Magnetic resonance imaging (MRI) was reviewed for presence of hypothalamic lesions. Of 156 patients, 34 had concurrent MS and hypothermia. Thirty-two (94%) had progressive disease at EH onset. Median MS duration was 19.9 years, and median expanded disability status scale (EDSS) was 8.0. Most patients presented with alterations in consciousness. Infection was suspected as the precipitating factor in 19 (56%), but clinically/laboratory supported in only 9 (28%). MRI lesions were evident within the hypothalamus in only 4 (14%). EH occurs predominantly in patients with advanced secondary progressive MS. The major manifestation is altered consciousness. Infection is often suspected as causal, but infrequently confirmed. Although commonly implicated, hypothalamic lesions were rarely evident on MRI and were absent in two post-mortem evaluations.

Therapeutic decision making in a new drug era in multiple sclerosis.

PubMed

Keegan, B Mark

2013-02-01

Multiple sclerosis is a presumed autoimmune, inflammatory disease of the central nervous system. Since the early 1990s, medications have been devised, tested, and approved for relapsing forms of multiple sclerosis (MS). MS treatments work by altering the immune system to reduce inflammatory MS activity, thus curtailing clinical relapses (attacks), thereby reducing short-term disability related to the MS attacks. The promise of long-term improvement in MS-related disability remains the most desirable therapeutic goal; to what degree current MS therapies are effective in reducing this is controversial. Recent years have seen a surge in novel MS therapies delivered both parenterally and orally that offer new therapeutic alternatives to MS patients and their treating providers. It remains essential to make an unequivocal diagnosis of MS and identify its clinical course prior to initiating therapies. Switching and altering MS therapies can now be done by rational approaches based on therapeutic efficacy and tolerability; however, these remain nonevidence-based for the most part. The high cost of MS therapies remains a significant concern. A new therapeutic era is at hand offering new hope for patients affected by this chronic, frequently disabling disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

An Updated Meta-Analysis of Risk of Multiple Sclerosis following Infectious Mononucleosis

PubMed Central

Handel, Adam E.; Williamson, Alexander J.; Disanto, Giulio; Handunnetthi, Lahiru; Giovannoni, Gavin; Ramagopalan, Sreeram V.

2010-01-01

Background Multiple sclerosis (MS) appears to develop in genetically susceptible individuals as a result of environmental exposures. Epstein-Barr virus (EBV) infection is an almost universal finding among individuals with MS. Symptomatic EBV infection as manifested by infectious mononucleosis (IM) has been shown in a previous meta-analysis to be associated with the risk of MS, however a number of much larger studies have since been published. Methods/Principal Findings We performed a Medline search to identify articles published since the original meta-analysis investigating MS risk following IM. A total of 18 articles were included in this study, including 19390 MS patients and 16007 controls. We calculated the relative risk of MS following IM using a generic inverse variance with random effects model. This showed that the risk of MS was strongly associated with IM (relative risk (RR) 2.17; 95% confidence interval 1.97–2.39; p<10−54). Discussion Our results establish firmly that a history of infectious mononucleosis significantly increases the risk of multiple sclerosis. Future work should focus on the mechanism of this association and interaction with other risk factors. PMID:20824132

European multiple sclerosis risk variants in the south Asian population.

PubMed

Pandit, Lekha; Ban, Maria; Beecham, Ashley Harris; McCauley, Jacob L; Sawcer, Stephen; D'Cunha, Anitha; Malli, Chaitra; Malik, Omar

2016-10-01

In less than a decade, genomewide association studies have identified over 100 single-nucleotide variants that are associated with increased risk of developing multiple sclerosis. However, since these studies have focused almost exclusively on European populations, it is unclear what role these variants might play in determining risk in other ethnic groups. To assess the effects of European multiple sclerosis-associated risk variants in the south Asian population. Using a combination of chip-based genotyping and next-generation sequencing, we have assessed 109 European-associated variants in a total of 270 cases and 555 controls from the south Asian population. We found that two-thirds of the tested variants (72/109) showed over representation of the European risk allele in south Asian cases (p < 0.0003). In the rest of the Immunochip array, the most associated variant was rs7318477 which maps close to TNFSF13B, the gene for the B-cell-related protein BAFF. Our data indicate substantial overlap in genetic risk architecture between Europeans and south Asians and suggest that the aetiology of the disease may be largely independent of ethnicity. © The Author(s), 2016.

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Venous compression syndrome of internal jugular veins prevalence in patients with multiple sclerosis and chronic cerebro-spinal venous insufficiency.

PubMed

Mandolesi, Sandro; Niglio, Tarcisio; Orsini, Augusto; De Sio, Simone; d'Alessandro, Alessandro; Mandolesi, Dimitri; Fedele, Francesco; d'Alessandro, Aldo

2016-01-01

Analysis of the incidence of Venous Compression Syndrome (VCS) with full block of the flow of the internal jugular veins (IJVs) in patients with Multiple Sclerosis and Chronic cerebro-spinal venous insufficiency. We included 769 patients with MS and CCSVI (299 males, 470 females) and 210 controls without ms and ccsvi (92 males, 118 females). each subject was investigated by echo-color-doppler (ecd). morphological and hemodynamic ecd data were recorded by a computerized mem-net maps of epidemiological national observatory on ccsvi and they were analyzed by mem-net clinical analysis programs. VCS of IJVs occurs in 240 subjects affected by CCSVI and MS (31% of total) and in 12 controls (6% of total). The differences between the two groups are statistical significant (X² = 36.64, p<0.0001). Up to day there are no longitudinal studies that allow us to identify the WC of jugular and/or vertebral veins as etiology of a chronic neurodegenerative disease, but we note that Venous Compression Syndrome of IJVs is strongly associated with MS and CCSVI. Chronic Cerebro-Spinal Venous Insufficiency, Multiple Sclerosis, Venous Compression Syndrome.

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.

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.

Evaluation of longitudinal tracking and data mining for an imaging informatics-based multiple sclerosis e-folder (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ma, Kevin C.; Forsyth, Sydney; Amezcua, Lilyana; Liu, Brent J.

2017-03-01

We have designed and developed a multiple sclerosis eFolder system for patient data storage, image viewing, and automatic lesion quantification results to allow patient tracking. The web-based system aims to be integrated in DICOM-compliant clinical and research environments to aid clinicians in patient treatments and data analysis. The system quantifies lesion volumes, identify and register lesion locations to track shifts in volume and quantity of lesions in a longitudinal study. We aim to evaluate the two most important features of the system, data mining and longitudinal lesion tracking, to demonstrate the MS eFolder's capability in improving clinical workflow efficiency and outcome analysis for research. In order to evaluate data mining capabilities, we have collected radiological and neurological data from 72 patients, 36 Caucasian and 36 Hispanic matched by gender, disease duration, and age. Data analysis on those patients based on ethnicity is performed, and analysis results are displayed by the system's web-based user interface. The data mining module is able to successfully separate Hispanic and Caucasian patients and compare their disease profiles. For longitudinal lesion tracking, we have collected 4 longitudinal cases and simulated different lesion growths over the next year. As a result, the eFolder is able to detect changes in lesion volume and identifying lesions with the most changes. Data mining and lesion tracking evaluation results show high potential of eFolder's usefulness in patientcare and informatics research for multiple sclerosis.

Physical activity and cognitive function in adults with multiple sclerosis: an integrative review.

PubMed

Morrison, Janet D; Mayer, Lori

2017-09-01

To identify and synthesize the research evidence concerning (1) the relationship between physical activity and cognitive performance in persons with multiple sclerosis (MS) and (2) to review the reported effects of physical activity interventions on neurocognitive performance conducted in this population. Relevant peer-reviewed journal articles were identified by searching PubMed, PsychINFO, and SPORTDiscus through May 2016. Full-text articles meeting the inclusion criteria were evaluated for quality using tools developed by the National Institutes of Health. Studies deemed to be of poor quality were excluded from the review. Nineteen studies meeting the inclusion/exclusion criteria were analyzed. Nine studies reported significant relationships between higher levels of physical activity or cardiorespiratory fitness and measures of cognitive function. Data extracted from 10 physical activity intervention studies reported mixed results on the effectiveness of physical activity to improve selected domains of cognitive function in persons with MS. Although correlational studies provide evidence to support a linkage between physical activity and cognitive function in persons with MS, this linkage is confounded by factors that may have influenced the studies' results. Evidence derived from intervention studies that could support a positive effect of physical activity on cognition in persons with MS is equivocal. Implications for Rehabilitation Physical activity has numerous benefits for persons with multiple sclerosis (MS) including improvements in balance, ambulation, depression, fatigue, and quality of life. Structured physical activity programs may contribute to cognitive function stability or improvement in persons with MS.

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.

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.

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.

Cells, Biomarkers, and Posttraumatic Stress Disorder: Evidence for Peripheral Involvement in a Central Disease

DTIC Science & Technology

2012-01-01

including; Alzheimer’s disease (Mac- cioni et al. 2009), Parkinson’s disease (Hirsch and Hunot 2009), spinal cord injury (Chan 2008), multiple sclerosis ...states such as multiple sclerosis (Kraus et al. 2000), human immunodeficiency virus dementia (Fischer- Smith et al. 2001), and meningitis (Cauwels et al...Immunologic mechanisms of multiple sclerosis . Neuroi- maging Clin. N. Am. 18, 577–588. Gaylord K. M. (2006) The psychosocial effects of combat: the frequently

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

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.

Modeling Disease Severity in Multiple Sclerosis Using Electronic Health Records

PubMed Central

Xia, Zongqi; Secor, Elizabeth; Chibnik, Lori B.; Bove, Riley M.; Cheng, Suchun; Chitnis, Tanuja; Cagan, Andrew; Gainer, Vivian S.; Chen, Pei J.; Liao, Katherine P.; Shaw, Stanley Y.; Ananthakrishnan, Ashwin N.; Szolovits, Peter; Weiner, Howard L.; Karlson, Elizabeth W.; Murphy, Shawn N.; Savova, Guergana K.; Cai, Tianxi; Churchill, Susanne E.; Plenge, Robert M.; Kohane, Isaac S.; De Jager, Philip L.

2013-01-01

Objective To optimally leverage the scalability and unique features of the electronic health records (EHR) for research that would ultimately improve patient care, we need to accurately identify patients and extract clinically meaningful measures. Using multiple sclerosis (MS) as a proof of principle, we showcased how to leverage routinely collected EHR data to identify patients with a complex neurological disorder and derive an important surrogate measure of disease severity heretofore only available in research settings. Methods In a cross-sectional observational study, 5,495 MS patients were identified from the EHR systems of two major referral hospitals using an algorithm that includes codified and narrative information extracted using natural language processing. In the subset of patients who receive neurological care at a MS Center where disease measures have been collected, we used routinely collected EHR data to extract two aggregate indicators of MS severity of clinical relevance multiple sclerosis severity score (MSSS) and brain parenchymal fraction (BPF, a measure of whole brain volume). Results The EHR algorithm that identifies MS patients has an area under the curve of 0.958, 83% sensitivity, 92% positive predictive value, and 89% negative predictive value when a 95% specificity threshold is used. The correlation between EHR-derived and true MSSS has a mean R2 = 0.38±0.05, and that between EHR-derived and true BPF has a mean R2 = 0.22±0.08. To illustrate its clinical relevance, derived MSSS captures the expected difference in disease severity between relapsing-remitting and progressive MS patients after adjusting for sex, age of symptom onset and disease duration (p = 1.56×10−12). Conclusion Incorporation of sophisticated codified and narrative EHR data accurately identifies MS patients and provides estimation of a well-accepted indicator of MS severity that is widely used in research settings but not part of the routine medical records. Similar approaches could be applied to other complex neurological disorders. PMID:24244385

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

European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS) - 7th Joint Triennial Congress (October 25-28, 2017 - Paris, France).

PubMed

Díaz, N

2017-10-01

The 7th Triennial Joint conference of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) was held in Paris, France. The meeting brought together attendees from a wide range of disciplines involved in multiple sclerosis (MS) research to explore an extensive program of teaching courses, plenary lectures, oral and poster sessions from approximately 2,000 abstracts submitted, and hot topic and young investigator presentations. These presentations covered topics including diagnostics, therapeutics and biomarkers, as well as a special section for MS nurses. Industry-sponsored symposia were also held. The report from this conference covers the latest developments in MS treatments.

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

PubMed

Uher, T; Vaneckova, M; Sormani, M P; Krasensky, J; Sobisek, L; Dusankova, J Blahova; Seidl, Z; Havrdova, E; Kalincik, T; Benedict, R H B; Horakova, D

2017-02-01

While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment. © 2016 EAN.

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps.

PubMed

Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2015-09-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. © The Author(s) 2014.

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

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

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

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.

Complementary and alternative medicine in multiple sclerosis

PubMed Central

Moawad, Heidi; Shepard, Katie M.; Satya-Murti, Saty

2015-01-01

Summary This article identifies payment policy perspectives of the American Academy of Neurology's guideline on complementary and alternative medicine (CAM) in multiple sclerosis (MS). The guideline is a reliable repository of information for advocating or not recommending certain CAM treatments in MS. It eases the burden of searching for information on each separate CAM treatment. It frequently emphasizes the need for patient counseling. To provide such generally undervalued, but needed, cognitive services, neurologists could use advanced practice providers and patient-friendly visual aids during or between visits. They should also rely on evaluation and management codes that recognize time spent predominantly on counseling or coordination of care. The guideline's categorization of probable effectiveness of certain therapies will not influence coverage decisions because payers do not generally cover CAM therapies. PMID:29443184

Venom therapy in multiple sclerosis.

PubMed

Mirshafiey, Abbas

2007-09-01

To date many people with multiple sclerosis (MS) seek complementary and alternative medicines (CAM) to treat their symptoms as an adjunct to conventionally used therapies. Among the common CAM therapies, there is a renewed interest in the therapeutic potential of venoms in MS. The efficacy of this therapeutic method remains unclear. However, venom-based therapy using bee, snakes and scorpions venom and/or sea anemones toxin has been recently developed because current investigations have identified the various components and molecular mechanism of the effects of venoms under in vitro and in vivo conditions. The aim of this review is to describe the recent findings regarding the role of venoms and their components in treatment of MS disease and that whether venom therapy could be recommended as a complementary treatment or not.

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.

Alemtuzumab Use in Clinical Practice: Recommendations from European Multiple Sclerosis Experts.

PubMed

Berger, Thomas; Elovaara, Irina; Fredrikson, Sten; McGuigan, Chris; Moiola, Lucia; Myhr, Kjell-Morten; Oreja-Guevara, Celia; Stoliarov, Igor; Zettl, Uwe K

2017-01-01

Alemtuzumab (Lemtrada™) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or more disease-modifying therapies (DMTs). In clinical trials, alemtuzumab demonstrated efficacy in treatment-naïve patients with active RRMS and those relapsing on prior DMTs, with a consistent and manageable safety and tolerability profile. The European Union indication provides physicians with significant flexibility regarding treatment decisions, affording the opportunity for individualized treatment. Thus, alemtuzumab may be an appropriate treatment choice across a broad range of patients with RRMS, including, for example, treatment-naïve patients with active disease, patients with highly active disease, or for patients relapsing on prior DMTs. There are several practicalities to consider when using alemtuzumab, including the unique dosing regimen, administered via intravenous infusion on 5 consecutive days at baseline and on 3 consecutive days 12 months later, and as-needed retreatment (3 consecutive days at least 12 months after the last course) in cases of disease recurrence. Additionally, routine monthly monitoring is required for up to 48 months after the last infusion to promptly identify potentially serious autoimmune adverse events. Given these considerations, it is beneficial to gain insight into how alemtuzumab is being used in the real-world clinical setting. Here, we report recommendations from European multiple sclerosis experts regarding best practices for alemtuzumab treatment, including management of adverse events and compliance with ongoing safety monitoring requirements.

Cannabinoids for spasticity due to multiple sclerosis or paraplegia: A systematic review and meta-analysis of randomized clinical trials.

PubMed

da Rovare, Victoria P; Magalhães, Gabriel P A; Jardini, Guilherme D A; Beraldo, Matheus L; Gameiro, Mariel O; Agarwal, Arnav; Luvizutto, Gustavo José; Paula-Ramos, Lucas; Camargo, Samira Esteves Afonso; de Oliveira, Luciane Dias; Bazan, Rodrigo; El Dib, Regina

2017-10-01

Spasticity remains highly prevalent in patients with spinal cord injury and multiple sclerosis. To summarize the effects of cannabinoids compared with usual care, placebo for spasticity due to multiple sclerosis (MS) or paraplegia. Searches of MEDLINE, EMBASE, CENTRAL and LILACS to March 2017 were performed to identify randomized controlled trials. The primary outcomes were spasticity and spasm frequency. The criteria were any patient with MS and spasticity affecting upper or lower limbs or both, and that had a confirmed diagnosis of MS based on validated criteria, or however defined by the authors of the included studies. 16 trials including 2597 patients were eligible. Moderate-certainty evidence suggested a non-statistically significant decrease in spasticity (standardized mean difference (SMD) 0.36 [confidential interval (CI) 95% -0.17 to 0.88; p=0.18; I2=88%]), and spasm frequency (SMD 0.04 [CI 95% -0.15 to 0.22]). There was an increase in adverse events such as dizziness (risk ratio (RR) 3.45 [CI 95% 2.71-4.4; p=0.20; I2=23%]), somnolence (RR 2.9 [CI 95% 1.98-4.23; p=0.77; I2=0%]), and nausea (RR 2.25 [CI 95% 1.62-3.13; p=0.83; I2=0%]). There is moderate certainty evidence regarding the impact of cannabinoids in spasticity (average 0.36 more spasticity; 0.17 fewer to 0.88 more) due to multiple sclerosis or paraplegia, and in adverse events such as dizziness (419 more dizziness/1000 over 19 weeks), somnolence (127 more somnolence/1000 over 19 weeks), and nausea (125 more somnolence/1000 over 19 weeks). Copyright © 2017. Published by Elsevier Ltd.

Diagnostic evaluation of dysphagia in multiple sclerosis patients using a Persian version of DYMUS questionnaire.

PubMed

Pajouh, Sahar Danesh; Moradi, Negin; Shaterzadeh Yazdi, Mohammad Jafar; Latifi, Seyed Mahmoud; Mehravar, Mohammad; Majdinasab, Nastaran; Olapour, Ali Reza; Soltani, Majid; Khanchezar, Fatemeh

2017-10-01

Multiple sclerosis is a chronic neurological disease that may cause swallowing disorders. Dysphagia is a common problem, which patients with different levels of disability may encounter, but it is usually underestimated; therefore, effective assessments need to be performed before any serious complications. The aim of this study was to identify the frequency and characteristics of dysphagia in multiple sclerosis patients of Khuzestan MS society, using a Persian version of Dysphagia in Multiple Sclerosis (DYMUS) questionnaire. 105 consecutive MS patients (84 F and 21 M, mean age 33.8 ± 8.5 years, mean disease duration 3.5 ± 3.1 years, mean Expanded Disability Status Scale (EDSS) 1.8 ± 1.3) participated in the study and the DYMUS questionnaire was administered by a trained speech therapist. The results have shown that 55 MS patients (52.4%) had dysphagia and the dysphagia was significantly associated with the disease course of MS (p = 0.02). However, significant associations between DYMUS values and EDSS, disease duration, age, and gender were not observed. (Respectively, p = 0.4, p = 0.09, p = 0.1, p = 1.0). In the dysphagia group, based on dysphagia severity, 17.1% and 35.2% of patients had mild and alarming dysphagia, respectively. Although, the patients with alarming dysphagia had longer disease duration, higher EDSS score and more with SP, PP and PR disease course than the patients with mild dysphagia, these differences were not significant. The oropharyngeal dysphagia in MS patients is very common even in early stages of the disease; therefore, it is important to assess these patients carefully and to initiate a treatment program if needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment and rehabilitation of driver skills: subjective experiences of people with multiple sclerosis and health professionals.

PubMed

Archer, Cherie; Morris, Libby; George, Stacey

2014-01-01

It is acknowledged in the literature that the physical and cognitive effects of the degenerative neurological condition of multiple sclerosis can impact upon driver safety. The aim of this study was to identify the experiences and needs of people with multiple sclerosis in relation to driver assessment and rehabilitation. Focus group discussions were conducted with people with multiple sclerosis (MS) who were: currently driving; no longer licensed or no longer driving and health professionals. The four themes that emerged from the data were: (1) from self-management to formal assessment - a journey of uncertainty and emotional dilemmas; (2) lost independence with grieving and adjustment by self and family; (3) alternative transport is challenging and unsatisfactory; (4) gaps in information and services exist. The results of this study highlight the need for ongoing support in relation to driving for people with MS, ranging from support for self-management, driving assessment and retraining, and preparation for loss of license. Standardised information needs to be developed and health professionals and licensing authorities require knowledge and skills to ensure driver assessment and rehabilitation processes and resources can better meet the needs of people with MS. There is a need for health professionals to examine driving in people with MS in a holistic manner taking into account the context for the person and the supports available. Self-management and self-assessment emerged as a preferred approach for the participants in this study, indicating that health professionals may need to engage with the process. Tools to support self-assessment of driving abilities for people with MS require further research. Indicators for review and formal assessment of driving abilities is needed. Alternative forms of transport require further investigation and improvement for people with MS.

Efficacy of aquatic therapy for multiple sclerosis: a systematic review.

PubMed

Corvillo, Iluminada; Varela, Enrique; Armijo, Francisco; Alvarez-Badillo, Antonio; Armijo, Onica; Maraver, Francisco

2017-12-01

Multiple sclerosis (MS) is a chronic, inflammatory, progressive, disabling autoimmune disease affecting the central nervous system. Symptoms and signs of MS vary widely and patients may lose their ability to walk. To date the benefits of aquatic therapy often used for rehabilitation in MS patients have not been reviewed. The aim of this study was to systematically review the current state of aquatic treatment for persons with MS (hydrotherapy, aquatic therapy, aquatic exercises, spa therapy) and to evaluate the scientific evidence supporting the benefits of this therapeutic option. The databases PubMed, Scopus, WoS and PEDro were searched to identify relevant reports published from January 1, 2011 to April 30, 2016. Of 306 articles identified, only 10 fulfilled the inclusion criteria: 5 randomized controlled, 2 simple randomized quasi-experimental, 1 semi-experimental, 1 blind controlled pilot and 1 pilot. Evidence that aquatic treatment improves quality of life in affected patients was very good in two studies, good in four, fair in two and weak in two.

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 ...

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.

Immunopharmacological role of the leukotriene receptor antagonists and inhibitors of leukotrienes generating enzymes in multiple sclerosis.

PubMed

Mirshafiey, Abbas; Jadidi-Niaragh, Farhad

2010-06-01

Multiple sclerosis (MS) is a chronic inflammatory disease that involves central nervous system, and is generally associated with demyelination and axonal lesion. The effective factors for initiation of the inflammatory responses have not been known precisely so far. Leukotrienes (LTs) are inflammatory mediators with increased levels in the cerebrospinal fluid of MS patients and in experimental models of multiple sclerosis. Inhibition of LT receptors with specific antagonists can decrease inflammatory responses. In this review article we try to clarify the role of LT receptor antagonists and also inhibitors of enzymes which are involved in LTs generating pathway for treating multiple sclerosis as new targets for MS therapy. Moreover, we suggest that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS.

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.

Diagnostic value of conventional visual evoked potentials applied to patients with multiple sclerosis.

PubMed

Balnytė, Renata; Ulozienė, Ingrida; Rastenytė, Daiva; Vaitkus, Antanas; Malcienė, Lina; Laučkaitė, Kristina

2011-01-01

The aim of this study was to determine the sensitivity and specificity of this classical technique employed at the Hospital of Lithuanian University of Health Sciences for the patients with multiple sclerosis and to assess its possible correlations with affected neurological systems. Pattern shift visual evoked potentials were recorded in 63 patients with multiple sclerosis, 17 (27%) of whom had a history of optic neuritis, and in 63 control patients with other neurological diseases. The latencies and amplitudes of P100 were measured. In total, 126 patients were referred to the inpatient department of neurology for differential diagnosis of demyelinating disorders between January and December of 2007. Abnormalities of visual evoked potentials were observed by 73% more frequently in patients with multiple sclerosis than in control patients (α=0.05, β<0.01). The combined monocular/interocular test showed a specificity of 90.5% and a sensitivity of 82.5%. The probability of an affection of the pyramidal system was 5 times greater (95% CI, 2.2-11.0; P<0.01) and the probability of the optic pathways involvement was 4.8 times greater (95% CI, 1.9-11.9; P<0.01) in patients with multiple sclerosis than in controls. Conventional visual evoked potentials must be reappraised in light of their diagnostic value in multiple sclerosis given their high diagnostic efficiency, relatively easy, short, and cheap implementation, and easy availability in everyday clinical practice.

Validity and reliability of the multidimensional assessment of fatigue scale in Iranian patients with relapsing-remitting subtype of multiple sclerosis.

PubMed

Behrangrad, Shabnam; Kordi Yoosefinejad, Amin

2018-03-01

The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart. Construct validity of the MAFS was assessed with the Fatigue Impact Scale. The MAFS had high internal consistency (Cronbach's alpha >0.9) and 3-d test-retest reliability (intraclass correlation coefficient = 0.99). Correlation between the Fatigue Impact Scale and MAFS was high (r = 0.99). Correlation between MAFS scores and the Expanded Disability Status Scale was also strong (r = 0.85). Questionnaire items showed acceptable item-scale correlation (0.968-0.993). The Persian version of the MAFS appears to be a valid and reliable questionnaire. It is an appropriate short multidimensional instrument to assess fatigue in patients with multiple sclerosis in clinical practice and research. Implications for Rehabilitation The Persian version of Multidimensional Assessment of Fatigue is a valid and reliable instrument for the assessment and monitoring the fatigue in Persian-language patients with multiple sclerosis. It is very easy to administer and a time efficient scale in comparison to other instruments evaluating fatigue in patients with multiple sclerosis.

Pain and Cognition in Multiple Sclerosis.

PubMed

Scherder, R; Kant, N; Wolf, E; Pijnenburg, A C M; Scherder, E

2017-10-01

The goal of the present study was to examine the relationship between pain and cognition in patients with multiple sclerosis. Cross-sectional. Nursing home and personal environment of the investigators. Two groups of participants were included: 91 patients with multiple sclerosis and 80 matched control participants. The level of pain was measured by the following pain scales: Number of Words Chosen-Affective, Colored Analogue Scale for pain intensity and suffering from pain, and the Faces Pain Scale. Mood was tested by administering the Beck Depression Inventory and the Symptom Check List-90 anxiety and depression subscale. Global cognitive functioning was assessed by the Mini Mental State Examination. Memory and executive functions were assessed by several neuropsychological tests. Multiple sclerosis (MS) patients scored significantly lower than control participants on the majority of the neuropsychological tests. The MS patients experienced more pain compared with control participants, despite the fact that they were taking significantly more pain medication. No significant correlation was observed between cognition and pain in MS patients. Verbal working memory explained 10% of pain intensity (trend). Mood appeared to be a significant predictor of pain in patients with multiple sclerosis. The lack of a relationship between cognition and pain might be explained by the fact that, compared with control participants, patients with multiple sclerosis activate other non-pain-related areas to perform executive functions and memory tasks. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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.

Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis.

PubMed

Petzold, Axel; Balcer, Laura J; Calabresi, Peter A; Costello, Fiona; Frohman, Teresa C; Frohman, Elliot M; Martinez-Lapiscina, Elena H; Green, Ari J; Kardon, Randy; Outteryck, Olivier; Paul, Friedemann; Schippling, Sven; Vermersch, Patrik; Villoslada, Pablo; Balk, Lisanne J

2017-10-01

Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots. Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference -20·10 μm, 95% CI -22·76 to -17·44; p<0·0001) and in MSNON eyes (-7·41 μm, -8·98 to -5·83; p<0·0001). The macula showed RNFL thinning of -6·18 μm (-8·07 to -4·28; p<0·0001) in MSON eyes and -2·15 μm (-3·15 to -1·15; p<0·0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was -16·42 μm (-19·23 to -13·60; p<0·0001) for MSON eyes and -6·31 μm (-7·75 to -4·87; p<0·0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0·77 μm, 0·25 to 1·28; p=0·003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1·21 μm, 0·24 to 2·19; p=0·01). The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research. None. Copyright © 2017 Elsevier Ltd. 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.

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

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

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

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... 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.

The indirect costs of multiple sclerosis: systematic review and meta-analysis.

PubMed

Stawowczyk, Ewa; Malinowski, Krzysztof Piotr; Kawalec, Paweł; Moćko, Paweł

2015-01-01

The aim of this systematic review is to collect and summarize all current data on the indirect costs related to absenteeism and presenteeism associated with multiple sclerosis. Searches were conducted using Medline, Embase and Centre for Reviews and Dissemination databases. All collected costs were recalculated to average annual cost per patient, expressed in 2014 prices US$ using the consumer price index and purchasing power parity (scenario 1) and expressed as proportion of specific gross domestic product in current local currency unit to adjust for country's development (scenario 2). Identified studies were then analyzed in order to assess their possible inclusion in the meta-analysis. The authors identified 63 records, of which 23 were eligible for meta-analysis. Overall indirect cost per patient calculated in scenario 1 was as high as US$20,167 with US$22,197 in Europe, US$17,382 in North America and US$153 in Asia. Overall indirect cost per patient calculated in scenario 2 was equal to US$16,939, with US$19,612 in Europe, US$11,592 in North America and US$899 in Asia. Overall indirect costs varied from US$3726 for patients with EDSS score less than 3 to US$19,264 for patients with Expanded Disability Status Scale score grater that 7. This review revealed the great economic burden of multiple sclerosis on society. The authors observed a great variety of the considered components of indirect costs and their definitions. Costs were higher for Europe than for other continents and were also higher for patients with a higher Expanded Disability Status Scale score.

Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

PubMed

Artusi, Carlo Alberto; Farooqi, Ashar; Romagnolo, Alberto; Marsili, Luca; Balestrino, Roberta; Sokol, Leonard L; Wang, Lily L; Zibetti, Maurizio; Duker, Andrew P; Mandybur, George T; Lopiano, Leonardo; Merola, Aristide

2018-03-06

In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

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

PubMed

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

2011-04-15

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

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

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.

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.

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.

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.

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.

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.

Factors Affecting Employment Among Informal Caregivers Assisting People with Multiple Sclerosis

PubMed Central

Huang, Chunfeng; Zheng, Zhida

2013-01-01

The objective of this study was to identify characteristics of informal caregivers, caregiving, and the people with multiple sclerosis (MS) receiving assistance that are associated with reduced caregiver employment. Data were collected during telephone interviews with 530 MS caregivers, including 215 employed caregivers, with these survey data analyzed using logistic regression. Poorer cognitive ability by the care recipient to make decisions about daily tasks and more caregiving hours per week predicted reduced caregiver employment. Better physical health domains of caregiver quality of life were associated with significantly lower odds of reduced employment. Health professionals treating informal caregivers, as well as those treating people with MS, need to be aware of respite, support, and intervention programs available to MS caregivers and refer them to these programs, which could reduce the negative impact of caregiving on employment. PMID:24453784

Effect of exercise interventions on perceived fatigue in people with multiple sclerosis: synthesis of meta-analytic reviews.

PubMed

Safari, Reza; Van der Linden, Marietta L; Mercer, Tom H

2017-06-01

Although exercise training has been advocated as a nonpharmacological treatment for multiple sclerosis (MS) related fatigue, no consensus exists regarding its effectiveness. To address this, we collated meta-analytic reviews that explored the effectiveness of exercise training for the treatment of MS-related fatigue. We searched five online databases for relevant reviews, published since 2005, and identified 172 records. Five reviews were retained for systematic extraction of information and evidence quality analysis. Although our review synthesis indicated that exercise training interventions have a moderate effect on fatigue reduction in people with MS, no clear insight was obtained regarding the relative effectiveness of specific types or modes of exercise intervention. Moreover, Grading of Recommendation Assessment, Development and Evaluation revealed that the overall quality of evidence emanating from these five reviews was 'very low'.

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

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.

Physical activity and exercise training in multiple sclerosis: a review and content analysis of qualitative research identifying perceived determinants and consequences.

PubMed

Learmonth, Yvonne C; Motl, Robert W

2016-01-01

This systematic review was conducted to provide rich and deep evidence of the perceived determinants and consequences of physical activity and exercise based on qualitative research in multiple sclerosis (MS). Electronic databases and article reference lists were searched to identify qualitative studies of physical activity and exercise in MS. Studies were included if they were written in English and examined consequences/determinants of physical activity in persons with MS. Content analysis of perceived determinants and consequences of physical activity and exercise was undertaken using an inductive analysis guided by the Physical Activity for people with Disabilities framework and Social Cognitive Theory, respectively. Nineteen articles were reviewed. The most commonly identified perceived barriers of physical activity and exercise were related to the environmental (i.e. minimal or no disabled facilities, and minimal or conflicting advice from healthcare professionals) and related to personal barriers (i.e. fatigue, and fear and apprehension). The most commonly identified perceived facilitators of physical activity were related to the environment (i.e. the type of exercise modality and peer support) and related to personal facilitators (i.e. appropriate exercise and feelings of accomplishment). The most commonly identified perceived beneficial consequences of physical activity and exercise were maintaining physical functions, increased social participation and feelings of self-management and control. The most commonly identified perceived adverse consequences were increased fatigue and feelings of frustration and lost control. Results will inform future research on the perceived determinants and consequences of physical activity and exercise in those with MS and can be adopted for developing professional education and interventions for physical activity and exercise in MS. Physical activity and exercise behaviour in people with multiple sclerosis (MS) is subject to a number of modifiable determinants. Healthcare professionals working to promote physical activity and exercise in those with MS should choose to endorse the positive benefits of participation. Future physical activity interventions for those with MS may be improved by incorporating behavioural management strategies.

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.

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

PubMed

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

2017-03-14

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

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 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.

Physical and social environment and the risk of multiple sclerosis.

PubMed

Magyari, Melinda; Koch-Henriksen, Nils; Pfleger, Claudia C; Sørensen, Per Soelberg

2014-09-01

The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men. The rapid epidemiological changes suggest that environmental factors may modify the risk of MS. To investigate whether occupational, physical, or social environmental influence the risk of MS differently in women than in men. The cohort consists of all 1403 patients (939 women, 464 men) identified through Danish Multiple Sclerosis Registry aged 1-55 of years at clinical onset between 2000 and 2004, and up to 25 control persons for each case, matched by sex, year of birth and residential municipality. The same cohort was previously used to investigate the influence of the reproductive factors on the risk of MS. By linkage to Danish population registers we found a slight albeit statistically significant excess for 6 female MS patients who had been employed in agriculture: OR 3.52; 95% CI 1.38-9.00, p=0.008 (0.046 when corrected for multiple significance) and a trend for exposure to outdoor work in 12 : OR 1.94, 95% CI 1.06-3.55, p=0.03 (0.09 when corrected for multiple significance), but the numbers of cases were small, and the effects were not found in men. Educational level, housing conditions in youth, or the presence of children unrelated by blood in the household did not influence the risk of MS. Our study did not reveal any additional factors beyond the previously published childbirths which could explain the extent of the MS incidence increase in women. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Rural-urban analyses of health-related quality of life among people with multiple sclerosis.

PubMed

Buchanan, Robert J; Zhu, Li; Schiffer, Randolph; Radin, Dagmar; James, Wesley

2008-01-01

Health-related quality of life (HRQOL) is a multi-dimensional construct including aspects of life quality or function that are affected by physical health and symptoms, psychosocial factors, and psychiatric conditions. HRQOL gives a broader measure of the burden of disease than physical impairment or disability levels. To identify factors associated with HRQOL among people with multiple sclerosis (MS) utilizing the SF-8 Health Survey. Data presented in this study were collected in a survey of 1,518 people with MS living in all 50 states. The survey sample was randomly selected from the database of the National Multiple Sclerosis Society, using ZIP codes to recruit the survey sample. A multiple linear regression model was employed to analyze the survey data, with the Physical Component Summary and the Mental Component Summary of the SF-8 the dependent variables. Independent variables were demographic characteristics, MS-disease characteristics, and health services utilized. People with MS in rural areas tended to report lower physically related HRQOL. Worsening MS symptoms were associated with reduced physical and mental dimensions of HRQOL. In addition, people with MS who received a diagnosis of depression tended to have reduced physical and mental dimensions of HRQOL. Receiving MS care at an MS clinic was associated with better physically related HRQOL, while having a neurologist as principal care physician was associated with better mental-related HRQOL. The challenge is to increase the access that people living with MS in rural areas have to MS-focused specialty care.

Predictors of the physical impact of Multiple Sclerosis following community-based, exercise trial.

PubMed

Kehoe, M; Saunders, J; Jakeman, P; Coote, S

2015-04-01

Studies evaluating exercise interventions in people with multiple sclerosis (PwMS) demonstrate small to medium positive effects and large variability on a number of outcome measures. No study to date has tried to explain this variability. This paper presents a novel exploration of data examining the predictors of outcome for PwMS with minimal gait impairment following a randomised, controlled trial evaluating community-based exercise interventions (N = 242). The primary variable was the physical component of the Multiple Sclerosis Impact Scale-29, version 2 (MSIS-29, v2) after a 10-week, controlled intervention period. Predictors were identified a priori and were measured at baseline. Multiple linear regression was conducted. Four models are presented lower MSIS-29, v2 scores after the intervention period were best predicted by a lower baseline MSIS-29,v2, a lower baseline Modified Fatigue Impact Score (physical subscale), randomisation to an exercise intervention, a longer baseline walking distance measured by the Six Minute Walk Test and female gender. This model explained 57.4% of the variance (F (5, 211) = 59.24, p < 0.01). These results suggest that fatigue and walking distance at baseline contribute significantly to predicting MSIS-29, v29 (physical component) after intervention, and thus should be the focus of intervention and assessment. Exercise is an important contributor to minimising the physical impact of MS, and gender-specific interventions may be warranted. © The Author(s), 2014.

Managing the oral side-effects of medications used to treat multiple sclerosis.

PubMed

Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J

2017-09-01

Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

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)

Real-world persistence with fingolimod for the treatment of multiple sclerosis: A systematic review and meta-analysis.

PubMed

Kantor, Daniel; Johnson, Kristen; Vieira, Maria Cecilia; Signorovitch, James; Li, Nanxin; Gao, Wei; Koo, Valerie; Duchesneau, Emilie; Herrera, Vivian

2018-05-15

To systematically review reports of fingolimod persistence in the treatment of relapsing-remitting multiple sclerosis (RRMS) across data sources and practice settings, and to develop a consensus estimate of the 1-year real-world persistence rate. A systematic literature review was conducted (MEDLINE, EMBASE, and abstracts from selected conferences [2013-2015]) to identify observational studies reporting 1-year fingolimod persistence among adult patients with RRMS (sample size ≥50). A random-effects meta-analysis was performed to estimate a synthesized 1-year persistence rate and to assess heterogeneity across studies. Of 527 publications identified, 25 real-world studies reporting 1-year fingolimod persistence rates were included. The studies included patients from different data sources (e.g., administrative claims, electronic medical records, or registries), used different definitions of persistence (e.g., based on prescriptions refills, patient report, or prescription orders), and spanned multiple geographic regions. Reported 1-year persistence rates ranged from 72%-100%, and exhibited statistical evidence of heterogeneity (I 2  = 93% of the variability due to heterogeneity across studies). The consensus estimate of the 1-year persistence rate was 82% (95% confidence interval: 79%-85%). Across heterogeneous study designs and patient populations found in real-world studies, the consensus 1-year fingolimod persistence rate exceeded 80%, consistent with persistence rates identified in the recently-completed trial, PREFERMS. Copyright © 2018. Published by Elsevier B.V.

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 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.

Identification of rare genetic variation of NLRP1 gene in familial multiple sclerosis.

PubMed

Maver, Ales; Lavtar, Polona; Ristić, Smiljana; Stopinšek, Sanja; Simčič, Saša; Hočevar, Keli; Sepčić, Juraj; Drulović, Jelena; Pekmezović, Tatjana; Novaković, Ivana; Alenka, Hodžić; Rudolf, Gorazd; Šega, Saša; Starčević-Čizmarević, Nada; Palandačić, Anja; Zamolo, Gordana; Kapović, Miljenko; Likar, Tina; Peterlin, Borut

2017-06-16

The genetic etiology and the contribution of rare genetic variation in multiple sclerosis (MS) has not yet been elucidated. Although familial forms of MS have been described, no convincing rare and penetrant variants have been reported to date. We aimed to characterize the contribution of rare genetic variation in familial and sporadic MS and have identified a family with two sibs affected by concomitant MS and malignant melanoma (MM). We performed whole exome sequencing in this primary family and 38 multiplex MS families and 44 sporadic MS cases and performed transcriptional and immunologic assessment of the identified variants. We identified a potentially causative homozygous missense variant in NLRP1 gene (Gly587Ser) in the primary family. Further possibly pathogenic NLRP1 variants were identified in the expanded cohort of patients. Stimulation of peripheral blood mononuclear cells from MS patients with putatively pathogenic NLRP1 variants showed an increase in IL-1B gene expression and active cytokine IL-1β production, as well as global activation of NLRP1-driven immunologic pathways. We report a novel familial association of MS and MM, and propose a possible underlying genetic basis in NLRP1 gene. Furthermore, we provide initial evidence of the broader implications of NLRP1-related pathway dysfunction in MS.

Factors perceived as being related to accidental falls by persons with multiple sclerosis.

PubMed

Nilsagård, Ylva; Denison, Eva; Gunnarsson, Lars-Gunnar; Boström, Katrin

2009-01-01

This study explores and describes factors that persons with multiple sclerosis (MS) perceive as being related to accidental falls. A qualitative content analysis with primarily deductive approach was conducted using the International Classification of Functioning, Disability and Health. Twelve persons with MS, and identified as fallers, were interviewed. Factors perceived to cause accidental falls that had not previously been targeted in MS populations in relation to falls were identified as divided attention, reduced muscular endurance, fatigue and heat sensitivity. Previously reported risk factors such as changed gait pattern, limited walking ability, impaired proprioception, vision and spasticity were supported. Activities involving walking, recreation and leisure, maintaining and changing body position, lifting or carrying, taking care of the home, washing the body, moving around, preparing meals and housekeeping were limited and considered to be risk activities. Supportive persons and assistive device reduced falls, and unsuitable physical environments and climate conditions induced falls. Several preventative strategies were described as partially compensating for the impairments, limitations and restrictions. Investigating accidental falls using the perspective of the patient gave important information about variables not earlier targeted in MS research.

[The portrayal of multiple sclerosis in television series].

PubMed

Karenberg, A

2009-04-01

An increasing number of television series deal with neurological disorders, including fictional portrayals of multiple sclerosis (MS). The aim of this paper was to analyze every available TV episode with an MS character. Productions were identified by film databases and by hand search. Each episode was evaluated along neurologic and cinematic lines. Between 1985 and 2006, portrayals of MS appeared in 17 episodes produced in Germany, the US, and the UK. The frequency of symptoms shown onscreen strongly differed from epidemiological data. In particular sensory, cognitive, and bladder symptoms as well as difficulties with sexual function were under-represented. The authenticity of the disease depiction was strongly dependent upon the genre. Coping stories could be identified as the most prominent genre. Television patients were often portrayed as "brave fighters", "refined characters", and "afflicted without symptoms". Television series attract millions of viewers and thus shape the public image of a disease. Sound knowledge of how symptoms, diagnosis, and therapeutic options are presented in mass media is therefore indispensable for all who deal with MS patients, relatives, and caregivers.

Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis

PubMed Central

Konradi, Christine; Sillivan, Stephanie E.; Clay, Hayley B.

2011-01-01

Gene expression studies of bipolar disorder (BPD) have shown changes in transcriptome profiles in multiple brain regions. Here we summarize the most consistent findings in the scientific literature, and compare them to data from schizophrenia (SZ) and major depressive disorder (MDD). The transcriptome profiles of all three disorders overlap, making the existence of a BPD-specific profile unlikely. Three groups of functionally related genes are consistently expressed at altered levels in BPD, SZ and MDD. Genes involved in energy metabolism and mitochondrial function are downregulated, genes involved in immune response and inflammation are upregulated, and genes expressed in oligodendrocytes are downregulated. Experimental paradigms for multiple sclerosis demonstrate a tight link between energy metabolism, inflammation and demyelination. These studies also show variabilities in the extent of oligodendrocyte stress, which can vary from a downregulation of oligodendrocyte genes, such as observed in psychiatric disorders, to cell death and brain lesions seen in multiple sclerosis. We conclude that experimental models of multiple sclerosis could be of interest for the research of BPD, SZ and MDD. PMID:21310238

Multiple sclerosis: 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.

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

Cognitive reserve in multiple sclerosis: Protective effects of education.

PubMed

Martins Da Silva, Ana; Cavaco, Sara; Moreira, Inês; Bettencourt, Andreia; Santos, Ernestina; Pinto, Cláudia; Gonçalves, Alexandra; Coutinho, Ester; Samões, Raquel; Dias, Cláudia C; Teixeira-Pinto, Armando; Da Silva, Berta Martins; Montalban, Xavier

2015-09-01

Recent data suggest that cognitive reserve modulates the adverse effects of multiple sclerosis (MS) pathology on cognitive functioning; however, the protective effects of education in MS are still unclear. To explore education as an indicator of cognitive reserve, while controlling for demographic, clinical and genetic features. A total of 419 MS patients and 159 healthy comparison (HC) subjects underwent a comprehensive neuropsychological (NP) assessment, and answered the Hospital Anxiety and Depression Scale. Based on the HC data, MS patients' NP scores were adjusted for sex, age and education; and the estimated 5(th) percentile (or 95(th) percentile, when appropriate) was used to identify any deficits. Patients also performed the Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1 and apolipoprotein E (ApoE) genotypes were investigated. Patients with higher education were less likely (p < 0.05) to have cognitive deficits than those with lower education, even when controlling for other covariates. Other significant predictors of cognitive deficit were: age, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course. No significant association was found with the HLA-DRB1*15:01 or ApoE ε4 alleles. These results provide support to the use of education as a proxy of cognitive reserve in MS and stress the need to take into account education when approaching cognition in MS. © The Author(s), 2015.

Employment, disability pension and income for children with parental multiple sclerosis.

PubMed

Moberg, Julie Yoon; Laursen, Bjarne; Koch-Henriksen, Nils; Thygesen, Lau Caspar; Brødsgaard, Anne; Soelberg Sørensen, Per; Magyari, Melinda

2017-07-01

Little is known about the consequences of parental multiple sclerosis (MS) on offspring's socioeconomic circumstances. To investigate employment, disability pension and income in offspring of parents with MS compared with matched reference persons in a nationwide register-based cohort study. All Danish-born persons with onset of MS during 1950-1986 were retrieved from the Danish Multiple Sclerosis Registry. Their offspring were identified using the Civil Registration System. One random offspring from each sibship was matched by sex and year of birth with eight random reference persons. We included 2456 MS offspring and 19,648 reference persons. At age 30, employment was lower among MS offspring than reference children (odds ratio (OR): 0.89; 95% confidence interval (CI): 0.84-0.95; p = 0.0003), and they more often received disability pension (OR: 1.31; 95% CI: 1.15-1.50; p < 0.0001) at ages 30 and 40 but not at age 50. Although the mean income was not significantly lower for the MS offspring cohort, most of them attained an annual personal income below 250,000 DKK (Danish krone), that is, ~33,650 EUR (OR: 0.91; 95% CI: 0.84-0.99; p = 0.04). Having had a parent with MS may affect employment and increase the risk of disability pension and low income in adult life.

A qualitative study exploring the usability of Nintendo Wii Fit among persons with multiple sclerosis.

PubMed

Plow, Matthew; Finlayson, Marcia

2014-03-01

The purpose of this study was to examine the usability of Nintendo Wii Fit to promote physical activity in adults with multiple sclerosis. Qualitative interviews were conducted as part of a pilot study that examined the health outcomes of a 14-week Wii Fit home-exercise programme in 30 adults with multiple sclerosis. We found participants reported that Wii Fit helped build confidence in abilities, achieve goals related to engagement in leisure activities and remove barriers associated with going to a gym to exercise. However, Wii Fit induced initial reactions of intimidation and worries about falling, and feedback during game play reminded participants of their impairments. Wii Fit was limited in its customizability to accommodate different functional levels. Understanding how to improve the usability and customizability of commercially available exergaming technology could be of benefit to people with disabling conditions. Before conducting randomized controlled trials of commercially available exergaming technology in adults with disabling conditions, we recommend that strategies be identified to remove usability barriers so those with moderate impairments can be included in the trial. This will reduce the likelihood of ceiling effects and clinical irrelevance. In terms of clinical recommendations, rehabilitation professionals need to consider patients' functional level, surrounding environment and preferences when prescribing a Wii Fit-based exercise programme. Copyright © 2013 John Wiley & Sons, Ltd.

Estimation of the marginal effect of regular drug use on multiple sclerosis in the Iranian population.

PubMed

Abdollahpour, Ibrahim; Nedjat, Saharnaz; Mansournia, Mohammad Ali; Schuster, Tibor

2018-01-01

There are only few reports regarding the role of lifetime drug or substance use in multiple sclerosis (MS) etiology. In this study, we investigated the potential effect of drug or substance exposure on the onset of MS diagnosis. We conducted a population-based incident case control study in Tehran. Cases (n = 547) were 15-50 years old persons with MS identified from the Iranian Multiple Sclerosis Society (IMSS) register during August 7, 2013, and November 17, 2015. Population-based controls (n = 1057) were 15-50 years old and were recruited by random digit telephone dialing. Inverse-probability-of-treatment weighing (IPTW) using two sets of propensity scores (PSs) was used to estimate marginal incidence odds ratios (ORs) for MS contrasting pre-specified substance use. The estimated marginal OR was 6.03 (95% confidence interval: 3.54;10.3, using trimmed weights at the 95th percentile of the stabilized weight distribution) in both IPTW analyses comparing lifetime substance use (opioids, cannabis, inhalants, hallucinogens and stimulants) for at least one time monthly during a six-months or longer period vs. no such history of drug use. Subject to limitation of causal claims based on case-control studies, this study suggests that monthly drug or substance use for a period of at least six consecutive months, may increase the risk of MS by factor 3.5 or higher.

Factors affecting continuation of clean intermittent catheterisation in people with multiple sclerosis: Results of the COSMOS mixed-methods study.

PubMed

McClurg, Doreen; Bugge, Carol; Elders, Andrew; Irshad, Tasneem; Hagen, Suzanne; Moore, Katherine N; Buckley, Brian; Fader, Mandy

2018-04-01

Clean intermittent catheterisation (CIC) is often recommended for people with multiple sclerosis (MS). To determine the variables that affect continuation or discontinuation of the use of CIC. A three-part mixed-method study (prospective longitudinal cohort ( n = 56), longitudinal qualitative interviews ( n = 20) and retrospective survey ( n = 456)) was undertaken, which identified the variables that influenced CIC continuation/discontinuation. The potential explanatory variables investigated in each study were the individual's age, gender, social circumstances, number of urinary tract infections, bladder symptoms, presence of co-morbidity, stage of multiple sclerosis and years since diagnosis, as well as CIC teaching method and intensity. For some people with MS the prospect of undertaking CIC is difficult and may take a period of time to accept before beginning the process of using CIC. Ongoing support from clinicians, support at home and a perceived improvement in symptoms such as nocturia were positive predictors of continuation. In many cases, the development of a urinary tract infection during the early stages of CIC use had a significant detrimental impact on continuation. Procedures for reducing the incidence of urinary tract infection during the learning period (i.e. when being taught and becoming competent) should be considered, as well as the development of a tool to aid identification of a person's readiness to try CIC.

A Systematic Review and Meta-Analysis of the Brief Cognitive Assessment for Multiple Sclerosis (BICAMS).

PubMed

Corfield, Freya; Langdon, Dawn

2018-06-19

Multiple sclerosis (MS) is a neurological disease of the central nervous system which can lead to a range of severe physical disabilities. A large proportion of those affected will experience cognitive impairment, which is associated with a worse prognosis. Effective assessment of cognition in MS has been problematic due to a lack of suitable scales. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was developed in 2010 as part of an international endeavour to facilitate cognitive assessment. The aim of this systematic review and meta-analysis was to synthesise the available literature published as part of the BICAMS international validation protocol. A literature search conducted using PubMed, PsycINFO and Google Scholar identified 16 studies for inclusion in the systematic review, 14 of which could be included in a meta-analysis. BICAMS has been widely validated across 11 languages and 14 individual cultures and locations. The meta-analysis demonstrated that BICAMS identified significantly reduced cognitive functioning in adults with MS compared to healthy controls. This was true for all three cognitive domains assessed by BICAMS: information processing speed (g = 0.943, 95% CI 0.839, 1.046, g < 0.001), immediate verbal recall memory (g = 0.688, 95% CI 0.554, 0.822, p < 0.001) and immediate visual recall memory (g = 0.635, 95% CI 0.534, 0.736, p < 0.001). BICAMS has been widely applied across cultures and languages to assess cognition in MS. BICAMS offers a feasible, cost-effective means of assessing cognition in MS worldwide. Further validation studies are underway to support this project.

Astrocytic TYMP and VEGFA drive blood–brain barrier opening in inflammatory central nervous system lesions

PubMed Central

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M.; Mariani, John N.; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S.

2015-01-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood–brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood–brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood–brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood–brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood–brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood–brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood–brain barrier breakdown. PMID:25805644

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

PubMed

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

2018-05-01

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

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.

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.

Cognitive evaluation by tasks in a virtual reality environment in multiple sclerosis.

PubMed

Lamargue-Hamel, Delphine; Deloire, Mathilde; Saubusse, Aurore; Ruet, Aurélie; Taillard, Jacques; Philip, Pierre; Brochet, Bruno

2015-12-15

The assessment of cognitive impairment in multiple sclerosis (MS) requires large neuropsychological batteries that assess numerous domains. The relevance of these assessments to daily cognitive functioning is not well established. Cognitive ecological evaluation has not been frequently studied in MS. The aim of this study was to determine the interest of cognitive evaluation in a virtual reality environment in a sample of persons with MS with cognitive deficits. Thirty persons with MS with at least moderate cognitive impairment were assessed with two ecological evaluations, an in-house developed task in a virtual reality environment (Urban DailyCog®) and a divided attention task in a driving simulator. Classical neuropsychological testing was also used. Fifty-two percent of the persons with MS failed the driving simulator task and 80% failed the Urban DailyCog®. Virtual reality assessments are promising in identifying cognitive impairment in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiple sclerosis and continence issues: an exploratory study.

PubMed

Wollin, Judy; Bennie, Mary; Leech, Christine; Windsor, Carol; Spencer, Nancy

The study described in this article aimed to identify issues relating to incontinence and assess the impact of referral to a continence adviser on the lives of people with multiple sclerosis (MS). The study design used an in-depth, two-phase anonymous mail survey within a general community as nominated by the participants. Fifty-six people participated in phase 1 and eleven people completed phase 2. The results indicated that incontinence is a problem for the vast majority of participants--people with MS. One-third of the eligible participants took up the option of a consultation, assessment and treatment from a continence nurse. Reasons for not taking up the visit from the continence nurse included 'managing OK', 'didn't think it would help', 'embarrassed' and 'too busy'. Increasing awareness of urinary incontinence in the community is important and education needs to focus on at-risk groups in presenting the range of options available to assist people experiencing incontinence.

Defining the clinical course of multiple sclerosis

PubMed Central

Reingold, Stephen C.; Cohen, Jeffrey A.; Cutter, Gary R.; Sørensen, Per Soelberg; Thompson, Alan J.; Wolinsky, Jerry S.; Balcer, Laura J.; Banwell, Brenda; Barkhof, Frederik; Bebo, Bruce; Calabresi, Peter A.; Clanet, Michel; Comi, Giancarlo; Fox, Robert J.; Freedman, Mark S.; Goodman, Andrew D.; Inglese, Matilde; Kappos, Ludwig; Kieseier, Bernd C.; Lincoln, John A.; Lubetzki, Catherine; Miller, Aaron E.; Montalban, Xavier; O'Connor, Paul W.; Petkau, John; Pozzilli, Carlo; Rudick, Richard A.; Sormani, Maria Pia; Stüve, Olaf; Waubant, Emmanuelle; Polman, Chris H.

2014-01-01

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined. PMID:24871874

The structural and functional role of myelin fast-migrating cerebrosides: pathological importance in multiple sclerosis

PubMed Central

Podbielska, Maria; Levery, Steven B; Hogan, Edward L

2011-01-01

A family of neutral glycosphingolipids containing a 3-O-acetyl-sphingosine galactosylceramide (3-SAG) has been characterized. Seven new derivatives of galactosylceramide (GalCer), designated as fast-migrating cerebrosides (FMCs) by TLC retention factor, have been identified. The simplest compounds – FMC-1 and FMC-2 – of this series have been characterized as the 3-SAG containing nonhydroxy and hydroxy fatty acyl, respectively. The next two – FMC-3 and FMC-4 – add 6-O-acetyl-galactose and the most complex glycosphingolipids, FMC-5, -6 and -7, are 2,3,4,6-tetra-O-acetyl-3-SAG. These hydrophobic myelin lipid biomarkers coappear with GalCer during myelinogenesis and disappear along with GalCer in de- or dys-myelinating disorders. Myelin lipid antigens, including FMCs, are keys to myelin biology, opening the possibility of new and novel immune modulatory tools for treatment of autoimmune diseases including multiple sclerosis. PMID:22701512

Reducing falls and improving mobility in multiple sclerosis.

PubMed

Sosnoff, Jacob J; Sung, JongHun

2015-06-01

Falls are common in persons with multiple sclerosis (MS), and are related to physical injury and reduce the quality of life. Mobility impairments are a significant risk factor for falls in persons with MS. Although there is evidence that mobility in persons with MS can be improved with rehabilitation, much less is known about fall prevention. This review focuses on fall prevention in persons with MS. Ten fall prevention interventions consisting of 524 participants with a wide range of disability were systematically identified. Nine of the 10 investigations report a reduction in falls and/or proportion of fallers following treatment. The vast majority observed an improvement in balance that co-occurred with the reduction in falls. Methodological limitations preclude any firm conclusions. Numerous gaps in the understanding of fall prevention in persons with MS are discussed. Well-designed randomized control trials targeting mobility and falls are warranted.

A Personalized Approach in Progressive Multiple Sclerosis: The Current Status of Disease Modifying Therapies (DMTs) and Future Perspectives

PubMed Central

D’Amico, Emanuele; Patti, Francesco; Zanghì, Aurora; Zappia, Mario

2016-01-01

Using the term of progressive multiple sclerosis (PMS), we considered a combined population of persons with secondary progressive MS (SPMS) and primary progressive MS (PPMS). These forms of MS cannot be challenged with efficacy by the licensed therapy. In the last years, several measures of risk estimation were developed for predicting clinical course in MS, but none is specific for the PMS forms. Personalized medicine is a therapeutic approach, based on identifying what might be the best therapy for an individual patient, taking into account the risk profile. We need to achieve more accurate estimates of useful predictors in PMS, including unconventional and qualitative markers which are not yet currently available or practicable routine diagnostics. The evaluation of an individual patient is based on the profile of disease activity.Within the neurology field, PMS is one of the fastest-moving going into the future. PMID:27763513

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

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)…

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.

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.

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.

Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis.

PubMed

Radue, Ernst-Wilhelm; O'Connor, Paul; Polman, Chris H; Hohlfeld, Reinhard; Calabresi, Peter; Selmaj, Krystof; Mueller-Lenke, Nicole; Agoropoulou, Catherine; Holdbrook, Frederick; de Vera, Ana; Zhang-Auberson, Lixin; Francis, Gordon; Burtin, Pascale; Kappos, Ludwig

2012-10-01

To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study. Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics. Worldwide, multicenter clinical trial. Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N=1272). We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume. Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability. These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution. clinicaltrials.gov Identifier: NCT00289978

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

Participant recruitment into a randomised controlled trial of exercise therapy for people with multiple sclerosis.

PubMed

Carter, Anouska; Humphreys, Liam; Snowdon, Nicky; Sharrack, Basil; Daley, Amanda; Petty, Jane; Woodroofe, Nicola; Saxton, John

2015-10-15

The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame. Despite an increase in research into the benefits of exercise in people with multiple sclerosis (PwMS), no trial has reported detailed data on effective recruitment strategies for large-scale randomised controlled trials. The main purpose of this report is to provide a detailed outline of recruitment strategies, rates and estimated costs in the Exercise Intervention for Multiple Sclerosis (ExIMS) trial to identify best practices for future trials involving multiple sclerosis (MS) patient recruitment. The ExIMS researchers recruited 120 PwMS to participate in a 12-week exercise intervention. Participants were randomly allocated to either exercise or usual-care control groups. Participants were sedentary, aged 18-65 years and had Expanded Disability Status Scale scores of 1.0-6.5. Recruitment strategies included attendance at MS outpatient clinics, consultant mail-out and trial awareness-raising activities. A total of 120 participants were recruited over the course of 34 months. To achieve this target, 369 potentially eligible and interested participants were identified. A total of 60 % of participants were recruited via MS clinics, 29.2 % from consultant mail-outs and 10.8 % through trial awareness. The randomisation yields were 33.2 %, 31.0 % and 68.4 % for MS clinic, consultant mail-outs and trial awareness strategies, respectively. The main reason for ineligibility was being too active (69.2 %), whilst for eligible participants the most common reason for non-participation was the need to travel to the study site (15.8 %). Recruitment via consultant mail-out was the most cost-effective strategy, with MS clinics being the most time-consuming and most costly. To reach recruitment targets in a timely fashion, a variety of methods were employed. Although consultant mail-outs were the most cost-effective recruitment strategy, use of this method alone would not have allowed us to obtain the predetermined number of participants in the required time period, thus leading to costly extensions of the project or failure to reach the number of participants required for sufficient statistical power. Thus, a multifaceted approach to recruitment is recommended for future trials. International Standard Randomised Controlled Trial Registry number: ISRCTN41541516 ; date registered: 5 February 2009.

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 extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

PubMed

Shepheard, Stephanie R; Chataway, Tim; Schultz, David W; Rush, Robert A; Rogers, Mary-Louise

2014-01-01

Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A) mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (p<0.001) than 12 controls (2.6±0.2 ng/mg creatinine) and 19 patients with other neurological disease (Parkinson's disease and Multiple Sclerosis; 4.1±0.2 ng/mg creatinine). Pilot data of disease progression rates in 14 MND patients indicates that p75NTR(ECD) levels were significantly higher (p = 0.0041) in 7 rapidly progressing patients as compared to 7 with slowly progressing disease. Extracellular neurotrophin receptor p75 was also readily detected in SOD1(G93A) mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

[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.

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.

Deficits in Social Cognition: An Unveiled Signature of Multiple Sclerosis.

PubMed

Chalah, Moussa A; Ayache, Samar S

2017-03-01

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues. Deficits in this cognitive faculty might have a drastic impact on interpersonal relationships and quality of life (QoL). Although exhaustive data exist for non-social cognitive functions in MS, only a little attention has been paid for social cognition. The objectives of the present work are to reappraise the definition and anatomy of social cognition and evaluate the integrity of this domain across MS studies. We will put special emphasis on neuropsychological and neuroimaging studies concerning social cognitive performance in MS. Studies were selected in conformity with PRISMA guidelines. We looked for computerized databases (PubMed, Medline, and Scopus) that index peer-reviewed journals to identify published reports in English and French languages that mention social cognition and multiple sclerosis, regardless of publication year. We combined keywords as follows: (facial emotion or facial expression or emotional facial expressions or theory of mind or social cognition or empathy or affective prosody) AND multiple sclerosis AND (MRI or functional MRI or positron emission tomography or functional imaging or structural imaging). We also scanned references from articles aiming to get additional relevant studies. In total, 26 studies matched the abovementioned criteria (26 neuropsychological studies including five neuroimaging studies). Available data support the presence of social cognitive deficits even at early stages of MS. The increase in disease burden along with the "multiple disconnection syndrome" resulting from gray and white matters pathology might exceed the "threshold for cerebral tolerance" and can manifest as deficits in social cognition. Admitting the impact of the latter on patients' social functioning, a thorough screening for such deficits is crucial to improving patients' QoL. (JINS, 2017, 23, 266-286).

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…

Students with Multiple Sclerosis Participating in Recess

ERIC Educational Resources Information Center

Lucas, Matthew D.; Brentlinger, Jamie

2012-01-01

The participation of a student with Multiple Sclerosis (MS) in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with MS and present basic solutions to improve the experience of these students in the recess setting. Initially, the definition and prevalence of…

Multiple Sclerosis and Employment: A Research Review Based on the International Classification of Function

ERIC Educational Resources Information Center

Frain, Michael P.; Bishop, Malachy; Rumrill, Phillip D., Jr.; Chan, Fong; Tansey, Timothy N.; Strauser, David; Chiu, Chung-Yi

2015-01-01

Multiple sclerosis (MS) is an unpredictable, sometimes progressive chronic illness affecting people in the prime of their working lives. This article reviews the effects of MS on employment based on the World Health Organization's International Classification of Functioning, Disability and Health model. Correlations between employment and…

Preliminary Evidence that Self-Efficacy Predicts Physical Activity in Multiple Sclerosis

ERIC Educational Resources Information Center

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

2009-01-01

Individuals with multiple sclerosis (MS) are less physically active than nondiseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and…

Intellectual Enrichment Is Linked to Cerebral Efficiency in Multiple Sclerosis: Functional Magnetic Resonance Imaging Evidence for Cognitive Reserve

ERIC Educational Resources Information Center

Sumowski, James F.; Wylie, Glenn R.; DeLuca, John; Chiaravalloti, Nancy

2010-01-01

The cognitive reserve hypothesis helps to explain the incomplete relationship between brain disease and cognitive status in people with neurologic diseases, including Alzheimer's; disease and multiple sclerosis. Lifetime intellectual enrichment (estimated with education or vocabulary knowledge) lessens the negative impact of brain disease on…

Marital Adjustment: A Valuable Resource for the Emotional Health of Individuals with Multiple Sclerosis.

ERIC Educational Resources Information Center

Rodgers, Jennifer; Calder, Peter

1990-01-01

Examined relationship of marital adjustment and level of disability of persons with multiple sclerosis (n=104) to emotional adjustment. Found emotional adjustment significantly related to perceived level of marital adjustment, but no relationship found for level of disability. Results suggest, although marital adjustment is important for emotional…

Case Report: "Purely" Psychiatric Presentation of Multiple Sclerosis in an Adolescent Boy

ERIC Educational Resources Information Center

Treadwell-Deering, Diane; Evankovich, Karen; Lotze, Tim

2007-01-01

We present the case of a 14-year-old Hispanic boy with a 6-month history of a psychotic disorder necessitating several hospitalizations who was incidentally found to have multiple sclerosis with no physical findings. Neuropsychological assessment has revealed impairments in word-finding, bilateral fine motor skills, and attention. Imaging and…

Evaluating Functional Decline in Patients with Multiple Sclerosis

ERIC Educational Resources Information Center

Rosenblum, Sara; Weiss, Patrice L.

2010-01-01

Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

2009-01-01

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

Satisfaction with Communicative Participation as Defined by Adults with Multiple Sclerosis: A Qualitative Study

ERIC Educational Resources Information Center

Yorkston, Kathryn M.; Baylor, Carolyn R.; Klasner, Estelle R.; Deitz, Jean; Dudgeon, Brian J.; Eadie, Tanya; Miller, Robert M.; Amtmann, Dagmar

2007-01-01

Purpose: This study examined satisfaction with communicative participation as reported by adults with multiple sclerosis (MS). Method: Eight community-dwelling adults with MS participated in semi-structured interviews. They were asked to discuss their satisfaction with their communication in a variety of situations. Interviews were analyzed using…

Control of Visually Guided Saccades in Multiple Sclerosis: Disruption to Higher-Order Processes

ERIC Educational Resources Information Center

Fielding, Joanne; Kilpatrick, Trevor; Millist, Lynette; White, Owen

2009-01-01

Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with more salient deficits reflecting tissue damage within brainstem and cerebellar circuits. However, MS may also result in disruption to higher level or cognitive control processes governing eye movement, including attentional processes that enhance the neural processing…

Central nervous system remyelination in culture--a tool for multiple sclerosis research.

PubMed

Zhang, Hui; Jarjour, Andrew A; Boyd, Amanda; Williams, Anna

2011-07-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. Copyright © 2011 Elsevier Inc. All rights reserved.

Central nervous system remyelination in culture — A tool for multiple sclerosis research

PubMed Central

Zhang, Hui; Jarjour, Andrew A.; Boyd, Amanda; Williams, Anna

2011-01-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. PMID:21515259

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.

Spasticity in multiple sclerosis and role of glatiramer acetate treatment

PubMed Central

Meca-Lallana, Jose Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

2015-01-01

Introduction Spasticity is one of the most disabling and difficult-to-treat symptoms shown by patients with multiple sclerosis, who often show a suboptimal and unsatisfactory response to classic treatment and new available nonpharmacological alternatives. Due to the progressive nature of this condition, the early management should be essential to improve long-term outcomes. Methods We performed a narrative literature review of the contribution of spasticity to the burden of multiple sclerosis and the potential role of classic disease-modifying drugs. Results Added to the underlying pathophysiology of spasticity, certain external factors and drugs such as interferon may exacerbate the existing condition, hence their awareness is crucial as part of an effective management of spasticity. Furthermore, the evidence for the effectiveness of glatiramer acetate in preventing spasticity in naïve patients and in those switching from interferon should not be ignored. Conclusions This literature review proposes the examination of spasticity and the influence of classic disease-modifying agents on the level of existing condition among the variables to be considered when deciding on therapy for multiple sclerosis in clinical practice. PMID:26445705

In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis.

PubMed

Varghese, Sreeja; Cotter, Michelle; Chevot, Franciane; Fergus, Claire; Cunningham, Colm; Mills, Kingston H; Connon, Stephen J; Southern, John M; Kelly, Vincent P

2017-02-28

Queuine is a modified pyrrolopyrimidine nucleobase derived exclusively from bacteria. It post-transcriptionally replaces guanine 34 in transfer RNA isoacceptors for Asp, Asn, His and Tyr, in almost all eukaryotic organisms, through the activity of the ancient tRNA guanine transglycosylase (TGT) enzyme. tRNA hypomodification with queuine is a characteristic of rapidly-proliferating, non-differentiated cells. Autoimmune diseases, including multiple sclerosis, are characterised by the rapid expansion of T cells directed to self-antigens. Here, we demonstrate the potential medicinal relevance of targeting the modification of tRNA in the treatment of a chronic multiple sclerosis model—murine experimental autoimmune encephalomyelitis. Administration of a de novo designed eukaryotic TGT substrate (NPPDAG) led to an unprecedented complete reversal of clinical symptoms and a dramatic reduction of markers associated with immune hyperactivation and neuronal damage after five daily doses. TGT is essential for the therapeutic effect, since animals deficient in TGT activity were refractory to therapy. The data suggest that exploitation of the eukaryotic TGT enzyme is a promising approach for the treatment of multiple sclerosis.

Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis

PubMed Central

Lovato, Laura; Willis, Simon N.; Rodig, Scott J.; Caron, Tyler; Almendinger, Stefany E.; Howell, Owain W.; Reynolds, Richard; Hafler, David A.

2011-01-01

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis. PMID:21216828

Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis.

PubMed

Lovato, Laura; Willis, Simon N; Rodig, Scott J; Caron, Tyler; Almendinger, Stefany E; Howell, Owain W; Reynolds, Richard; O'Connor, Kevin C; Hafler, David A

2011-02-01

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.

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.

Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging

PubMed Central

Haacke, E. Mark; Makki, Malek; Ge, Yulin; Maheshwari, Megha; Sehgal, Vivek; Hu, Jiani; Selvan, Madeswaran; Wu, Zhen; Latif, Zahid; Xuan, Yang; Khan, Omar; Garbern, James; Grossman, Robert I.

2009-01-01

Purpose To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging. Materials and Methods Twenty-seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre- and post-contrast T1-weighted, T2-weighted, FLAIR, and SWI at 1.5T, 3T and 4T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were re-evaluated for their iron content using the SWI filtered phase images. Results There were a variety of new lesion characteristics identified by SWI and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established. Conclusion The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus. PMID:19243035

Up-Regulation of Soluble Axl and Mer Receptor Tyrosine Kinases Negatively Correlates with Gas6 in Established Multiple Sclerosis Lesions

PubMed Central

Weinger, Jason G.; Omari, Kakuri M.; Marsden, Kurt; Raine, Cedric S.; Shafit-Zagardo, Bridget

2009-01-01

Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer (∼150 kd), and soluble Axl (80 kd) were all significantly elevated in homogenates from established multiple sclerosis lesions comprised of both chronic active and chronic silent lesions. Whereas in normal tissue Gas6 positively correlated with soluble Axl and Mer, there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin, proteins that are associated with Axl and Mer solubilization. Soluble Axl and Mer are both known to act as decoy receptors and block Gas6 binding to membrane-bound receptors. These data suggest that in multiple sclerosis lesions, dysregulation of protective Gas6 receptor signaling may prolong lesion activity. PMID:19541935

Analysis of the quantitative dermatoglyphics of the digito-palmar complex in patients with multiple sclerosis.

PubMed

Supe, S; Milicić, J; Pavićević, R

1997-06-01

Recent studies on the etiopathogenesis of multiple sclerosis (MS) all point out that there is a polygenetical predisposition for this illness. The so called "MS Trait" determines the reactivity of the immunological system upon ecological factors. The development of the glyphological science and the study of the characteristics of the digito-palmar dermatoglyphic complex (for which it was established that they are polygenetically determined characteristics) all enable a better insight into the genetic development during early embriogenesis. The aim of this study was to estimate certain differences in the dermatoglyphics of digito-palmar complexes between the group with multiple sclerosis and the comparable, phenotypically healthy groups of both sexes. This study is based on the analysis of 18 quantitative characteristics of the digito-palmar complex in 125 patients with multiple sclerosis (41 males and 84 females) in comparison to a group of 400 phenotypically healthy patients (200 males and 200 females). The conducted analysis pointed towards a statistically significant decrease of the number of digital and palmar ridges, as well as with lower values of atd angles in a group of MS patients of both sexes. The main discriminators were the characteristic palmar dermatoglyphics with the possibility that the discriminate analysis classifies over 80% of the examinees which exceeds the statistical significance. The results of this study suggest a possible discrimination of patients with MS and the phenotypically health population through the analysis of the dermatoglyphic status, and therefore the possibility that multiple sclerosis is genetically predisposed disease.

Use of Vitamins and Dietary Supplements by Patients With Multiple Sclerosis: A Review.

PubMed

Evans, Emily; Piccio, Laura; Cross, Anne H

2018-04-23

Surveys of patients with multiple sclerosis report that most are interested in modifying their diet and using supplements to potentially reduce the severity and symptoms of the disease. This review provides an updated overview of the current state of evidence for the role that vitamins and dietary supplements play in multiple sclerosis and its animal models, with an emphasis on recent studies, and addresses biological plausibility and safety issues. Several vitamins and dietary supplements have been recently explored both in animal models and by patients with multiple sclerosis. Most human trials have been small or nonblinded, limiting their generalizability. Biotin and vitamin D are currently being tested in large randomized clinical trials. Smaller trials are ongoing or planned for other supplements such as lipoic acid and probiotics. The results of these studies may help guide clinical recommendations. At the present time, the only vitamin with sufficient evidence to support routine supplementation for patients with multiple sclerosis is vitamin D. Vitamin deficiencies should be avoided. It is important for clinicians to know which supplements their patients are taking and to educate patients on any known efficacy data, along with any potential medication interactions and adverse effects of individual supplements. Given that dietary supplements and vitamins are not subject to the same regulatory oversight as prescription pharmaceuticals in the United States, it is recommended that vitamins and supplements be purchased from reputable manufacturers with the United States Pharmacopeia designation.

QualiCOP: real-world effectiveness, tolerability, and quality of life in patients with relapsing-remitting multiple sclerosis treated with glatiramer acetate, treatment-naïve patients, and previously treated patients.

PubMed

Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer

2016-04-01

Treatment of symptoms and signs beyond the expanded disability status scale remains a major target in multiple sclerosis. QualiCOP was an observational, non-interventional, open-label study conducted at 170 sites in Germany. Of the 754 enrolled patients, 96 % had relapsing-remitting multiple sclerosis (MS) and were either disease-modifying therapy naïve (de novo, n = 481) or previously treated (n = 237) with once-daily, subcutaneous 20-mg/mL glatiramer acetate (GA). Assessments of relapse rate, disease progression, overall functioning, quality of life (QoL), cognition, fatigue, and depression were performed over 24 months. GA treatment over 24 months was associated with reduced annual relapse rate for previously treated (from 0.98 to 0.54 relapses) and de novo (from 0.81 to 0.48 relapses) patients. Multiple Sclerosis Functional Composite scores showed slight improvement in both cohorts (all p < 0.01). Paced Auditory Serial Addition Test and Multiple Sclerosis Inventory Cognition scale scores showed robust improvement in cognition among previously treated and de novo cohorts (all p < 0.001). General Depression Scale scores showed significantly reduced depressive symptoms (p < 0.001). Disease severity, fatigue, and QoL were stable over the observational period. These real-world findings suggest that patients with MS show benefit from GA treatment in important QoL parameters beyond standard measures of relapse and disease severity.

Acute Responses of a Physical Training Session with a Nintendo Wii on Hemodynamic Variables of an Individual with Multiple Sclerosis.

PubMed

Monteiro Junior, Renato Sobral; Dantas, Aretha; de Souza, Cíntia Pereira; da Silva, Elirez Bezerra

2012-12-01

Multiple sclerosis is a neurological illness that decreases motor functions. This disease can cause weakness of cardiorespiratory muscles and impaired functional capacity and quality of life. Therefore it requires preventive treatments. This study investigated the acute responses of a virtual physical training session with the Nintendo(®) (Kyoto, Japan) Wii™ on hemodynamic variables of an individual with multiple sclerosis (relapsing-remitting). A 34-year-old man with multiple sclerosis with previous experience in aerobic, strength, and functional training (2 years) was tested. His Expanded Disability Status Scale was 2.5. We compared the heart rate, blood pressure, and double product obtained at rest and during (heart rate) and after the Nintendo Wii games "Boxing" and "Sword Play." In rest, the variables were measured in the supine position. Our results showed positive hemodynamic alterations after execution of both games. The peak of heart rate was 121 beats per minute (65% of maximal heart rate) and 104 beats per minute (56% of maximal heart rate) for "Boxing" and "Sword Play," respectively. The training session with "Boxing" was able to stimulate the heart rate to achieve the recommended values for the maintenance of physical fitness in accordance with the American College of Sports Medicine guidelines. We conclude that an exercise training program with the Nintendo Wii may improve physical fitness in people with multiple sclerosis. Moreover, these activities could improve affective status and perhaps maintain the individual engaged at treatment program.

Amyloid PET in pseudotumoral multiple sclerosis.

PubMed

Matías-Guiu, Jordi A; Cabrera-Martín, María Nieves; Cortés-Martínez, Ana; Pytel, Vanesa; Moreno-Ramos, Teresa; Oreja-Guevara, Celia; Carreras, José Luis; Matías-Guiu, Jorge

2017-07-01

Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter. We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer 18 F-florbetaben. The patient had developed word-finding difficulties and right hemianopia twelve years ago. In that time, MRI showed a lesion on the left hemisphere with an infiltrating aspect in frontotemporal lobes. Brain biopsy showed demyelinating areas and inflammation. During the following years, two new clinical relapses occurred. 18 F-florbetaben PET showed lower uptake in the white matter lesion visualized in the CT and MRI images. Decreased tracer uptake was also observed in a larger area of the left hemisphere beyond the lesions observed on MRI or CT. White matter lesion volume on FLAIR was 44.2mL, and tracer uptake change between damaged white matter and normal appearing white matter was - 40.5%. Standardized uptake value was inferior in the pseudotumoral lesion than in the other white matter lesions. We report the findings of amyloid PET in a patient with pseudotumoral multiple sclerosis. This case provides further evidence on the role of amyloid PET in the assessment of white matter and demyelinating diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebrospinal fluid ATP metabolites in multiple sclerosis.

PubMed

Lazzarino, G; Amorini, A M; Eikelenboom, M J; Killestein, J; Belli, A; Di Pietro, V; Tavazzi, B; Barkhof, F; Polman, C H; Uitdehaag, B M J; Petzold, A

2010-05-01

Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis. Our objective was to test whether ATP depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis. The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up. Central ATP depletion (sum of ATP metabolites >19.7 micromol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p< 0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort (r= 0.66, p= 0.001) and subgroups (relapsing-remitting patients: r= 0.79, p< 0.05 and secondary progressive/primary progressive patients: r= 0.69, p< 0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration. The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.

Sequence analysis of human rhinovirus aspirated from the nasopharynx of patients with relapsing-remitting MS.

PubMed

Kneider, M; Bergström, T; Gustafsson, C; Nenonen, N; Ahlgren, C; Nilsson, S; Andersen, O

2009-04-01

Upper respiratory infections were reported to trigger multiple sclerosis relapses. A relationship between picornavirus infections and MS relapses was recently reported. To evaluate whether human rhinovirus is associated with multiple sclerosis relapses and whether any particular strain is predominant. Nasopharyngeal fluid was aspirated from 36 multiple sclerosis patients at pre-defined critical time points. Reverse-transcriptase-PCR was performed to detect human rhinovirus-RNA. Positive amplicons were sequenced. We found that rhinovirus RNA was present in 17/40 (43%) of specimens obtained at the onset of a URTI in 19 patients, in 1/21 specimens during convalescence after URTI in 14 patients, in 0/6 specimens obtained in 5 patients on average a week after the onset of an "at risk" relapse, occurring within a window in time from one week before to three weeks after an infection, and in 0/17 specimens obtained after the onset of a "not at risk" relapse not associated with any infection in 12 patients. Fifteen specimens from healthy control persons not associated with URTI were negative. The frequency of HRV presence in URTI was similar to that reported for community infections. Eight amplicons from patients represented 5 different HRV strains. We were unable to reproduce previous findings of association between HRV infections and multiple sclerosis relapses. HRV was not present in nasopharyngeal aspirates obtained during "at risk" or "not at risk" relapses. Sequencing of HRV obtained from patients during URTI did not reveal any strain with predominance in multiple sclerosis.

Evaluation of the 2010 McDonald multiple sclerosis criteria in children with a clinically isolated syndrome.

PubMed

Kornek, Barbara; Schmitl, Beate; Vass, Karl; Zehetmayer, Sonja; Pritsch, Martin; Penzien, Johann; Karenfort, Michael; Blaschek, Astrid; Seidl, Rainer; Prayer, Daniela; Rostasy, Kevin

2012-12-01

Magnetic resonance imaging diagnostic criteria for paediatric multiple sclerosis have been established on the basis of brain imaging findings alone. The 2010 McDonald criteria for the diagnosis of multiple sclerosis, however, include spinal cord imaging for detection of lesion dissemination in space. The new criteria have been recommended in paediatric multiple sclerosis. (1) To evaluate the 2010 McDonald multiple sclerosis criteria in children with a clinically isolated syndrome and to compare them with recently proposed magnetic resonance criteria for children; (2) to assess whether the inclusion of spinal cord imaging provided additional value to the 2010 McDonald criteria. We performed a retrospective analysis of brain and spinal cord magnetic resonance imaging scans from 52 children with a clinically isolated syndrome. Sensitivity, specificity and accuracy of the magnetic resonance criteria were assessed. The 2010 McDonald dissemination in space criteria were more sensitive (85% versus 74%) but less specific (80% versus 100%) compared to the 2005 McDonald criteria. The Callen criteria were more accurate (89%) compared to the 2010 McDonald (85%), the 2005 McDonald criteria for dissemination in space (81%), the KIDMUS criteria (46%) and the Canadian Pediatric Demyelinating Disease Network criteria (76%). The 2010 McDonald criteria for dissemination in time were more accurate (93%) than the dissemination in space criteria (85%). Inclusion of the spinal cord did not increase the accuracy of the McDonald criteria.

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.

A personalized, intense physical rehabilitation program improves walking in people with multiple sclerosis presenting with different levels of disability: a retrospective cohort.

PubMed

Kalron, Alon; Nitzani, Dalia; Magalashvili, David; Dolev, Mark; Menascu, Shay; Stern, Yael; Rosenblum, Uri; Pasitselsky, Diana; Frid, Lior; Zeilig, Gabi; Barmatz, Caroline; Givon, Uri; Achiron, Anat

2015-03-04

People with multiple sclerosis (PwMS) endure walking limitations. To address this restriction, various physical rehabilitation programs have been implemented with no consensus regarding their efficacy. Our objective was to report on the efficacy of an integrated tailored physical rehabilitation program on walking in people with multiple sclerosis categorized according to their level of neurological disability. Retrospective data were examined and analyzed. Specifically, data obtained from all patients who participated in the Multiple Sclerosis Center's 3 week rehabilitation program were extracted for in depth exploration. The personalized rehabilitation program included three major components modified according to the patient's specific impairments and functional needs: (a) goal directed physical therapy (b) moderately intense aerobic exercise training on a bicycle ergometer and (c) aquatic therapy chiefly oriented to body structures appropriate to movement. Gait outcome measurements included the 10 meter, 20 meter, Timed up and go and 2 minute walking tests measured pre and post the rehabilitation program. Three hundred and twelve people with relapsing-remitting multiple sclerosis were included in the final analysis. Patients were categorized into mild (n = 87), moderate (n = 104) and severely (n = 121) disabled groups. All clinical walking outcome measurements demonstrated statistically significant improvements, however, only an increase in the 2 minute walking test was above the minimal clinical difference value. The moderate and severe groups considerably improved compared to the mild gait disability group. Mean change scores (%) of the pre-post intervention period of the 2 minute walking test were 19.0 (S.E. = 3.4) in the moderate group, 16.2 (S.E. = 5.4) in the severe group and 10.9 (S.E. = 2.3) in the mild gait disability group. We presented comprehensive evidence verifying the effects of an intense goal-directed physical rehabilitation program on ambulation in people with multiple sclerosis presenting with different neurological impairment levels.

Systematic Review: The Effectiveness of Interventions to Reduce Falls and Improve Balance in Adults With Multiple Sclerosis.

PubMed

Gunn, Hilary; Markevics, Sophie; Haas, Bernhard; Marsden, Jonathan; Freeman, Jennifer

2015-10-01

To evaluate the effectiveness of interventions in reducing falls and/or improving balance as a falls risk in multiple sclerosis (MS). Computer-based and manual searches included the following medical subject heading keywords: "Multiple Sclerosis AND accidental falls" OR "Multiple Sclerosis AND postural balance" OR "Multiple Sclerosis AND exercise" OR "Multiple Sclerosis AND physical/physio therapy" NOT animals. All literature published to November 2014 with available full-text details were included. Studies were reviewed against the PICO (participants, interventions, comparisons, outcomes) selection criteria: P, adults with MS; I, falls management/balance rehabilitation interventions; C, randomized/quasi-randomized studies comparing intervention with usual care or placebo control; O, falls outcomes and measures of balance. Fifteen articles of the original 529 search results were included. Two reviewers independently extracted data and assessed methodological quality using the Cochrane Risk of Bias tool. Random-effects meta-analysis indicated a small decrease in falls risk (risk ratio, .74), although the 95% confidence interval (CI) crossed 1 (95% CI, .12-4.38). The pooled standardized mean difference (SMD) for balance outcomes was .55 (95% CI, .35-.74). SMD varied significantly between exercise subgroupings; gait, balance, and functional training interventions yielded the greatest pooled effect size (ES) (SMD=.82; 95% CI, 0.55-1.10). There was a moderate positive correlation between program volume (min/wk) and ES (Cohen's d) (r=.70, P=.009), and a moderate negative correlation between program duration in weeks and ES (r=-.62, P=.03). Variations in interventions and outcomes and methodological limitations mean that results must be viewed with caution. This review suggests that balance may improve through exercise interventions, but that the magnitude of the improvements achieved in existing programs may not be sufficient to impact falls outcomes. Supporting participants to achieve an appropriate intensity of practice of highly challenging balance activities appears to be critical to maximizing effectiveness. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[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.

Physiologic and thermal responses of male and female patients with multiple sclerosis to head and neck cooling

NASA Technical Reports Server (NTRS)

Ku, Y. T.; Montgomery, L. D.; Wenzel, K. C.; Webbon, B. W.; Burks, J. S.

1999-01-01

Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. The objective of this study was to determine the thermal and physiologic responses of patients with multiple sclerosis to short-term maximal head and neck cooling. A Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used to cool the head and neck regions of 24 female and 26 male patients with multiple sclerosis in this study. The subjects, seated in an upright position at normal room temperature (approximately 22 degrees C), were cooled for 30 min by the liquid cooling garment, which was operated at its maximum cooling capacity. Oral, right, and left ear temperatures and cooling system parameters were logged manually every 5 min. Forearm, calf, chest, and rectal temperatures, heart rate, and respiration rate were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. This protocol was performed during the winter and summer to investigate the seasonal differences in the way patients with multiple sclerosis respond to head and neck cooling. No significant differences were found between the male and female subject group's mean rectal or oral temperature responses during any phase of the experiment. The mean oral temperature decreased significantly (P < 0.05) for both groups approximately 0.3 degrees C after 30 min of cooling and continued to decrease further (approximately 0.1-0.2 degrees C) for a period of approximately 15 min after removal of the cooling helmet. The mean rectal temperatures decreased significantly (P < 0.05) in both male and female subjects in the winter studies (approximately 0.2-0.3 degrees C) and for the male subjects during the summer test (approximately 0.2 degrees C). However, the rectal temperature of the female subjects did not change significantly during any phase of the summer test. These data indicate that head and neck cooling may, in general, be used to reduce the oral and body temperatures of both male and female patients with multiple sclerosis by the approximate amount needed for symptomatic relief as shown by other researchers. However, thermal response of patients with multiple sclerosis may be affected by gender and seasonal factors, which should be considered in the use of liquid cooling therapy.