Levite, Mia; Marino, Franca; Cosentino, Marco
Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in
... 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 ...
Dietary approaches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls Elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: study protocol for a randomized controlled trial.
Wahls, Terry; Scott, Maria O; Alshare, Zaidoon; Rubenstein, Linda; Darling, Warren; Carr, Lucas; Smith, Karen; Chenard, Catherine A; LaRocca, Nicholas; Snetselaar, Linda
Fatigue is one of the most disabling symptoms of multiple sclerosis (MS) and contributes to diminishing quality of life. Although currently available interventions have had limited success in relieving MS-related fatigue, clinically significant reductions in perceived fatigue severity have been reported in a multimodal intervention pilot study that included a Paleolithic diet in addition to stress reduction, exercise, and electrical muscle stimulation. An optimal dietary approach to reducing MS-related fatigue has not been identified. To establish the specific effects of diet on MS symptoms, this study focuses on diet only instead of the previously tested multimodal intervention by comparing the effectiveness of two dietary patterns for the treatment of MS-related fatigue. The purpose of this study is to determine the impact of a modified Paleolithic and low saturated fat diet on perceived fatigue (primary outcome), cognitive and motor symptoms, and quality of life in persons with relapsing-remitting multiple sclerosis (RRMS). This 36-week randomized clinical trial consists of three 12-week periods during which assessments of perceived fatigue, quality of life, motor and cognitive function, physical activity and sleep, diet quality, and social support for eating will be collected. The three 12-week periods will consist of the following: 1. Participants continue eating their usual diet. 2. Participants will be randomized to a modified Paleolithic or low saturated fat diet for the intervention period. Participants will receive support from a registered dietitian (RD) through in-person coaching, telephone calls, and emails. 3. Participants will continue the study diet for an additional 12 weeks with minimal RD support to assess the ability of the participants to sustain the study diet on their own. Because fatigue is one of the most common and disabling symptoms of MS, effective management and reduction of MS-related fatigue has the potential to increase quality of
Martínez-Lapiscina, Elena H; Fraga-Pumar, Elena; Gabilondo, Iñigo; Martínez-Heras, Eloy; Torres-Torres, Ruben; Ortiz-Pérez, Santiago; Llufriu, Sara; Tercero, Ana; Andorra, Magi; Roca, Marc Figueras; Lampert, Erika; Zubizarreta, Irati; Saiz, Albert; Sanchez-Dalmau, Bernardo; Villoslada, Pablo
Multiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations. The MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway. The analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.
Singer, Nora G.; Whitbred, Joy; Bowen, Michael A.; Lin, Feng
CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. CD6-deficient T cells exhibited augmented activation, but also significantly reduced survival and proliferation after activation, leading to overall decreased Th1 and Th17 polarization. Activated CD6-deficient T cells also showed impaired infiltration through brain microvascular endothelial cell monolayers. Furthermore, by developing CD6 humanized mice, we identified a mouse anti-human CD6 monoclonal antibody that is highly effective in treating established EAE without depleting T cells. These results suggest that (i) CD6 is a negative regulator of T-cell activation, (ii) at the same time, CD6 is a positive regulator of activated T-cell survival/proliferation and infiltration; and (iii) CD6 is a potential new target for treating MS and potentially other T-cell–driven autoimmune conditions. PMID:28209777
Martin, Roland; Sospedra, Mireia; Rosito, Maria; Engelhardt, Britta
Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, T-cell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imaging observations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Shatila, A R; Koussa, S; Jabbour, R; Mourad, A; Aouad, A; Sabbagh, G; Kallab, K; Hilal, R; Khalifeh, R; Gebeily, S; Tourbah, A
The prevalence of multiple sclerosis (MS) in Lebanon is unknown, as there are no available or reliable epidemiological studies to date. The circumstances of Middle East countries are different from those of Europe and North America in terms of differential diagnoses and disease management. The aim of the conference is to establish guidelines for diagnosis, treatment, follow-up and management of patients with MS in Lebanon. Another objective is to discuss and participate in research projects based on epidemiology, clinical trials and more fundamental aspects of the disease in the future. Under the authority of the Lebanese Society of Neurology (LSN), a group of neurologists took the initiative to participate in this LSN MS committee with the purpose of establishing a consensus for the management of patients with MS, and under the supervision of a Coordinator (A.T.) designed by the LSN board. Diagnostic and therapeutic, follow-up and research recommendations were proposed with special emphasis on the specific needs and circumstances of Lebanon. The experts highlighted the importance of considering particular needs, the identification of patients at high risk of developing MS in order to maximize therapeutic opportunities, and cost-effective control of treatment efficacy, as well as global assessment of disability. The experts established guidelines concerning diagnosis, treatment, and follow-up of patients with MS in Lebanon. Furthermore, they recommended some clinical and fundamental research projects. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Hanna, Joshua; Santo, Jonathan B; Blair, Mervin; Smolewska, Kathy; Warriner, Erin; Morrow, Sarah A
Depression is more common among persons with multiple sclerosis (MS) than the general population. Depression in MS is associated with reduced quality of life, transition to unemployment, and cognitive impairment. Two proposed screening measures for depression in MS populations are the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory-Fast Screen (BDI-FS). Our objective was to compared the associations of the BDI-FS and the HADS-D scores with history of depressive symptoms, fatigue, and functional outcomes to determine the differential clinical utility of these screening measures among persons with MS. We reviewed charts of 133 persons with MS for demographic information; scores on the HADS, BDI-FS, a fatigue measure, and a processing speed measure; and employment status. Structural equation modeling results indicated the HADS-D predicted employment status, disability status, and processing speed more effectively than did the BDI-FS, whereas both measures predicted fatigue. This study suggests the HADS-D is more effective than the BDI-FS in predicting functional outcomes known to be associated with depression among persons with MS. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol.
Deutsch, Stephen I; Rosse, Richard B; Connor, Julie M; Burket, Jessica A; Murphy, Mary E; Fox, Fiona J
Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.
Charvet, L E; Cleary, R E; Vazquez, K; Belman, A L; Krupp, L B
Pediatric-onset multiple sclerosis (MS) patients represent a subpopulation who are diagnosed during the course of development. Social cognitive deficits have recently been recognized in adults with MS. It is critical to identify whether these youngest patients with the disorder are also at risk. To determine whether pediatric-onset MS is associated with social cognitive deficits. Consecutively-recruited participants with pediatric-onset MS were compared to a group of age- and gender-matched healthy controls on Theory of Mind (ToM) task performance. Tasks measured facial affect recognition (Reading the Mind in the Eyes Test), detecting social faux pas (Faux Pas Test), and understanding the perspective of another (False Beliefs Task). Twenty-eight (28) pediatric-onset MS participants (median age 17 years) and 32 healthy controls (median age 16 years) completed the study. The MS participants performed worse than controls on all three ToM tasks: Reading the Mind in the Eyes Test (p = 0.008), the Faux Pas Test (p = 0.009), and the False Beliefs Task (p = 0.06). While more MS than control participants were impaired on a measure of information processing speed (the Symbol Digit Modalities Test; 38% versus 6%), it did not account for the differences in ToM performance. Social cognition may represent an area of cognitive functioning affected by MS in the pediatric-onset population. These processes are especially important to study in younger patients as they may have long range implications for social adjustment, employment, and well-being. © The Author(s) 2014.
Charvet, LE; Cleary, RE; Vazquez, K; Belman, A; Krupp, LB
Background Pediatric-onset multiple sclerosis (MS) patients represent a subpopulation who are diagnosed during the course of development. Social cognitive deficits have recently been recognized in adults with MS. It is critical to identify if these youngest patients with the disorder are also at risk. Objective To determine whether pediatric-onset MS is associated with social cognitive deficits. Methods Consecutively-recruited participants with pediatric-onset MS were compared to a group of age- and gender-matched healthy controls on Theory of Mind (ToM) task performance. Tasks measured facial affect recognition (Reading the Mind in the Eyes Test), understanding social faux pas (Faux Pas Test), and understanding the perspective of another (False Beliefs Task). Results Twenty-eight (28) pediatric-onset MS participants (median age 17 years) and 32 healthy controls (median age 16 years) completed the study. The MS participants performed worse than controls on all three ToM tasks: Reading the Mind in the Eyes Test (p=0.008), the Faux-Pas Test (p=0.009), and the False Beliefs Task (p=0.06). While more MS than control participants were impaired on a measure of information processing speed (the Symbol Digit Modalities Test; 38% versus 6%), it did not account for the differences in ToM performance. Conclusions Social cognition may represent an area of cognitive functioning affected by MS in the pediatric-onset population. These processes are especially important to study in younger patients as these deficits could have long range implications on social adjustment, employment, and well-being. PMID:24647558
Newland, Pamela; Flick, Louise; Salter, Amber; Dixon, David; Jensen, Mark P
In individuals with multiple sclerosis (MS) comorbidities and quality of life (QOL) may be affected by tobacco use. To evaluate the associations between smoking status, in particular quit attempts, and comorbidities among individuals with MS. We used a web-based survey to obtain cross-sectional data from 335 individuals with MS who were members of the Gateway Chapter of the National MS Society email registry. We then examined the associations between smoking variables (current use, frequency, and quit attempts) and comorbidities. The prevalence of participants who ever smoked was 50%, which is greater than that reported for the general population; 20% were current smokers. Migraine headaches were associated with current use and everyday smoking, and those with recent failed quit attempts had a higher prevalence of depression than those who were current smokers but who did not attempt to quit or had successfully quit in the past year. Given the associations between smoking and comorbidities in individuals with MS, health care providers should both (1) assess smoking history and quit attempts, and (2) encourage individuals with MS who smoke to become non-smokers and refer for treatment, as indicated. In order to increase the chances that individuals will be successful in becoming non-smokers, clinicians would do well to also assess and treat depression in their patients who smoke and are also depressed. Copyright © 2017 Elsevier Inc. All rights reserved.
Lo Re, Marianna; Capobianco, Marco; Ragonese, Paolo; Realmuto, Sabrina; Malucchi, Simona; Berchialla, Paola; Salemi, Giuseppe; Bertolotto, Antonio
Natalizumab (NTZ) discontinuation can be followed by multiple sclerosis (MS) disease reactivation. Currently no disease-modifying drug (DMD) has been shown to be able to abolish disease reactivation. The aims of the current study were: (1) to determine the frequency of MS reactivation after NTZ discontinuation; (2) to evaluate predictors of reactivation risk, and (3) to compare the effect of different treatments in reducing this risk. Data from 132 patients with MS followed-up for 2 years before NTZ treatment and 1 year after interruption were collected from two Italian MS centers and retrospectively evaluated. Overall, 72 of 132 patients (54.5%) had relapses after NTZ discontinuation and 60 of 125 patients (48%), who had magnetic resonance imaging, had radiological reactivation. Rebound was observed in 28 of 132 patients (21.2%). A higher number of relapses in the 2 years before NTZ treatment, a longer washout period, and a lower number NTZ infusions correlated with reactivation and rebound. Untreated patients (n = 37) had higher clinical and radiological activity and rebound in comparison to patients receiving DMDs. Moreover, a lower risk of relapses was found in patients treated with second-line therapies (NTZ and fingolimod) than in those treated with first-line therapies (interferon beta, glatiramer acetate, teriflunomide, azathioprine). Interestingly, no disease reactivation in off-label treatment (rituximab, autologous hematopoietic stem cell transplantation) was observed. NTZ discontinuation is a risk for MS reactivation and rebound. An alternative treatment should be promptly resumed mainly in patients with a previous very active disease course and with a shorter NTZ therapy. Second-line therapies demonstrate superiority in preventing relapses after NTZ discontinuation.
Wattjes, Mike P; Wijburg, Martijn T; Vennegoor, Anke; Witte, Birgit I; Roosendaal, Stefan D; Sanchez, Esther; Liu, Yaou; Martins Jarnalo, Carine O; Richert, Nancy D; Uitdehaag, Bernard Mj; Barkhof, Frederik; Killestein, Joep
In natalizumab-treated multiple sclerosis (MS) patients, magnetic resonance imaging (MRI) is considered as a sensitive tool in detecting both MS disease activity and progressive multifocal leukoencephalopathy (PML). To investigate the performance of neuroradiologists using brain MRI in detecting new MS lesions and asymptomatic PML lesions and in differentiating between MS and PML lesions in natalizumab-treated MS patients. The secondary aim was to investigate interrater variability. In this retrospective diagnostic study, four blinded neuroradiologists assessed reference and follow-up brain MRI scans of 48 natalizumab-treated MS patients with new asymptomatic PML lesions (n = 21) or new MS lesions (n = 20) or no new lesions (n = 7). Sensitivity and specificity for detection of new lesions in general (MS and PML lesions), MS and PML lesion differentiation, and PML detection were determined. Interrater agreement was calculated. Overall sensitivity and specificity for the detection of new lesions, regardless of the nature of the lesions, were 77.4% and 89.3%, respectively; for PML-MS lesion differentiation, 74.2% and 84.7%, respectively; and for asymptomatic PML lesion detection, 59.5% and 91.7%, respectively. Interrater agreement for the tested categories was fair to moderate. The diagnostic performance of trained neuroradiologists using brain MRI in pharmacovigilance of natalizumab-treated MS patients is moderately good. Interrater agreement among trained readers is fair to moderate. © The Author(s), 2015.
Li, Shengwen Calvin; Yin, Hong Zhen; Loudon, William G; Weiss, John H
This editorial addresses the current challenges and future directions in the use of stem cells as an approach for treating amyotrophic lateral sclerosis. A wide variety of literature has been reviewed to enlighten the reader on the many facets of stem cell research that are important to consider before using them for a cell based therapy. PMID:23516096
Jouve, Léa; Benrabah, Rabah; Héron, Emmanuel; Bodaghi, Bahram; Le Hoang, Phuc; Touitou, Valérie
Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (p<0.05), with a tendency toward a higher rate of chronic uveitis (p = 0.06). MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.
Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J
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.
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.
Zivadinov, Robert; Medin, Jennie; Khan, Nasreen; Korn, Jonathan R; Bergsland, Niels; Dwyer, Michael G; Chitnis, Tanuja; Naismith, Robert T; Alvarez, Enrique; Kinkel, Peter; Cohan, Stanley; Hunter, Samuel F; Silva, Diego; Weinstock-Guttman, Bianca
Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of active disease (NEAD). MS and clinical outcome and MRI in the United States (MS-MRIUS) is a multicenter, retrospective study that included 590 relapsing-remitting MS patients, who initiated fingolimod, and were followed for a median of 16 months. Patients with active disease at baseline (245, 41.5%) were defined as those who had one or more relapses in the year previous starting fingolimod, and/or displayed gadolinium enhancing lesions(s) at baseline MRI scan, whereas patients with NEAD at baseline (345, 58.5%) did not fulfill these criteria. Annualized percentage brain volume change (PBVC) and percentage lateral ventricle volume change (PLVVC) over the follow-up were analyzed in both groups. Over the follow-up, the rate of PBVC was -.38% in active disease and -.25% in NEAD patients (P = .076), whereas PLLVC was 1.76% in active disease and .28% in NEAD patients (P = .046). No changes in timed 25-foot walk (P = .619) and Expanded Disability Status Scale (P = .275) scores or MRI lesion accumulation (P > 0.08) were detected, although the active disease group had a higher proportion of relapses during the follow-up period (P = .02). The study provides real-world evidence that rate of brain atrophy in MS patients with underlying active disease and NEAD in fingolimod treated patients is below the established pathological cutoff for loss of whole brain volume (>-.4%) or expansion of lateral ventricles (> 3.5%). Copyright © 2018 by the American Society of Neuroimaging.
Aharony, Shachar; Lam, Ornella; Lapierre, Yves; Corcos, Jacques
Multiple sclerosis (MS) is a unique central nervous system (CNS) inflammatory disease with a broad spectrum of clinical presentations, which are time- and disease progression-related. It usually affects young adults, with a female predominance of 3:1. Men are more likely to develop symptoms at a slightly older age with a more progressive disease course. Diagnosis relies on a combination of clinical, radiological, and laboratory investigations, with a central role of magnetic resonance imaging (MRI). Although the exact etiology is still obscure, the leading hypothesis behind MS relapses is acute inflammatory attacks on CNS myelin and axons. This complex process involves B and T cells together with macrophages and microglia. Genetic and environmental factors are thought to be major contributors to the disease's evolution. MS therapies consist of long-term (immunomodulatory) management, focusing on disease modification, and short-term symptomatic control. Symptomatic treatment includes pharmacological and non-pharmacological methods to protect function and restore quality of life (QoL). The introduction and development of disease-modifying medications provide opportunities to change the face of this disease, enhancing QoL over the long-term. Interferon (INF) and Glatiramer acetate (GLAT) represent first line medications with limited effect and relatively fair safety profile. Newer medications with improved efficacy along with a more hazardous side effect profile are now considered second line therapy. The present review summarizes current knowledge of this frequent disease. Urologists must acquire a deeper understanding for better integration of practice recommendations. © 2015 Wiley Periodicals, Inc.
Alwan, Sura; Chambers, Christina D; Armenti, Vincent T; Sadovnick, A Dessa
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.
Gich, Jordi; Freixenet, Jordi; Garcia, Rafael; Vilanova, Joan Carles; Genís, David; Silva, Yolanda; Montalban, Xavier; Ramió-Torrentà, Lluís
Cognitive rehabilitation is often delayed in multiple sclerosis (MS). To develop a free and specific cognitive rehabilitation programme for MS patients to be used from early stages that does not interfere with daily living activities. MS-line!, cognitive rehabilitation materials consisting of written, manipulative and computer-based materials with difficulty levels developed by a multidisciplinary team. Mathematical, problem-solving and word-based exercises were designed. Physical materials included spatial, coordination and reasoning games. Computer-based material included logic and reasoning, working memory and processing speed games. Cognitive rehabilitation exercises that are specific for MS patients have been successfully developed. © The Author(s), 2014.
Nielsen, Suzanne; Germanos, Rada; Weier, Megan; Pollard, John; Degenhardt, Louisa; Hall, Wayne; Buckley, Nicholas; Farrell, Michael
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.
Fernández, O; Delvecchio, M; Edan, G; Fredrikson, S; Giovannoni, G; Hartung, H-P; Havrdova, E; Kappos, L; Pozzilli, C; Soerensen, P S; Tackenberg, B; Vermersch, P; Comi, G
The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Respondents generally favoured changing rather than stopping disease-modifying treatment (DMT) in patients transitioning from relapsing-remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium-enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice-based questions and management are summarized. Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines. © 2018 EAN.
Bettencourt, Andreia; Silva, Ana Martins; Carvalho, Cláudia; Leal, Bárbara; Santos, Ernestina; Costa, Paulo P; Silva, Berta M
Killer Immunoglobulin-like Receptor (KIR) genes may influence both resistance and susceptibility to different autoimmune diseases, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. We investigated the influence of KIR genes on MS susceptibility in 447 MS Portuguese patients, and also whether genetic interactions between specific KIR genes and their HLA class I ligands could contribute to the pathogenesis of MS. We observed a negative association between the activating KIR2DS1 gene and MS (adjusted OR=0.450, p=0.030) independently from the presence of HLA-DRB1*15 allele. The activating KIR2DS1 receptor seems to confer protection against MS most probably through modulation of autoreactive T cells by Natural Killer cells. Copyright © 2014 Elsevier B.V. All rights reserved.
Ruiz-Argüelles, Alejandro; Gastélum-Cano, Jose M; Méndez-Huerta, Mariana A; Rodríguez-Gallegos, Alma B; Ruiz-Argüelles, Guillermo J
Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function.
treating amyotrophic lateral sclerosis . PRINCIPAL INVESTIGATOR: Raymond J. Grill CONTRACTING ORGANIZATION: University of Texas Health...treating Amyotrophic lateral sclerosis 5a. CONTRACT NUMBER W 5b. GRANT NUMBER W81XWH-12-1-0612 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...survival in a mouse model of amyotrophic lateral sclerosis . This project involves work performed at both UT-Health and Rice University; combining the
Fox, Robert J; Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim
Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS.
Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim
Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. PMID:22917690
Parsons, Martin Em; O'Connell, Karen; Allen, Seamus; Egan, Karl; Szklanna, Paulina B; McGuigan, Christopher; Ní Áinle, Fionnuala; Maguire, Patricia B
Thrombin is well recognised for its role in the coagulation cascade but it also plays a role in inflammation, with enhanced thrombin generation observed in several inflammatory disorders. Although patients with multiple sclerosis (MS) have a higher incidence of thrombotic disease, thrombin generation has not been studied to date. The aim of this study was to characterise calibrated automated thrombography parameters in patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) in comparison to healthy controls (HCs). Calibrated automated thrombography was performed on platelet poor plasma from 15 patients with RRMS, 15 with PPMS and 19 HCs. We found that patients with RRMS generate thrombin at a significantly faster rate than the less inflammatory subtype, PPMS or HCs. In addition, the speed of thrombin generation was significantly correlated with time from clinical diagnosis in both subtypes. However, in RRMS the rate of thrombin generation was increased with increased time from clinical diagnosis, while in PPMS the rate of thrombin generation decreased with increased time from clinical diagnosis. These data likely reflect the differential active proinflammatory states in each MS subtype and provide novel mechanistic insights into the clinically relevant prothrombotic state observed in these patients.
Nauta, Ilse M; Speckens, Anne E M; Kessels, Roy P C; Geurts, Jeroen J G; de Groot, Vincent; Uitdehaag, Bernard M J; Fasotti, Luciano; de Jong, Brigit A
Cognitive problems frequently occur in patients with multiple sclerosis (MS) and profoundly affect their quality of life. So far, the best cognitive treatment options for MS patients are a matter of debate. Therefore, this study aims to investigate the effectiveness of two promising non-pharmacological treatments: cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT). Furthermore, this study aims to gain additional knowledge about the aetiology of cognitive problems among MS patients, since this may help to develop and guide effective cognitive treatments. In a dual-centre, single-blind randomised controlled trial (RCT), 120 MS patients will be randomised into one of three parallel groups: CRT, MBCT or enhanced treatment as usual (ETAU). Both CRT and MBCT consist of a structured 9-week program. ETAU consists of one appointment with an MS specialist nurse. Measurements will be performed at baseline, post-intervention and 6 months after the interventions. The primary outcome measure is the level of subjective cognitive complaints. Secondary outcome measures are objective cognitive function, functional brain network measures (using magnetoencephalography), psychological symptoms, well-being, quality of life and daily life functioning. To our knowledge, this will be the first RCT that investigates the effect of MBCT on cognitive function among MS patients. In addition, studying the effect of CRT on cognitive function may provide direction to the contradictory evidence that is currently available. This study will also provide information on changes in functional brain networks in relation to cognitive function. To conclude, this study may help to understand and treat cognitive problems among MS patients. This trial was prospectively registered at the Dutch Trial Registration (number NTR6459 , registered on 31 May 2017).
Veldhuijzen van Zanten, Jet Jcs; Pilutti, Lara A; Duda, Joan L; Motl, Robert W
Historically, people with multiple sclerosis (MS) have been considered sedentary, although the actual scientific study of sedentary behaviour in MS did not originate until 2011. Sedentary behaviour, which is conceptually distinct from physical inactivity, is defined as any waking activity characterised by an energy expenditure ⩽ 1.5 metabolic equivalents and in a sitting or reclining posture. In the general population, the volume of sitting time is associated with increased risks of morbidity and mortality, independent of physical activity, and has been suggested to carry a greater risk of mortality than smoking behaviour. There are many symptoms of MS (e.g. mobility disability and fatigue) that could increase the prevalence of sedentary behaviour, and sedentary behaviour may have considerable implications for the development of comorbid conditions prevalent in MS. This review provides a summary of the rates, correlates, consequences and interventions attempting to reduce sedentary behaviour in MS. We provide a research agenda that guides future research on sedentary behaviour in MS. This paper provides a clarion call that it is time to 'stand up against MS'. © The Author(s), 2016.
Riñon, Alberto; Buch, Mandy; Holley, Derek; Verdun, Elisabetta
Background Treatment of multiple sclerosis (MS) with disease-modifying drugs (DMDs) can reduce relapse frequency and delay disability progression. Although adherence to DMDs is difficult to measure accurately, evidence suggests that poor adherence is common and can compromise treatment success. There are likely to be multiple factors underlying poor adherence. To better understand these factors, the global MS Choices Survey investigated patient and physician perspectives regarding key aspects of MS diagnosis, treatment adherence and persistence, and disease management. Methods The survey was conducted in seven countries and involved patients with MS (age 18–60 years; MS diagnosis for ≥1 year; current treatment with a DMD) and physicians (neurologist for 3–30 years; treating ≥15 patients with MS per average month; >60% of time spent in clinical practice). Separate questionnaires were used for physicians and patients, each containing approximately 30 questions. Results Questionnaires were completed by 331 patients and 280 physicians. Several differences were observed between the responses of patients and physicians, particularly for questions relating to treatment adherence. Overall, the proportion of patients reporting taking a treatment break (31%) was almost twice that estimated by physicians (on average 17%). The reasons cited for poor adherence also differed between patients and physicians. For example, more physicians cited side effects as the main reason for poor patient adherence (82%), than responding patients (42%). Conclusions Physicians may underestimate the scale of poor adherence to DMDs, which could impact on their assessment of treatment efficacy and result in inappropriate treatment escalation. In addition, disparities were identified between patient and physician responses regarding the underlying reasons for poor adherence. Improvements in the dialog between patients and neurologists may increase adherence to DMDs. PMID:22259240
McFadden, Estelle; Horton, Mike C; Ford, Helen L; Gilworth, Gill; McFadden, Majella; Tennant, Alan
Multiple sclerosis (MS) mainly presents amongst those of working age. Depending upon the type of MS, many people embark upon a long period of managing their day-to-day work-related needs in the face of intermittent and sometimes persistent disabling symptoms. The objective of this study was to explore the concept of work instability (WI) following the onset of MS and develop a Work Instability Scale (WIS) specific to this population. WI amongst those with MS in work was explored through qualitative interviews which were then used to generate items for a WIS. Rasch analysis was used to refine the scaling properties of the MS-WIS, which was then validated against expert vocational assessment by occupational health physiotherapists and ergonomists. The resulting measure is a 22-item, self-administered scale which can be scored in three bands indicating low, medium and high risk of WI (job retention) problems. The scale meets modern psychometric requirements for measurement, indicated by adequate fit to the Rasch model with absence of local dependency and differential item functioning (DIF) by age, gender and hours worked. The scale presents an opportunity in routine clinical practice to take positive action to reduce sickness absence and prevent job loss.
Wingo, Brooks C; Young, Hui-Ju; Motl, Robert W
Persons with multiple sclerosis (MS) have many health conditions related to overweight and obesity, but little is known about how body composition among those with MS compares to those without MS at the same weight. To compare differences in whole body and regional body composition between persons with and without MS matched for sex and body mass index (BMI). Persons with MS (n = 51) and non-MS controls (n = 51) matched for sex and BMI. Total mass, lean mass, fat mass, and percent body fat (%BF) of total body and arm, leg, and trunk segments were assessed using dual-energy X-ray absorptiometry (DXA). Men with MS had significantly less whole body lean mass (mean difference: 9933.5 ± 3123.1 g, p < 0.01) and higher fat mass (mean difference: 6079.0 ± 2137.4 g, p = .01) and %BF (mean difference: 9.43 ± 2.04%, p < 0.01) than BMI-matched non-MS counterparts. Further, men with MS had significantly lower lean mass in the arm (p = 0.02) and leg (p < 0.01) and higher fat mass in the arm (p = 0.01), leg (p = 0.03) and trunk (p = 0.03) than men without MS. Men with MS had significantly higher %BF in all three regions (p < 0.01) than men without MS. There were no differences between women with and without MS. We observed significant differences in whole body and regional body composition between BMI-matched men with and without MS. Additional research is needed to further explore differences in body composition, adipose distribution, and the impact of these differences on the health and function of men with MS. Copyright © 2017 Elsevier Inc. All rights reserved.
Motl, Robert W
Supervised exercise training has substantial benefits for persons with multiple sclerosis (MS), yet 80% of those with MS do not meet recommended levels of moderate-to-vigorous physical activity (MVPA). This same problem persisted for decades in the general population of adults and prompted a paradigm shift away from "exercise training for fitness" toward "physical activity for health." The paradigm shift reflects a public health approach of promoting lifestyle physical activity through behavioral interventions that teach people the skills, techniques, and strategies based on established theories for modifying and self-regulating health behaviors. This paper describes: (a) the definitions of and difference between structured exercise training and lifestyle physical activity; (b) the importance and potential impact of the paradigm shift; (c) consequences of lifestyle physical activity in MS; and (d) behavioral interventions for changing lifestyle physical activity in MS. The paper introduces the "new kid on the MS block" with the hope that lifestyle physical activity might become an accepted partner alongside exercise training for inclusion in comprehensive MS care. © The Author(s) 2014.
Glatigny, Simon; Bettelli, Estelle
Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system (CNS) leading to the progressive destruction of the myelin sheath surrounding axons. It can present with variable clinical and pathological manifestations, which might reflect the involvement of distinct pathogenic processes. Although the mechanisms leading to the development of the disease are not fully understood, numerous evidences indicate that MS is an autoimmune disease, the initiation and progression of which are dependent on an autoimmune response against myelin antigens. In addition, genetic susceptibility and environmental triggers likely contribute to the initiation of the disease. At this time, there is no cure for MS, but several disease-modifying therapies (DMTs) are available to control and slow down disease progression. A good number of these DMTs were identified and tested using animal models of MS referred to as experimental autoimmune encephalomyelitis (EAE). In this review, we will recapitulate the characteristics of EAE models and discuss how they help shed light on MS pathogenesis and help test new treatments for MS patients. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.
Chataway, Jeremy; Martin, Keith; Barrell, Kevin; Sharrack, Basil; Stolt, Pelle; Wraith, David C
To assess safety, tolerability, and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using different treatment protocols to induce tolerance. Two open-label trials in adult participants with relapsing multiple sclerosis were conducted. Study 1 was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.) (cohort 1) with subcutaneous (cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800-μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a phase 2a, multicenter, single-arm trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 μg i.d. on day 1 to 200 μg on day 15 and 800 μg on day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety endpoints included treatment-emergent adverse events and injection-site reactions. In study 1, there was a significant decrease in new/persisting T1 gadolinium-enhanced (GdE) lesions in cohort 1 from baseline to week 16, returning to baseline values at week 48. In study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post treatment. Further trials of ATX-MS-1467 are warranted. This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions. © 2018 American Academy of Neurology.
Mousavi, Shokoufeh; Zare, Hossein; Etemadifar, Masoud; Taher Neshatdoost, Hamid
The main cognitive impairments in multiple sclerosis (MS) affect the working memory, processing speed, and performances that are in close interaction with one another. Cognitive problems in MS are influenced to a lesser degree by disease recovery medications or treatments,but cognitive rehabilitation is considered one of the promising methods for cure. There is evidence regarding the effectiveness of cognitive rehabilitation for MS patients in various stages of the disease. Since the impairment in working memory is one of the main MS deficits, a particular training that affects this cognitive domain can be of a great value. This study aims to determine the effectiveness of memory rehabilitation on the working memory performance of MS patients. Sixty MS patients with cognitive impairment and similar in terms of demographic characteristics, duration of disease, neurological problems, and mental health were randomly assigned to three groups: namely, experimental, placebo, and control. Patients' cognitive evaluation incorporated baseline assessments immediately post-intervention and 5 weeks post-intervention. The experimental group received a cognitive rehabilitation program in one-hour sessions on a weekly basis for 8 weeks. The placebo group received relaxation techniques on a weekly basis; the control group received no intervention. The results of this study showed that the cognitive rehabilitation program had a positive effect on the working memory performance of patients with MS in the experimental group. These results were achieved in immediate evaluation (post-test) and follow-up 5 weeks after intervention. There was no significant difference in working memory performance between the placebo group and the control group. According to the study, there is evidence for the effectiveness of a memory rehabilitation program for the working memory of patients with MS. Cognitive rehabilitation can improve working memory disorders and have a positive effect on the
Ivanen, Dina R; Kulminskaya, Anna A; Shabalin, Konstantin A; Isaeva-Ivanova, Luydmila V; Ershova, Nadezhda A; Saveliev, Andrew N; Nevinsky, Gregory A; Neustroev, Kirill N
Recently, amylolytic activity was detected in IgMs isolated from the sera of the patients with multiple sclerosis. All purified samples of IgM were electrophoretically homogenous and did not contain any co-purified a-amylase and a-glucosidase activities, in accordance with a set of criteria developed for abzymes. The amylolytic activity of abzymes was studied in the hydrolysis of p-nitrophenyl a-D-maltooligosaccharides with different degrees of polymerization from 1 to 8 by TLC and reverse-phase HPLC techniques. All IgM samples isolated from 54 patients with clinically definite multiple sclerosis demonstrated hydrolytic activity towards the above artificial substrates. The Michaelis constant values (Km) in the hydrolysis of p-nitrophenyl a-D-maltoheptaoside were in the range of 10 p-nitrophenyl or p-nitrophenyl a-D-glucosides, thus indicating the presence of an a-D-glucosidase activity. For a number of the investigated samples, specific amylolytic activity increased depending on the length of substrates (from p-nitrophenyl maltopentaoside to p-nitrophenyl maltohexaoside); for other IgMs, the opposite dependence was observed. All IgMs studied did not exhibit any other glycoside hydrolase activities toward p-nitrophenyl glycoside substrates. Abzyme fractions from different donors demonstrated catalytic heterogeneity in Michaelis-Menten parameters and different modes of action in the hydrolysis of p-nitrophenyl maltooligosaccharides. Enzymatic properties of the IgMs tested varied from human a-amylases. All investigated abzyme samples did not show transglycosylating ability.
Shahbazi, Majid; Abdolmohammadi, Reza; Ebadi, Hamid; Farazmandfar, Touraj
Interactions between several genes and environment may play a role in susceptibility to multiple sclerosis (MS). The IGF-1 plays a key role in proliferation, maintenance and survival of nerve cells. Therefore, we hypothesized that IGF-1 may be a target for prediction and control MS. We aimed to analysis IGF-1 gene promoter sequence, to investigate the effect of the single nucleotide variants on IGF-1 expression and its association with MS. We enrolled 339 MS patients and 431 healthy controls. A specific region in IGF-1 gene promoter was investigated by SSCP analysis. All samples were genotyped by SSP-PCR. In-vitro and in-vivo IGF-1 production was measured by ELISA assay. IGF-1 expression in PBMCs was measured using real-time PCR. We identified a T to C single nucleotide substitution at position -1089 and a C to T at position -383 from transcription start site in the IGF-1 gene promoter. There was a significant association between MS and genotypes IGF-1(-383) C/T (p=0.001) and IGF-1(-383) C/C (p<0.001). There was also a significant association between IGF-1(-383) allele C and MS (p=0.001). In-vitro and in-vivo IGF-1 level showed that IGF-1 production in samples with genotype IGF-1(-383) C/C significantly was less than T/T (p=0.004) but not T/C (p=0.220). According to IGF-1 roles in CNS and our results, this study suggests that low IGF-1 level may be associated with susceptibility to MS. Copyright © 2017 Elsevier B.V. All rights reserved.
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
de Oliveira, Ademar Francisco; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier
ABSTRACT Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. PMID:27759834
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.
Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer
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.
Cook, S; Vermersch, P; Comi, G; Giovannoni, G; Rammohan, K; Rieckmann, P; Sørensen, P Soelberg; Hamlett, A; Miret, M; Weiner, J; Viglietta, V; Musch, B; Greenberg, S J
Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy. To report in detail the safety findings from the 96-week, phase III, double-blind CLARITY study, which evaluated treatment with cladribine tablets in relapsing-remitting MS. A total of 1,326 patients were randomized 1:1:1 to two short-course regimens of cladribine tablets (3.5 or 5.25 mg/kg cumulative dose over 96 weeks) or placebo. Safety assessments included monitoring for adverse events (AEs), routine physical and neurologic examinations and frequent laboratory parameter assessments. Of the randomized patients, 88.6% completed treatment with cladribine tablets versus 86.3% with placebo. Lymphopenia was the most commonly reported AE in patients treated with cladribine tablets and was anticipated based on the mechanism of action. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators. Herpes zoster infections developed in 20 (2.3%) cladribine-treated patients; all cases were dermatomal. There were no herpes zoster infections in the placebo group. Nine (1.0%) patients experienced events related to uterine leiomyomas in the cladribine tablets groups versus one (0.2%) with placebo. Three isolated cases of malignancy were reported in cladribine-treated patients during the study; a fourth was reported during post-study surveillance. A pre-malignant cervical carcinoma in situ was also reported. The incidence of malignancies during the study did not exceed the expected rate in a population standardized for country, gender and age. The safety and tolerability profile observed in the CLARITY study together with the reported efficacy support the potential for cladribine tablets as an MS therapy.
Król, Joanna; Nocoń, Danuta; Kubaszewski, Przemysław; Rzepa, Teresa; Nowacki, Przemysław
Multiple Sclerosis (MS) is the most common, primary neurogenic cause of disability among young adults. We investigated demographic and clinical factors associated with unemployment on the example of 150 MS patients receiving immunomodulatory treatment in Poland. This study was based on clinical evaluation and collection of self-reported questionnaires, with an attention to self-motivation, severe fatigue and moderate disability. Patients who were unemployed (40% of all patients) had a mean disease duration of almost 5 years. Older (p<0.001), less educated (p = 0.007) and more severely disabled patients (p<0,001) were most likely to be unemployed. Moderate disability (OR = 11.089 95% CI: 4.11–34.201, p<0,001), severe fatigue (OR = 2.625 95% CI: 1.02–6.901, p = 0,046) and lower level of self-motivation (KNS) (OR = 0.947, 95% CI: 0.896–0.006, p = 0.042) were independently associated with unemployment. PMID:29634737
Ziemssen, Tjalf; Phillips, Glenn; Shah, Ruchit; Mathias, Adam; Foley, Catherine; Coon, Cheryl; Sen, Rohini; Lee, Andrew; Agarwal, Sonalee
The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundant items which were removed leading to the final nine-item EMIQ. The nine-item EMIQ performed well with respect to: test-retest reliability (ICC = 0.858); internal consistency (α = 0.893); convergent validity; and known-groups methods for construct validity. A cut-point of 41 on the 0-to-100 scale resulted in sufficient sensitivity and specificity statistics for viably identifying patients with mobility impairment. The EMIQ is a content valid and psychometrically sound instrument for capturing MS patients' experience with mobility impairments in a clinical practice setting. Additional research is suggested to further confirm the EMIQ's screening properties over time.
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 ...
Brütting, Christine; Emmer, Alexander; Kornhuber, Malte; Staege, Martin S
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.
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
Ramió-Torrentà, L; Álvarez-Cermeño, J C; Arroyo, R; Casanova-Estruch, B; Fernández, O; García-Merino, J A; Hernández, M A; Izquierdo, G; Martínez-Yélamos, S; Meca, J; Moral, E; Olascoaga, J; Prieto, J M; Saiz, A
Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Kerling, Arno; Keweloh, Karin; Tegtbur, Uwe; Kück, Momme; Grams, Lena; Horstmann, Hauke; Windhagen, Anja
The aim of this prospective randomized controlled trial was to investigate if a short-term endurance or combined endurance/resistance exercise program was sufficient to improve aerobic capacity and maximum force in adult patients (18-65 years) with multiple sclerosis (MS). All patients performed a three-month exercise program consisting of two training sessions per week, lasting 40 min each, with moderate intensity. All patients had a maximum value of 6 (low to moderate disability) on the Expanded Disability Status Scale (EDSS). One group (combined workout group (CWG); 15 females, 4 males) completed a combined endurance/resistance workout (20 min on a bicycle ergometer, followed by 20 min of resistance training), while the other group (endurance workout group (EWG); 13 females, 5 males) completed a 40 min endurance training program. Aerobic capacity was assessed as peak oxygen uptake, ventilatory anaerobic threshold, and workload expressed as Watts. Maximum force of knee and shoulder extensors and flexors was measured using isokinetic testing. Quality of life was assessed with the SF-36 questionnaire, and fatigue was measured using the Modified Fatigue Impact Scale. Both training groups increased in aerobic capacity and maximum force. EWG, as well as CWG, showed improvement in several subscales of the SF-36 questionnaire and decrease of their fatigue. A short exercise intervention increased both aerobic capacity and maximum force independent of whether endurance or combined endurance/resistance workouts were performed.
Golalipour, Masoud; Maleki, Zahra; Farazmandfar, Touraj; Shahbazi, Majid
Multiple Sclerosis (MS) is a degenerative disease of central nervous system caused by an immune response against the myelin. About half of MS patients suffers from sleep disturbances. The circadian clock genes such as PER3 controls circadian rhythm and sleep. Due to the role of PER3 in sleep disturbances and regulation of immune response, it is possible that PER3 dysregulation increase risk of MS disease. Study groups included 160 MS patients and 160 healthy volunteers. PER3 VNTR polymorphism was evaluated by PCR method. The genotypic and allelic distribution analyzed by chi square test. There was a significant association between genotype PER3 4/4 , and 4-repeat allele with MS disease (p = 0.014 and p < 0.001 respectively). The association analysis of PER3 VNTR polymorphism with gender status among MS group, and MS onset showed that there was a significant correlation between PER3 4/4 genotype with female gender and early onset of MS disease (p = 0.033 and p = 0.028 respectively). Our data suggest that, PER3 4/4 genotype may accelerate the course of disease in MS susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.
Dunn, Shannon E; Gunde, Eva; Lee, Hyunwoo
It is well known that a number of autoimmune diseases including multiple sclerosis (MS) predominantly affect women and there has been much attention directed toward understanding why this is the case. Past research has revealed a number of sex differences in autoimmune responses that can account for the female bias in MS. However, much less is known about why the incidence of MS has increased exclusively in women over the past half century. The recency of this increase suggests that changing environmental or lifestyle factors are interacting with biological sex to increase MS risk predominantly in females. Indeed, a number of recent studies have identified sex-specific differences in the effect of environmental factors on MS incidence. The first part of this chapter will overview this evidence and will discuss the possible scenarios of how the environment may be interacting with autoimmune mechanisms to contribute to the preferential rise in MS incidence in women. Despite the strong female bias in MS incidence, culminating evidence from natural history studies, and imaging and pathology studies suggests that males who develop MS may exhibit a more rapid decline in disability and cognitive functioning than women. Very little is known about the biological basis of this more rapid deterioration, but some insights have been provided by studies in rodent models of demyelination/remyelination. The second part of this chapter will overview the evidence that males with relapsing-onset MS undergo a more rapid progression of disease than females and will discuss potential biological mechanisms that account for this sex difference.
Santos-García, D; Prieto, J M; Lema, M
The risk of side effects secondary to global and non-specific immune suppression has limited the systematic application of immunosuppressive therapy in multiple sclerosis (MS). However, when a patient with MS develops a cancer, cytostatic drugs as treatment for the neoplastic process may induce improvement not only of the cancer but also of MS. We present a series of four women with clinically defined MS and subjected to cytostatic therapy (cisplatin, 5-fluorouracil, leukovorin, adriamycin, tamoxifen and anastrozole) after the development of cancer: two presented breast cancer, one colon cancer, and the fourth parotid gland malignancy. Their clinical and neuroimaging course is described, following chemotherapy for the malignant disease. None of the patients have suffered further MS outbreaks. The four women have improved and remain clinically stable after neoplastic treatment. Magnetic resonance imaging showed persistence of the same lesion burden in three patients, and reduction in the other. At the present one patient receives weekly intramuscular interferon-beta 1a, whereas the other did not received any treatment. Probably there are no specific cytostatics for MS. Immunosuppressive therapy could be a therapeutic option among patients with an aggressive clinical course.
de Ceuninck van Capelle, Archie; Visser, Leo H; Vosman, Frans
In this study the authors explored how people with recently diagnosed multiple sclerosis (MS) experience their disease within their family lives. Ten people in various stages of the cycle of family life (leaving home, finding a partner, raising children, parenting adolescents, launching children) who had been diagnosed with MS were interviewed in half-structured conversational interviews. Transcriptions were analyzed following a phenomenological approach. Five themes were found: (a) dwindling capacity for housekeeping and childcare (b) struggling to ask for or to accept help, (c) countering awkward attitudes toward my illness, (d) suspecting family members of concealing their, and (e) watching family members wrestle with your illness. The participants described that their illness affected their ability to care for their family and home as they used to. Only a couple of studies have addressed the first person perspective of patients on family and MS. The study expands on these studies by exploring not previously examined perspectives on leaving home, finding a partner, parenting adolescents, and launching children. The findings on family and MS, approached as elements of the first person perspective of MS patients, may guide future research. Given the pivotal role of worries on family in patient experience of MS, we argue that acknowledgment of family as a constitutive element of the patient perspective should be integrated in regular MS care. The authors suggest that the clinical handling of MS as a family issue needs to be done thoughtfully and with attention to the specifics of each unique family situation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Motl, Robert W; Mowry, Ellen M; Ehde, Dawn M; LaRocca, Nicholas G; Smith, Kathy E; Costello, Kathleen; Shinto, Lynne; Ng, Alexander V; Sullivan, Amy B; Giesser, Barbara; McCully, Kevin K; Fernhall, Bo; Bishop, Malachy; Plow, Matthew; Casaccia, Patrizia; Chiaravalloti, Nancy D
Background: People with multiple sclerosis (MS) have identified “wellness” and associated behaviors as a high priority based on “social media listening” undertaken by the National MS Society (i.e. the Society). Objective: The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. Method: The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. Results: That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society’s Wellness Research Working Group. Conclusion: The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences. PMID:28080254
Background Fatigue is a common and debilitating symptom in multiple sclerosis (MS). Best-practice guidelines suggest that health services should repeatedly assess fatigue in persons with MS. Several fatigue scales are available but concern has been expressed about their validity. The objective of this study was to examine the reliability and validity of a new scale for MS fatigue, the Neurological Fatigue Index (NFI-MS). Methods Qualitative analysis of 40 MS patient interviews had previously contributed to a coherent definition of fatigue, and a potential 52 item set representing the salient themes. A draft questionnaire was mailed out to 1223 people with MS, and the resulting data subjected to both factor and Rasch analysis. Results Data from 635 (51.9% response) respondents were split randomly into an 'evaluation' and 'validation' sample. Exploratory factor analysis identified four potential subscales: 'physical', 'cognitive', 'relief by diurnal sleep or rest' and 'abnormal nocturnal sleep and sleepiness'. Rasch analysis led to further item reduction and the generation of a Summary scale comprising items from the Physical and Cognitive subscales. The scales were shown to fit Rasch model expectations, across both the evaluation and validation samples. Conclusion A simple 10-item Summary scale, together with scales measuring the physical and cognitive components of fatigue, were validated for MS fatigue. PMID:20152031
Huang, Zhongming; Qi, Yiying; Du, Shaohua; Chen, Guangnan; Yan, Weiqi
Multiple sclerosis (MS) and osteoporosis (OP) affect a substantial proportion of the population. Accumulating evidence suggests that MS patients are at high risk for OP. We performed a meta-analysis to identify risk factors for lowered bone mineral density (BMD) in MS patients. We searched for articles within the Medline, Embase and Cochrane Library databases, published up to March 2014, pertaining to associations between MS and BMD. A total of 11 studies was included in the meta-analysis. The analysis indicated that MS patients have reduced lumbar spine, femur neck, and hip BMD compared with healthy controls (lumbar spine, standardized mean difference (SMD) = -0.76, 95% CI: -1.07, -0.45; femur neck, SMD = -0.56, 95% CI: -0.84, -0.29; and hip, SMD = -0.62, 95% CI: -0.96, -0.29). Further subgroup analysis revealed that a disease duration of >7 years, total steroid dose during the disease of >15 g, and an Expanded Disability Status Scale (EDSS) score of > 3, increased the risk of reduced BMD in the lumbar spine and femoral neck, but not in the hip. Meta-regression analysis did not explain the heterogeneity in the clinical characteristics or outcome definitions. Our meta-analysis suggests that MS patients have reduced overall BMD compared with healthy controls. Furthermore, disease duration (>7 years), total steroid dose (>15 g), and EDSS score (>3) are risk factors for reduced BMD in MS patients.
Pröbstel, Anne-Katrin; Baranzini, Sergio E
Multiple sclerosis (MS) is the prototypic complex disease, in which both genes and the environment contribute to its pathogenesis. To date, > 200 independent loci across the genome have been associated with MS risk. However, these only explain a fraction of the total phenotypic variance, suggesting the possible presence of additional genetic factors, and, most likely, also environmental factors. New DNA sequencing technologies have enabled the sequencing of all kinds of microorganisms, including those living in and around humans (i.e., microbiomes). The study of bacterial populations inhabiting the gut is of particular interest in autoimmune diseases owing to their key role in shaping immune responses. In this review, we address the potential crosstalk between B cells and the gut microbiota, a relevant scenario in light of recently approved anti-B-cell therapies for MS. In addition, we review recent efforts to characterize the gut microbiome in patients with MS and discuss potential challenges and future opportunities. Finally, we describe the international MS microbiome study, a multicenter effort to study a large population of patients with MS and their healthy household partners to define the core MS microbiome, how it is shaped by disease-modifying therapies, and to explore potential therapeutic interventions.
Mirsky, Matthew M; Marrie, Ruth Ann; Rae-Grant, Alexander
Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: "Power searches" were built to test the relationship between antidepressant drug use and DMT in the MS population. Searches were built to produce a cohort of individuals diagnosed as having MS in the past 3 years taking a specific DMT who were then given any antidepressant drug. The antidepressant drug therapy prevalence was tested in the MS population on the following DMTs: IFNβ-1a, IFNβ-1b, combined IFNβ, glatiramer acetate, natalizumab, fingolimod, and dimethyl fumarate. Results: In patients with MS, the rate of antidepressant drug use in those receiving DMTs was 40.60% to 44.57%. The rate of antidepressant drug use for combined IFNβ DMTs was 41.61% (males: 31.25%-39.62%; females: 43.10%-47.33%). Antidepressant drug use peaked in the group aged 45 to 54 years for five of six DMTs. Conclusions: We found no association between IFNβ treatment and antidepressant drug use in the MS population compared with other DMTs. The EPM database has been validated against the Patten et al. data for future use in the MS population.
Motl, Robert W; Mowry, Ellen M; Ehde, Dawn M; LaRocca, Nicholas G; Smith, Kathy E; Costello, Kathleen; Shinto, Lynne; Ng, Alexander V; Sullivan, Amy B; Giesser, Barbara; McCully, Kevin K; Fernhall, Bo; Bishop, Malachy; Plow, Matthew; Casaccia, Patrizia; Chiaravalloti, Nancy D
People with multiple sclerosis (MS) have identified "wellness" and associated behaviors as a high priority based on "social media listening" undertaken by the National MS Society (i.e. the Society). The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society's Wellness Research Working Group. The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences.
Fares, Jawad; Nassar, Anwar H; Gebeily, Souheil; Kobeissy, Firas; Fares, Youssef
Objective The Lebanese Multiple Sclerosis (LeMS) study aims to assess the influence of pregnancy and delivery on the clinical course of multiple sclerosis (MS) in Lebanese women. Setting This prospective multicentre study took place in three MS referral university medical centres in Lebanon. Participants Included were 29 women over 18 years who had been diagnosed with MS according to the McDonald criteria, and became pregnant between 1995 and 2015. Participating women should have stopped treatment 3 months before conception and become pregnant after the onset of MS. Women were followed up from 1 year preconceptionally and for 4 years postpartum. Main outcome measures The annualised relapse rates per participant during each 3-month period during pregnancy and each year postpartum were compared with the relapse rate during the year before pregnancy using the paired two-tailed t test. p Values <0.05 were considered statistically significant for all analyses (95% CI). Results 64 full-term pregnancies were recorded. All pregnancies (100%) resulted in live births, with no complications or other diseases. In comparison with the prepregnancy year, in which the mean relapse rate±SE was 0.17±0.07, there was a significant reduction in the relapse rate during pregnancy and in the first year postpartum (p=0.02), but an increase in the rate in the second year postpartum (0.21±0.08). Thereafter, from the third year postpartum through the following fourth year, the annualised relapse rate fell slightly but did not differ from the annualised relapse rate recorded in the prepregnancy year (0.17±0.07). Conclusions Pregnancy in Lebanese women with MS does not seem to increase the risk of complications. No relapses were observed during pregnancy and in the first year postpartum; however, relapses rebounded in the second year postpartum, and over the long term, returned to the levels that preceded pregnancy. PMID:27178979
Calvo-Barreiro, Laura; Eixarch, Herena; Montalban, Xavier; Espejo, Carmen
The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.
Ehde, Dawn M; Alschuler, Kevin N; Sullivan, Mark D; Molton, Ivan P; Ciol, Marcia A; Bombardier, Charles H; Curran, Mary C; Gertz, Kevin J; Wundes, Annette; Fann, Jesse R
Evidence-based pharmacological and behavioral interventions are often underutilized or inaccessible to persons with multiple sclerosis (MS) who have chronic pain and/or depression. Collaborative care is an evidence-based patient-centered, integrated, system-level approach to improving the quality and outcomes of depression care. We describe the development of and randomized controlled trial testing a novel intervention, MS Care, which uses a collaborative care model to improve the care of depression and chronic pain in a MS specialty care setting. We describe a 16-week randomized controlled trial comparing the MS Care collaborative care intervention to usual care in an outpatient MS specialty center. Eligible participants with chronic pain of at least moderate intensity (≥3/10) and/or major depressive disorder are randomly assigned to MS Care or usual care. MS Care utilizes a care manager to implement and coordinate guideline-based medical and behavioral treatments with the patient, clinic providers, and pain/depression treatment experts. We will compare outcomes at post-treatment and 6-month follow up. We hypothesize that participants randomly assigned to MS Care will demonstrate significantly greater control of both pain and depression at post-treatment (primary endpoint) relative to those assigned to usual care. Secondary analyses will examine quality of care, patient satisfaction, adherence to MS care, and quality of life. Study findings will aid patients, clinicians, healthcare system leaders, and policy makers in making decisions about effective care for pain and depression in MS healthcare systems. (PCORI- IH-1304-6379; clinicaltrials.gov: NCT02137044). This trial is registered at ClinicalTrials.gov, protocol NCT02137044. Copyright © 2017 Elsevier Inc. All rights reserved.
Brola, Waldemar; Sobolewski, Piotr; Fudala, Małgorzata; Flaga, Stanisław; Jantarski, Konrad; Ryglewicz, Danuta; Potemkowski, Andrzej
The aim of the study was to analyze selected clinical and sociodemographic factors and their effects on the quality of life (QoL) of multiple sclerosis (MS) patients registered in the Polish MS Registry. This was a cross-sectional observational study performed in Poland. Data on personal and disease-specific factors were collected between January 1, 2011, and December 31, 2015, via the web portal of the Polish MS Registry. All patients were assessed by a physician and asked to complete the Polish language versions of the following self-evaluation questionnaires: EuroQol 5-Dimensions, EuroQoL Visual Analog Scale, and Multiple Sclerosis Impact Scale. Univariate analysis and logistic regression were performed to determine the factors associated with QoL. The study included 2,385 patients (female/male ratio 2.3:1) with clinically confirmed MS (mean age 37.8±9.2 years). Average EuroQol 5-Dimensions index was 0.72±0.24, and the mean EuroQoL Visual Analog Scale score was 64.2±22.8. The average Multiple Sclerosis Impact Scale score was 84.6±11.2 (62.2±18.4 for physical condition and 23.8±7.2 for mental condition). Lower QoL scores were significantly associated with higher level of disability (odds ratio [OR], 0.932; 95% confidence interval [CI], 0.876-0.984; P=0.001), age >40 years (OR, 1.042; 95% CI, 0.924-1.158; P=0.012), longer disease duration (OR, 0.482; 95% CI, 0.224-0.998; P=0.042), and lack of disease modifying therapies (OR, 0.024; 95% CI, 0.160-0.835; P=0.024). No significant associations were found between QoL, sex, type of MS course, patient's education, and marital status. The Polish MS Registry is the first national registry for long-term observation that allows for self-evaluation of the QoL. QoL of Polish patients with MS is significantly lower compared with the rest of the population. The parameter is mainly affected by the level of disability, duration of the disease, and limited access to immunomodulatory therapy.
Hofmann, A; Stellmann, J P; Kasper, J; Ufer, F; Elias, W G; Pauly, I; Repenthin, J; Rosenkranz, T; Weber, T; Köpke, S; Heesen, C
Balancing treatment benefits and risks is part of a shared decision-making process before initiating any treatment in multiple sclerosis (MS). Patients understand, appreciate and profit from evidence-based patient information (EBPI). While these processes are well known, long-term risk awareness and risk processing of patients has not been studied. Mitoxantrone treatment in MS is associated with long-term major potential harms - leukaemia (LK) and cardiotoxicity (CT). The risk knowledge and perception among patients currently or previously treated with mitoxantrone is unknown. The objective of this article is to conduct a retrospective cohort study in greater Hamburg, Germany, to estimate risk awareness and perception in MS patients treated with mitoxantrone. MS patients with at least one dose of mitoxantrone between 1991 and 2010 from six major MS centres in greater Hamburg received a questionnaire assessing risk awareness and perception as well as a written EBPI about mitoxantrone-associated LK and CT. Fifty-one per cent in the cohort of n = 575 patients returned the questionnaire. Forty per cent correctly estimated the risk of LK (CT 16%); 56% underestimated the risk (CT 82%). Reading the information increased the accuracy of LK risk estimation, and patients did not report an increase of worries. The EBPI was appreciated and recommended by 85%. Risk awareness of mitoxantrone-treated patients is insufficient, but can be increased by EBPI without increasing worries. Continued patient information during and after treatment should be implemented in management algorithms.
Giovannoni, Gavin; Cutter, Gary; Sormani, Maria Pia; Belachew, Shibeshih; Hyde, Robert; Koendgen, Harold; Knappertz, Volker; Tomic, Davorka; Leppert, David; Herndon, Robert; Wheeler-Kingshott, Claudia A M; Ciccarelli, Olga; Selwood, David; di Cantogno, Elisabetta Verdun; Ben-Amor, Ali-Frederic; Matthews, Paul; Carassiti, Daniele; Baker, David; Schmierer, Klaus
Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms. However, anti-inflammatory therapies may modify these damaged pathways, but with a therapeutic lag that may take years to manifest. Based on these observations we propose that clinically apparent neurodegenerative components of progressive MS may occur in a length-dependent manner and asynchronously. If this hypothesis is confirmed it may have major implications for the future design of progressive MS trials. Copyright © 2016 Elsevier B.V. All rights reserved.
Pétrin, Julie; Akbar, Nadine; Turpin, Karen; Smyth, Penelope; Finlayson, Marcia
We aimed to understand participants' experiences with a self-guided fatigue management resource, Multiple Sclerosis: An Interactive Fatigue Management Resource ( MS INFoRm), and the extent to which they found its contents relevant and useful to their daily lives. We recruited 35 persons with MS experiencing mild to moderate fatigue, provided them with MS INFoRm, and then conducted semistructured interviews 3 weeks and 3 months after they received the resource. Interpretive description guided the analysis process. Findings indicate that participants' experience of using MS INFoRm could be understood as a process of change, influenced by their initial reactions to the resource. They reported experiencing a shift in knowledge, expectations, and behaviors with respect to fatigue self-management. These shifts led to multiple positive outcomes, including increased levels of self-confidence and improved quality of life. These findings suggest that MS INFoRm may have a place in the continuum of fatigue management interventions for people with MS.
Abo Youssef, Nadim; Schneider, Marc P; Mordasini, Livio; Ineichen, Benjamin V; Bachmann, Lucas M; Chartier-Kastler, Emmanuel; Panicker, Jalesh N; Kessler, Thomas M
To review systematically all the available evidence on efficacy and safety of cannabinoids for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of the Cochrane register, Embase, Medline, Scopus (last search on 11 November 2016). After screening 8 469 articles, we included two randomized controlled trials and one open-label study, in which a total of 426 patients were enrolled. Cannabinoids relevantly decreased the number of incontinence episodes in all three studies. Pooling data showed the mean difference in incontinence episodes per 24 h to be -0.35 (95% confidence interval -0.46 to -0.24). Mild adverse events were frequent (38-100%), but only two patients (0.7%) reported a serious adverse event. Preliminary data imply that cannabinoids might be an effective and safe treatment option for NLUTD in patients with MS; however, the evidence base is poor and more high-quality, well-designed and adequately powered and sampled studies are urgently needed to reach definitive conclusions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.
Rieckmann, Peter; Centonze, Diego; Elovaara, Irina; Giovannoni, Gavin; Havrdová, Eva; Kesselring, Jurg; Kobelt, Gisela; Langdon, Dawn; Morrow, Sarah A; Oreja-Guevara, Celia; Schippling, Sven; Thalheim, Christoph; Thompson, Heidi; Vermersch, Patrick; Aston, Karen; Bauer, Birgit; Demory, Christy; Giambastiani, Maria Paz; Hlavacova, Jana; Nouvet-Gire, Jocelyne; Pepper, George; Pontaga, Maija; Rogan, Emma; Rogalski, Chrystal; van Galen, Pieter; Ben-Amor, Ali-Frédéric
Patient engagement is vital in multiple sclerosis (MS) in order to optimise outcomes for patients, society and healthcare systems. It is essential to involve all stakeholders in potential solutions, working in a multidisciplinary way to ensure that people with MS (PwMS) are included in shared decision-making and disease management. To start this process, a collaborative, open environment between PwMS and healthcare professionals (HCPs) is required so that similarities and disparities in the perception of key areas in patient care and unmet needs can be identified. With this patient-centred approach in mind, in 2016 the MS in the 21st Century Steering Group formed a unique collaboration to include PwMS in the Steering Group to provide a platform for the patient voice. The MS in the 21st Century initiative set out to foster engagement through a series of open-forum joint workshops. The aims of these workshops were: to identify similarities and disparities in the perception and prioritisation in three key areas (unmet needs, the treatment burden in MS, and factors that impact patient engagement), and to provide practical advice on how the gaps in perception and understanding in these key areas could be bridged. Combined practical advice and direction are provided here as eight actions: 1. Improve communication to raise the quality of HCP-patient interaction and optimise the limited time available for consultations. 2. Heighten the awareness of 'hidden' disease symptoms and how these can be managed. 3. Improve the dialogue surrounding the benefit versus risk issues of therapies to help patients become fully informed and active participants in their healthcare decisions. 4. Provide accurate, lucid information in an easily accessible format from reliable sources. 5. Encourage HCPs and multidisciplinary teams to acquire and share new knowledge and information among their teams and with PwMS. 6. Foster greater understanding and awareness of challenges faced by PwMS and
Langer-Gould, Annette; Lucas, Robyn; Xiang, Anny H; Chen, Lie H; Wu, Jun; Gonzalez, Edlin; Haraszti, Samantha; Smith, Jessica B; Quach, Hong; Barcellos, Lisa F
Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from the membership of Kaiser Permanente Southern California into the MS Sunshine Study to simultaneously examine sun exposure and 25OHD, accounting for genetic ancestry and other factors. Higher lifetime ultraviolet radiation exposure (a rigorous measure of sun exposure) was associated with a lower risk of MS independent of serum 25OHD levels in blacks (adjusted OR = 0.53, 95% CI = 0.31-0.83; p = 0.007) and whites (OR = 0.68, 95% CI = 0.48-0.94; p = 0.020) with a similar magnitude of effect that did not reach statistical significance in Hispanics (OR = 0.66, 95% CI = 0.42-1.04; p = 0.071). Higher serum 25OHD levels were associated with a lower risk of MS only in whites. No association was found in Hispanics or blacks regardless of how 25OHD was modeled. Lifetime sun exposure appears to reduce the risk of MS regardless of race/ethnicity. In contrast, serum 25OHD levels are not associated with MS risk in blacks or Hispanics. Our findings challenge the biological plausibility of vitamin D deficiency as causal for MS and call into question the targeting of specific serum 25OHD levels to achieve health benefits, particularly in blacks and Hispanics.
Christophi, George P.; Christophi, Jennifer A.; Gruber, Ross C.; Mihai, Cornelia; Mejico, Luis J.; Massa, Paul T.; Jubelt, Burk
Interferon-β (IFN-β) is a current effective treatment for multiple sclerosis (MS) and exerts its therapeutic effects by down-modulating the systemic immune response and cytokine signaling. In clinical practice there are several formulations of interferon including a low dose of IFN-β 1a formulation of 30μg IM once weekly (Avonex) and a high dose formulation of 44 μg SC three times weekly (Rebif). Recent studies suggest that Rebif is more efficacious compared to Avonex in preventing relapses and decreasing MRI activity in relapsing remitting MS (RRMS) patients. This study examines whether there are quantitative gene expression changes in interferon-treated RRMS patients that can explain the difference in efficacy and side effects between Rebif and Avonex. Herein, RRMS patients were treated for three months with IFN-β 1a and the levels of plasma cytokines and gene expression in peripheral blood mononuclear cells were examined. Thirty-two normal subjects were compared to thirty-two RRMS patients, of which ten were treated with Rebif and ten with Avonex. Rebif and Avonex both significantly and equally suppressed plasma TNF-α and IL-6 levels. Rebif suppressed IL-13 significantly more than Avonex. Rebif also significantly suppressed the levels of the chemokines CCL17 and RANTES, the protease ADAM8, and COX-2 at a higher degree compared to Avonex. The STAT1-inducible genes IP-10 and caspase 1 were significantly increased with Rebif compared to Avonex. In conclusion, the higher dosed, more frequently administered IFN-β 1a Rebif when compared to IFN β-1a Avonex has more potent immunomodulatory effects. These quantitative results might relate to efficacy and side-effect profile of the two IFN-β 1a formulations and provide prospective practical clinical tools to monitor treatment and adjust dosage. PMID:21658727
Dorn, Jonas F; Burggraaff, Jessica; Kamm, Christian Philipp; Steinheimer, Saskia Marie; Kontschieder, Peter; Criminisi, Antonio; Uitdehaag, Bernard; Dahlke, Frank; Kappos, Ludwig; Sellen, Abigail
Background Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between
Morrison, Cecily; D'Souza, Marcus; Huckvale, Kit; Dorn, Jonas F; Burggraaff, Jessica; Kamm, Christian Philipp; Steinheimer, Saskia Marie; Kontschieder, Peter; Criminisi, Antonio; Uitdehaag, Bernard; Dahlke, Frank; Kappos, Ludwig; Sellen, Abigail
Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients' level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. In typical
O'Connell, K; Langdon, D; Tubridy, N; Hutchinson, M; McGuigan, C
Cognitive impairment is common in multiple sclerosis (MS) irrespective of disease stage or subtype. It is typically underreported and neuropsychological testing can be required to detect more subtle evidence of cognitive impairment. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) was an initiative undertaken by a panel of experts with the primary objective of identifying a brief cognitive assessment tool that could be administered by healthcare professionals without formal neuropsychological training to identify early or subtle cognitive impairment among MS patients. To validate BICAMS in Irish patients with MS and healthy controls. Consecutive patients attending the MS outpatient department from January to April 2014 were recruited. Age, gender, education, handedness, MS subtype, expanded disability status scale (EDSS) and disease duration were recorded. They were administered BICAMS composed of Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT-II) and Brief Visuospatial Memory Test (BVMT-R). Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). Control participants were composed of unaffected relatives, spouses or carers attending the clinic with a patient and were matched by age, gender and years of education. Impairment on individual tests was defined as -1.5 SD below reference group means. 67 patients [73% women; mean age: 43.9 yrs (12.1); mean years of education: 13.6 yrs (2.7)] and 66 controls [68% women; mean age 42.7 yrs (12.7); mean years of education: 14.1 yrs (3.2)] were recruited. Of the MS patient group: 70% were classified as having relapsing remitting MS, 28% secondary progressive MS and 2% primary progressive MS (PPMS). Mean EDSS scores were 1.8 (SD: 0.9), 5.7 (SD: 1.4) and 7.0 in each group respectively with mean disease duration of 10.2 (SD: 8.4) years, 20.6 (10.2) and 17 years. Mean scores and standard deviations for patients and control participants
Dolati, Sanam; Ahmadi, Majid; Rikhtegar, Reza; Babaloo, Zohreh; Ayromlou, Hormoz; Aghebati-Maleki, Leili; Nouri, Mohammad; Yousefi, Mehdi
MS is a chronic inflammatory disease that causes to brain inflammation and Th17 cells are considered to be important in multiple sclerosis pathogenesis. In the current study, we aimed to identify nanocurcumin effects on Th17 cells frequency, cytokines secretion, and expression of transcription factor of patients with relapsing-remitting multiple sclerosis (RRMS). In this study we investigated frequency of Th17 lymphocytes; the expression of transcription factor, associated cytokines and the concentration of them in 35 healthy controls, and from 25 patients at baseline and after 6 months of nanocurcumin treatment and also from 25 patients whose received placebo by flowcytometry, real-time PCR and ELISA, respectively. Our analysis revealed that the proportions of Th17 were increased dramatically, along with increases in the levels of IL-17A, IL-23, and RORγt expression in MS patients in compared with healthy control group. Post-treatment evaluation of the nanocurcumin group revealed a significant decrease in Th17 associated parameters such as Th17 frequency (p = 0.029), expression levels of RORγt (p < 0.0001) and IL-17 (p = 0.0044) and also secretion level of IL-17 (p = 0.0011), but IL-23 mRNA expression levels and IL-23 concentration were not influenced by nanocurcumin. However, in the placebo group there is no significant changes in these factors. Our study suggests that the increase in proportion of Th17 cells might contribute to the pathogenesis of RRMS. The results of the current work indicated that nanocurcumin is able to restore the dysregulated of Th17 cells in MS patients. Copyright © 2018 Elsevier B.V. All rights reserved.
Saposnik, Gustavo; Maurino, Jorge; Sempere, Angel P; Ruff, Christian C; Tobler, Philippe N
Herding is a phenomenon by which individuals follow the behavior of others rather than deciding independently on the basis of their own private information. A herding-like phenomenon can occur in multiple sclerosis (MS) when a neurologist follows a therapeutic recommendation by a colleague even though it is not supported by best practice clinical guidelines. Limited information is currently available on the role of herding in medical care. The objective of this study was to determine the prevalence (and its associated factors) of herding in the management of MS. We conducted a study among neurologists with expertise in MS care throughout Spain. Participants answered questions regarding the management of 20 case scenarios commonly encountered in clinical practice and completed 3 surveys and 4 experimental paradigms based on behavioral economics. The herding experiment consisted of a case scenario of a 40-year-old woman who has been stable for 3 years on subcutaneous interferon and developed a self-limited neurological event. There were no new magnetic resonance imaging (MRI) lesions. Her neurological examination and disability scores were unchanged. She was advised by an MS neurologist to switch from interferon to fingolimod against best practice guidelines. Multivariable logistic regression analysis was conducted to evaluate factors associated with herding. Out of 161 neurologists who were invited to participate, 96 completed the study (response rate: 60%). Herding was present in 75 (78.1%), having a similar prevalence in MS experts and general neurologists (68.8% vs 82.8%; P =0.12). In multivariate analyses, the number of MS patients seen per week was positively associated with herding (odds ratio [OR] 1.08, 95% CI 1.01-1.14). Conversely, physician's age, gender, years of practice, setting of practice, or risk preferences were not associated with herding. Herding was a common phenomenon affecting nearly 8 out of 10 neurologists caring for MS patients. Herding may
Bateman, Grant A; Lechner-Scott, Jeannette; Lea, Rodney A
It has been suggested there is a chronic neurodegenerative disorder, underlying the pathophysiology of multiple sclerosis (MS), which is distinct from the more obvious immune-mediated attack on the white matter. Limited data exists indicating there is an alteration in pulse wave propagation within the craniospinal cavity in MS, similar to the findings in normal pressure hydrocephalus (NPH). It is hypothesized MS may harbor pulse wave encephalopathy. The purpose of this study is to compare blood flow and pulse wave measurements in MS patients with a cohort of NPH patients and control subjects, to test this hypothesis. Twenty patients with MS underwent magnetic resonance (MR) flow quantification techniques. Mean blood flow and stroke volume were measured in the arterial inflow and venous out flow from the sagittal (SSS) and straight sinus (ST). The arteriovenous delay (AVD) was defined. The results were compared with both age-matched controls and NPH patients. In MS there was a 35 % reduction in arteriovenous delay and a 5 % reduction in the percentage of the arterial inflow returning via the sagittal sinus compared to age matched controls. There was an alteration in pulse wave propagation, with a 26 % increase in arterial stroke volume but 30 % reduction in SSS and ST stroke volume. The AVD and blood flow changes were in the same direction to those of NPH patients. There are blood flow and pulsation propagation changes in MS patients which are similar to those of NPH patients. The findings would be consistent with an underlying pulse wave encephalopathy component in MS.
Tettey, Prudence; Simpson, Steve; Taylor, Bruce V; van der Mei, Ingrid A F
We reviewed the evidence for the co-occurrence of type 1 diabetes mellitus (T1D) and multiple sclerosis (MS), and assessed the clinical significance of this association and the shared aetiological features of the two diseases. T1D and MS contribute considerably to the burden of autoimmune diseases in young adults. The co-occurrence of MS and T1D has been reported by a number of studies, suggesting that the two conditions share one or more aetiological components. Both conditions have been associated with distinct human leukocyte antigen (HLA) haplotypes but share a number of similarities in clinical, epidemiological and immunological features, leading to suggestions of possible common mechanisms of development. While underlying genetic factors may be important for the co-occurrence of both conditions, some evidence suggests that environmental factors such as vitamin D deficiency may also modulate an individual's risk for the development of both conditions. Evidence on whether the co-occurrence of the two autoimmune conditions will affect the disease course and severity of MS is merely absent. Further studies need to be conducted to ascertain whether the neuropathology associated with T1D might influence the disease course and contribute to the severity of MS. Copyright © 2014 Elsevier B.V. All rights reserved.
Hoang, Huong; Laursen, Bjarne; Stenager, Elsebeth N; Stenager, Egon
Studies of depression and anxiety in multiple sclerosis (MS) patients have reported higher rates in MS patients than the general population. To estimate the risk of depression and anxiety and the use of tricyclic antidepressant and selective serotonin reuptake inhibitors (SSRI) prescriptions, in the pre-diagnostic and the post-diagnostic period of MS compared to the background population. A cohort of 5084 MS patients was included and matched with a control population of 24,771 persons linked to nationwide registers. Logistic regression analyses were performed estimating odds ratios (OR). In the pre-diagnostic period, the OR for having a diagnosis of depression and anxiety is 1.4 (95% confidence interval (CI) =1.05-1.88), and the OR of redemption prescriptions of TCAs is 1.90 (CI=1.54-2.34) and OR is 1.34 (CI= 1.20-1.51) for SSRI. In the post-diagnostic period the OR is 1.23 (CI= 0.92-1.64) for depression and anxiety diagnosis. The OR is 6.70 (CI=5.81-7.72) for TCA and OR is 2.46 (CI= 2.25-2.69) for SSRI. During both the pre- diagnostic and post-diagnostic period, MS patient have increased risk of depression and anxiety diagnoses and redemption of antidepressant and anxiolytic prescriptions, compared to the background population. © The Author(s), 2015.
Magalhaes, Sandra; Banwell, Brenda; Bar-Or, Amit; Fortier, Isabel; Hanwell, Heather E; Lim, Ming; Matt, Georg E; Neuteboom, Rinze F; O'Riordan, David L; Schneider, Paul K; Pugliatti, Maura; Shatenstein, Bryna; Tansey, Catherine M; Wassmer, Evangeline; Wolfson, Christina
While studying the etiology of multiple sclerosis (MS) in children has several methodological advantages over studying etiology in adults, studies are limited by small sample sizes. Using a rigorous methodological process, we developed the Pediatric MS Tool-Kit, a measurement framework that includes a minimal set of core variables to assess etiological risk factors. We solicited input from the International Pediatric MS Study Group to select three risk factors: environmental tobacco smoke (ETS) exposure, sun exposure, and vitamin D intake. To develop the Tool-Kit, we used a Delphi study involving a working group of epidemiologists, neurologists, and content experts from North America and Europe. The Tool-Kit includes six core variables to measure ETS, six to measure sun exposure, and six to measure vitamin D intake. The Tool-Kit can be accessed online ( www.maelstrom-research.org/mica/network/tool-kit ). The goals of the Tool-Kit are to enhance exposure measurement in newly designed pediatric MS studies and comparability of results across studies, and in the longer term to facilitate harmonization of studies, a methodological approach that can be used to circumvent issues of small sample sizes. We believe the Tool-Kit will prove to be a valuable resource to guide pediatric MS researchers in developing study-specific questionnaire.
Sevim, Serhan; Kaleağası, Hakan; Fidancı, Halit
Sleep bruxism refers to a nocturnal parafunctional activity including the clenching, grinding or gnashing of teeth. While most of the nocturnal bruxism cases seen in the general population are apparently idiopathic, it has been reported to be associated with a range of neurological diseases such as Huntington's disease, cranio-cervical dystonia and post-anoxic brain damage, but not multiple sclerosis (MS). We describe three cases of MS patients who have had moderate to severe complaints of bruxism in the two weeks following their relevant MS attacks. None of the three patients had a diagnosis of bruxism prior to her attack. The diagnosis was confirmed in one out of three by a polysomnography. One patient did not have any complaints related to bruxism previous to her attack, whereas two had mild and infrequent complaints. The symptoms of the relevant attacks were left hemihypesthesia in all and hemiparesis in two. None of the patients had spasticity that could result in severe teeth clenching. All three patients presented with morning headaches and jaw pain or tightness and were treated successfully with botulinum toxin (Btx) injections applied to their masseter and temporalis muscles. The cause of bruxism is controversial but lesions of the cortico-basalganglia-thalamo-cotrical loops are thought to be most likely. However, acute or chronic lesions in those pathways were not demonstrated in the 3 patients. It is feasible that they had normal appearing white matter interruptions in their cortico-basalganglia-thalamocortical loops along with their relevant attack. Copyright © 2015 Elsevier B.V. All rights reserved.
Benito-León, Julián; Rivera-Navarro, Jesús; Guerrero, Angel Luis; de Las Heras, Virginia; Balseiro, José; Rodríguez, Elena; Belló, Mireia; Martínez-Martín, Pablo
To develop and test the first specific instrument for assessing caregiver health-related quality of life (HRQOL) in multiple sclerosis (MS) (CAREQOL-MS). Questionnaire items were derived from a literature review and the views of patients, caregivers, and experts. Instrument was reduced after the analyses of caregivers' interviews and experts' opinions. CAREQOL-MS psychometric properties were assessed in 276 MS caregivers. The final version consisted of 24 items (five subscales) and was free of floor or ceiling effects. For subscales, the Cronbach's alpha coefficient ranged from 0.75 to 0.90. The item-total correlation was 0.62-0.74 for subscale I (physical burden/global health); 0.56-0.74 for subscale II (social impact); 0.52-0.62 for subscale III (emotional impact), and 0.58-0.65 for subscale IV (need of help); subscale V (emotional reactions) had only two items. The intraclass correlation coefficient (0.96 for the total score; 0.75-0.95 for subscales) suggested satisfactory reproducibility. Association was close between CAREQOL-MS subscales and the Zarit burden interview and moderate with short form 36 mental/physical components. CAREQOL-MS subscales scores significantly increased (worse HRQOL) with increasing caregivers' age and Expanded Disability Status Scale. The standard error of the measurement ranged from 0.91 to 2.43 for subscales. Our results provided initial evidence of the usefulness and satisfactory psychometric properties of the CAREQOL-MS. Copyright © 2011 Elsevier Inc. All rights reserved.
Strober, L B
Personality has long been considered a factor that can account for differences in health, well-being, and overall quality of life (QOL). A 'Distressed or Type D Personality' has been studied in medical populations as a predictor of several outcomes. The purpose of the present investigation was to determine the presence of Type D Personality in multiple sclerosis (MS) and its role on disease symptoms, disease management, health-related behaviors, coping, psychological well-being, and overall QOL and functioning. Two hundred and thirty (230) individuals with MS completed a survey assessing personality, disease symptoms, disease management, coping, self-efficacy, locus of control (LOC), psychological well-being, and QOL. Thirty-seven (16%) individuals were found to be 'Type D+.' Such individuals reported greater fatigue, pain, depression, and anxiety and worse disease management and adherence. They also reported engaging in maladaptive means of coping. Compared to 'Type D-' they reported lower self-efficacy, LOC, QOL and greater perceived stress. Finally, 'Type D+' individuals were more likely to be considering leaving the workforce. Findings suggest that 'Type D' Personality is associated with various negative outcomes in MS. Consideration of the routine assessment of personality in MS seems warranted and may better inform interventions and ward off poor outcomes.
Fares, Jawad; Nassar, Anwar H; Gebeily, Souheil; Kobeissy, Firas; Fares, Youssef
The Lebanese Multiple Sclerosis (LeMS) study aims to assess the influence of pregnancy and delivery on the clinical course of multiple sclerosis (MS) in Lebanese women. This prospective multicentre study took place in three MS referral university medical centres in Lebanon. Included were 29 women over 18 years who had been diagnosed with MS according to the McDonald criteria, and became pregnant between 1995 and 2015. Participating women should have stopped treatment 3 months before conception and become pregnant after the onset of MS. Women were followed up from 1 year preconceptionally and for 4 years postpartum. The annualised relapse rates per participant during each 3-month period during pregnancy and each year postpartum were compared with the relapse rate during the year before pregnancy using the paired two-tailed t test. p Values <0.05 were considered statistically significant for all analyses (95% CI). 64 full-term pregnancies were recorded. All pregnancies (100%) resulted in live births, with no complications or other diseases. In comparison with the prepregnancy year, in which the mean relapse rate±SE was 0.17±0.07, there was a significant reduction in the relapse rate during pregnancy and in the first year postpartum (p=0.02), but an increase in the rate in the second year postpartum (0.21±0.08). Thereafter, from the third year postpartum through the following fourth year, the annualised relapse rate fell slightly but did not differ from the annualised relapse rate recorded in the prepregnancy year (0.17±0.07). Pregnancy in Lebanese women with MS does not seem to increase the risk of complications. No relapses were observed during pregnancy and in the first year postpartum; however, relapses rebounded in the second year postpartum, and over the long term, returned to the levels that preceded pregnancy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Bamm, Vladimir V; Geist, Arielle M; Harauz, George
We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.
Leclercq, Eugénie; Cabaret, Maryline; Guilbert, Alma; Jougleux, Caroline; Vermersch, Patrick; Moroni, Christine
The aim of this study was to dissociate age and duration of illness effects on cognitive impairment of patients with relapsing-remitting multiple sclerosis. Cognitive impairment among patients with multiple sclerosis (MS) is well known. However, few studies were devoted to assess the respective role of disease duration and age on cognitive functions in MS patients. Therefore, two studies were carried out on relapsing-remitting MS (RR-MS) patients using some tests of the BCcogSEP--a French test battery evaluating cognitive functions in MS. The cognitive deficits of RR-MS patients aged 50 years and over and whose symptoms had been present for more than 20 years were more severe than those of MS patients with a shorter illness duration (less than 10 years) or matched-age control participants. The more impaired cognitive functions were information-processing speed, episodic memory, verbal fluency and attention. On the other hand, cognitive performances of young RR-MS patients were similar to those of older RR-MS patients when all patients had the same illness duration (8 years in this study). Older patients even achieved better performance than younger ones on verbal fluency. This can be partly explained by the theory of cognitive reserve, as reported in previous cognitive aging studies. In RR-MS patients, the influence of illness duration seems to be a predominant factor in the development of cognitive impairment.
Collins, Mahlon A; An, Jiyan; Hood, Brian L; Conrads, Thomas P; Bowser, Robert P
Analysis of the cerebrospinal fluid (CSF) proteome has proven valuable to the study of neurodegenerative disorders. To identify new protein/pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis (ALS), we performed comparative proteomic profiling of CSF from sporadic ALS (sALS), healthy control (HC), and other neurological disease (OND) subjects using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1712 CSF proteins were detected and relatively quantified by spectral counting. Levels of several proteins with diverse biological functions were significantly altered in sALS samples. Enrichment analysis was used to link these alterations to biological pathways, which were predominantly related to inflammation, neuronal activity, and extracellular matrix regulation. We then used our CSF proteomic profiles to create a support vector machines classifier capable of discriminating training set ALS from non-ALS (HC and OND) samples. Four classifier proteins, WD repeat-containing protein 63, amyloid-like protein 1, SPARC-like protein 1, and cell adhesion molecule 3, were identified by feature selection and externally validated. The resultant classifier distinguished ALS from non-ALS samples with 83% sensitivity and 100% specificity in an independent test set. Collectively, our results illustrate the utility of CSF proteomic profiling for identifying ALS protein/pathway alterations and candidate disease biomarkers.
Saposnik, Gustavo; Sempere, Angel Perez; Raptis, Roula; Prefasi, Daniel; Selchen, Daniel; Maurino, Jorge
The management of multiple sclerosis (MS) is rapidly changing by the introduction of new and more effective disease-modifying agents. The importance of risk stratification was confirmed by results on disease progression predicted by different risk score systems. Despite these advances, we know very little about medical decisions under uncertainty in the management of MS. The goal of this study is to i) identify whether overconfidence, tolerance to risk/uncertainty, herding influence medical decisions, and ii) to evaluate the frequency of therapeutic inertia (defined as lack of treatment initiation or intensification in patients not at goals of care) and its predisposing factors in the management of MS. This is a prospective study comprising a combination of case-vignettes and surveys and experiments from Neuroeconomics/behavioral economics to identify cognitive distortions associated with medical decisions and therapeutic inertia. Participants include MS fellows and MS experts from across Spain. Each participant will receive an individual link using Qualtrics platform(©) that includes 20 case-vignettes, 3 surveys, and 4 behavioral experiments. The total time for completing the study is approximately 30-35 min. Case vignettes were selected to be representative of common clinical encounters in MS practice. Surveys and experiments include standardized test to measure overconfidence, aversion to risk and ambiguity, herding (following colleague's suggestions even when not supported by the evidence), physicians' reactions to uncertainty, and questions from the Socio-Economic Panel Study (SOEP) related to risk preferences in different domains. By applying three different MS score criteria (modified Rio, EMA, Prosperini's scheme) we take into account physicians' differences in escalating therapy when evaluating medical decisions across case-vignettes. The present study applies an innovative approach by combining tools to assess medical decisions with experiments from
Moss-Morris, Rona; Dennison, Laura; Landau, Sabine; Yardley, Lucy; Silber, Eli; Chalder, Trudie
Objective: The aims were (a) to test the effectiveness of a nurse-led cognitive behavioral therapy (CBT) program to assist adjustment in the early stages of multiple sclerosis (MS) and (b) to determine moderators of treatment including baseline distress, social support (SS), and treatment preference. Method: Ninety-four ambulatory people with MS…
Saposnik, Gustavo; Maurino, Jorge; Sempere, Angel P; Ruff, Christian C; Tobler, Philippe N
Purpose Herding is a phenomenon by which individuals follow the behavior of others rather than deciding independently on the basis of their own private information. A herding-like phenomenon can occur in multiple sclerosis (MS) when a neurologist follows a therapeutic recommendation by a colleague even though it is not supported by best practice clinical guidelines. Limited information is currently available on the role of herding in medical care. The objective of this study was to determine the prevalence (and its associated factors) of herding in the management of MS. Methods We conducted a study among neurologists with expertise in MS care throughout Spain. Participants answered questions regarding the management of 20 case scenarios commonly encountered in clinical practice and completed 3 surveys and 4 experimental paradigms based on behavioral economics. The herding experiment consisted of a case scenario of a 40-year-old woman who has been stable for 3 years on subcutaneous interferon and developed a self-limited neurological event. There were no new magnetic resonance imaging (MRI) lesions. Her neurological examination and disability scores were unchanged. She was advised by an MS neurologist to switch from interferon to fingolimod against best practice guidelines. Multivariable logistic regression analysis was conducted to evaluate factors associated with herding. Results Out of 161 neurologists who were invited to participate, 96 completed the study (response rate: 60%). Herding was present in 75 (78.1%), having a similar prevalence in MS experts and general neurologists (68.8% vs 82.8%; P=0.12). In multivariate analyses, the number of MS patients seen per week was positively associated with herding (odds ratio [OR] 1.08, 95% CI 1.01–1.14). Conversely, physician’s age, gender, years of practice, setting of practice, or risk preferences were not associated with herding. Conclusion Herding was a common phenomenon affecting nearly 8 out of 10
Oliveira, Ademar Francisco de; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier
Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. RESUMO Esclerose lateral amiotrófica é uma doença neurodegenerativa progressiva e fatal, caracterizada pela degeneração dos neurônios motores, as células do sistema nervoso central que controlam os movimentos voluntários dos músculos. A salivação excessiva (sialorreia) está presente em cerca de 50% dos casos de esclerose lateral amiotrófica. Dessa forma, surgem medidas terapêuticas alternativas como drogas anticolinérgicas e cirurgia, e recentemente, o uso da toxina botulínica, aplicada em um ponto central das glândulas salivares, muitas vezes guiado por ultrassonografia, demostrou resultados positivos. Objetivou-se revisar a literatura no intuito de demonstrar um método alternativo aos tratamentos de sialorreia em pacientes com esclerose lateral amiotrófica. Em estudos recentes, a eficácia do tratamento com toxina botulínica foi confirmada e, mesmo requerendo novas aplicações, os efeitos colaterais são ínfimos. Ela surge então como alternativa não só ao
Haase, Rocco; Kullmann, Jennifer S.; Ziemssen, Tjalf
Background: Improved clinical effectiveness and therefore positive modification of multiple sclerosis (MS) with basic therapy can be achieved by long-term regular intake of drugs as prescribed but investigations have shown that a high percentage of patients do not take their medications as prescribed. Objectives: We assessed the satisfaction and adherence of patients with MS with their current disease-modifying treatment under clinical practice conditions. We compared different facets of satisfaction as well as their internal relationship and identified predictors in an exploratory manner. Methods: Therapy satisfaction in patients with relapsing–remitting multiple sclerosis (THEPA-MS) was a noninterventional, prospective cross-sectional study performed throughout Germany in 2013 and 2014, and included patients with clinically isolated syndrome or relapsing–remitting MS. We applied a standardized approach to document satisfaction and adherence by patient-reported outcomes (Treatment Satisfaction Questionnaire for Medication) as well as by physician ratings. Results: Of 3312 patients with a mean age of 43.7 years, 73.3% were women and the mean level of disability according to the Expanded Disability Status Scale was 2.29; 13.3% did not receive any medication at the time of documentation, 21.3% received interferon β1a intramuscularly, 20.7% had interferon β1a subcutaneously, 17.0% had interferon β1b subcutaneously and 23.7% had glatiramer acetate. Adherence rates varied between 60% (lifetime) and 96.5% (current medication). Differences between current medications were found for side effects and convenience scores but not for effectiveness, satisfaction and adherence. Higher global satisfaction and effectiveness were associated with fewer relapses, longer duration of medication, lower disability score and the absence of several side effects. Conclusion: In a connected model of patient satisfaction, effectiveness, side effects, convenience and adherence
Moss-Morris, Rona; Dennison, Laura; Landau, Sabine; Yardley, Lucy; Silber, Eli; Chalder, Trudie
The aims were (a) to test the effectiveness of a nurse-led cognitive behavioral therapy (CBT) program to assist adjustment in the early stages of multiple sclerosis (MS) and (b) to determine moderators of treatment including baseline distress, social support (SS), and treatment preference. Ninety-four ambulatory people with MS within 10 years of diagnosis were randomized to receive 8 individual sessions of CBT (n = 48) or supportive listening (n = 46), most delivered on the telephone, in a multicenter randomized controlled trial. The primary outcomes were distress and functional impairment. Secondary outcomes included global improvement, acceptance of illness, and dysfunctional cognitions. Assessments were completed at home and were coordinated by a blind assessor. Data were analyzed by intention-to-treat using multilevel models. The CBT group was significantly less distressed at the end of treatment (estimated General Health Questionnaire group difference = 3.2 points, 95\\% CI 1.1 to 5.4 points) and at the 12-month follow-up (estimated group difference = 2.2 points, 95\\% CI 0.01 to 4.4 points). There were no differences between the groups on functional impairment. The CBT group also demonstrated significantly greater improvements on secondary outcomes at the end of treatment but not at the 12-month follow-up. CBT participants with poor SS and/or clinically defined levels of distress at baseline showed significantly greater gains on both primary outcomes. Treatment preference did not moderate treatment effects. CBT is more effective than supportive listening in reducing distress in people with MS. CBT appears most effective for patients with poor SS and high levels of distress. The loss of gains in the secondary outcomes by 12 months suggests further follow-up sessions may be warranted.
van der Maas, Nico Arie
The Multiple Sclerosis Questionnaire for Physical Therapists (MSQPT) is a patient-rated outcome questionnaire for evaluating the rehabilitation of persons with multiple sclerosis (MS). Responsiveness was evaluated, and minimal important difference (MID) estimates were calculated to provide thresholds for clinical change for four items, three sections and the total score of the MSQPT. This multicentre study used a combined distribution- and anchor-based approach with multiple anchors and multiple rating of change questions. Responsiveness was evaluated using effect size, standardized response mean (SRM), modified SRM and relative efficiency. For distribution-based MID estimates, 0.2 and 0.33 standard deviations (SD), standard error of measurement (SEM) and minimal detectable change were used . Triangulation of anchor- and distribution-based MID estimates provided a range of MID values for each of the four items, the three sections and the total score of the MSQPT. The MID values were tested for their sensitivity and specificity for amelioration and deterioration for each of the four items, the three sections and the total score of the MSQPT. The MID values of each item and section and of the total score with the best sensitivity and specificity were selected as thresholds for clinical change. The outcome measures were the MSQPT, Hamburg Quality of Life Questionnaire for Multiple Sclerosis (HAQUAMS), rating of change questionnaires, Expanded Disability Status Scale, 6-metre timed walking test, Berg Balance Scale and 6-minute walking test. The effect size ranged from 0.46 to 1.49. The SRM data showed comparable results. The modified SRM ranged from 0.00 to 0.60. Anchor-based MID estimates were very low and were comparable with SD- and SEM-based estimates. The MSQPT was more responsive than the HAQUAMS in detecting improvement but less responsive in finding deterioration. The best MID estimates of the items, sections and total score, expressed in percentage of their
Charvet, Leigh E; Beekman, Rachel; Amadiume, Nneka; Belman, Anita L; Krupp, Lauren B
To evaluate the Symbol Digit Modalities Test (SDMT) as a tool for identifying pediatric-onset MS patients at risk for cognitive impairment. The SDMT is a brief measure of cognitive processing speed that is often used in adult MS patients. Approximately one-third of pediatric-onset MS patients have cognitive impairment and there is a need for an effective screening instrument. Seventy (70) consecutive outpatients with pediatric-onset MS underwent clinical evaluations including the SDMT and were compared to those with other pediatric neurological diagnoses (OND, n=40) and healthy controls (HC, n=32). A subset of the MS group and all healthy controls completed neuropsychological evaluation within one year of SDMT administration. The MS group performed worse on the SDMT compared to the HC group (p=0.02). Thirty-seven percent (37%) of the MS, 20% of the OND, and 9% of HC groups scored in the impaired range. For MS participants who underwent neuropsychological testing (n=31), the SDMT showed 77% sensitivity and 81% specificity for detecting neuropsychological impairment when administered within one year and reached 100% sensitivity when the interval was under two months (n=17). Overall, older age and increased disability predicted poorer SDMT performance (age r=-0.26, p=0.03) and the Expanded Disability Status Scale score or EDSS (r=-0.47, p<0.001), while a history of optic neuritis predicted better performance (p=0.04). Optical coherence tomography measures were not related to SDMT performance. In this preliminary study, the SDMT was an effective brief screen for detecting cognitive impairment in pediatric-onset MS. Copyright © 2014 Elsevier B.V. All rights reserved.
Ryan, Jennifer M; Fortune, Jennifer; Stennett, Andrea; Kilbride, Cherry; Anokye, Nana; Victor, Christina; Hendrie, Wendy; Abdul, Mohamed; DeSouza, Lorraine; Lavelle, Grace; Brewin, Debbie; David, Lee; Norris, Meriel
Although physical activity may reduce disease burden, fatigue and disability, and improve quality of life among people with multiple sclerosis (MS), many people with MS are physically inactive and spend significant time in sedentary behaviour. Behaviour change interventions may assist people with MS to increase physical activity and reduce sedentary behaviour. However, few studies have investigated their effectiveness using objective measures of physical activity, particularly in the long term. Further, interventions that have proven effective in the short term may not be feasible in clinical practice because of the large amount of support provided. The iStep-MS trial aims to determine the safety, feasibility and acceptability of a behaviour change intervention to increase physical activity and reduce sedentary behaviour among people with MS. Sixty people with MS will be randomised (1:1 ratio) to receive a 12-week intervention or usual care only. The intervention consists of four physical activity consultations with a physiotherapist supported by a handbook and pedometer. Outcomes assessed at baseline, 12 weeks and 9 months are physical activity (ActiGraph wGT3X-BT accelerometer), sedentary behaviour (activPAL3µ), self-reported activity and sitting time, walking capability, fatigue, self-efficacy, participation, quality of life and health service use. The safety of the intervention will be determined by assessing change in pain and fatigue and the incidence of adverse events during the follow-up period. A parallel process evaluation will assess the feasibility and acceptability of the intervention through assessment of fidelity to the programme and semistructured interviews exploring participants' and therapists' experiences of the intervention. The feasibility of conducting an economic evaluation will be determined by collecting data on quality of life and resource use. Research ethics committee approval has been granted from Brunel University London. Results of
Ryan, Jennifer M; Fortune, Jennifer; Stennett, Andrea; Kilbride, Cherry; Anokye, Nana; Victor, Christina; Hendrie, Wendy; Abdul, Mohamed; DeSouza, Lorraine; Lavelle, Grace; Brewin, Debbie; David, Lee; Norris, Meriel
Introduction Although physical activity may reduce disease burden, fatigue and disability, and improve quality of life among people with multiple sclerosis (MS), many people with MS are physically inactive and spend significant time in sedentary behaviour. Behaviour change interventions may assist people with MS to increase physical activity and reduce sedentary behaviour. However, few studies have investigated their effectiveness using objective measures of physical activity, particularly in the long term. Further, interventions that have proven effective in the short term may not be feasible in clinical practice because of the large amount of support provided. The iStep-MS trial aims to determine the safety, feasibility and acceptability of a behaviour change intervention to increase physical activity and reduce sedentary behaviour among people with MS. Methods and analysis Sixty people with MS will be randomised (1:1 ratio) to receive a 12-week intervention or usual care only. The intervention consists of four physical activity consultations with a physiotherapist supported by a handbook and pedometer. Outcomes assessed at baseline, 12 weeks and 9 months are physical activity (ActiGraph wGT3X-BT accelerometer), sedentary behaviour (activPAL3µ), self-reported activity and sitting time, walking capability, fatigue, self-efficacy, participation, quality of life and health service use. The safety of the intervention will be determined by assessing change in pain and fatigue and the incidence of adverse events during the follow-up period. A parallel process evaluation will assess the feasibility and acceptability of the intervention through assessment of fidelity to the programme and semistructured interviews exploring participants’ and therapists’ experiences of the intervention. The feasibility of conducting an economic evaluation will be determined by collecting data on quality of life and resource use. Ethics and dissemination Research ethics committee
Bisseriex, Hélène; Guinet-Lacoste, Amandine; Chevret-Méasson, Marie; Costa, Pierre; Sheikh Ismael, Samer; Rousseau, Alexandra; Amarenco, Gerard
Until now, no questionnaire has been developed to study specific expectations concerning sexual dysfunction management and the availability of information on sexuality in the female population affected by multiple sclerosis (MS). Understanding and meeting the patient's expectations is an issue of considerable importance in the evaluation of medical care. We present the development and validation of a specific questionnaire designed for women with MS in order to assess their expectations in terms of sexual dysfunction management: the SEA-MS-F (Sexual Dysfunction Management and Expectations Assessment in Multiple Sclerosis-Female). This questionnaire was created and validated by an expert panel, using the Delphi method. The psychometric evaluation was obtained with a sample of 40 female MS patients. Cronbach's alpha index and principal component analysis were used to measure the questionnaire's internal consistency. A consensus on the questionnaire was reached with the Delphi method. The SEA-MS-F is fully compliant with the criteria for psychometric validation among female MS patients, and its internal consistency is excellent (Cronbach's alpha 0.948). The SEA-MS-F appears to be a useful tool that could be used either in routine medical situations or in prospective studies of MS in order to ascertain women's expectations concerning the management of their sexual dysfunction. © 2014 International Society for Sexual Medicine.
Hasegawa, Minoru; Takehara, Kazuhiko
Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. Although the pathogenesis remains unclear, a variety of cells contribute to the fibrotic process via interactions with each other and production of various cytokines. Recent literature related to the immunologic pathogenesis and future strategies for treating the fibrosis of SSc are discussed and, especially, this literature-based review that includes the authors' perspective, focused on leukocytes and cytokines. A PubMed search for articles published between January 2005 and January 2012 was conducted using the following keywords: systemic sclerosis, leukocyte, cytokine, growth factor, and chemokine. The reference lists of identified articles were searched for further articles. Targeting profibrogenic cytokines, including transforming growth factor-β, is still a very active area of research in SSc and most cellular studies have focused on the roles of fibroblasts in SSc. However, a growing number of recent studies indicate a role for B cells in the development of SSc and other autoimmune diseases such as systemic lupus erythematosus. Therefore, B-cell-targeted therapies, including currently available monoclonal antibodies against CD19, CD20, CD22, and B-cell-activating factor, belonging to the tumor necrosis factor family represent possible treatment options. Furthermore, the modulation of T-cell costimulatory molecules such as a recombinant fusion protein of cytotoxic T-lymphocyte antigen-4 may be as effective in SSc as it is in treating other autoimmune diseases. Approaches to antagonize interleukin (IL)-1, IL-6, or IL-17A signaling may also be attractive. This review describes recent advances in the treatment of fibrosis in SSc patients focused on immunologic strategies, such as leukocyte- or cytokine-targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.
Wain, Helen; Kneebone, Ian I; Cropley, Mark
Depression is common in those with MS. The hopelessness theory of depression, emphasizing the role of attributional style, is supported in this population. Cognitive behaviour therapy (CBT) that can affect attributional style can reduce depression in people who have MS. The present study aimed to consider whether changing attributional style would reduce depression in two people with MS, thereby supporting the importance of this component of CBT with this population. Two female participants with MS were offered a 5-session intervention designed to alter attributional style. The study followed an ABA design. Attributional style and depressive symptoms were the principal measures considered. Negative life events and MS related stresses were also monitored. The intervention appeared effective for one of the participants, with predicted changes in attributional style and sizeable reductions in depressive symptoms from pre- to post-treatment that were sustained at 3-month follow-up. Improvement was still evident at 6 months, although with some reduction of effect. The intervention was less successful for the other participant who declined further treatment after three sessions. Some support for the hopelessness theory of depression was found, indicating its relevance to CBT interventions for those who have MS and depression.
de J Guerrero-García, José; Rojas-Mayorquín, Argelia E; Valle, Yeminia; Padilla-Gutiérrez, Jorge R; Castañeda-Moreno, Víctor A; Mireles-Ramírez, Mario A; Muñoz-Valle, José F; Ortuño-Sahagún, Daniel
The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into account as possible prognostic markers when analyzing the disease progress of MS in order to provide more personalized treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.
Kurtzke, J F; Page, W F
In previous papers of this series, we explored the epidemiology of MS, examining the effects of race, sex, geography, latitude and climate, migration, age at onset, population ancestry, and individual ethnicity on the risk of MS, using an unusually large cohort of MS cases and pre-illness matched controls comprising US veterans of World War II (WWII) and the Korean Conflict (KC). In this paper, we examine primarily the effect of other factors on the risk of MS in this cohort and their relation to those previously studied. We found here that latitude tier of residence at entry into active duty (EAD), years of education, and socioeconomic class (coded from occupation) were similarly associated with MS risk among white men, black men, and white women. Higher levels of each factor showed increased MS risk. Multivariate analyses indicated that for white male WWII subjects an urban address, 9 or more years of education, uncorrected visual acuity less than 20/20 at EAD, a more northern latitude, and a higher proportion of the subject's EAD state population reporting Swedish ancestry each significantly increased the risk of MS. White male KC subjects showed roughly the same patterns, except that uncorrected visual acuity less than 20/20 was associated with lower MS risk (ancestry/ethnicity was not studied). For black male WWII and KC subjects combined, a similar analysis (omitting ancestry/ethnicity) showed that only latitude at EAD and 9 or more years of education were independently associated with a significantly higher MS risk, and for WWII plus KC white women (also without ancestry/ethnicity), only latitude was a significant risk factor in these multivariate analyses. The smaller number of subjects, especially in these last two groups, limited the power to detect statistically significant risks in these last analyses. Similarities to white men of WWII in univariate analyses for all other groups suggest that findings for the former would otherwise apply to the latter
Background Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). It involves damage to the myelin sheath surrounding axons and to the axons themselves. MS most often presents with a series of relapses and remissions but then evolves over a variable period of time into a slowly progressive form of neurological dysfunction termed secondary progressive MS (SPMS). The reasons for this change in clinical presentation are unclear. The absence of a diagnostic marker means that there is a lag time of several years before the diagnosis of SPMS can be established. At the same time, understanding the mechanisms that underlie SPMS is critical to the development of rational therapies for this untreatable stage of the disease. Results Using high performance liquid chromatography-coupled mass spectrometry (HPLC); we have established a highly specific and sensitive selected reaction monitoring (SRM) assay. Our multiplexed SRM assay has facilitated the simultaneous detection of surrogate peptides originating from 26 proteins present in cerebrospinal fluid (CSF). Protein levels in CSF were generally ~200-fold lower than that in human sera. A limit of detection (LOD) was determined to be as low as one femtomol. We processed and analysed CSF samples from a total of 22 patients with SPMS, 7 patients with SPMS treated with lamotrigine, 12 patients with non-inflammatory neurological disorders (NIND) and 10 healthy controls (HC) for the levels of these 26 selected potential protein biomarkers. Our SRM data found one protein showing significant difference between SPMS and HC, three proteins differing between SPMS and NIND, two proteins between NIND and HC, and 11 protein biomarkers showing significant difference between a lamotrigine-treated and untreated SPMS group. Principal component analysis (PCA) revealed that these 26 proteins were correlated, and could be represented by four principal components. Overall, we established an efficient platform
Carrozza, Cinzia; Lapolla, Rosa; Gervasoni, Jacopo; Rota, Carlo Antonio; Locantore, Pietro; Pontecorvi, Alfredo; Zuppi, Cecilia; Persichilli, Silvia
Mitotane is an adrenocytolytic agent used in adrenocortical carcinoma, inducing adrenal insufficiency, requiring replacement treatment. Such therapy is not easy to monitor because of mitotane interference. Salivary cortisol reflects a free fraction of plasma cortisol and may be useful in such patients. The aim of our study was to evaluate salivary cortisol by HPLC coupled to tandem-mass spectrometry (LC-MS/MS) and by an electrochemiluminescence immunoassay (ECLIA) in patients treated with mitotane. We enrolled 6 patients receiving mitotane and 2 Addison disease patients as negative controls and determined salivary cortisol rhythm. We also determined the salivary cortisol rhythm in 8 healthy subjects. Salivary samples (n=112) were assayed by ECLIA, using Roche Modular E170, and by LC-MS/MS. The mean values obtained by ECLIA were significantly higher than those obtained by LC-MS/MS in the mitotane group (p<0.001). In fact, in the group measured by LC-MS/MS, we observed several peaks eluting at a retention time different from the cortisol group, presumably due to cortisol-like analogues. In Addison disease, since steroidogenesis is absent, salivary cortisol values measured by the two methods did not show any significant difference (p=0.61). Salivary cortisol measured by LC-MS/MS is a selective method, excluding cortisol analogues accumulating in treated patients. Therefore, LC-MS/MS offers an effective system to monitor replacement therapy in mitotane treated patients.
Azodi, Shila; Nair, Govind; Enose-Akahata, Yoshimi; Charlip, Emily; Vellucci, Ashley; Cortese, Irene; Dwyer, Jenifer; Billioux, B Jeanne; Thomas, Chevaz; Ohayon, Joan; Reich, Daniel S; Jacobson, Steven
Previous work measures spinal cord thinning in chronic progressive myelopathies, including human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Quantitative measurements of spinal cord atrophy are important in fully characterizing these and other spinal cord diseases. We aimed to investigate patterns of spinal cord atrophy and correlations with clinical markers. Spinal cord cross-sectional area was measured in individuals (24 healthy controls [HCs], 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 relapsing-remitting MS [RRMS], 17 secondary progressive MS [SPMS], and 40 primary progressive MS [PPMS]) from C1 to T10. Clinical disability scores, viral markers, and immunological parameters were obtained for patients and correlated with representative spinal cord cross-sectional area regions at the C2 to C3, C4 to C5, and T4 to T9 levels. In 2 HAM/TSP patients, spinal cord cross-sectional area was measured over 3 years. All spinal cord regions are thinner in HAM/TSP (56 mm 2 [standard deviation, 10], 59 , 23 ) than in HC (76 , 83 , 38 ) and AC (71 , 78 , 36 ). SPMS (62 , 66 , 32 ) and PPMS (65 , 68 , 35 ) have thinner cervical cords than HC and RRMS (73 , 77 , 37 ). Clinical disability scores (Expanded Disability Status Scale [p = 0.009] and Instituto de Pesquisas de Cananeia [p = 0.03]) and CD8 + T-cell frequency (p = 0.04) correlate with T4 to T9 spinal cord cross-sectional area in HAM/TSP. Higher cerebrospinal fluid HTLV-1 proviral load (p = 0.01) was associated with thinner spinal cord cross-sectional area. Both HAM/TSP patients followed longitudinally showed thoracic thinning followed by cervical thinning. Group average spinal cord cross-sectional area in HAM/TSP and progressive MS show spinal cord atrophy. We further hypothesize in HAM/TSP that is possible that neuroglial loss from a thoracic inflammatory
... 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 ...
Thewissen, Kristof; Nuyts, Amber H; Deckx, Nathalie; Van Wijmeersch, Bart; Nagels, Guy; D'hooghe, Marie; Willekens, Barbara; Cras, Patrick; Eijnde, Bert O; Goossens, Herman; Van Tendeloo, Viggo F I; Stinissen, Piet; Berneman, Zwi N; Hellings, Niels; Cools, Nathalie
The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112). Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.
Croteau, David; Flowers, Charlene; Kulick, Corrinne G; Brinker, Allen; Kortepeter, Cindy M
To evaluate acute acalculous cholecystitis (AAC) as a potential safety risk for patients treated with alemtuzumab. The Food and Drug Administration Adverse Event Reporting System and the medical literature were searched for cases of AAC in conjunction with alemtuzumab for all clinical indications. Eight spontaneously reported cases meeting the case definition of AAC in close temporal association with alemtuzumab use were identified. Based on established criteria within the Food and Drug Administration Division of Pharmacovigilance for causality assessment, 4 cases were assessed as probable while 4 were possible. All cases occurred in patients with relapsing-remitting multiple sclerosis. Seven of the 8 cases presented with AAC during or shortly after alemtuzumab treatment, thereby suggesting an acute cytokine release syndrome as a putative pathogenic mechanism. The cases identified in this review differ from the typical AAC cases described in the medical literature based on female preponderance, lack of concurrent critical illnesses, inconsistent presence of other risk factors, and resolution with conservative treatment in the majority of cases. AAC represents a new and potentially life-threatening adverse event associated with alemtuzumab use in relapsing-remitting multiple sclerosis. In cases seen to date, early and conservative treatment resulted in good clinical outcome, although the natural history of AAC in this population without critical illness is not well defined. Awareness of this safety risk by general and specialty neurologists is important for prompt recognition and optimal management. © 2018 American Academy of Neurology.
Meissner, Axel; Limmroth, Volker
Fingolimod (FTY720) has been approved as the first oral representative of the class of sphingosine-1-phosphate (S1P) receptor modulators for the treatment of relapsing-remitting multiple sclerosis (MS). Besides inducing vaso-relaxation, fingolimod can also influence electrical conduction in the myocardium and vascular endothelium by having a transient negative chronotropic effect on the sinus node. Cardiac safety and tolerability of fingolimod in the cardiac sense were reviewed by analysing the data collected from the FREEDOMS and TRANSFORMS studies -both relevant studies for marketing authorisation, from their extension studies, as well as the clinical data collected from a practice-related MS patient cohort with cardiovascular risk factors and corresponding co-medication (FIRST study). The safety analyses on file gave no indication of any increased cardiovascular risk. The 2-3mmHg increase in blood pressure observed after the first dose of fingolimod has no therapeutic consequences. The first dose of 0.5mg fingolimod resulted in an average decrease in heart rate of 7-8beats/min. The onset of effect occurred approximately 1-2h after the first dose and the nadir was reached after approximately 4-5h. This negative chronotropic effect returned to normal after internalisation of the S1P1 receptors on maintenance therapy. There were no indications that patients with cardiac risk factors required closer observation beyond the monitoring recommended by the EMA following the first dose of fingolimod. Case study observations from the routine clinical setting show that patients accept this method of monitoring, which they assess as being a positive aspect of attentive medical care and concern. Copyright © 2016 Elsevier B.V. All rights reserved.
Kasschau, Margaret; Sherman, Kathleen; Haider, Lamia; Frontario, Ariana; Shaw, Michael; Datta, Abhishek; Bikson, Marom; Charvet, Leigh
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.
De Stefano, Nicola; Giorgio, Antonio; Battaglini, Marco; De Leucio, Alessandro; Hicking, Christine; Dangond, Fernando; Giovannoni, Gavin; Sormani, Maria Pia
Neuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage. In the CLARITY study ( ClinicalTrials.gov NCT00213135), the effect of 2 years' treatment with cladribine tablets on annualized percentage brain volume change (PBVC/y) was evaluated in patients with relapsing MS (RMS). Compared with placebo (-0.70% ± 0.79), PBVC/y was reduced in patients treated with cladribine tablets 3.5 mg/kg (-0.56% ± 0.68, p = 0.010) and 5.25 mg/kg (-0.57% ± 0.72, p = 0.019). After adjusting for treatment group, PBVC/y showed a significant correlation with the cumulative probability of disability progression (HR = 0.67, 95% CI = 0.571, 0.787; p < 0.001), with patients with lower PBVC/y showing the highest probability of remaining free from disability progression at 2 years and vice versa. Cladribine tablets given annually for 2 years in short-duration courses in patients with RMS in the CLARITY study significantly reduced brain atrophy in comparison with placebo treatment, with residual rates in treated patients being close to the physiological rates.
Moss-Morris, Rona; McCrone, Paul; Yardley, Lucy; van Kessel, Kirsten; Wills, Gary; Dennison, Laura
The majority of people affected by Multiple Sclerosis (paMS) experience severe and disabling fatigue. A recent randomised controlled trial (RCT) showed that cognitive behaviour therapy with a clinical psychologist was an effective treatment for MS fatigue. An Internet-based version of this intervention, MS Invigor8, was developed for the current study using agile design and input from paMS. MS Invigor8 includes eight tailored, interactive sessions. The aim was to test the feasibility and potential efficacy and cost-effectiveness of the programme in a pilot RCT. 40 patients were randomised to MS Invigor8 (n=23) or standard care (n=17). The MS Invigor8 group accessed sessions over 8-10 weeks and received up to three 30-60min telephone support sessions. Participants completed online standardised questionnaires assessing fatigue, mood, quality of life and service use at baseline and 10 weeks follow-up. Large between group treatment effects were found for the primary outcomes of fatigue severity (d=1.19) and impact (d=1.02). The MS Invigor8 group also reported significantly greater improvements in anxiety, depression and quality-adjusted life years. These data suggest that Internet-based CBT may be a clinically and cost-effective treatment for MS fatigue. A larger RCT with longer term follow-up is warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.
Heesen, Christoph; Kleiter, Ingo; Nguyen, Franziska; Schäffler, Nina; Kasper, Jürgen; Köpke, Sascha; Gaissmaier, Wolfgang
Natalizumab is associated with the potentially life-threatening side-effect progressive multifocal leukoencephalopathy (PML). Little is known about patients' and physicians' risk estimates and attitudes towards natalizumab treatment. Consecutive natalizumab-treated patients (n = 69) and neurologists (n = 66) in two centres and cooperating private practices received an evidence-based three-page information leaflet about natalizumab-associated PML and an evaluation sheet. After reading the information, patients were significantly more likely than physicians to intend continuation of natalizumab treatment and willing to accept higher risks of PML: 49% of physicians would stop treatment at a PML risk of 2:10,000 or lower, while only 17% of patients would do so (p < 0.001). This difference could not be explained by risk calculation abilities or lack of understanding. Both groups overestimated natalizumab treatment effects. Patients had a significantly worse perception of multiple sclerosis as a malignant disease. We conclude that patients were willing to accept a higher risk of PML than neurologists. Coherent with their perception of risks and benefits, patients were also more willing to continue treatment. Open information about treatment-related risks is appreciated and might support shared decision making.
Shahbazi, Mona; Holzberg, Shara; Thirunavukkarasu, Saeyoan; Ciani, Gioia
Amyotrophic Lateral Sclerosis (ALS) may not affect an individual's sexual function directly, but it can indirectly impact their sexual activity. Sexual partners often become caregivers, diminishing sexuality within a relationship. This can result in decline of quality of life. The study aimed to explore the perspectives of individuals with ALS and their treating clinicians regarding the importance of sexuality in rehabilitation within a multidisciplinary ALS center. We hypothesize that individuals with ALS will express the need for sexuality-related discussions as a therapy. Electronic 11-item questionnaires were anonymously completed by individuals with ALS (n = 21) and ALS healthcare professionals (n = 81) between August 2014 to June 2016. Descriptive statistics were performed in STATA 14. Majority (90%, n = 92) of respondents stated that ALS impacts the sexuality of an individual with ALS, and agreed that sexuality-related discussion is needed as a complementary therapy. Over 75% of clinicians reported they were not familiar with any strategies or interventions to help the patients. ALS indirectly affects sexuality, thus confirming the need for promoting awareness regarding sexuality-related topics among individuals with ALS and healthcare professionals. ALS multidisciplinary clinics need to improve their delivery of care to address sexual rehabilitation as a complementary therapy.
Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla
Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193
Sívori, Martín; Rodríguez, Gabriel E; Pascansky, Daniel; Sáenz, César; Sica, Roberto E P
Sporadic amyotrophic lateral sclerosis (sALS) is a progressive degenerative motor neuron disorder lacking specific treatment. Riluzole is the only drug able to modestly slow down the course of the disease. Respiratory insufficiency is the main cause of death; non invasive ventilation (NIV) has shown to improve survival. Our aim was to evaluate the effect of NIV and riluzole on survival. Ninety seven patients with a diagnosis of sALS were assessed and followed up for 60 months. Twenty nine patients received NIV and 68 did not (nNIV). Overall median survival In the NIV group was 15.41 +/- 7.78 months vs. 10.88 +/- 7.78 months in the nNIV group (p= 0.028). Median survival time was not different in patients receiving riluzole (n=44), as compared with those who did not (n=53), although at month 4th and 5th riluzole treated patients showed a modest benefit. In those who only received NIV (n=11) or only riluzole (n=26), survival time was 13.45 +/- 13.44 months and 11.19 +/- 7.79 months, respectively. Patients who received both NIV and riluzole (n=18) had a median survival time of 16.61 +/- 10.97 months vs. 10.69 +/- 7.86 months for those who received only supportive treatment (n=42) (p= 0.021). NIV improved survival in our series of patients. Riluzole did not show any significant impact on survival when employed as the only therapy. Patients receiving both treatments simultaneously had a significant longer survival.
Rationale and design of the tele-exercise and multiple sclerosis (TEAMS) study: A comparative effectiveness trial between a clinic- and home-based telerehabilitation intervention for adults with multiple sclerosis (MS) living in the deep south.
Rimmer, James H; Thirumalai, Mohanraj; Young, Hui-Ju; Pekmezi, Dori; Tracy, Tracy; Riser, Emily; Mehta, Tapan
Long-term exercise/rehabilitation is an integral component of the continual care for people with multiple sclerosis (MS). However, access to this care, which includes comprehensive exercise/rehabilitation services to people with MS, remains a significant challenge, especially in rural, low-income areas. Telerehabilitation, or what we refer to as teleexercise, can help fill service gaps for underserved MS populations in this region. This pragmatic, cluster randomized controlled effectiveness trial will compare a 12-week, 20 session complementary and alternative medicine (CAM) intervention composed of neurorehabilitative (functional) exercise, yoga and Pilates delivered at home, using pre-loaded tablets and Interactive Voice Response (IVR) system technology (TeleCAM), to the same intervention delivered in clinic by a therapist (DirectCAM). Eight hundred and twenty people with MS are being recruited across Alabama, Mississippi and Tennessee. Primary self-reported patient-centered health outcomes are: pain, fatigue, quality of life and physical activity. Secondary outcomes include four physical functioning measures: balance, endurance, gait, and strength. Each of these outcomes will be examined by age, race, sex, severity of MS and other demographics to determine if outcomes are beneficial across all groups (i.e., heterogeneity of treatment effect). The project is important to people with MS and/or caregivers because it aims to reduce their barriers to receiving exercise treatment and increases the convenience and appeal of such programs through technology. Clinical Trials.gov Identifier: NCT03117881. Copyright © 2017. Published by Elsevier Inc.
Akbar, Nadine; Turpin, Karen; Petrin, Julie; Smyth, Penny; Finlayson, Marcia
Fatigue management interventions for individuals with multiple sclerosis (MS) often feature structured programmes requiring repeated, in-person attendance that is not possible for all individuals. We sought to determine whether MS INFoRm, a self-directed fatigue management resource for individuals with MS, was worth further, more rigorous evaluation. Our indicators of worthiness were actual use of the resource by participants over 3 months, reductions in fatigue impact and increases in self-efficacy, and participant reports of changes in fatigue management knowledge and behaviours. This was a single-group, mixed-methods, before-after pilot study in individuals with MS reporting mild to moderate fatigue. Thirty-five participants were provided with MS INFoRm by a USB flash drive to use at home for 3 months, on their own volition. Twenty-three participants completed all standardized questionnaires, semi-structured interviews and study process measures. Participants reported actively using MS INFoRm over the 3-month study period (median total time spent using MS INFoRm=315 min) as well as significantly lower overall fatigue impact (Modified Fatigue Impact Scale: t=2.6, P=0.01), increased knowledge of MS fatigue (z=-2.8, P=0.01) and greater confidence in managing MS fatigue (z=-3.3, P=0.001). Individuals with significant reductions in fatigue impact also reported behavioural changes including tracking fatigue, better communication with others, greater awareness, improved quality of life and being more proactive. This study provides evidence that further rigorous evaluation of MS INFoRm, a self-directed resource for managing fatigue, is worth pursuing.
van der Hiele, Karin; van Gorp, Dennis A M; Heerings, Marco A P; van Lieshout, Irma; Jongen, Peter J; Reneman, Michiel F; van der Klink, Jac J L; Vosman, Frans; Middelkoop, Huub A M; Visser, Leo H
Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading up to unemployment, many may experience a reduction in hours or work responsibilities and increased time missed from work. The MS@Work study examines various factors that may influence work participation in relapsing-remitting MS patients, including disease-related factors, the working environment and personal factors. The MS@Work study is a multicenter, 3-year prospective observational study on work participation in patients with relapsing-remitting MS. We aim to include 350 patients through 15-18 MS outpatient clinics in the Netherlands. Eligible participants are 18 years and older, and either currently employed or within three years since their last employment. At baseline and after 1, 2 and 3 years, the participants are asked to complete online questionnaires (including questions on work participation, work problems and accommodations, cognitive and physical ability, anxiety, depression, psychosocial stress, quality of life, fatigue, empathy, personality traits and coping strategies) and undergo cognitive and neurological examinations. After six months, patients are requested to only complete online questionnaires. Patient perspectives on maintaining and improving work participation and reasons to stop working are gathered through semi-structured interviews in a sub-group of patients. Prospective studies with long-term follow-up on work participation in MS are rare, or take into account a limited number of factors. The MS@Work study provides a 3-year follow-up on various factors that may influence work participation in patients with relapsing-remitting MS. We aim to identify factors that relate to job loss and to provide information about preventative measures for physicians
Saldívar-Uribe, Christina; de la Portilla-Villanueva, Mario Alberto; Esau-Mendoza-García, Alberto
The aim was to compare active disease in patients diagnosed with multiple sclerosis, brain by MRI after gadolinium application at one minute and 20 minutes. A longitudinal, prospective, observational, analytical and comparative study was conducted in 18 patients over 18 years of age diagnosed with multiple sclerosis (MS). An analysis was made for each patient, watching for inflammatory activity in MS lesions, comparing the results to one minute and 20 minutes after the application of gadolinium. For the descriptive analysis, absolute frequencies and percentages were used, as well as means and standard deviations or medians with ranges for the inferential analysis comparing the presence or absence of enhancement in lesions at one minute and 20 minutes; the exact probability test used was Fisher. Finally, the results were analyzed, looking at the gender distribution: 14 (77.8%) were female. The average age was 36.2 ± 9.5 years, with a minimum age of 18 years and a maximum of 55 years; four patients (22.2%) presented further highlight active lesions at 20 minutes, and two patients (11.1%) presented enhancement at one minute. Concluding that MRI in the diagnosis of MS is very important for the detection of activity in lesions caused by the disease, it is evident that the optimum time for evaluation of postcontrast sequences is 20 minutes.
Ceuninck van Capelle, Archibald de; Meide, Hanneke van der; Vosman, Frans J H; Visser, Leo H
Physicians commonly advise patients to begin disease modifying therapies (DMT's) shortly after the establishment of a diagnosis of Multiple Sclerosis (MS) to prevent further relapses and disease progression. However, little is known about the meaning for patients going through the process of the diagnosis of MS and of making decisions on DMT's in early MS. To explore the patient perspective on using DMT's for MS. Methods: Ten participants with a recent (< 2 years) relapsing-remitting MS diagnosis were interviewed. Seven of them were using DMT's at the time of the interview. All interviews were transcribed and analyzed using a hermeneutical-phenomenological approach. The analysis revealed the following themes: (1) Constant confrontation with the disease, (2) Managing inevitable decline, (3) Hope of delaying the progression of the disease, and, (4) The importance of social support. The themes show that patients associate the recommendation to begin DMT's (especially injectable DMT's) with views about their bodies as well as their hopes about the future. Both considering and adhering to treatment are experienced by patients as not only matters of individual and rational deliberation, but also as activities that are lived within a web of relationships with relatives and friends. From the patient perspective, the use of DMT's is not a purely rational and individual experience. More attention to the use of DMT's as relational and lived phenomena will improve the understanding of the process of decision-making for DMT's in MS.
Argento, Ornella; Incerti, Chiara C; Quartuccio, Maria E; Magistrale, Giuseppe; Francia, Ada; Caltagirone, Carlo; Pisani, Valerio; Nocentini, Ugo
Cognitive dysfunction occurs in almost 50-60% of patients with multiple sclerosis (MS) even in early stages of the disease and affects different aspects of patient's life. Aims of the present study were (1) to introduce and validate an Italian version of the minimal assessment of cognitive functions in MS (MACFIMS) battery and (2) to propose the use of the Cognitive Impairment Index (CII) as a scoring procedure to define the degree of impairment in relapsing-remitting (RRMS) and secondary-progressive (SPMS) patients. A total of 240 HC and 123 MS patients performed the Italian version of the MACFIMS composed by the same tests as the original except for the Paced Auditory Serial Addition Test. The CII was derived for each score of the 11 scales for participants of both groups. The results of the study show that cognitive impairment affects around 50% of our sample of MS patients. In RRMS group, only the 15.7% of patients reported a severe impairment, while in the group of SPMS, the 51.4% of patients felt in the "severely impaired" group. Results are in line with previously reported percentages of impairment in MS patients, showing that the calculation of the CII applied to the Italian version of the MACFIMS is sensitive and reliable in detecting different degrees of impairment in MS patients.
Nishshanka, Upul; Jayasuriya, Hiranthi; Chattopadhaya, Chaitali; Kijak, Philip J; Chu, Pak-Sin; Reimschuessel, Renate; Tkachenko, Andriy; Ceric, Olgica; De Alwis, Hemakanthi G
Since 2007, the U.S. FDA's Center for Veterinary Medicine (CVM) has been investigating reports of pets becoming ill after consuming jerky pet treats. Jerky used in pet treats contains glycerin, which can be made from vegetable oil or as a byproduct of biodiesel production. Because some biodiesel is produced using oil from Jatropha curcas, a plant that contains toxic compounds including phorbol esters, CVM developed a liquid chromatography-mass spectrometry (LC-MS) screening method to evaluate investigational jerky samples for the presence of these toxins. Results indicated that the samples analyzed with the new method did not contain Jatropha toxins at or above the lowest concentration tested. Published by Elsevier B.V.
Gahlen, Anna; Trampe, Anne-Kathrin; Haupeltshofer, Steffen; Ringelstein, Marius; Aktas, Orhan; Berthele, Achim; Wildemann, Brigitte; Gold, Ralf; Jarius, Sven
Objective: To evaluate (1) the frequency of aquaporin-4 antibody (AQP4-ab)-seropositive cases among patients treated with natalizumab (NAT) and previously diagnosed with MS (MSNAT) in a nationwide cohort, (2) the clinical course of NAT-treated AQP4-ab–seropositive neuromyelitis optica spectrum disorder (NMOSD) patients (NMONAT), (3) AQP4-ab titers in NMONAT and AQP4-ab–seropositive NMOSD treated with other immunotherapies (NMOIT), and (4) immune mechanisms influencing disease activity in NMONAT. Methods: MSNAT serum samples were retrospectively screened with a cell-based assay for AQP4-IgG and titers determined by ELISA. The annualized relapse rate (ARR) and disability progression were assessed. Serum levels of proinflammatory cytokines (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, and interferon [IFN]-γ) and the chemokine CXCL-10 of NMONAT patients identified in this (n = 4) and a previous study (n = 5) were measured by cytometric bead array and ELISA. Results: Of the 1,183 MSNAT patients (851 female, median 9 NAT infusions), only 4 (0.33%; 3 female, 1 male) had AQP4-IgG. Of these, 2 fulfilled the 2006 NMO criteria and all met the 2015 NMOSD criteria. The ARR was higher in NMONAT vs MSNAT (p = 0.0182). All 4 NMONAT patients had relapses and 2 had an increase of disability. AQP4-ab titers were higher in NMONAT (n = 9) vs NMOIT (n = 13; p = 0.0059). IL-8, IL-1β, and IFN-γ serum levels were significantly higher, and CXCL-10 was significantly lower in NMONAT vs NMOIT. Conclusions: Misdiagnosis of NMOSD with MS is rare. NAT was not able to control disease activity in NMONAT patients, who had higher serum levels of AQP4-IgG and proinflammatory cytokines than patients with NMOSD treated with other immunotherapies. PMID:28642888
Le Berre, L; Rousse, J; Gourraud, P-A; Imbert-Marcille, B-M; Salama, A; Evanno, G; Semana, G; Nicot, A; Dugast, E; Guérif, P; Adjaoud, C; Freour, T; Brouard, S; Agbalika, F; Marignier, R; Brassat, D; Laplaud, D-A; Drouet, E; Van Pesch, V; Soulillou, J-P
The etiology of multiple sclerosis (MS) remains elusive. Among the possible causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of Infectious mononucleosis (IMN) may damage the integrity of the blood-brain barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti-α1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated syndrome (CIS) patients, as well as age/gender-matched healthy individuals. Anti-Gal and anti-Neu5Gc are significantly increased during IMN (p=0.02 and p<1.10 -4 respectively), but not in acute CMV primo-infection. We show that, whereas there was no change in anti-Neu5Gc in MS/CIS, the two populations exhibit a significant decrease in anti-Gal (combined p=2.7.10 -3 ), in contrast with patients with non-MS/CIS central nervous system pathologies. Since anti-Gal result from an immunization against α1,3 Gal, lacking in humans but produced in the gut, our data suggest that CIS and MS patients have an altered microbiota or an altered response to this microbiotic epitope. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Gich, Jordi; Freixanet, Jordi; García, Rafael; Vilanova, Joan Carles; Genís, David; Silva, Yolanda; Montalban, Xavier; Ramió-Torrentà, Lluís
MS-Line! was created to provide an effective treatment for cognitive impairment in multiple sclerosis (MS) patients. To assess the efficacy of MS-Line!. A randomized, controlled, single-blind, 6-month pilot study. Patients were randomly assigned to an experimental group (cognitive rehabilitation with the programme) or to a control group (no cognitive rehabilitation). Randomization was stratified by cognitive impairment level. Cognitive assessment included: selective reminding test, 10/36 spatial recall test (10/36 SPART), symbol digit modalities test, paced auditory serial addition test, word list generation (WLG), FAS test, subtests of WAIS-III, Boston naming test (BNT), and trail making test (TMT). Forty-three patients (22 in the experimental group, 21 in the control group) were analyzed. Covariance analysis showed significant differences in 10/36 SPART (P=0.0002), 10/36 SPART delayed recall (P=0.0021), WLG (P=0.0123), LNS (P=0.0413), BNT (P=0.0007) and TMT-A (P=0.010) scores between groups. The study showed a significant improvement related to learning and visual memory, executive functions, attention and information processing speed, and naming ability in those patients who received cognitive rehabilitation. The results suggest that MS-Line! is effective in improving cognitive impairment in MS patients. © The Author(s), 2015.
Chacińska, Weronika; Brzostowska, Marta; Nojszewska, Monika; Podlecka-Piętowska, Aleksandra; Jędrzejczak, Wiesław W; Snarski, Emilian
New aggressive treatments promise improvement of results in the treatment of multiple sclerosis (MS), however, with high risk of serious complications. In this study, we analyzed patients' acceptance for risks connected with the MS treatment. The study was designed as a prospective nonanonymous online questionnaire. Responders were asked about the definition of the "cure" for MS and crucial goals in the treatment. One hundred and eighty patients filled in the questionnaire (129 women and 51 men), and the mean age was 33 years ( SD = 10.29). The MS forms were as follows: relapsing-remitting (65%), secondary progressive (14%), primary progressive (10%), and other (11%), with mean EDSS score of 3 points ( SD = 2.6). For 50% of the patients, relief of symptoms such as fatigue (72%), paresis (66%), and balance disorders (65%) was synonymous with "cure." The patients with faster progression of the disease were likely to accept risky "curative" treatments-with average 68% accepted mortality risk ( p = .003). Over 81% of patients accepted mortality rates over 1% for the treatment that achieves self-defined cure. The study shows that the MS patients are likely to accept even very risky treatments as long as they promise patient-defined "cure."
Khan, Fary; Amatya, Bhasker; Galea, Mary
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
Newland, Pamela K; Lunsford, Valerie; Flach, Alicia
In addition to the underlying health problems and disability associated with multiple sclerosis (MS) and cardiovascular disease (CVD), adults with each of these chronic illnesses are independently known to experience fatigue. While fatigue's influence on physical activity and health related quality of life (HRQOL) with each of these illnesses has been discussed, what is lacking is information on how fatigue impacts physical activity and health related quality of life, and ultimately self-management for adults with these conditions. Additionally, individuals may be unaware of the significance of maintaining optimal physical activity in order to maintain everyday function and self-management. Thus, the purpose of this article is to discuss the complex effect of fatigue on physical activity and HRQOL among adults with MS and CVD, and to present potential self-management strategies. Copyright © 2016 Elsevier Inc. All rights reserved.
Al Jumah, Mohammed A.; Abumaree, Mohamed H.
Mesenchymal stem cells (MSCs) are multipotent cells that differentiate into the mesenchymal lineages of adipocytes, osteocytes and chondrocytes. MSCs can also transdifferentiate and thereby cross lineage barriers, differentiating for example into neurons under certain experimental conditions. MSCs have anti-proliferative, anti-inflammatory and anti-apoptotic effects on neurons. Therefore, MSCs were tested in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), for their effectiveness in modulating the pathogenic process in EAE to develop effective therapies for MS. The data in the literature have shown that MSCs can inhibit the functions of autoreactive T cells in EAE and that this immunomodulation can be neuroprotective. In addition, MSCs can rescue neural cells via a mechanism that is mediated by soluble factors, which provide a suitable environment for neuron regeneration, remyelination and cerebral blood flow improvement. In this review, we discuss the effectiveness of MSCs in modulating the immunopathogenic process and in providing neuroprotection in EAE. PMID:22942767
Vanotti, Sandra; Smerbeck, Audrey; Benedict, Ralph H B; Caceres, Fernando
The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is an international assessment tool for monitoring cognitive function in multiple sclerosis (MS) patients. BICAMS comprises the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test - Second Edition (CVLT II) and the Brief Visuospatial Memory Test - Revised (BVMT-R). Our objective was to validate and assess the reliability of BICAMS as applied in Argentina and to obtain normative data in Spanish for this population. The sample composed of 50 MS patients and 100 healthy controls (HC). In order to test its reliability, BICAMS was re-administered in a subset of 25 patients. The sample's average age was 43.42 ± 10.17 years old, and average years of schooling were 14.86 ± 2.78. About 74% of the participants were women. The groups did not differ in age, years of schooling, or gender. The MS group performed significantly worse than the HC group across the three neuropsychological tests, yielding the following Cohen's d values: SDMT: .85; CVLT I: .87; and BVMT-R: .40. The mean raw scores for Argentina normative data were as follows: SDMT: 56.71 ± 10.85; CVLT I: 60.88 ± 10.46; and BVMT-R: 23.44 ± 5.84. Finally, test-retest reliability coefficients for each test were as follows: SDMT: r = .95; CVLT I: r = .87; and BVMT-R: r = .82. This BICAMS version is reliable and useful as a monitoring tool for identifying MS patients with cognitive impairment.
Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial.
Chan, Dennis; Binks, Sophie; Nicholas, Jennifer M; Frost, Chris; Cardoso, M Jorge; Ourselin, Sebastien; Wilkie, David; Nicholas, Richard; Chataway, Jeremy
In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348. Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6-7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8-8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated
Pützer, Manfred; Wokurek, Wolfgang; Moringlane, Jean Richard
The effect of deep brain stimulation (DBS) on phonatory behavior and voice quality in eight patients with multiple sclerosis (MS) was examined instrumentally and perceptually. The acoustic signals of vowel productions obtained from patients (produced with and without stimulation) and from a group of 16 healthy control speakers were analyzed to prove statistically the changes of phonatory behavior and voice quality. This is a randomized study. Firstly, a new parametrization was used to determine phonatory behavior. Secondly, a perceptual evaluation of voice quality of the same speech material was performed. With stimulation, phonation has a greater tendency to be strained. The results of perceptual evaluation support this strained phonation behavior under stimulation, resulting in a smaller degree of breathiness ratings of all raters. Without stimulation, an impaired and partly disturbed adduction of the vocal folds can be shown. These findings are also supported in the perceptual experiment providing a higher degree of hoarseness ratings of all raters for these signals. High-frequency electrical impulses to the thalamus in patients with MS influence the phonatory behavior of their vocal folds. The results suggest the need for long-term monitoring of phonatory behavior during DBS to initiate adequate treatments without delay. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Background TREFAMS is an acronym for TReating FAtigue in Multiple Sclerosis, while ACE refers to the rehabilitation treatment methods under study, that is, Aerobic training, Cognitive behavioural therapy, and Energy conservation management. The TREFAMS-ACE research programme consists of four studies and has two main objectives: (1) to assess the effectiveness of three different rehabilitation treatment strategies in reducing fatigue and improving societal participation in patients with MS; and (2) to study the neurobiological mechanisms of action that underlie treatment effects and MS-related fatigue in general. Methods/Design Ambulatory patients (n = 270) suffering from MS-related fatigue will be recruited to three single-blinded randomised clinical trials (RCTs). In each RCT, 90 patients will be randomly allocated to the trial-specific intervention or to a low-intensity intervention that is the same for all RCTs. This low-intensity intervention consists of three individual consultations with a specialised MS-nurse. The trial-specific interventions are Aerobic Training, Cognitive Behavioural Therapy, and Energy Conservation Management. These interventions consist of 12 individual therapist-supervised sessions with additional intervention-specific home exercises. The therapy period lasts 16 weeks. All RCTs have the same design and the same primary outcome measures: fatigue - measured with the Checklist Individual Strength, and participation - measured with the Impact on Participation and Autonomy questionnaire. Outcomes will be assessed 1 week prior to, and at 0, 8, 16, 26 and 52 weeks after randomisation. The assessors will be blinded to allocation. Pro- and anti-inflammatory cytokines in serum, salivary cortisol, physical fitness, physical activity, coping, self-efficacy, illness cognitions and other determinants will be longitudinally measured in order to study the neurobiological mechanisms of action. Discussion The TREFAMS-ACE programme is unique in its aim to
Sadeghi Bahmani, Dena; Esmaeili, Leila; Shaygannejad, Vahid; Gerber, Markus; Kesselring, Juerg; Lang, Undine E.; Holsboer-Trachsler, Edith; Brand, Serge
Background: Previous research of patients with multiple sclerosis (MS) focused prevalently on fatigue, depression, and cognitive dysfunction during the clinical course. By contrast, research on the longer-term characteristics of physical activity (PA), psychological functioning, and sleep problems is scarce. The aims of the present study were therefore to examine changes in PA, mental toughness (MT) as a proxy of psychological functioning, and sleep disturbances over a 2-year period of time after disease onset. Methods: A total of 18 patients with diagnosed MS (mean age: M = 34.29 years) took part in this longitudinal study. First, 1–4 weeks after the first symptoms, a neurologist diagnosed the MS. Second, they completed a series of questionnaires covering socio-demographic data, PA, MT, and sleep disturbances. Third, the same questionnaires were completed again 2 years later (follow-up). Last, a neurologist assessed the degree of disability with the Expanded Disability Status Scale (EDSS). Results: Two years after MS onset, patients had lower levels of vigorous PA, but no statistically significant changes in moderate PA were observed. Further, walking time increased and sedentary time decreased. Patients with sleep disturbances at disease onset also reported poor sleep 2 years later. MT scores remained stable over time. EDSS scores worsened, though, change in EDSS was not associated with PA, MT, or sleep. Conclusions: Two years after disease onset, patients with MS reported similar MT levels and sleep disturbances. PA shifted from vigorous PA toward walking and a less sedentary lifestyle, while moderate PA remained unchanged. The pattern of results of the present pilot study suggests that at the early stage of the MS course, there is no obstacle for being physically active, nor did sleep and MT as a proxy of psychological functioning decrease in a substantial way. PMID:29867606
Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle
Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.
Teh, C L; Kuan, Y C; Wong, J S
We performed a cross-sectional study of the demography, clinical and laboratory features of patients with systemic sclerosis patients followed up in our centre from 1984 to 2007. There were 23 cases with the majority of them (96%) being female. They have a mean age of 50.3 years and a mean disease duration of 6.02 (SD 5.82) years. Our patients comprised of multi-ethnic groups with predominantly Chinese (52%), Sarawak natives (35%) and Malays (13%). They have a mean lag time to diagnosis of 24.8 (SD 34.8) months. All the patients have sclerodermatous skin changes with 16(70%) having diffuse scleroderma and 7(30%) having limited scleroderma. The common clinical manifestations found in our patients were Raynaud's phenomenon (91%), sclerodactyly (65%), digital ulcers (52%) and pulmonary fibrosis (52%). There was low incidence of pulmonary hypertension (13%) and renal involvement (4%). The majority of our patients (67%) have positive ANA with 33% positive Scl-70. The majority received calcium channel blockers (87%), aspirin (48%) and low-dose prednisolone (48%). One patient developed adenocarcinoma of the lung on follow-up. This study demonstrated the rarity of systemic sclerosis in our centre with considerable lag time to diagnosis in our patients. Diffuse cutaneous systemic scleroderma is more common in our centre with rare pulmonary hypertension and renal involvement.
Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert
Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS. Copyright © 2015 Elsevier Inc. All rights reserved.
Bauer, Kerry M; Lambert, Paul A; Hummon, Amanda B
A label-free mass spectrometric strategy was used to examine the effect of 5-fluorouracil (5-FU) on the primary and metastatic colon carcinoma cell lines, SW480 and SW620, with and without treatment. 5-FU is the most common chemotherapeutic treatment for colon cancer. Pooled biological replicates were analyzed by nanoLC-MS/MS and protein quantification was determined via spectral counting. Phenotypic and proteomic changes were evident and often similar in both cell lines. The SW620 cells were more resistant to 5-FU treatment, with an IC(50) 2.7-fold higher than that for SW480. In addition, both cell lines showed pronounced abundance changes in pathways relating to antioxidative stress response and cell adhesion remodeling due to 5-FU treatment. For example, the detoxification enzyme NQO1 was increased with treatment in both cell lines, while disparate members of the peroxiredoxin family, PRDX2 or PRDX5 and PRDX6, were elevated with 5-FU exposure in either SW480 or SW620, respectively. Cell adhesion-associated proteins CTNNB1 and RhoA showed decreased expression with 5-FU treatment in both cell lines. The differential quantitative response in the proteomes of these patient-matched cell lines to drug treatment underscores the subtle molecular differences separating primary and metastatic cancer cells. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Zivadinov, Robert; Khan, Nasreen; Medin, Jennie; Christoffersen, Pia; Price, Jennifer; Korn, Jonathan R; Bonzani, Ian; Dwyer, Michael G; Bergsland, Niels; Carl, Ellen; Silva, Diego; Weinstock-Guttman, Bianca
To describe methodology, interim baseline, and longitudinal magnetic resonance imaging (MRI) acquisition parameter characteristics of the multiple sclerosis clinical outcome and MRI in the United States (MS-MRIUS). The MS-MRIUS is an ongoing longitudinal and retrospective study of MS patients on fingolimod. Clinical and brain MRI image scan data were collected from 600 patients across 33 MS centers in the United States. MRI brain outcomes included change in whole-brain volume, lateral ventricle volume, T2- and T1-lesion volumes, and new/enlarging T2 and gadolinium-enhancing lesions. Interim baseline and longitudinal MRI acquisition parameters results are presented for 252 patients. Mean age was 44 years and 81% were female. Forty percent of scans had 3-dimensional (3D) T1 sequence in the preindex period, increasing to 50% in the postindex period. Use of 2-dimensional (2D) T1 sequence decreased over time from 85% in the preindex period to 65% in the postindex. About 95% of the scans with FLAIR and 2D T1-WI were considered acceptable or good quality compared to 99-100% with 3D T1-WI. There were notable changes in MRI hardware, software, and coil (39.5% in preindex to index and 50% in index to postindex). MRI sequence parameters (orientation, thickness, or protocol) differed for 36%, 29%, and 20% of index/postindex scans for FLAIR, 2D T1-WI, and 3D T1-WI, respectively. The MS-MRIUS study linked the clinical and brain MRI outcomes into an integrated database to create a cohort of fingolimod patients in real-world practice. Variability was observed in MRI acquisition protocols overtime. © 2016 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.
Sebastião, Emerson; McAuley, Edward; Shigematsu, Ryosuke; Motl, Robert W
We propose a randomized controlled trial (RCT) examining the feasibility of square-stepping exercise (SSE) delivered as a home-based program for older adults with multiple sclerosis (MS). We will assess feasibility in the four domains of process, resources, management and scientific outcomes. The trial will recruit older adults (aged 60 years and older) with mild-to-moderate MS-related disability who will be randomized into intervention or attention control conditions. Participants will complete assessments before and after completion of the conditions delivered over a 12-week period. Participants in the intervention group will have biweekly meetings with an exercise trainer in the Exercise Neuroscience Research Laboratory and receive verbal and visual instruction on step patterns for the SSE program. Participants will receive a mat for home-based practice of the step patterns, an instruction manual, and a logbook and pedometer for monitoring compliance. Compliance will be further monitored through weekly scheduled Skype calls. This feasibility study will inform future phase II and III RCTs that determine the actual efficacy and effectiveness of a home-based exercise program for older adults with MS.
Strober, Lauren B; Chiaravalloti, Nancy; DeLuca, John
Rates of unemployment among individuals with multiple sclerosis (MS) are as high as 80%. While several factors for such high rates of unemployment have been identified, they do not account for the majority of the variance. This study examines person-specific factors such as personality and coping, which may better account for individuals leaving the workforce. Forty individuals with MS (20 considering reducing work hours or leaving the workforce and 20 remaining employed) were matched on age, gender, education, disease duration, and disease course, and administered a comprehensive survey of factors purported to be related to employment status. Based on multiple, logistic regression analyses certain disease factors and person-specific factors differentiate those who are considering leaving work or reducing work hours and those staying employed. In particular, those expressing the need to reduce work hours or leaving the workforce reported more fatigue, anxiety, depression, and use of behavioral disengagement as a means of coping. In contrast, those staying employed reported greater levels of extraversion, self-efficacy, and use of humor as a means of coping. Together, fatigue, use of humor, and use of behavioral disengagement as a means of coping were the most significant factors, accounting for 44% of the variance. Findings suggest that greater consideration be given to these factors and that interventions tailored to address these factors may assist individuals with MS staying employed and/or making appropriate accommodations.
Bianchi, L; Monaldi, F; Paolucci, S; Iani, C; Lacquaniti, F
The aim of this study was to develop quantitative analytical methods in the application of the pendulum test to both normal and spastic subjects. The lower leg was released by a torque motor from different starting positions. The resulting changes in the knee angle were fitted by means of a time-varying model. Stiffness and viscosity coefficients were derived for each half-cycle oscillation in both flexion and extension, and for all knee starting positions. This method was applied to the assessment of the effects of Botulinum toxin A (BTX) in progressive multiple sclerosis patients in a follow-up study. About half of the patients showed a significant decrement in stiffness and viscosity coefficients.
Nakhaei-Nejad, Maryam; Barilla, David; Lee, Chieh-Hsin; Blevins, Gregg; Giuliani, Fabrizio
Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY). Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients. We compared patients untreated (NT) or treated with FTY or DMF who did (DMF-L) or did not (DMF-N) develop lymphopenia. All FTY patients developed lymphopenia in both T-cell and B-cell compartments. CD41 T cells were more affected by this treatment than CD81 cells. In the B-cell compartment, the CD271IgD2 subpopulation was reduced. T cells but not B cells were significantly reduced in DMF-L. However, within the B cells, CD271 cells were significantly lower. Both CD41 and CD81 subpopulations were reduced in DMF-L. Within the remaining CD41 and CD81 compartments, there was an expansion of the naive subpopulation and a reduction of the effector memory subpopulation. Unactivated lymphocyte from DMF-L patients had significantly higher levels of interferon-γ, interleukin (IL)-12, IL-2, IL-4, IL-6, and IL-1β compared with DMF-N. In plasma, TNFβ was significantly higher in DMF-N and DMF-L compared with NT, whereas CCL17 was significantly higher in DMF-L compared with NT and DMF-N. This study shows that different treatments can target different lymphocyte compartments and suggests that lymphopenia can induce compensatory mechanisms to maintain immune homeostasis.
Nakhaei-Nejad, Maryam; Barilla, David; Lee, Chieh-Hsin; Blevins, Gregg
Objective: Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY). Methods: Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients. We compared patients untreated (NT) or treated with FTY or DMF who did (DMF-L) or did not (DMF-N) develop lymphopenia. Results: All FTY patients developed lymphopenia in both T-cell and B-cell compartments. CD41 T cells were more affected by this treatment than CD81 cells. In the B-cell compartment, the CD271IgD2 subpopulation was reduced. T cells but not B cells were significantly reduced in DMF-L. However, within the B cells, CD271 cells were significantly lower. Both CD41 and CD81 subpopulations were reduced in DMF-L. Within the remaining CD41 and CD81 compartments, there was an expansion of the naive subpopulation and a reduction of the effector memory subpopulation. Unactivated lymphocyte from DMF-L patients had significantly higher levels of interferon-γ, interleukin (IL)-12, IL-2, IL-4, IL-6, and IL-1β compared with DMF-N. In plasma, TNFβ was significantly higher in DMF-N and DMF-L compared with NT, whereas CCL17 was significantly higher in DMF-L compared with NT and DMF-N. Conclusions: This study shows that different treatments can target different lymphocyte compartments and suggests that lymphopenia can induce compensatory mechanisms to maintain immune homeostasis. PMID:29296636
D'hooghe, Marie; Van Gassen, Geert; Kos, Daphne; Bouquiaux, Olivier; Cambron, Melissa; Decoo, Danny; Lysandropoulos, Andreas; Van Wijmeersch, Bart; Willekens, Barbara; Penner, Iris-Katharina; Nagels, Guy
Fatigue is a frequently occurring, often disabling symptom in MS with no single effective treatment. In current fatigue management interventions, personalized, real-time follow-up is often lacking. The objective of the study is to assess the feasibility of the MS TeleCoach, a novel intervention offering telemonitoring of fatigue and telecoaching of physical activity and energy management in persons with MS (pwMS) over a 12-week period. The goal of the MS TeleCoach, conceived as a combination of monitoring, self-management and motivational messages, is to enhance levels of physical activity thereby improving fatigue in pwMS in an accessible and interactive way, reinforcing self-management of patients. We conducted a prospective, open-label feasibility study of the MS TeleCoach in pwMS with Expanded Disability Status Scale ≤ 4 and moderate to severe fatigue as measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC). Following a 2-week run-in period to assess the baseline activity level per patient, the target number of activity counts was gradually increased over the 12-week period through telecoaching. The primary efficacy outcome was change in FSMC total score from baseline to study end. A subset of patients was asked to fill in D-QUEST 2.0, a usability questionnaire, to evaluate the satisfaction with the MS TeleCoach device and the experienced service. Seventy-five patients were recruited from 16 centres in Belgium, of which 57 patients (76%) completed the study. FSMC total score (p = 0.009) and motor and cognitive subscores (p = 0.007 and p = 0.02 respectively) decreased from baseline to week 12, indicating an improvement in fatigue. One third of participants with severe fatigue changed to a lower FSMC category for both FSMC total score and subscores. The post-study evaluation of patient satisfaction showed that the intervention was well accepted and that patients were very satisfied with the quality of the professional services
Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex PRINCIPAL...Approved Memantine and Newer NitroMemantine Derivatives to Treat 5a. CONTRACT NUMBER W81XWH-13-1-0053 Neurological Manifestations in Rodent Models of...to investigate if administration of the FDA-approved drug, Memantine , an uncompetitive/fast off-rate antagonist of the N- methyl-D-aspartate-type
Saposnik, Gustavo; Sempere, Angel P; Prefasi, Daniel; Selchen, Daniel; Ruff, Christian C; Maurino, Jorge; Tobler, Philippe N
Limited information is available on physician-related factors influencing therapeutic inertia (TI) in multiple sclerosis (MS). Our aim was to evaluate whether physicians' risk preferences are associated with TI in MS care, by applying concepts from behavioral economics. In this cross-sectional study, participants answered questions regarding the management of 20 MS case scenarios, completed 3 surveys, and 4 experimental paradigms based on behavioral economics. Surveys and experiments included standardized measures of aversion ambiguity in financial and health domains, physicians' reactions to uncertainty in patient care, and questions related to risk preferences in different domains. The primary outcome was TI when physicians faced a need for escalating therapy based on clinical (new relapse) and magnetic resonance imaging activity while patients were on a disease-modifying agent. Of 161 neurologists who were invited to participate in the project, 136 cooperated with the study (cooperation rate 84.5%) and 96 completed the survey (response rate: 60%). TI was present in 68.8% of participants. Similar results were observed for definitions of TI based on modified Rio or clinical progression. Aversion to ambiguity was associated with higher prevalence of TI (86.4% with high aversion to ambiguity vs. 63.5% with lower or no aversion to ambiguity; p = 0.042). In multivariate analyses, high aversion to ambiguity was the strongest predictor of TI (OR 7.39; 95%CI 1.40-38.9), followed by low tolerance to uncertainty (OR 3.47; 95%CI 1.18-10.2). TI is a common phenomenon affecting nearly 7 out of 10 physicians caring for MS patients. Higher prevalence of TI was associated with physician's strong aversion to ambiguity and low tolerance of uncertainty.
Salehpoor, Ghasem; Rezaei, Sajjad; Hosseininezhad, Mozaffar
Background: Although studies have demonstrated significant negative relationships between quality of life (QOL), fatigue, and the most common psychological symptoms (depression, anxiety, stress), the main ambiguity of previous studies on QOL is in the relative importance of these predictors. Also, there is lack of adequate knowledge about the actual contribution of each of them in the prediction of QOL dimensions. Thus, the main objective of this study is to assess the role of fatigue, depression, anxiety, and stress in relation to QOL of multiple sclerosis (MS) patients. Materials and Methods: One hundred and sixty-two MS patients completed the questionnaire on demographic variables, and then they were evaluated by the Persian versions of Short-Form Health Survey Questionnaire (SF-36), Fatigue Survey Scale (FSS), and Depression, Anxiety, Stress Scale-21 (DASS-21). Data were analyzed by Pearson correlation coefficient and hierarchical regression. Results: Correlation analysis showed a significant relationship between QOL elements in SF-36 (physical component summary and mental component summary) and depression, fatigue, stress, and anxiety (P < 0.01). Hierarchical regression analysis indicated that among the predictor variables in the final step, fatigue, depression, and anxiety were identified as the physical component summary predictor variables. Anxiety was found to be the most powerful predictor variable amongst all (β = −0.46, P < 0.001). Furthermore, results have shown depression as the only significant mental component summary predictor variable (β = −0.39, P < 0.001). Conclusions: This study has highlighted the role of anxiety, fatigue, and depression in physical dimensions and the role of depression in psychological dimensions of the lives of MS patients. In addition, the findings of this study indirectly suggest that psychological interventions for reducing fatigue, depression, and anxiety can lead to improved QOL of MS patients. PMID:25558256
Salehpoor, Ghasem; Rezaei, Sajjad; Hosseininezhad, Mozaffar
Although studies have demonstrated significant negative relationships between quality of life (QOL), fatigue, and the most common psychological symptoms (depression, anxiety, stress), the main ambiguity of previous studies on QOL is in the relative importance of these predictors. Also, there is lack of adequate knowledge about the actual contribution of each of them in the prediction of QOL dimensions. Thus, the main objective of this study is to assess the role of fatigue, depression, anxiety, and stress in relation to QOL of multiple sclerosis (MS) patients. One hundred and sixty-two MS patients completed the questionnaire on demographic variables, and then they were evaluated by the Persian versions of Short-Form Health Survey Questionnaire (SF-36), Fatigue Survey Scale (FSS), and Depression, Anxiety, Stress Scale-21 (DASS-21). Data were analyzed by Pearson correlation coefficient and hierarchical regression. Correlation analysis showed a significant relationship between QOL elements in SF-36 (physical component summary and mental component summary) and depression, fatigue, stress, and anxiety (P < 0.01). Hierarchical regression analysis indicated that among the predictor variables in the final step, fatigue, depression, and anxiety were identified as the physical component summary predictor variables. Anxiety was found to be the most powerful predictor variable amongst all (β = -0.46, P < 0.001). Furthermore, results have shown depression as the only significant mental component summary predictor variable (β = -0.39, P < 0.001). This study has highlighted the role of anxiety, fatigue, and depression in physical dimensions and the role of depression in psychological dimensions of the lives of MS patients. In addition, the findings of this study indirectly suggest that psychological interventions for reducing fatigue, depression, and anxiety can lead to improved QOL of MS patients.
Parisé, Hélène; Laliberté, François; Lefebvre, Patrick; Duh, Mei Sheng; Kim, Edward; Agashivala, Neetu; Abouzaid, Safiya; Weinstock-Guttman, Bianca
MS relapses are unpredictable and can be concerning to patients and their caregivers. To assess the direct and indirect cost burden associated with relapses of different severities in MS patients and with MS relapse frequency on spouse caregivers. Using a U.S. insurance claims and employee disability database (1999-2011), we studied adult MS patients (ICD-9-CM: 340.x) and their spouse caregivers. A previously published algorithm to identify relapses was used to stratify: (1) MS patients into cohorts of no, low/moderate, and high severity relapse based on the most severe relapse within one year of follow-up (if any); (2) caregivers into cohorts of no, less, and more frequent relapses based on the overall frequency of relapses of their spouse. Adjusted cost differences and 95% confidence intervals evaluating the yearly incremental costs at 12 months of follow-up (MS patients) and overall (caregivers) associated with relapses are reported. Among the 9421 MS patients (N: no relapse=7686; low/moderate severity relapse=1220; high severity relapse=515) identified, both relapse cohorts incurred significantly higher annual incremental direct costs than the no relapse cohort (low/moderate severity=$8269 [6565-10,115]; high severity=$24,180 [20,263-28,482]) and indirect costs (low/moderate severity=$1429 [759-2147]; high severity=$2714 [1468-4035]). More frequent relapses versus no relapse also translated into a significantly greater cost burden for caregivers (direct+indirect=$1725 [376-2885]) but less frequent relapses did not. Relapse severity was significantly and increasingly associated with greater direct and indirect costs in MS patients. More frequent relapses also translated into a significant cost burden in spouse caregivers. Copyright © 2013 Elsevier B.V. All rights reserved.
Pollack, Sarah F; Geffrey, Alexandra L; Thiele, Elizabeth A; Shah, Uzma
Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by a congenital malformation of the lymphatic vessels of the small intestine causing insufficient drainage and leakage of lymph fluid. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems. While the lymphatic system has been implicated in TSC through lymphangioleiomyomatosis (LAM) and lymphedema, this paper reports the first case of PIL in TSC, a female patient with a TSC2 mutation. She developed persistent and significant abdominal distension with chronic diarrhea during her first year of life. Due to lack of treatment options and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor, rapamycin, was initiated. This treatment was highly effective, with improvement in clinical symptoms of PIL as well as abnormal laboratory values including VEGF-C, which was elevated to over seven times the normal upper limit before treatment. This case suggests that PIL is a rare manifestation of TSC, warranting the use of mTOR inhibitors in future studies. © 2015 Wiley Periodicals, Inc.
Ramirez-Ramirez, V.; Macias-Islas, M. A.; Ortiz, G. G.; Pacheco-Moises, F.; Torres-Sanchez, E. D.; Sorto-Gomez, T. E.; Cruz-Ramos, J. A.; Orozco-Aviña, G.; Celis de la Rosa, A. J.
Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNFα levels; secondary outcomes were IL-1β 1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNFα, IL-1β, IL-6, and nitric oxide metabolites compared with placebo group (P ≤ 0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found. Conclusion. Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS. PMID:23861993
Rainone, Nunzia; Chiodi, Alessandro; Lanzillo, Roberta; Magri, Valeria; Napolitano, Anna; Morra, Vincenzo Brescia; Valerio, Paolo; Freda, Maria Francesca
To investigate the moderating role of resilience in the relationship between affective disorders and Health-Related Quality of Life (HRQoL) for adolescents and young adults with multiple sclerosis (MS). A quantitative methodology was adopted. Fifty-three adolescents and young adults were interviewed to assess resilience as a personality trait (Ego-Resiliency Scale) and resilience as an interactive competence (CYRM-28), Health-Related Quality of Life (PedsQL 4.0), depression and anxiety (BDI-II and STAI-Y). Affective disorders, both depression (β = -.38, p < .001) and anxiety (State β = -.35, p < .001; Trait β = -.41, p < .001), were negatively associated with HRQoL. Data also showed that the resilience competencies using Individual (β = .22, p < .001) and relational resources (β = .12, p < .05) are significantly associated HRQoL. According to the regression analyses, we tested the moderating role of resilience competence using individual resources on the relationship between the Depression Cognitive Factor and Emotional Functioning. Data show that in step 2 of the regression analysis, we obtained a variation of β = -.45 (p < .001) to β = -.30 (p < .001) in the dimension for the Depression Cognitive Factor. The Sobel test showed that the moderating effect of resilience was significant regarding the increase in R 2 (p < .01). Resilience competence using individual resources moderates the relationship between the Depression Cognitive Factor and Emotional Functioning in adolescents with MS. Our study suggests that to improve well-being for adolescents with MS resilience could play a key role.
Suzuki, Ippei; Kubota, Hiroki; Ohtsuki, Takashi; Tatebe, Chiye; Tada, Atsuko; Yano, Takeo; Akiyama, Hiroshi; Sato, Kyoko
A rapid, sensitive, and specific analytical method for the determination of 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) on uncooked foods after treatment with a peracetic acid-based sanitizer (PAS) was developed. The method involves simple sample preparation steps and analysis using ion chromatography (IC) coupled with tandem mass spectrometry (MS/MS). The quantification limits of HEDP on uncooked foods are 0.007 mg/kg for vegetables and fruits and 0.2 mg/kg for meats. The recovery and relative standard deviation (RSD) of HEDP analyses of uncooked foods ranged from 73.9 to 103.8% and 1.9 to 12.6%, respectively. The method's accuracy and precision were evaluated by inter-day recovery tests. The recovery for all samples ranged from 93.6 to 101.2%, and the within-laboratory repeatability and reproducibility were evaluated based on RSD values, which were less than 6.9 and 11.5%, respectively. Analyses of PAS-treated fruits and vegetables using the developed method indicated levels of HEDP ranging from 0.008 to 0.351 mg/kg. Therefore, the results of the present study suggest that the proposed method is an accurate, precise, and reliable way to determine residual HEDP levels on PAS-treated uncooked foods.
Bagnato, Francesca; Centonze, Diego; Galgani, Simonetta; Grasso, Maria Grazia; Haggiag, Shalom; Strano, Stefano
Importance of the field Pain, dysphagia, respiratory problems, sexual and cardiovascular dysfunctions may occur in patients with multiple sclerosis (MS). Areas covered in the field In the present review we attempt to summarize the current knowledge on the impact that pain, dysphagia, respiratory problems, sexual and cardiovascular dysfunctions have in patients with MS. What the reader will gain The current understanding on pain, dysphagia, respiratory problems, sexual and cardiovascular dysfunctions and future research perspectives to expand the knowledge of this field. Take home message To effectively manage MS it is essential that these symptoms are recognised as early as possible and treated by a rehabilitative multidisciplinary approach, based on proven scientific evidence. PMID:21323633
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.
Leist, Thomas P; Comi, Giancarlo; Cree, Bruce A C; Coyle, Patricia K; Freedman, Mark S; Hartung, Hans-Peter; Vermersch, Patrick; Casset-Semanaz, Florence; Scaramozza, Matthew
Patients who develop relapsing-remitting multiple sclerosis (MS) present with a first clinical demyelinating event. In this double-blind, multicentre, randomised, phase 3 study we investigated the effect of oral cladribine on conversion to clinically definite MS in patients with a first clinical demyelinating event, when given at the same doses shown to be effective in relapsing-remitting MS. Between Oct 21, 2008, and Oct 11, 2010, we recruited patients aged 18-55 years, inclusive, from 160 hospitals, private clinics, or treatment centres in 34 countries. Eligible patients had a first clinical demyelinating event within 75 days before screening, at least two clinically silent lesions of at least 3 mm on a T2-weighted brain MRI scan, and an Expanded Disability Status Scale score of 5.0 or lower. Patients with a first clinical demyelinating event ≤75 days before screening were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5.25 mg/kg or 3.5 mg/kg or placebo. Randomisation was done with a central web-based randomisation system and was stratified by geographic region. Masking was maintained using a two-physician model. The primary endpoint of this 96-week study was time to conversion to clinically definite MS according to the Poser criteria. This study is registered with ClinicalTrials.gov, number NCT00725985. Of 903 participants assessed for eligibility, 616 patients received cladribine 5.25 mg/kg (n=204), cladribine 3.5 mg/kg (n=206), or placebo (n=206). At trial termination on Oct 25, 2011, cladribine was associated with a risk reduction versus placebo for time to conversion to clinically definite MS (hazard ratio [HR] for 5.25 mg/kg=0.38, 95% CI 0.25-0.58, p<0.0001; HR for 3.5 mg/kg=0.33, 0.21-0.51, p<0.0001). Adverse events were reported in 165 (81%) patients in the cladribine 5.25 mg/kg group, 168 (82%) patients in the cladribine 3.5 mg/kg group, and 162 (79%) patients in the placebo group. We noted no increase in risk of adverse
neuronal marker ( choline acetyltransferase) and quantified image analysis. Motoneurons were counted in the anterior horn region of the lumbar spinal...cord (both sides , then averaged). We do not detect a statistical difference in surviving motoneurons between PEG-HCC and vehicle-treated subjects...beyond this particular funding mechanism in order to better develop PEG-HCCs as a novel and effective treatment for ALS. What was the impact on other
Giovannoni, Gavin; Wiendl, Heinz; Turner, Benjamin; Umans, Kimberly; Mokliatchouk, Oksana; Castro-Borrero, Wanda; Greenberg, Steven J; McCroskery, Peter; Giannattasio, Giorgio
Reversible lymphocyte count reductions have occurred following daclizumab beta treatment for relapsing-remitting multiple sclerosis. To analyse total and differential lymphocyte levels and relationship with infection status. In DECIDE, blood samples were collected at 12-week intervals from daclizumab beta- ( n = 919) or intramuscular interferon beta-1a-treated ( n = 922) patients. Infections/serious infections were assessed proximate to grade 2/3 lymphopenia or low CD4 + /CD8 + T-cell counts. Total safety population (TSP) data were additionally analysed from the entire clinical development programme ( n = 2236). Over 96 weeks in DECIDE, mean absolute lymphocyte count (ALC), CD4 + and CD8 + T-cell counts decreased <10% (7.1% vs 1.6%, 9.7% vs 2.0%, 9.3% vs 5.9%: daclizumab beta vs interferon beta-1a, respectively); shifts to ALC below lower limit of normal occurred in 13% versus 15%, respectively. Grade 3 lymphopenia was uncommon (TSP: <1%) and transient. Lymphocyte changes generally occurred within 24 weeks after treatment initiation and were reversible within 12 weeks of discontinuation. In DECIDE, mean CD4 + /CD8 + T-cell counts were similar regardless of infection status. TSP data were consistent with DECIDE. When observed, ALC and CD4 + /CD8 + T-cell count decreases in daclizumab beta-treated patients were generally mild-to-modest, reversible upon treatment discontinuation and not associated with increased risk of infections, including opportunistic infections.
Treating Post-traumatic Stress Disorder in Patients with Multiple Sclerosis: A Randomized Controlled Trial Comparing the Efficacy of Eye Movement Desensitization and Reprocessing and Relaxation Therapy
Carletto, Sara; Borghi, Martina; Bertino, Gabriella; Oliva, Francesco; Cavallo, Marco; Hofmann, Arne; Zennaro, Alessandro; Malucchi, Simona; Ostacoli, Luca
Objective: Multiple Sclerosis (MS) is a demyelinating autoimmune disease that imposes a significant emotional burden with heavy psychosocial consequences. Several studies have investigated the association between MS and mental disorders such as depression and anxiety, and recently researchers have focused also on Post-traumatic Stress Disorder (PTSD). This is the first study that investigates the usefulness of proposing a treatment for PTSD to patients with MS. Methods: A randomized controlled trial with patients with MS diagnosed with PTSD comparing Eye Movement Desensitization and Reprocessing (EMDR; n = 20) and Relaxation Therapy (RT; n = 22). The primary outcome measure was the proportion of participants that no longer meet PTSD diagnosis as measured with Clinician Administered PTSD Scale 6-months after the treatment. Results: The majority of patients were able to overcome their PTSD diagnosis after only 10 therapy sessions. EMDR treatment appears to be more effective than RT in reducing the proportion of patients with MS suffering from PTSD. Both treatments are effective in reducing PTSD severity, anxiety and depression symptoms, and to improve Quality of Life. Conclusion: Although our results can only be considered preliminary, this study suggests that it is essential that PTSD symptoms are detected and that brief and cost-effective interventions to reduce PTSD and associated psychological symptoms are offered to patients, in order to help them to reduce the psychological burden associated with their neurological condition. Trial registration: NCT01743664, https://clinicaltrials.gov/ct2/show/NCT01743664 PMID:27148134
Mirshafiey, Abbas; Jadidi-Niaragh, Farhad
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.
Phé, Véronique; Pakzad, Mahreen; Curtis, Carmel; Porter, Bernadette; Haslam, Collette; Chataway, Jeremy; Panicker, Jalesh N
Urinary tract infections (UTIs) are commonly reported by people with multiple sclerosis (PwMS) and significantly impact quality of life. To provide an overview of the problem of UTIs in PwMS and offer a practical approach for the diagnosis and management. A review of the literature through a Pubmed search up to October 2015 was performed using the following keywords: multiple sclerosis, neurogenic bladder, urinary tract infections, relapse, dipsticks, culture, recurrent and prevention. Noteworthy topics include the definition of a confirmed symptomatic UTI as a positive urine culture defined by >10(5) colony-forming units (CFU)/mL or >10(4) CFU/mL if a urethral catheter urine sample is taken, or any count of bacteria in a suprapubic bladder puncture specimen, both in addition to symptoms including fever, pain, changes in lower urinary tract symptoms or neurological status. Urinalysis is useful to exclude a UTI; however, on its own is insufficient to confirm a UTI, for which urine culture is required. Experts advise asymptomatic UTIs should not be treated except in the context of an acute relapse. From international guidelines, there is no validated strategy to prevent recurrent UTIs in PwMS. This review provides an overview of the diagnosis, treatment and prevention of UTIs in the setting of multiple sclerosis (MS). © The Author(s), 2016.
Gandolfi, Marialuisa; Geroin, Christian; Picelli, Alessandro; Munari, Daniele; Waldner, Andreas; Tamburin, Stefano; Marchioretto, Fabio; Smania, Nicola
Background: Extensive research on both healthy subjects and patients with central nervous damage has elucidated a crucial role of postural adjustment reactions and central sensory integration processes in generating and “shaping” locomotor function, respectively. Whether robotic-assisted gait devices might improve these functions in Multiple sclerosis (MS) patients is not fully investigated in literature. Purpose: The aim of this study was to compare the effectiveness of end-effector robot-assisted gait training (RAGT) and sensory integration balance training (SIBT) in improving walking and balance performance in patients with MS. Methods: Twenty-two patients with MS (EDSS: 1.5–6.5) were randomly assigned to two groups. The RAGT group (n = 12) underwent end-effector system training. The SIBT group (n = 10) underwent specific balance exercises. Each patient received twelve 50-min treatment sessions (2 days/week). A blinded rater evaluated patients before and after treatment as well as 1 month post treatment. Primary outcomes were walking speed and Berg Balance Scale. Secondary outcomes were the Activities-specific Balance Confidence Scale, Sensory Organization Balance Test, Stabilometric Assessment, Fatigue Severity Scale, cadence, step length, single and double support time, Multiple Sclerosis Quality of Life-54. Results: Between groups comparisons showed no significant differences on primary and secondary outcome measures over time. Within group comparisons showed significant improvements in both groups on the Berg Balance Scale (P = 0.001). Changes approaching significance were found on gait speed (P = 0.07) only in the RAGT group. Significant changes in balance task-related domains during standing and walking conditions were found in the SIBT group. Conclusion: Balance disorders in patients with MS may be ameliorated by RAGT and by SIBT. PMID:24904361
Longo, Leonardo; Postiglione, Marco; Gabellini, Massimiliano; Longo, Diego
The topic concerns the effect of LLLT on ALS. The purpose is to find a new and effective approach to treat ALS by utilizing the beneficial biological effects on human tissues provided by LLLT and by testing the effectiveness of a specific treatment protocol. There are no reports in literature dealing with this topic. A 69 year old male with signs of lower motor neuron degeneration diagnosed in 2003 as ALS was given LLLT. Two different types of LASERs (wavelengths 810 and 890 nm) where used with specific parameters in March 2007. Three cycles of 20 daily sessions at 40 days interval were given. Gradual and significant improvements were noted after each cycle particularly appreciated by the patient especially in muscular mobility and respiratory functions. However signs of improvement 20 days after the third cycle showed a tendency to regression. Results obtained indicate that LLLT with the specific protocol used gives significant improvement of the ALS clinical picture but that its duration is not permanent. Further research on a large cohort is justified especially as regards LASER parameters and treatment cycles.
... ENVIRONMENTAL PROTECTION AGENCY [Docket EPA-RO4-SFUND-2011-0201, FRL-9280-3] Picayune Wood... entered into a settlement for reimbursement of past response costs concerning the Picayune Wood Treating... No. EPA-RO4- SFUND-2011-0201 or Site name Picayune Wood Treating Superfund Site by one of the...
Bakathir, Manal A
Multiple sclerosis (MS) is a chronic, autoimmune inflammatory disorder of the central nervous system (CNS) that affects myelinated axons, destroying the myelin and damaging axons to varying degrees. The course of MS is highly varied and unpredictable. Metals used during orthodontic treatment can negatively affect imaging techniques used to diagnose and monitor the progression of MS, while medications used to treat MS can negatively affect orthodontic tooth movement. The present case report highlights some of the challenges encountered during orthodontic treatment of a patient with MS and how to overcome them. The patient was a 20-year-old woman with complaints of diastema and spacing in the upper arch. Although closing the spaces was challenging due to some of the MS medications, she was treated successfully, without complications, within 20 months using closing loops. PMID:28717636
Tichá, Veronika; Kodým, Roman; Počíková, Zuzana; Kadlecová, Pavla
Once-daily oral fingolimod is approved in the EU as escalation treatment for adult patients with highly active relapsing multiple sclerosis (MS). The efficacy and safety profiles of fingolimod have been well established in a large clinical development programme and several papers reflecting the experience with fingolimod in real-world settings have been published to date. The GOLEMS study was designed to evaluate the efficacy, safety and tolerability of fingolimod and the impact of fingolimod treatment on disability progression and work capability in patients with MS in routine clinical practice in the Czech Republic. GOLEMS was a national, multicentre, non-interventional, single-arm study conducted to analyse the outcomes of a minimum of 12 months of fingolimod therapy on primary and secondary endpoints. The primary endpoint was to assess the proportion of relapse-free patients and severity of MS relapses in patients treated with fingolimod for 12 months. Secondary endpoints included assessment of changes in disability progression evaluated by the Expanded Disability Status Scale (EDSS) score and work capability assessment measured through voluntary completion of the WPAI-GH questionnaire. The predictive factors for relapse-free status during fingolimod treatment were also analysed. Of the 240 enrolled patients, 219 completed the 12-month treatment period at the time of final analysis. In the efficacy set (N = 237), the proportion of relapse-free patients increased from 47 patients (19.6 %; 95 % confidence interval [CI] 14.8-25.2) in the year before fingolimod initiation to 152 patients (64.1 %; 95 % CI 58.0-70.2) after 1 year of fingolimod treatment. Of the 85 patients who experienced at least one relapse after 1 year of fingolimod treatment, 53 (62.4 %; 95 % CI 51.7-71.9) reported only one relapse, while 25 (29.4 %; 95 % CI 20.8-39.8) and seven (8.2 %; 95 % CI 4.0-16.0) patients had ≥2 relapses, respectively. No significant changes were
Kim, Yumi; Lee, In-Seung; Kim, Kang-Hoon; Park, Jiyoung; Lee, Ji-Hyun; Bang, Eunjung; Jang, Hyeung-Jin; Na, Yun-Cheol
Artemisia Capillaris (AC) and Alisma Rhizome (AR) are natural products for the treatment of liver disorders in oriental medicine clinics. Here, we report metabolomic changes in the evaluation of the treatment effects of AC and AR on fatty livers in diabetic mice, along with a proposition of the underlying metabolic pathway. Hydrophobic and hydrophilic metabolites extracted from mouse livers were analyzed using HPLC-QTOF and CE-QTOF, respectively, to generate metabolic profiles. Statistical analysis of the metabolites by PLS-DA and OPLA-DA fairly discriminated between the diabetic, and the AC- and AR-treated mice groups. Various PEs mostly contributed to the discrimination of the diabetic mice from the normal mice, and besides, DG (18:1/16:0), TG (16:1/16:1/20:1), PE (21:0/20:5), and PA (18:0/21:0) were also associated with discrimination by s-plot. Nevertheless, the effects of AC and AR treatment were indistinct with respect to lipid metabolites. Of the 97 polar metabolites extracted from the CE-MS data, 40 compounds related to amino acid, central carbon, lipid, purine, and pyrimidine metabolism, with [Formula: see text] values less than 0.05, were shown to contribute to liver dysregulation. Following treatment with AC and AR, the metabolites belonging to purine metabolism preferentially recovered to the metabolic state of the normal mice. The AMP/ATP ratio of cellular energy homeostasis in AR-treated mice was more apparently increased ([Formula: see text]) than that of AC-treated mice. On the other hand, amino acids, which showed the main alterations in diabetic mice, did not return to the normal levels upon treatment with AR or AC. In terms of metabolomics, AR was a more effective natural product in the treatment of liver dysfunction than AC. These results may provide putative biomarkers for the prognosis of fatty liver disorder following treatment with AC and AR extracts.
Kundu, Amartya; Fitzgibbons, Timothy P
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
Mendibe Bilbao, M; Boyero Durán, S; Bárcena Llona, J; Rodriguez-Antigüedad, A
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.
Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan
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…
Hunt, Laura; Nikopoulou-Smyrni, Panagiota; Reynolds, Frances
Individuals living with Multiple Sclerosis (MS) often face progressive loss of function, uncertainty and disruption to self-image and valued roles. Previous studies show that creative self-expression is valued by some people living with long-term illness, yet its meaning for people living with MS is unclear. This research study explored the meanings of leisure-based visual art-making for people living with MS. This qualitative study followed guidelines for Interpretative Phenomenological Analysis (IPA). Single semi-structured interviews were conducted with five adults (2 males; 3 females; 40-65 years), recruited from MS Ireland. Participants valued art-making for contributing to a more satisfying way of life; for filling occupational voids and using time well. Deep immersion offered respite from worry about illness. Creative classes offered social camaraderie and opportunities for learning and development. Art-making processes and products were highly affirmative, increasing emotional well-being and promoting self-worth. Most felt that they expressed valued aspects of self through their art. Art-making appeared to assist with identity maintenance, accommodating functional losses associated with MS whilst opening "new doors". Art-making offered a multi-faceted means of supporting identity and increasing fulfilment in lives that were restricted in many ways by MS.
Yamout, Bassem I; Alroughani, Raed
Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune etiology, mediated by activated T cells with evolving evidence of a significant contribution from B cells and cells of the innate immune system. The disease is thought to be due to a complex interaction between different genetic and environmental factors. The prevalence of MS is rising all over the world, due on one hand to earlier diagnosis and prolonged survival, and on the other to a true increase in incidence of the disease. The diagnosis of MS remains clinical despite recent advances in diagnostics and relies on demonstrating dissemination in space and time while excluding alternative diagnoses. The Mc Donald diagnostic criteria, with their recent 2017 revision, are currently widely accepted in the MS community. Although no cure is yet available, many disease-modifying therapies (DMTs) have shown different levels of efficacy in preventing relapses, accumulation of lesions on magnetic resonance imaging (MRI), and disability progression. Current treatment strategies include gradual escalation based on clinical and radiological criteria that determine treatment response, or initial induction with high efficacy DMTs especially in patients with an early aggressive course. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
da Luz, Suzane Rickes; Pazdiora, Paulo Cesar; Dallagnol, Leandro José; Dors, Giniani Carla; Chaves, Fábio Clasen
Wheat (Triticum aestivum) is an annual crop, cultivated in the winter and spring and susceptible to several pathogens, especially fungi, which are managed with fungicides. It is also one of the most consumed cereals, and can be contaminated by mycotoxins and fungicides. The objective of this study was to validate an analytical method by LC-MS for simultaneous determination of mycotoxins and fungicide residues in wheat grains susceptible to fusarium head blight treated with fungicides, and to evaluate the relationship between fungicide application and mycotoxin production. All parameters of the validated analytical method were within AOAC and ANVISA limits. Deoxynivalenol was the prevalent mycotoxin in wheat grain and epoxiconazole was the fungicide residue found in the highest concentration. All fungicidal treatments induced an increase in AFB2 production when compared to the control (without application). AFB1 and deoxynivalenol, on the contrary, were reduced in all fungicide treatments compared to the control. Copyright © 2016 Elsevier Ltd. All rights reserved.
Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 1 historical and established therapies. MS Neurology Group of the Australian and New Zealand Association of Neurologists.
Broadley, Simon A; Barnett, Michael H; Boggild, Mike; Brew, Bruce J; Butzkueven, Helmut; Heard, Robert; Hodgkinson, Suzanne; Kermode, Allan G; Lechner-Scott, Jeannette; Macdonell, Richard A L; Marriott, Mark; Mason, Deborah F; Parratt, John; Reddel, Stephen W; Shaw, Cameron P; Slee, Mark; Spies, Judith; Taylor, Bruce V; Carroll, William M; Kilpatrick, Trevor J; King, John; McCombe, Pamela A; Pollard, John D; Willoughby, Ernest
Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.
Zinger, Anna; Latham, Sharissa L; Combes, Valery; Byrne, Scott; Barnett, Michael H; Hawke, Simon; Grau, Georges E
No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. © The Author(s), 2016.
Benedict, Ralph; Enzinger, Christian; Filippi, Massimo; Geurts, Jeroen J.; Hamalainen, Paivi; Hulst, Hanneke; Inglese, Matilde; Leavitt, Victoria M.; Rocca, Maria A.; Rosti-Otajarvi, Eija M.; Rao, Stephen
Cognitive decline is recognized as a prevalent and debilitating symptom of multiple sclerosis (MS), especially deficits in episodic memory and processing speed. The field aims to (1) incorporate cognitive assessment into standard clinical care and clinical trials, (2) utilize state-of-the-art neuroimaging to more thoroughly understand neural bases of cognitive deficits, and (3) develop effective, evidence-based, clinically feasible interventions to prevent or treat cognitive dysfunction, which are lacking. There are obstacles to these goals. Our group of MS researchers and clinicians with varied expertise took stock of the current state of the field, and we identify several important practical and theoretical challenges, including key knowledge gaps and methodologic limitations related to (1) understanding and measurement of cognitive deficits, (2) neuroimaging of neural bases and correlates of deficits, and (3) development of effective treatments. This is not a comprehensive review of the extensive literature, but instead a statement of guidelines and priorities for the field. For instance, we provide recommendations for improving the scientific basis and methodologic rigor for cognitive rehabilitation research. Toward this end, we call for multidisciplinary collaborations toward development of biologically based theoretical models of cognition capable of empirical validation and evidence-based refinement, providing the scientific context for effective treatment discovery. PMID:29343470
Paolicelli, Damiano; Direnzo, Vita; Manni, Alessia; D'Onghia, Mariangela; Tortorella, Carla; Zoccolella, Stefano; Di Lecce, Valentina; Iaffaldano, Antonio; Trojano, Maria
Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was approved as add-on therapy for spasticity in patients with multiple sclerosis (MS). We show our 40-week postmarketing experience regarding efficacy and safety of THC/CBD spray in an Italian cohort of 102 MS patients. Patients were evaluated using the Expanded Disability Status Scale (EDSS) score, the Numerical Rating Scale (NRS) for spasticity, the Ambulation Index (AI), and Timed 25-Foot Walk (T25-FW) at the beginning of treatment and then every 3 months. After 4 weeks, if a clinically significant improvement in spasticity (at least 20% of baseline NRS score) was not seen, administration of the drug was stopped. In our cohort, patients received an average of 6.5 ± 1.6 sprays each day. The mean reduction to the NRS spasticity score was 2.5 ± 1.2 points (P < .0001). Thirty-seven patients (36.2%) discontinued the treatment. The incidence of adverse events (AEs) was 40.2%. Fifty-eight patients (56.9%) were also assessed using the NRS for pain, and 46 patients (45.1%) with bladder dysfunction were assessed for the IPSS (International Prostatic Symptoms Score) score, showing a significant improvement in these scales (P = .011 and P = .001, respectively). In conclusion, treatment with THC/CBD spray appears to be a valid answer to some of the unmet needs in MS patients, such as spasticity and other refractory-to-treatment symptoms. © 2015, The American College of Clinical Pharmacology.
Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 2 new and emerging therapies and their efficacy. MS Neurology Group of the Australian and New Zealand Association of Neurologists.
Broadley, Simon A; Barnett, Michael H; Boggild, Mike; Brew, Bruce J; Butzkueven, Helmut; Heard, Robert; Hodgkinson, Suzanne; Kermode, Allan G; Lechner-Scott, Jeannette; Macdonell, Richard A L; Marriott, Mark; Mason, Deborah F; Parratt, John; Reddel, Stephen W; Shaw, Cameron P; Slee, Mark; Spies, Judith; Taylor, Bruce V; Carroll, William M; Kilpatrick, Trevor J; King, John; McCombe, Pamela A; Pollard, John D; Willoughby, Ernest
In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.
Keegan, B Mark
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.
Cantarel, Brandi L.; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z.; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M.; Mowry, Ellen M.
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
Abstract Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system, affecting over 2.3 million people worldwide. According to the National Institute of Neurological Disorders and Stroke, the age of disease onset is typically between 20 and 40 years, with a higher incidence in women. Individuals with MS experience a wide range of symptoms, including declining physical, emotional, and psychological symptoms (e.g., fatigue, imbalance, spasticity, chronic pain, cognitive impairment, bladder and bowel dysfunction, visual and speech impairments, depression, sensory disturbance, and mobility impairment). To date, both the cause of and cure for MS remain unknown. In recent years, more individuals with MS have been pursuing alternative methods of treatment to manage symptoms of the disease, including mind-body therapies such as yoga, meditation, breathing, and relaxation techniques. It has been suggested that the practice of yoga may be a safe and effective way of managing symptoms of MS. Therefore, the purpose of this paper is to summarize the most relevant literature on exercise and mind-body modalities to treat MS symptoms and, more specifically, the benefits and potential role of yoga as an alternative treatment of symptom management for individuals with MS. The article also discusses future directions for research. PMID:26270955
Yadav, Vijayshree; Shinto, Lynne; Bourdette, Dennis
Multiple sclerosis (MS) is a chronic disabling disease of the CNS that affects people during early adulthood. Despite several US FDA-approved medications, the treatment options in MS are limited. Many people with MS explore complementary and alternative medicine (CAM) treatments to help control their MS and treat their symptoms. Surveys suggest that up to 70% of people with MS have tried one or more CAM treatment for their MS. People with MS using CAM generally report deriving some benefit from the therapies. The CAM therapies most frequently used include diet, omega-3 fatty acids and antioxidants. There is very limited research evaluating the safety and effectiveness of CAM in MS. The most promising among CAM therapies that warrant further investigation are a low-fat diet, omega-3 fatty acids, lipoic acid and vitamin D supplementation as potential anti-inflammatory and neuroprotective agents in both relapsing and progressive forms of MS. There is very limited research evaluating the safety and effectiveness of CAM in MS. However, in recent years, the NIH and the National MS Society have been actively supporting the research in this very important area. PMID:20441425
Luo, Qing; Wang, Shiyu; Sun, Li-Na; Wang, Hui
Phytoremediation is an effective method to remediate Pb-contaminated soils and root exudates play an important role in this process. Based on gas chromatography-mass spectrometry (GC-MS) and metabolomics method, this study focuses on the comparative metabolic profiling analysis of root exudates from the Pb-accumulating and non-accumulating ecotypes of Sedum alfredii treated with 0 and 50 μmol/L Pb. The results obtained show that plant type and Pb stress can significantly change the concentrations and species of root exudates, and fifteen compounds were identified and assumed to be potential biomarkers. Leaching experiments showed that l-alanine, l-proline and oxalic acid have a good effect to activate Pb in soil, glyceric acid and 2-hydroxyacetic acid have a general effect to activate Pb in soil. 4-Methylphenol and 2-methoxyphenol might be able to activate Pb in soil, glycerol and diethyleneglycol might be able to stabilize Pb in soil, but these activation effect and stabilization effect were all not obvious.
Virtanen, Jussi Oskari; Jacobson, Steve
Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents. PMID:22583435
Raviv, Gil; Shefi, Shai; Nizani, Dalia; Achiron, Anat
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.
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
Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations. MS Neurology Group of the Australian and New Zealand Association of Neurologists.
Broadley, Simon A; Barnett, Michael H; Boggild, Mike; Brew, Bruce J; Butzkueven, Helmut; Heard, Robert; Hodgkinson, Suzanne; Kermode, Allan G; Lechner-Scott, Jeannette; Macdonell, Richard A L; Marriott, Mark; Mason, Deborah F; Parratt, John; Reddel, Stephen W; Shaw, Cameron P; Slee, Mark; Spies, Judith; Taylor, Bruce V; Carroll, William M; Kilpatrick, Trevor J; King, John; McCombe, Pamela A; Pollard, John D; Willoughby, Ernest
In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.
Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active
Freedman, Samantha N; Shahi, Shailesh K; Mangalam, Ashutosh K
Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.
Wang, Yingfeng; Man, Hongxue; Gao, Jian; Liu, Xinfeng; Ren, Xiaolei; Chen, Jianxin; Zhang, Jiayu; Gao, Kuo; Li, Zhongfeng; Zhao, Baosheng
Lang-du (LD) has been traditionally used to treat human diseases in China. Plasma metabolic profiling was applied in this study based on LC-MS to elucidate the toxicity in rats induced by injected ethanol extract of LD. LD injection was given by intraperitoneal injection at doses of 0.1, 0.05, 0.025 and 0 g kg(-1) body weight per day to rats. The blood biochemical levels of alanine aminotransferase, direct bilirubin, creatinine, serum β2-microglobulin and low-density lipoprotein increased in LD-injected rats, and the levels of total protein and albumin decreased in these groups. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structures discriminate analysis (OPLS-DA). The metabolic characters in rats injected with LD were perturbed in a dose-dependent manner. By OPLS-DA, 18 metabolites were served as the potential toxicity biomarkers. Moreover, LD treatment resulted in an increase in the p-cresol, p-cresol sulfate, lysophosphatidylethanolamine (LPE) (18:0), LPE (16:0), lysophosphatidylcholine (16:0) and 12-HETE concentrations, and a decrease in hippuric acid, cholic acid and N-acetyl-l-phenylalanine. These results suggested that chronic exposure to LD could cause a disturbance in lipids metabolism and amino acids metabolism, etc. Therefore, an analysis of the metabolic profiles can contribute to a better understanding of the adverse effects of LD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina
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.
Krieger, Stephen C
The diagnosis, categorization, and treatment of multiple sclerosis (MS) and other demyelinating diseases have shifted over the past decade, and many of the fundamental principles of MS pathogenesis and clinical course are being rewritten. Fundamental issues include selecting the right disease-modifying therapy for someone with active disease and how, or even if, patients with purely progressive MS should be treated. This article provides an overview and introduction to the current thinking in MS diagnosis and therapy with an emphasis on the data-driven and proactive approach that has come to define the current state of the art.
Buchanan, Robert J; Zuniga, Miguel A; Carrillo-Zuniga, Genny; Chakravorty, Bonnie J; Tyry, Tuula; Moreau, Rachel L; Huang, Chunfeng; Vollmer, Timothy
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.
The objective of this study was to identify characteristics of informal caregivers, caregiving, and people with multiple sclerosis (MS) receiving this assistance that are associated with the strength of the care-giver/care recipient relationship. Data were collected in a national survey of informal caregivers and analyzed using an ordered logistic regression model to identify factors associated with caregiver perceptions of the strength of the relationship with the person with MS. The overall health of the person with MS was significantly associated with caregiver perceptions that providing assistance strengthened the caregiver/care recipient relationship, with poor health having a negative impact on the relationship. A spousal relationship between the caregiver and the person with MS was associated with significantly lower perceptions of a strengthened relationship. Conversely, caregiver perceptions that MS symptoms interfered with the independence of the person with MS in daily life were associated with caregiver perceptions of a strengthened relationship. Longer duration of caregiving and more hours per week spent providing assistance also were associated with a stronger relationship. In contrast, we found a significant negative association between caregiver perceptions that assisting the person with MS was burdensome and the strength of the relationship. Similarly, higher levels of education among caregivers tended to have a significantly negative impact on the caregiver/care recipient relationship. Our findings highlight the importance of addressing the needs and concerns of spousal caregivers. Health professionals who treat informal caregivers, as well as those treating people with MS, should be sensitive to the impact caregiving has on caregivers, especially spouses providing assistance. PMID:24453723
Holloman, Jameson P; Ho, Calvin C; Hukki, Arushi; Huntley, Jennifer L; Gallicano, G Ian
This article examines the current use and future implications of stem cell therapy in treating Multiple Sclerosis (MS). MS is the most common neurological disease in young adults, affecting approximately two million people worldwide. Currently there is no cure for MS. The standard treatment of MS involves disease-modifying drugs, which work to alleviate the symptoms of MS. However, these drugs carry adverse side effects and are ineffective in preventing disease progression in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first used in 1995 to treat patients with severe rapidly progressing MS. The HSCT treatment protocol has evolved into a less intense conditioning regimen that is currently demonstrating efficacy in treating patients with variable disease severity—with best results in early-stage rapidly progressing MS patients with active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental stem cell therapy currently undergoing clinical trials. Animal models and early clinical trials have shown promise that MSCT might be a low risk treatment to precipitate neuroregeneration and immunomodulation in MS patients. Specifically, neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial therapeutic approach, holds promise for a better treatment for MS. PMID:23862098
Raknes, Guttorm; Småbrekke, Lars
Low dose naltrexone (LDN) has become a popular off-label therapy for multiple sclerosis (MS). A few small, randomized studies indicate that LDN may have beneficial effects in MS and other autoimmune diseases. If proven efficacious, it would be a cheap and safe alternative to the expensive treatments currently recommended for MS. We investigated whether a sudden increase in LDN use in Norway in 2013 was followed by changes in dispensing of other medications used to treat MS. We performed a quasi-experimental before-and-after study based on population data from the Norwegian Prescription Database (NorPD). We included all patients that collected at least one LDN prescription in 2013, and had collected at least two medications with a reimbursement code for MS, or collected a medication with MS as the only indication in 2009 or 2010. Outcomes were differences in cumulative dispensed doses and incidence of users of disease modifying MS therapies, and medications used to treat MS symptoms two years before and two years after dispensing the initial LDN prescription. The eligible 341 patients collected 20 921 prescriptions in the observation period. Apart from changes in line with general trends in MS therapy in Norway, there was no difference in neither dispensed cumulative doses or number of prevalent users of MS specific medication. Initiation of LDN was not followed by reductions of other medications used to treat symptoms associated with MS.
Ntranos, Achilles; Lublin, Fred
Multiple sclerosis (MS) is one of the most diverse human diseases. Since its first description by Charcot in the nineteenth century, the diagnostic criteria, clinical course classification, and treatment goals for MS have been constantly revised and updated to improve diagnostic accuracy, physician communication, and clinical trial design. These changes have improved the clinical outcomes and quality of life for patients with the disease. Recent technological and research breakthroughs will almost certainly further change how we diagnose, classify, and treat MS in the future. In this review, we summarize the key events in the history of MS, explain the reasoning behind the current criteria for MS diagnosis, classification, and treatment, and provide suggestions for further improvements that will keep enhancing the clinical practice of MS.
Wang, Chun-Kai; Lin, Chi-Kang; Wang, Tun-Jun; Wang, Chen-Yu; Hsu, Po-Chao; Su, Her-Young
Multiple sclerosis (MS) preferentially affects females of reproductive age, making reproduction an important issue for women with MS. An increased incidence of poor labor progress often results in assisted vaginal delivery or a cesarean section. However, with good pre-pregnancy counseling and management, women with MS can conceive and give birth safely. Here, we present a case of pregnancy with MS, which was carried to term uneventfully and ended with unassisted vaginal delivery. A 36-year-old woman was treated for MS for three years before she conceived. Because of her mild clinical presentation, medication was discontinued when her pregnancy was confirmed. Counseling was completed, and she had a smooth pregnancy course and gave birth vaginally at 38 weeks and two days. Based on this case report, women with mild clinical presentation of MS before pregnancy can conceive and carry successfully to term with no or improved disease presentation. Copyright © 2018. Published by Elsevier B.V.
Zhou, Yifan; Huang, Qiao; Lu, Tingting; Sun, Xiaobo; Fang, Ling; Lu, Zhengqi; Hu, Xueqiang; Kermode, Allan; Qiu, Wei
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.
Drug adherence and multidisciplinary care in patients with multiple sclerosis: protocol of a prospective, web-based, patient-centred, nation-wide, Dutch cohort study in glatiramer acetate treated patients (CAIR study).
Jongen, Peter J; Hengstman, Gerald; Hupperts, Raymond; Schrijver, Hans; Gilhuis, Job; Vliegen, Joseph H; Hoogervorst, Erwin; van Huizen, Marc; van Munster, Eric; Samijn, Johnny; de Schryver, Els; Siepman, Theodora; Tonk, Martijn; Zandbergen, Eveline; ten Holter, Jacques; van der Kruijk, Ruud; Borm, George
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression. First line DMDs include glatiramer acetate (GA), interferon-beta (INFb)-1a and INFb-1b, which are all administered via injections. Effectiveness of DMD treatment depends on adequate adherence, meaning year-long continuation of injections with a minimum of missed doses. In real-life practice DMD-treated patients miss 30% of doses. The 6-month discontinuation rate is up to 27% and most patients who discontinue do so in the first 12 months.Treatment adherence is influenced by the socio-economic situation, health care and caregivers, disease, treatment and patient characteristics. Only a few studies have dealt with adherence-related factors in DMD-treated patients. Self-efficacy expectations were found to be related to GA adherence. Patient education and optimal support improve adherence in general. Knowledge of the aspects of care that significantly relate to adherence could lead to adherence-improving measures. Moreover, identification of patients at risk of inadequate adherence could lead to more efficient care.In the near future new drugs will become available for RRMS. Detailed knowledge on factors prognostic of adherence and on care aspects that are associated with adequate adherence will improve the chances of these drugs becoming effective treatments. We investigate in RRMS patients the relationship between drug adherence and multidisciplinary care, as well as factors associated with adherence. Given the differences in the frequency of administration and in the side effects between the DMDs we decided to study patients treated with the same DMD, GA. The Correlative analyses of Adherence In Relapsing remitting MS (CAIR) study is an investigator-initiated, prospective, web
Analysis of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its brominated analogues in chlorine-treated water by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS).
Planas, Carles; Ventura, Francesc; Caixach, Josep; Martín, Jordi; Boleda, M Rosa; Paraira, Miquel
A simple, selective and sensitive method for the analysis of the strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its brominated analogues (BMXs) in chlorine-treated water has been developed. The method is based on gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS), previous liquid-liquid extraction (LLE) of a smaller sample volume compared to other methods and on-line derivatization with a silylation reactive. GC-QqQ-MS/MS has been raised as an alternative easier to perform than gas chromatography coupled to high resolution mass spectrometry (GC-HRMS) for the analysis of MX and BMXs, and it allows to achieve low LODs (0.3 ng/L for MX and 0.4-0.9 ng/L for BMXs). This technique had not been previously described for the analysis of MX and BMXs. Quality parameters were calculated and real samples related to 3 drinking water treatment plants (DWTPs), tap water and both untreated and chlorinated groundwater were analyzed. Concentrations of 0.3-6.6 ng/L for MX and 1.0-7.3 ng/L for BMXs were detected. Results were discussed according to five of the main factors affecting MX and BMXs formation in chlorine-treated water (organic precursors, influence of bromide ions, evolution of MX and BMXs in the drinking water distribution system, groundwater chlorination and infiltration of water coming from chlorination processes in groundwater). Copyright © 2015 Elsevier B.V. All rights reserved.
Fernández, O; Delvecchio, M; Edan, G; Fredrikson, S; Gionvannoni, G; Hartung, H-P; Havrdova, E; Kappos, L; Pozzilli, C; Soerensen, P S; Tackenberg, B; Vermersch, P; Comi, G
Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe. © 2017 EAN.
Amato, Laura; Minozzi, Silvia; Mitrova, Zuzana; Parmelli, Elena; Saulle, Rosella; Cruciani, Fabio; Vecchi, Simona; Davoli, Marina
medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington DC (May 2015) have introduced laws to permit the medical use of cannabis. Within the European Union, medicinal cannabis laws and praxis vary wildly between Countries. to provide evidence for benefits and harms of cannabis (including extracts and tinctures) treatment for adults in the following indications: control of spasticity and pain in patients with multiple sclerosis; control of pain in patients with chronic neuropathic pain; control of nausea and vomiting in adults with cancer receiving chemotherapy. we searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE from inception to September 2016. We also searched for on-going studies via ClinicalTrials.gov and the World Health Organization and International Clinical Trials Registry Platform (ICTRP) search portal. All searches included also non-English language literature. All relevant randomized controlled trials (RCTs) evaluating the safety and efficacy of cannabis (including extracts and tinctures) compared with placebo or other pharmacological agents were included. Three authors independently evaluated the titles and abstracts of studies identified in the literature searches for their eligibility. For studies considered eligible, we retrieved full texts. Three investigators independently extracted data. For the assessment of the quality of evidence, we used the standard methodological procedures recommended by Cochrane and GRADE working Group. 41 trials (4,550 participants) were included; 15 studies considered efficacy and safety of cannabis for patients with multiple sclerosis, 12 for patients with chronic pain, and 14 for patients with cancer receiving chemotherapy. The included studies were published between 1975 and 2015, and the majority of them were conducted in Europe. We judged almost 50% of these studies to be at
Davis, Scott L; Wilson, Thad E; White, Andrea T; Frohman, Elliot M
Multiple sclerosis (MS) is a progressive neurological disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60-80% of MS patients experience temporary worsening of clinical signs and neurological symptoms with heat exposure. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. This review focuses on five main themes regarding the current understanding of thermoregulatory dysfunction in MS: 1) heat sensitivity; 2) central regulation of body temperature; 3) thermoregulatory effector responses; 4) heat-induced fatigue; and 5) countermeasures to improve or maintain function during thermal stress. Heat sensitivity in MS is related to the detrimental effects of increased temperature on action potential propagation in demyelinated axons, resulting in conduction slowing and/or block, which can be quantitatively characterized using precise measurements of ocular movements. MS lesions can also occur in areas of the brain responsible for the control and regulation of body temperature and thermoregulatory effector responses, resulting in impaired neural control of sudomotor pathways or neural-induced changes in eccrine sweat glands, as evidenced by observations of reduced sweating responses in MS patients. Fatigue during thermal stress is common in MS and results in decreased motor function and increased symptomatology likely due to impairments in central conduction. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacological) for the MS patient to preserve function and decrease symptom worsening during heat stress.
Diotti, Roberta Antonia; Capra, Ruggero; Moiola, Lucia; Caputo, Valeria; De Rossi, Nicola; Sangalli, Francesca; Martinelli, Vittorio; Burioni, Roberto; Clementi, Massimo; Mancini, Nicasio
The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment.
Namey, Marie; Halper, June
Optimal health of people with multiple sclerosis (MS) can be promoted by patients' sharing of health information gained through periodic self-monitoring with their health-care providers. The purpose of this study was to develop a valid and reliable self-administered scale to obtain information about MS patients' health status and the impact of the disease on their daily lives. We named this scale “Monitoring My Multiple Sclerosis” (MMMS). A cross-sectional survey was conducted of 171 MS patients who completed the MMMS and Patient-Determined Disease Steps (PDDS) scales and provided information on their MS disease classification and demographic characteristics. Data analysis included several parametric procedures. Factor analysis of the 26-item MMMS resulted in four factors with satisfactory α reliability coefficients for the total scale (0.90) and factored subscales: Physical (0.85), Relationships (0.80), Energy (0.70), and Cognitive/Mental (0.67). Analysis of variance demonstrated that the total scale and the Physical subscale, but not the Relationships subscale, showed significantly worse functioning for patients with either moderate or severe disability as measured by the PDDS than for patients with mild disability (P < .001). The Cognitive/Mental subscale showed significantly worse functioning for patients with moderate disability than for patients with mild disability (P < .05). However, the Energy subscale showed significantly worse functioning among moderately disabled patients than among severely disabled patients (P < .01). Independent t tests demonstrated that patients classified as having secondary progressive multiple sclerosis had significantly worse scores on the total MMMS (P < .05) and the Physical subscale (P < .001) than those classified as having relapsing-remitting multiple sclerosis. The MMMS demonstrated satisfactory reliability and validity and is recommended for use by MS patients and their health-care providers as a mechanism to promote
Egger, Alexander E; Theiner, Sarah; Kornauth, Christoph; Heffeter, Petra; Berger, Walter; Keppler, Bernhard K; Hartinger, Christian G
Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to study the spatially-resolved distribution of ruthenium and platinum in viscera (liver, kidney, spleen, and muscle) originating from mice treated with the investigational ruthenium-based antitumor compound KP1339 or cisplatin, a potent, but nephrotoxic clinically-approved platinum-based anticancer drug. Method development was based on homogenized Ru- and Pt-containing samples (22.0 and 0.257 μg g(-1), respectively). Averaging yielded satisfactory precision and accuracy for both concentrations (3-15% and 93-120%, respectively), however when considering only single data points, the highly concentrated Ru sample maintained satisfactory precision and accuracy, while the low concentrated Pt sample yielded low recoveries and precision, which could not be improved by use of internal standards ((115)In, (185)Re or (13)C). Matrix-matched standards were used for quantification in LA-ICP-MS which yielded comparable metal distributions, i.e., enrichment in the cortex of the kidney in comparison with the medulla, a homogenous distribution in the liver and the muscle and areas of enrichment in the spleen. Elemental distributions were assigned to histological structures exceeding 100 μm in size. The accuracy of a quantitative LA-ICP-MS imaging experiment was validated by an independent method using microwave-assisted digestion (MW) followed by direct infusion ICP-MS analysis.
Devereux, C.K.; Vidaver, R.; Hafstein, M.P.
Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferiormore » margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.« less
Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (21 May 2009), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2009, issue 2, MEDLINE (PubMed) (1966-21 May 2009), EMBASE (1974-21 May 2009). Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer however this was not necessary. The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one randomized cross-over trial. In this study patients were exposed to both acetyl L-carnitine (ALCAR(tm)) 2 grams daily and amantadine 200 mg daily in adult patients with relapsing-remitting and secondary progressive MS. The effects of
Pato Pato, A; Costa Arpín, E; Rodríguez Regal, A; Rodríguez Constenla, I; Cimas Hernando, I; Muñoz Pousa, I; Naya Ríos, L; Lorenzo González, J R; Amigo Jorrín, M C; Prieto González, J M
The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters. We performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions. The study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti-JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy. Natalizumab is highly effective as measured by the NEDA long-term remission parameter. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Dixit, Aakanksha; Tanaka, Akane; Greer, Judith M.
The evolutionary response to endemic infections with parasitic worms (helminth) was the development of a distinct regulatory immune profile arising from the need to encapsulate the helminths while simultaneously repairing tissue damage. According to the old friend’s hypothesis, the diminished exposure to these parasites in the developed world has resulted in a dysregulated immune response that contributes to the increased incidence of immune mediated diseases such as Multiple Sclerosis (MS). Indeed, the global distribution of MS shows an inverse correlation to the prevalence of helminth infection. On this basis, the possibility of treating MS with helminth infection has been explored in animal models and phase 1 and 2 human clinical trials. However, the possibility also exists that the individual immune modulatory molecules secreted by helminth parasites may offer a more defined therapeutic strategy. PMID:29027962
Dixit, Aakanksha; Tanaka, Akane; Greer, Judith M; Donnelly, Sheila
The evolutionary response to endemic infections with parasitic worms (helminth) was the development of a distinct regulatory immune profile arising from the need to encapsulate the helminths while simultaneously repairing tissue damage. According to the old friend's hypothesis, the diminished exposure to these parasites in the developed world has resulted in a dysregulated immune response that contributes to the increased incidence of immune mediated diseases such as Multiple Sclerosis (MS). Indeed, the global distribution of MS shows an inverse correlation to the prevalence of helminth infection. On this basis, the possibility of treating MS with helminth infection has been explored in animal models and phase 1 and 2 human clinical trials. However, the possibility also exists that the individual immune modulatory molecules secreted by helminth parasites may offer a more defined therapeutic strategy.
No evidence of disease activity in patients receiving fingolimod at private or academic centers in clinical practice: a retrospective analysis of the multiple sclerosis, clinical, and magnetic resonance imaging outcomes in the USA (MS-MRIUS) study.
Zivadinov, Robert; Khan, Nasreen; Korn, Jonathan R; Lathi, Ellen; Silversteen, Jason; Calkwood, Jonathan; Kolodny, Scott; Silva, Diego; Medin, Jennie; Weinstock-Guttman, Bianca
The impact of multiple sclerosis (MS) center type on outcomes has not been investigated. This study aimed to evaluate baseline characteristics and clinical and magnetic resonance imaging (MRI) outcomes in patients with MS receiving fingolimod over 16 months' follow-up at private or academic centers in the USA. Clinical and MRI data collected in clinical practice from patients initiating fingolimod were stratified by center type and retrospectively analyzed. No evidence of disease activity (NEDA-3) was defined as patients with no new/enlarged T2/gadolinium-enhancing lesions, no relapses, and no disability progression (Expanded Disability Status Scale scores). Data were collected for 398 patients from 25 private centers and 192 patients from eight academic centers. Patients were older (median age = 43 vs 41 years; p = .0047) and had a numerically shorter median disease duration (7.0 vs 8.5 years; p = .0985) at private vs academic centers. Annualized relapse rate (ARR) was higher in patients at private than academic centers in the pre-index (0.40 vs 0.29; p = .0127) and post-index (0.16 vs 0.08; p = .0334) periods. The opposite was true for T2 lesion volume in the pre-index (2.86 vs 5.23 mL; p = .0002) and post-index (2.86 vs 5.11 mL; p = .0016) periods; other MRI outcomes were similar between center types. After initiating fingolimod, ARRs were reduced, disability and most MRI outcomes remained stable, and a similar proportion of patients achieved NEDA-3 at private and academic centers (64.1% vs 56.1%; p = .0659). Patient characteristics differ between private and academic centers. Over 55% of patients achieved NEDA-3 during fingolimod treatment at both center types.
Schwartz, C E; Vollmer, T; Lee, H
To describe the results of a multicenter study that validated two new patient-reported measures of neurologic impairment and disability for use in MS clinical research. Self-reported data can provide a cost-effective means to assess patient functioning, and can be useful for screening patients who require additional evaluation. Thirteen MS centers from the United States and Canada implemented a cross-sectional validation study of two new measures of neurologic function. The Symptom Inventory is a measure of neurologic impairment with six subscales designed to correlate with localization of brain lesion. The Performance Scales measure disability in eight domains of function: mobility, hand function, vision, fatigue, cognition, bladder/bowel, sensory, and spasticity. Measures given for comparison included a neurologic examination (Expanded Disability Status Scale, Ambulation Index, Disease Steps) as well as the patient-reported Health Status Questionnaire and the Quality of Well-being Index. Participants included 274 MS patients and 296 healthy control subjects who were matched to patients on age, gender, and education. Both the Symptom Inventory and the Performance Scales showed high test-retest and internal consistency reliability. Correlational analyses supported the construct validity of both measures. Discriminant function analysis reduced the Symptom Inventory to 29 items without sacrificing reliability and increased its discriminant validity. The Performance Scales explained more variance in clinical outcomes and global quality of life than the Symptom Inventory, and there was some evidence that the two measures complemented each other in predicting Quality of Well-being Index scores. The Symptom Inventory and the Performance Scales are reliable and valid measures.
Traboulsee, A.; Simon, J.H.; Stone, L.; Fisher, E.; Jones, D.E.; Malhotra, A.; Newsome, S.D.; Oh, J.; Reich, D.S.; Richert, N.; Rammohan, K.; Khan, O.; Radue, E.-W.; Ford, C.; Halper, J.; Li, D.
SUMMARY An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available. PMID:26564433
Laplaud, D-A; Lefrère, F; Leray, E; Barrière, P; Wiertlewski, S
In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.
Fragoso, Yara Dadalti; Adoni, Tarso; Alves-Leon, Soniza Vieira; Apostolos-Pereira, Samira Luisa; Araujo, Yuna Ribeiro de; Becker, Jefferson; Brooks, Joseph Bruno Bidin; Correa, Eber Castro; Damasceno, Alfredo; Damasceno, Carlos Augusto de Albuquerque; Ferreira, Maria Lucia B; Gama, Paulo Diniz da; Gama, Rodrigo Assad Diniz da; Gomes, Sidney; Goncalves, Marcus Vinicius Magno; Grzesiuk, Anderson Kuntz; Machado, Suzana Costa Nunes; Matta, Andre Palma da Cunha; Mendes, Maria Fernanda; Ribeiro, Taysa Alexandrino Goncalves Jube; Rocha, Cristiane Franklin da; Ruocco, Heloisa Helena; Sato, Henry; Simm, Renata Faria; Tauil, Carlos Bernardo; Vasconcelos, Claudia Cristina Ferreira; Vieira, Vera Lucia Ferreira
Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.
Huang, Chunfeng; Zheng, Zhida
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
Algahtani, Hussein; Shirah, Bader; Algahtani, Raghad; Alkahtani, Abdulah; Alwadie, Saeed
Vogt Koyanagi Harada (VKH) Syndrome, also called uveomeningioencephalitis, is a chronic disorder characterized by inflammation of the uvea, meninges, auditory system, and integumentary system. The association between VKH syndrome and multiple sclerosis (MS) has been reported only once in the literature in a patient who developed VKH syndrome after two years of the diagnosis of MS. In this article, we report a case who was misdiagnosed and treated as MS until she was proven to have VKH syndrome, and a diagnosis of MS was excluded. VKH syndrome is a systemic disorder that may present with clinical and/or radiological features mimicking MS. Applying diagnostic criteria is extremely important for confirming or excluding the diagnosis. Detailed history and physical examination are of paramount importance to score the final diagnosis. Rigorous search for red flags for both conditions is very helpful. Copyright © 2017 Elsevier B.V. All rights reserved.
de Sa, João Carlos Correia; Airas, Laura; Bartholome, Emmanuel; Grigoriadis, Nikolaos; Mattle, Heinrich; Oreja-Guevara, Celia; O’Riordan, Jonathan; Sellebjerg, Finn; Stankoff, Bruno; Vass, Karl; Walczak, Agata; Wiendl, Heinz; Kieseier, Bernd C.
As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Research into how such comorbidities and symptoms can be diagnosed and treated within the MS population is lacking. This information gap adds further complexity to disease management and represents an unmet need in MS, particularly as early recognition and treatment of these conditions can improve patient outcomes. In this manuscript, we sought to review the literature on the comorbidities and symptoms of MS and to summarize the evidence for treatments that have been or may be used to alleviate them. PMID:21694816
Chalk, Holly McCartney
Given the high incidence and unique symptomatology of depression in multiple sclerosis (MS) patients, the current study examined the role of cognitive and behavioral variables in predicting psychosocial adjustment in this population, in order to suggest psychotherapeutic interventions tailored specifically to MS patients. Data from 329 MS patients indicated that problem solving coping, acceptance coping, and challenge appraisals were associated with positive psychological adjustment (i.e., high life satisfaction, low depression and anxiety), whereas variables measuring disease severity (i.e., illness duration, subjective health status, and self-reported disability) were not associated with adjustment. These findings suggest that MS patients' psychological outcomes are more related to controllable cognitive and behavioral factors than to the physical effects of the disease. Consequently, it is expected that interventions that target these specific coping strategies and cognitive appraisals will be effective in treating the emotional effects of MS.
Kaufmann, Timothy J.; Weinshenker, Brian G.; Kantarci, Orhun H.; Schmalstieg, William F.; Paz Soldan, M. Mateo; Flanagan, Eoin P.
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
Karamyan, A; Brandtner, H; Grinzinger, S; Chroust, V; Bacher, C; Otto, F; Reisp, M; Hauer, L; Sellner, J
Patients with multiple sclerosis (MS) experience higher mortality rates as compared to the general population. While the risk of intensive care unit (ICU) admission is also reported to be higher, little is known about causes of death CoD in critically ill MS patients. To study the causes of death (CoD) in the series of critically ill patients with MS verified by autopsy. We reviewed hospital electronic charts of MS patients treated at the neurological ICU of a tertiary care hospital between 2000 and 2015. We compared clinical and pathological CoD for those who were autopsied. Overall, 10 patients were identified (seven female; median age at death 65 years, range 27-80), and six of them were autopsied. The median MS duration prior to ICU admission was 27.5 years (range 1-50), and the median EDSS score at the time of ICU admission was 9 (range 5-9.5). The median length of ICU stay was 3 days (range 2-213). All the individuals in our series had experienced respiratory insufficiency during their ICU stay. The autopsy examination of brain tissue did not reveal evidences of MS lesions in one patient. In another patient, Lewy bodies were found on brain immunohistochemistry. Mortality in critically ill MS patients is largely driven by respiratory complications. Sporadic disparities between clinical and pathological findings can be expected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Rønning, O M; Tornes, K D
A majority of patients with advanced multiple sclerosis (MS) need symptomatic treatment. Many MS-related symptoms may not be recognized and thus are not treated. We conducted a study to estimate the prevalence of inadequate symptomatic treatment of patients with advanced MS. Patients with advanced MS admitted to a specialist MS rehabilitation clinic were included in this study. Severity was assessed using the Expanded Disability Status Scale (EDSS). The information we collected included age of onset, initial course, time to sustained disability, pharmacological treatment, degree of spasticity, pain and bladder dysfunction, and unmet needs of symptomatic treatment. In total, we assessed demographic and clinical characteristics in 129 patients with a mean age of 56 years and a median EDSS of 7.5. The proportion with inadequate symptom treatment was regarding spasticity 46%, pain 28%, and bladder dysfunction 23%. This study showed that a large proportion of patients with advanced MS had lack of symptomatic treatment. These patients probably underuse neurological specialist services. Better symptomatic treatment could contribute to improving quality of life of people with MS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Río, Jordi; Auger, Cristina; Rovira, Àlex
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.
Broza, Yoav Y; Har-Shai, Lior; Jeries, Raneen; Cancilla, John C; Glass-Marmor, Lea; Lejbkowicz, Izabella; Torrecilla, José S; Yao, Xuelin; Feng, Xinliang; Narita, Akimitsu; Müllen, Klaus; Miller, Ariel; Haick, Hossam
Multiple sclerosis (MS) is the most common chronic neurological disease affecting young adults. MS diagnosis is based on clinical characteristics and confirmed by examination of the cerebrospinal fluids (CSF) or by magnetic resonance imaging (MRI) of the brain or spinal cord or both. However, neither of the current diagnostic procedures are adequate as a routine tool to determine disease state. Thus, diagnostic biomarkers are needed. In the current study, a novel approach that could meet these expectations is presented. The approach is based on noninvasive analysis of volatile organic compounds (VOCs) in breath. Exhaled breath was collected from 204 participants, 146 MS and 58 healthy control individuals. Analysis was performed by gas-chromatography mass-spectrometry (GC-MS) and nanomaterial-based sensor array. Predictive models were derived from the sensors, using artificial neural networks (ANNs). GC-MS analysis revealed significant differences in VOC abundance between MS patients and controls. Sensor data analysis on training sets was able to discriminate in binary comparisons between MS patients and controls with accuracies up to 90%. Blinded sets showed 95% positive predictive value (PPV) between MS-remission and control, 100% sensitivity with 100% negative predictive value (NPV) between MS not-treated (NT) and control, and 86% NPV between relapse and control. Possible links between VOC biomarkers and the MS pathogenesis were established. Preliminary results suggest the applicability of a new nanotechnology-based method for MS diagnostics.
... around the nails Coughing or shortness of breath Mental disabilities or developmental problems Causes & Risk Factors How did my child get this disorder? About half of the time, tuberous sclerosis is passed from a parent to ...
White, Lesley J; Dressendorfer, Rudolph H
The pathophysiology of multiple sclerosis (MS) is characterised by fatigue, motor weakness, spasticity, poor balance, heat sensitivity and mental depression. Also, MS symptoms may lead to physical inactivity associated with the development of secondary diseases. Persons with MS are thus challenged by their disability when attempting to pursue an active lifestyle compatible with health-related fitness. Although exercise prescription is gaining favour as a therapeutic strategy to minimise the loss of functional capacity in chronic diseases, it remains under-utilised as an intervention strategy in the MS population. However, a growing number of studies indicate that exercise in patients with mild-to-moderate MS provides similar fitness and psychological benefits as it does in healthy controls. We reviewed numerous studies describing the responses of selected MS patients to acute and chronic exercise compared with healthy controls. All training studies reported positive outcomes that outweighed potential adverse effects of the exercise intervention. Based on our review, this article highlights the role of exercise prescription in the multidisciplinary approach to MS disease management for improving and maintaining functional capacity. Despite the often unpredictable clinical course of MS, exercise programmes designed to increase cardiorespiratory fitness, muscle strength and mobility provide benefits that enhance lifestyle activity and quality of life while reducing risk of secondary disorders. Recommendations for the evaluation of cardiorespiratory fitness, muscle performance and flexibility are presented as well as basic guidelines for individualised exercise testing and training in MS. Special considerations for exercise, including medical management concerns, programme modifications and supervision, in the MS population are discussed.
Henze, Thomas; von Mackensen, Sylvia; Lehrieder, Gerald; Zettl, Uwe K; Pfiffner, Carmen; Flachenecker, Peter
Multiple sclerosis (MS) is an inflammatory disease where many of the patients suffer from spasticity impacting their quality-of-life. The purpose of this paper was to linguistically validate and psychometrically test the Multiple Sclerosis Spasticity Scale (MSSS-88) in German speaking MS patients. The study had two stages: 1) forward/backward translations of the original MSSS-88 scale into German, discussions with MS-experts and cognitive debriefings with MS patients; 2) psychometric evaluation of the German version. Data collection took part in an observational multi-centre study in Germany (MOVE2). The German translation of the MSSS-88 scale was discussed with three MS-experts; followed by two cognitive debriefing sessions with 12 MS patients. For psychometric evaluation the MSSS-88 was filled in by 87 MS patients with a mean age of 50.2 ± 10.4 years; 26.4% of them had severe spasticity. Data quality was acceptable. Missing data for items of the MSSS-88 were low (range 0-5.75%). Psychometric testing of the MSSS-88 revealed excellent values for reliability and validity. Significant differences between groups regarding severity, grading, type and self-ratings of MS-spasticity and sleep disturbances were found. Sensitivity to change could be demonstrated for the MSSS-88 in the group of MS patients treated with cannabinoid oromucosal spray vs. non-treated patients. In the treated group significant changes with a moderate effect size were found for 'muscle spasms', 'emotional health' and 'pain/discomfort'. No significant changes could be detected in the non-treated group. Preliminary evidence from this small study supports reliability, validity, and responsiveness of the German version of the MSSS-88 for measuring the impact of spasticity in MS.
Lucas, Matthew D.; Brentlinger, Jamie
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…
Wijburg, Martijn T; Kleerekooper, Iris; Lissenberg-Witte, Birgit I; de Vos, Marlieke; Warnke, Clemens; Uitdehaag, Bernard M J; Barkhof, Frederik; Killestein, Joep; Wattjes, Mike P
The JC virus (JCV) was named after the first patient to be described with progressive multifocal leukoencephalopathy (PML), John Cunningham. Detection of JC virus DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and of specific lesions by brain magnetic resonance imaging (MRI), are both considered essential for the diagnosis of natalizumab-associated PML (NTZ-PML) in patients with multiple sclerosis. However, strict pharmacovigilance by MRI can result in detection of patients with small lesions and undetectable JCV DNA in CSF. To investigate the association of PML lesion characteristics on MRI with both qualitative and quantitative JCV PCR results in CSF of patients with NTZ-PML. This was a retrospective, cross-sectional study conducted from January 2007 to December 2014 in patients considered to have NTZ-PML based on a set of predefined criteria. Follow-up was at least 6 months. Data of patients from the Dutch-Belgian NTZ-PML cohort and patients treated at multiple medical centers in Belgium and the Netherlands and selected for research purposes were included as a convenience sample. Brain MRI scans were analyzed for PML lesion volume, location, dissemination, and signs of inflammation. Associations of the qualitative and quantitative CSF JCV PCR results with PML MRI characteristics were calculated. Of the 73 patients screened, 56 were included (37 were women). At inclusion, 9 patients (16.1%) had undetectable JCV DNA in CSF. Patients with a positive PCR had larger total PML lesion volumes than those with undetectable JCV DNA (median volume, 22.9 mL; interquartile range, 9.2-60.4 mL vs median volume, 6.7 mL; interquartile range, 4.9-14.7 mL; P = .008), and logistic regression showed that a lower PML lesion volume significantly increased the probability for undetectable JCV DNA. There was a positive correlation between PML lesion volume and JCV copy numbers (Spearman ρ, 0.32; P = .03). Progressive multifocal leukoencephalopathy lesion
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
Johnson, Bridgette; Nichols, Scott
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.
Benedict, Ralph H.B.; Gromisch, Elizabeth S.; DeLuca, John
Cognitive dysfunction is observed in about half of people with multiple sclerosis (MS), and MS health-care professionals face the challenge of screening, assessing, and treating patients for cognitive problems. Considering the inconsistent or limited empirical evidence to assist in this task, a multidisciplinary consensus conference of MS experts, sponsored by the Consortium of Multiple Sclerosis Centers (CMSC), was held on September 24, 2010, to address these issues. Key articles from the literature on these topics were distributed prior to the meeting, and CMSC member professionals were surveyed on clinical practices related to screening, assessment, and treatment for cognitive problems. The purpose of the meeting was threefold: 1) to achieve a multidisciplinary perspective on practices for screening, monitoring, evaluating, and treating MS patients for cognitive problems; 2) to propose consensus candidate measures for screening and/or monitoring for cognitive problems in MS that neurologists or nurses might administer on a regular basis; and 3) to propose consensus treatment approaches from a multidisciplinary perspective. This article summarizes the conclusions of the conference participants and provides preliminary suggestions for screening and brief assessment. PMID:24453735
Karam, Rehab A; Rezk, Noha A; Amer, Mona M; Fathy, Hala A
Interferon (IFN)-β is one of the disease modifying drugs used in the treatment of multiple sclerosis. A predictive marker that indicates good or poor response to the treatment is highly desirable. We aimed to investigate the relation between the immune response genes receptors (IFNAR1, IFNAR2, and CCR5) expression and their polymorhic variants and multiple sclerosis (MS) susceptibility as well as the response to IFN-β therapy. The immune response genes receptors expression and genotyping were analyzed in 80 patients with MS, treated with IFN-β and in 110 healthy controls. There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group. Also, the level of IFNAR1, IFNAR2, and CCR5 mRNA expression was found to be significantly lower in the responders than nonresponders. Carriers of IFNAR1 18417 C/C genotype and C allele had an increased risk of developing MS. There was a significant relation between CCR5 Δ32 allele and IFN-β treatment response in MS patients. Our results highlighted the significance of IFNAR and CCR5 genes in multiple sclerosis risk and the response to IFN-β therapy. © 2016 IUBMB Life, 68(9):727-734, 2016. © 2016 International Union of Biochemistry and Molecular Biology.
Lin, Pei-Jung; Saret, Cayla J; Neumann, Peter J; Sandberg, Eileen A; Cohen, Joshua T
Although it is well recognized that people with multiple sclerosis (MS) may experience impairments in addition to limited mobility, there has been little effort to study their relative importance to patients with the condition. The objective of this study was to assess patient preferences for addressing various MS symptoms. This study was conducted at Tufts Medical Center, Boston, Massachusetts. We developed a national online survey of MS patients and neurologists to estimate the value each group places on treating specific MS symptoms. Each respondent was presented with two randomly selected scenarios with different symptoms and treatments. MS patients were asked about their own preferences, whereas neurologists were asked to consider what a patient of theirs would do or think in each scenario. We used a bidding game approach to elicit respondents' willingness to pay (WTP) for the treatments. To treat mobility alone, WTP for MS patients averaged US$410-US$520 per month, depending on the scenario. For paired symptoms, MS patients would pay most to treat mobility and upper limb function (US$525/month) or mobility and cognition (US$514/month), somewhat less to treat mobility and eyesight (US$445/month), and least to treat mobility and fatigue (US$371/month). Patient WTP values increased with income and education. Neurologists believed their patients would be willing to pay US$216-US$249 per month to treat mobility alone, depending on the scenario. For paired symptoms, neurologists believed patients would pay most to treat mobility and fatigue (US$263/month) and least to treat mobility and upper limb function (US$177/month). Our findings suggest MS patients may value one outcome (e.g., improved arm and hand coordination) over another (e.g., less fatigue). Further, MS patients and neurologists may rank the importance of treating various symptoms differently. Given this potential mismatch, it is crucial for MS patients and their clinicians to discuss treatment
Owens, Gary M
Multiple sclerosis (MS) is disease that has an early age of onset and may intensify and subside with disease relapses or exacerbations interrupted by periods of stability. Because of this, patients, their families and caregivers, employers, and the entire healthcare system carry substantial clinical and economic burdens associated with the disease over of a period of many years. Although most patients with MS are covered by health insurance, the management landscape has become increasingly complex over the past decade with the introduction and approval of several new disease-modifying therapies that, while remarkably effective and well tolerated, usually come with a very high cost. Whereas the main goal of treating patients with MS is to prevent disease progression and disability, healthcare and benefit providers are faced with an ever-tipping balance point between effectively managing the disease and maximizing the value of high-cost disease-modifying therapies in an already overburdened healthcare system. Treatment of MS should be individualized, and shared decision making between patients and healthcare providers must be preserved. Healthcare providers and payers need to collaborate to ensure that resources are used optimally and not wasted, reducing both the clinical and economic burdens related to this complex chronic disorder.
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
Courtheyn, D; Vercammen, J; Logghe, M; Seghers, H; De Wasch, K; De Brabander, H
The use of corticosteroids in combination with other hormonal substances has long been known to result in increased mass gain with bovines. Practice has demonstrated, however, that even the single use of a glucocorticoid may result in growth promoting effects. In addition to the popular dexamethasone, more recently other corticosteroids have also been misused for fattening purposes. The first part of this study deals with the detection of two of them, namely betamethasone and triamcinolone acetonide. Betamethasone was administered orally to a cow at a dose of 50 mg d-1 for 5 d, then later the same cow was injected intramuscularly with a dose of 50 mg of betamethasone dipropionate. Excretion in urine and faeces was followed with both HPLC-enzyme immunoassay and a previously described method based on negative chemical ionization mass spectrometry (NCI-MS) after oxidation. For the triamcinolone acetonide study a cow was treated with 50 mg d-1 of the drug during a 7 d period. Excretion in faeces was followed with GC-NCI-MS. As triamcinolone acetonide is resistant to the previously described oxidation procedure, however, a hydrolysis step had to be introduced prior to oxidation. In addition to this specific modification necessary for triamcinolone acetonide, in a subsequent part of this study the original oxidation procedure with pyridinium chlorochromate was re-investigated especially to shorten the procedure. With the introduction of potassium dichromate the reaction time could be decreased from 3 h to 10 min.
Calvano, Cosima D; De Ceglie, Cristina; Zambonin, Carlo G
In foodstuffs, one of the main factors inducing modifications in phospholipids (PLs) structure is the heat treatment. Among PLs, only phosphatidylethanolamines and phosphatidylserines, due to their free amino group, can be involved in Maillard reaction and can form adducts with reducing sugars, besides other by-products called advanced glycation end-products. To date, glycated lipid products are less characterized in comparison to proteins. The aim of this work was to develop a novel, rapid and sensitive extraction protocol for the detection and characterization of modified PLs (glycated and oxidized) by means of matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). At first, to investigate the formation of glycated and/or short chain by-products in different classes of PLs, representative standards were heated with or without sugar (lactose or glucose) and subjected to traditional lipid extraction methods as Bligh and Dyer and to the novel direct in matrix extraction (DIME) using 1,8-bis(dimethylamino)naphthalene as preconcentrating matrix. MALDI-MS analysis in negative ion mode allowed detecting glycation and oxidation products both on fatty acid and glucose moieties. Then, the procedure was successfully applied to different heat-treated and powdered samples (milk powders, pasteurized milk, ultra-high-temperature milk and soy flour) for the detection of modified PLs in complex foods. The currently developed DIME protocol could be a powerful tool for understanding lipid glycation also in biological samples. Copyright © 2014 John Wiley & Sons, Ltd.
Rybakowska, I M; Slominska, E M; Romaszko, P; Olkowicz, M; Kaletha, K; Smolenski, R T
AMP-regulated protein kinase (AMPK) is involved in regulation of energy-generating pathways in response to the metabolic needs in different organs including the heart. The activity of AMPK is mainly controlled by AMP concentration that in turn could be affected by nucleotide metabolic pathways. This study aimed to develop a procedure for measurement of AMPK activity together with nucleotide metabolic enzymes and its application for studies of mice treated with high-fat diet. The method developed was based on analysis of conversion of AMARA peptide to pAMARA by partially purified heart homogenate by liquid chromatography/mass spectrometry (LC/MS). Activities of the enzymes of nucleotide metabolism were evaluated by analysis of conversion of substrates into products by HPLC. The method was applied for analysis of hearts of mice fed 12 weeks with low- (LFD) or high-fat diet (HFD). The optimized method for AMPK activity analysis (measured in presence of AMP) revealed change of activity from 0.089 ± 0.035 pmol/min/mg protein in LFD to 0.024 ± 0.002 in HFD. This coincided with increase of adenosine deaminase (ADA) activity from 0.11 ± 0.02 to 0.19 ± 0.06 nmol/mg tissue/min and decrease of AMP-deaminase (AMPD) activity from 1.26 ± 0.35 to 0.56 ± 0.15 nmol/mg tissue/min for LFD and HFD, respectively. We have proven quality of our LC/MS method for analysis of AMPK activity. We observed decrease in AMPK activity in the heart of mice treated with high-fat diet. However, physiological consequences of this change could be modulated by decrease in AMPD activity.
Owens, Gregory P.; Gilden, Don; Burgoon, Mark P.; Yu, Xiaoli; Bennett, Jeffrey L.
Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler’s murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel. PMID:22130640
Feinstein, Anthony; Pavisian, Bennis
Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known. Depression, severity of depression, social isolation, and alcohol abuse are associated with thoughts of suicide. The variables linked with suicide and suicidal intent are therefore well defined and should be readily available from routine clinical inquiry. While vigilance on the part of clinicians is required, particularly in the context of high-risk patients, it is also recognized that prevention is dependent on full disclosure of intent.
The therapeutic approach in multiple sclerosis (MS) requires a personalized medicine frame beyond the precision medicine concept, which is not currently implementable due to the lack of robust biomarkers and detailed understanding of MS pathogenesis. Personalized medicine demands a patient-focused approach, with disease taxonomy informed by characterization of pathophysiological processes. Important questions concerning MS taxonomy are: when does MS begin? When does the progressive phase begin? Is MS really two or three diseases? Does a therapeutic window truly exist? Newer evidence points to a disease spectrum and a therapeutic lag of several years for benefits to be observed from disease-modifying therapy. For personalized treatment, it is important to ascertain disease stage and any worsening of focal inflammatory lesions over time.
Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.
Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter
Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise
Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554
Li, Jing; Lin, Wensi; Lin, Weiwei; Xu, Peng; Zhang, Jianmei; Yang, Haisong; Ling, Xiaomei
Despite the recent advances in understanding toxicity mechanism of cyclophosphamide (CTX), the development of biomarkers is still essential. CTX-induced immunotoxicity in rats by a metabonomics approach was investigated using high-performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry (HPLC-ESI-IT-TOF-MS). The rats were orally administered CTX (30 mg/kg/day) for five consecutive days, and on the fifth day samples of urine, thymus and spleen were collected and analyzed. A significant difference in metabolic profiling was observed between the CTX-treated group and the control group by partial least squares-discriminant analysis (PLS-DA), which indicated that metabolic disturbances of immunotoxicity in CTX-treated rats had occurred. One potential biomarker in spleen, three in urine and three in thymus were identified. It is suggested that the CTX-toxicity mechanism may involve the modulation of tryptophan metabolism, phospholipid metabolism and energy metabolism. This research can help to elucidate the CTX-influenced pathways at a low dose and can further help to indicate the patients' pathological status at earlier stages of toxicological progression after drug administration. Copyright © 2014 John Wiley & Sons, Ltd.
Lidster, Katie; Jackson, Samuel J.; Ahmed, Zubair; Munro, Peter; Coffey, Pete; Giovannoni, Gavin; Baker, Mark D.; Baker, David
Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine) or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment. PMID:24223903
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…
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
Rosenblum, Sara; Weiss, Patrice L.
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…
... months or even years. Small increases in body temperature can temporarily worsen signs and symptoms of MS, ... or Native American descent have the lowest risk. Climate. MS is far more common in countries with ...
Dehghani, Leila; Meamar, Rokhsareh; Etemadifar, Masoud; Sheshde, Zahra Dehghani; Shaygannejad, Vahid; Sharifkhah, Mostafa; Tahani, Soheil
Multiple sclerosis (MS) is an autoimmune disease of central nerves system, in which neurological disabilities occur in young adults. Despite increasing number of studies on MS, some aspects of this disorder are still unclear. In the previous studies, it has been proven that there is direct relation between MS incidence and vitamin D deficiency. Thereby, strong evidence in MS pathogenesis suggests that endothelial cells (EC) could be harmed in MS. In addition, functional changes in EC and macrovascular injuries lead blood-brain barrier disruption in MS. Current study is the first investigation to elucidate positive influences of vitamin D against EC apoptosis in MS. Human umbilical vein endothelial cells (HUVECs) were cultured and then treated with sera from patients with active MS (in relapse) and sera from healthy volunteer participants as control group (each group n=15). 3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay for cell surveillance and cell-death detection kit for evaluating apoptosis were used in this study. There was a significant decrease in apoptosis rate by the serum of patients, just when 1,25(OH)2D3 applied before treating HUVECs with sera from active MS (in relapse). Furthermore, the cells surveillance increased markedly with the presence of 1,25(OH)(2)D(3) in culture, too. Withregard to increment in EC apoptosis rate, which treated by the sera from MS patients and decrement in apoptosis rate by the presence of vitamin D in culture media, it could be proposed that vitamin D pre-treatment can be used for MS patients, due to its beneficial effects on protecting EC apoptosis.
Zettl, Uwe K.; Rommer, Paulus; Hipp, Petra; Patejdl, Robert
Spasticity, one of the main symptoms of multiple sclerosis (MS), can affect more than 80% of MS patients during the course of their disease and is often not treated adequately. δ-9-Tetrahydrocannabinol-cannabidiol (THC-CBD) oromucosal spray is a plant-derived, standardized cannabinoid-based oromucosal spray medicine for add-on treatment of moderate to severe, resistant multiple sclerosis-induced spasticity. This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity. Results from both randomized controlled phase III studies involving about,1600 MS patients or 1500 patient-years and recently published studies on everyday clinical practice involving more than 1000 patients or more than,1000 patient-years are presented. PMID:26788128
Zettl, Uwe K; Rommer, Paulus; Hipp, Petra; Patejdl, Robert
Spasticity, one of the main symptoms of multiple sclerosis (MS), can affect more than 80% of MS patients during the course of their disease and is often not treated adequately. δ-9-Tetrahydrocannabinol-cannabidiol (THC-CBD) oromucosal spray is a plant-derived, standardized cannabinoid-based oromucosal spray medicine for add-on treatment of moderate to severe, resistant multiple sclerosis-induced spasticity. This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity. Results from both randomized controlled phase III studies involving about,1600 MS patients or 1500 patient-years and recently published studies on everyday clinical practice involving more than 1000 patients or more than,1000 patient-years are presented.
Achiron, Anat; Aref, Hany; Inshasi, Jihad; Harb, Mohamad; Alroughani, Raed; Bijarnia, Mahendra; Cooke, Kathryn; Yuksel, Ozgur
Evidence on the use of fingolimod in real-world clinical practice and data on patient-reported health-related quality of life (HRQoL) in countries such as the Middle East are sparse. The Prospective Evaluation of Treatment with Fingolimod for Multiple Sclerosis (PERFORMS) study assessed HRQoL and effectiveness and safety of fingolimod in patients with relapsing-remitting multiples sclerosis (RRMS), primarily in Middle Eastern countries. This 12-month, observational, multicentre, prospective, real-world study was conducted in patients with RRMS who initiated fingolimod or another approved disease-modifying treatment (DMT) within 4 weeks before study entry. Patients were enrolled in a 2:1 ratio to obtain more data in fingolimod and parallel in other DMTs cohort by physicians during routine medical care. Key study outcomes included HRQoL assessed using MS International QoL (MusiQoL), MS relapses and disability. Safety was assessed throughout the study period. Due to the observational nature of the study, no neuroimaging assessments were mandated and central reading was not performed. Of 249 enrolled patients, 247 were included in the analysis (fingolimod cohort 172; other DMTs cohort 75). Overall, the mean age of patients was 36.5 years, 64.4% were women and ~90% were Caucasians. At baseline, mean MS duration since diagnosis was 7.2 years in the fingolimod and 4.8 years in the other DMTs cohorts. Overall, mean changes in MusiQoL index scores were -2.1 in the fingolimod cohort and -0.7 in the other DMTs cohort at Month 12, but improvement was not significant vs. baseline in both cohorts. Proportion of relapse-free patients increased significantly during the study vs. 0-12 months before the study in the fingolimod cohort (80.2% vs. 24.4%; p < 0.0001). Proportion of patients free from disability progression was 86.5% in the fingolimod cohort. The incidences of AEs were 59.9% and 50.6% in the fingolimod and other DMTs cohorts, respectively. First-dose monitoring of
Birnbaum, Howard G; Ivanova, Jasmina I; Samuels, Seth; Davis, Matthew; Cremieux, Pierre Y; Phillips, Amy L; Meletiche, Dennis
The study objective is to compare the annual total medical and indirect costs of newly treated and untreated employees with multiple sclerosis (MS). A retrospective database analysis of employer medical, drug, and disability claims database (Ingenix Employer database, 1999-2005; 17 large US companies) was conducted for employees 18-64 years of age with > or =1 MS diagnosis after January 1, 2002. Employees with > or =1 MS disease-modifying drug (DMD) claim comprised the newly treated group; employees with MS but no DMD at any time comprised the untreated, comparison group. Index date was the day after the most recent claim (treated, DMD claim; untreated, MS claim) meeting the following requirements: continuous health coverage for 3 months before (baseline period) and 12 months after the index date (study period) and actively employed during baseline. Total medical costs and indirect (work loss) costs over the 1-year study period (2006 $US) were compared for DMD-treated and untreated MS employees, adjusting for baseline characteristics, including comorbidities. During the baseline, MS employees who became treated (n = 258) were younger (40.9 vs. 44.4 years, p < 0.0001) and had a higher proportion of women (72 vs. 62%, p = 0.007) than the untreated group of MS employees who never received DMD treatment (n = 322). The 3-month baseline MS-related medical costs were higher among treated MS employees ($2520 vs. $1012, p < 0.0001). There was a nonsignificant trend toward higher baseline non-MS-related medical costs in untreated versus treated MS employees. Risk-adjusted total annual medical costs ($4393 vs. $6187, p < 0.0001) and indirect costs ($2252 vs. $3053, p < 0.0001) were significantly lower for treated MS employees than for untreated MS employees. Initiation of MS disease-modifying drugs was associated with substantial significant medical and indirect savings for employees with MS. Study findings should be considered in the context of the study limitations (e
Pryce, Gareth; Baker, David
There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS). These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms. This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS.
Ayatollahi, Azin; Mohajeri-Tehrani, Mohammad Reza
Background Multiple sclerosis (MS) is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD). Methods 51 definite relapsing-remitting MS patients according to McDonald's criteria (45 females, 6 males aged between 20 and 50 years) participated in this study. The control group included 407 females aged from 20 to 49 years; they were healthy and had no history of the diseases affecting bone metabolism. Femoral and lumbar BMD were measured by Dual Energy X-ray Absorptiometry (DXA). The disability of MS patients was evaluated by Expanded Disability Status Scale (EDSS). The patient's quality of life was evaluated by the validated Persian version of multiple sclerosis impact scale (MSIS-29). Results Patients’ mean age was 36 ± 3.3 years and their mean disease duration was 8.7 ± 1.7 years. The mean EDSS score and the mean body mass index (BMI) of the patients were 3 ± 0.9 and 23.5 ± 2.3 kg/m2, respectively. 29% of the patients had never been treated by ß-interferon and 6% of them had not received glucocorticoids (GCs) pulses since their MS had been diagnosed. 26% of the patients had a history of fracture.18% of our patients were osteoporotic and 43% of them were osteopenic. Femoral BMD was significantly lower among MS patients than age matched controls (P < 0.001), but lumbar BMD showed no difference. There was no correlation between administration of GCs pulses, interferon and BMD; however, we found a significant correlation between EDSS score, quality of life (QoL), disease duration and BMD of both site. Conclusion As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients’ treatment protocols
The Mark VII MicroClimate Medical Personal Cooling system enables multiple sclerosis' victims, as well as cerebral palsy, spinabifida patients and others to lower their body temperatures. Although this is not a cure, cooling can produce a dramatic improvement in symptoms. The Multiple Sclerosis Association of America has placed cool suits in MS research care centers. This technology originated in the need for cooling systems in spa@esuits. "Cool Suits" are now used by hazardous materials workers, armored vehicle crews, firefighters and crop dusters. A surgical personal cooling system has also been developed for medical personnel working in hot operating room environments.
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
Yang, Ting-Ting; Wang, Li; Deng, Xiao-Yang; Yu, Gang
Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software. A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue. Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs. Copyright © 2017. Published by Elsevier B.V.
Paul, F; Ruprecht, K
Following the introduction of interferon beta 1b as the first immunomodulatory therapy for multiple sclerosis (MS) in 1993, there are currently nine substances or substance classes approved for the treatment of MS (i.e. alemtuzumab, azathioprine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab and teriflunomide). Major developments during the last 5 years include the approval of orally administered medications (i.e. fingolimod, teriflunomide and dimethyl fumarate), a monoclonal antibody (alemtuzumab), as well as glatiramer acetate with an administration frequency three times a week and a pegylated formulation of interferon beta 1a. The broadened therapeutic options enable a more differentiated and individualized therapy of MS; however, evidence-based data for therapeutic decision-making relevant in clinical practice are not always available. Rare but potentially severe and even life-threatening side effects of immunotherapies for MS require continuous pharmacovigilance and adherence to risk management plans.
Duff, Whitney R.D.; Andrushko, Justin W.; Renshaw, Doug W.; Chilibeck, Philip D.; Farthing, Jonathan P.; Danielson, Jana
Abstract Background: Pilates is a series of exercises based on whole-body movement and may improve mobility in people with multiple sclerosis (MS). The purpose of this study was to determine the effect of Pilates on walking performance in people with MS. Methods: 30 individuals with MS who were not restricted to a wheelchair or scooter (Patient-Determined Disease Steps scale score <7) were randomized to receive Pilates (twice weekly) and massage therapy (once weekly) or once-weekly massage therapy only (control group). The Pilates was delivered in a group setting (five to ten participants per session). The primary outcome was change in walking performance (6-Minute Walk Test) after 12 weeks. Secondary outcomes included functional ability (Timed Up and Go test), balance (Fullerton Advanced Balance Scale), flexibility (sit and reach test), body composition (dual-energy X-ray absorptiometry), core endurance (plank-hold test), and muscle strength and voluntary activation (quadriceps). Intention-to-treat analysis was performed using a two-factor repeated-measures analysis of variance. Results: Walking distance increased by a mean (SD) of 52.4 (40.2) m in the Pilates group versus 15.0 (34.1) m in the control group (group × time, P = .01). Mean (SD) time to complete the Timed Up and Go test decreased by 1.5 (2.8) seconds in the Pilates group versus an increase of 0.3 (0.9) seconds in the control group (group × time, P = .03). There were no other significant differences between groups over time. Conclusions: Pilates improved walking performance and functional ability in persons with MS and is a viable exercise option to help manage the disease. PMID:29670495
Mathur, Deepali; María-Lafuente, Eva; Ureña-Peralta, Juan R.; Sorribes, Lucas; Hernández, Alberto; Casanova, Bonaventura; López-Rodas, Gerardo; Coret-Ferrer, Francisco; Burgal-Marti, Maria
Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity. PMID:29267205
Scherder, R; Kant, N; Wolf, E; Pijnenburg, A C M; Scherder, E
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: firstname.lastname@example.org
Background In previous studies we found that MHC2TA +1614 genotype frequency was very different when MS patients with and without human herpesvirus 6 (HHV-6) in serum samples were compared; a different clinical behavior was also described. The purpose of the study was: 1. To evaluate if MHC2TA expression in MS patients was influenced by interferon beta (IFN-beta) treatment. 2. To study MHC2TA expression in MS patients with and without minor allele C. 3. To analyze the relation between MHC2TA mRNA levels and HHV-6 active infection in MS patients. Methods Blood and serum samples of 154 MS patients were collected in five programmed visits: basal (prior to beginning IFN-beta treatment), six, twelve, eighteen and twenty-four months later. HHV-6 in serum and MHC2TA mRNA levels were evaluated by PCR and RT-PCR, respectively. Neutralizing antibodies (NAbs) against IFN-beta were analyzed by the cytopathic effect assay. Results We found that MHC2TA mRNA levels were significantly lower among MS patients with HHV-6 active infection at the basal visit (without treatment) than in those MS patients without HHV-6 active infection at the basal visit (p = 0.012); in all the positive samples we only found variant A. Furthermore, 58/99 (58.6%) MS patients without HHV-6 along the five programmed visits and an increase of MHC2TA expression after two-years of IFN-beta treatment were clinical responders vs. 5/21 (23.8%) among those MS patients with HHV-6 and a decrease of MHC2TA mRNA levels along the two-years with IFN-beta treatment (p = 0.004); no differences were found between patients with and without NAbs. Conclusions MHC2TA mRNA levels could be decreased by the active replication of HHV-6; the absence of HHV-6 in serum and the increase of MHC2TA expression could be further studied as markers of good clinical response to IFN-beta treatment. PMID:23009575
Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis; Hasselbalch, Hans Carl
The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007–2012. We describe the patients' history and treatment. A potential link between MS and MPNs has not been previously recognized. This observation calls attention to potential environmental factors and/or previously unrecognized genetic factors predisposing these patients to both MS and MPNs. PMID:24371783
Schee, Jie Ping; Viswanathan, Shanthi
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.
Background Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. Discussion In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. Summary These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient. PMID:24655543
Jahromi, Soodeh Razeghi; Sahraian, Mohammad Ali; Ashtari, Fereshteh; Ayromlou, Hormoz; Etemadifar, Massoud; Ghaffarpour, Majid; Mohammadianinejad, Ehsan; Nafissi, Shahriar; Nickseresht, Alireza; Shaygannejad, Vahid; Togha, Mansoreh; Torabi, Hamid Reza; Ziaie, Shadi
Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient.
Klein, Eran P.; Bourdette, Dennis
Objective: To describe the clinical characteristics of encounters with patients misdiagnosed with multiple sclerosis (MS). Methods: A cross-sectional Internet-based physician survey of MS specialists was performed. Results: The response rate for the survey was 50.4%. Of those who responded, the majority (95%) reported having evaluated 1 or more patients who had been diagnosed with MS, but who they strongly felt did not have MS, within the last year. The majority of respondents (>90%) also reported the use of disease-modifying therapy in a proportion of these patients. Most respondents (94%) found clinical encounters with these patients equally or more challenging than giving a new diagnosis of MS. Fourteen percent of respondents reported that they did not always inform such patients of their opinion that they did not have MS. Conclusions: The misdiagnosis of MS is common and has significant consequences for patient care and health care system costs. Caring for a patient with a misdiagnosis of MS is challenging, and at times honest disclosure of a misdiagnosis represents an important ethical concern for neurologists. More data are needed on this patient population to improve diagnostic acumen and the care of these patients. PMID:22581930
Inglese, Matilde; Petracca, Maria
Although the prevalence of neurodegenerative diseases is increasing as a consequence of the growing aging population, the exact pathophysiological mechanisms leading to these diseases remains obscure. Multiple sclerosis (MS), an autoimmune disease of the central nervous system and the most frequent cause of disability among young people after traumatic brain injury, is characterized by inflammatory/demyelinating and neurodegenerative processes that occurr earlier in life. The ability to make an early diagnosis of MS with the support of conventional MRI techniques, provides the opportunity to study neurodegeneration and the underlying pathophysiological processes in earlier stages than in classical neurodegenerative diseases. This review summarizes mechanisms of neurodegeneration common to MS and to Alzheimer disease, Parkinson disease, and amiotrophic lateral sclerosis, and provides a brief overview of the neuroimaging studies employing MRI and PET techniques to investigate and monitor neurodegeneration in both MS and classical neurodegenerative diseases. PMID:23117868
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Di Stadio, Arianna; Bernitsas, Evanthia; Restivo, Domenico Antonio; Alfonsi, Enrico; Marchese-Ragona, Rosario
This study aims to evaluate the effect of botulin toxin A in patients with multiple sclerosis (MS) affected by spasmodic dysphonia (SD) and to show the safety and effectiveness of this treatment in long-term observation. This is a pilot study on three relapsing-remitting MS patients with SD and their response to botulin toxin A. None of the patients reported dysphagia or other adverse events. Significant improvement was observed in terms of both voice quality and laryngostroboscopy results. The treatment effect was durable for 6-8 months. Botulin toxin A is a safe treatment that can be successfully used to treat SD in patients with MS. Larger studies are necessary to confirm our results. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Trebst, Corinna; Reising, Ansgar; Kielstein, Jan T; Hafer, Carsten; Stangel, Martin
Plasma exchange (PE) is well established for conditions such as rapid progressive vasculitis associated with autoantibodies against neutrophil cytoplasmic antigens (ANCA), anti-glomerular basement membrane (GBM) antibody disease, or thrombotic thrombocytopenic purpura (TTP). Also, several neurological disorders, such as acute worsening in myasthenia gravis, Guillan-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), can successfully be treated with PE. Only small case series have previously shown that PE is also effective in relapses in patients with multiple sclerosis (MS). We report our experiences of PE therapy in a series of 20 patients with 21 steroid unresponsive MS relapses. A marked-to-moderate clinical response with clear gain of function in 76% of patients with uni- or bilateral optic neuritis and in 87.5% of patients with relapses other than optic neuritis was observed. PE is an effective and well tolerated therapeutic option for steroid-unresponsive MS relapses.
Matsuda, Patricia N; Shumway-Cook, Anne; Bamer, Alyssa M; Johnson, Shana L; Amtmann, Dagmar; Kraft, George H
To examine incidence, associated factors, and health care provider (HCP) response to falls in persons with multiple sclerosis (MS). Cross-sectional retrospective design. Community setting. Four hundred seventy-four persons with MS. Mailed survey questionnaire examined incidence, risk factors, and HCP response to falls in persons with MS who were dwelling in the community. Univariate and multiple ordinal regression analysis identified variables associated with single and multiple falls. Falls, causes and perceived reasons for falls, and HCP response. A total of 265 participants (58.2%) reported one or more falls in the previous 6 months, and 58.5% of falls were medically injurious. Trips/slips while walking accounted for 48% of falls. Factors associated with falls included use of a cane or walker (odds ratio [OR] 2.62; 95% confidence interval [CI] 1.66-4.14), income <$25,000 (OR 1.85; 95% CI 1.13-3.04), balance problems (OR 1.28; 95% CI 1.11-1.49), and leg weakness (OR 1.26; 95% CI 1.09-1.46). Fifty-one percent of those who fell (135/265) reported speaking to an HCP about their falls; recommended strategies included safety strategies (53.2%), use of gait assistive devices (42.1%), exercise/balance training (22.2%), and home modifications (16.6%). Factors associated with falls in persons with MS are similar to those in other populations with neurologic diseases. Despite the high incidence of falls, fewer than 50% of people with MS receive information about prevention of falls from an HCP. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
Suneetha, A; Raja Rajeswari, K
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via
Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS) is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients’ dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease. PMID:24250908
Leist, Thomas; Hunter, Samuel F; Kantor, Daniel; Markowitz, Clyde
Multiple sclerosis (MS) affects an estimated 300,000 individuals in the United States. No cure exists and although there is a lack of consensus on management, strategies to modify disease course are available. These strategies involve initiating disease-modifying therapies that have been found to slow disease progression and prevent disability symptoms, thereby improving function for MS patients. The overall goal of early disease management is to intervene prior to irreversible neuronal destruction in order to delay disability progression and improve quality of life. Maintaining a lower level of disability for a longer period of time postpones and ultimately attempts to prevent reaching a level of immobility and irreversible disability. However, due to the complex nature of disease and its unique, individual patient course, no patient can be treated alike and no patient responds to therapy similarly. Therefore, MS research is continuous in its evolution of therapeutic development, focusing on neuroprotective effects and agents with distinctive mechanisms of action allowing for unique safety and efficacy profiles. Investigations include novel oral agents and monoclonal antibodies. Many of the approved agents also are continually being investigated in order to evaluate comparative data, the most appropriate means of implementing subsequent therapy upon failure, responsiveness to therapeutic agent when switched, and long-term safety and efficacy. This multimedia webcast educational activity will cover the current state of MS science, current therapies in MS, emerging treatments in clinical trials for MS as well as differences between physicians in diagnosis and management of MS and their evolving practices. Copyright © 2014. Published by Elsevier Inc.
Kern, S; Kühn, M; Ziemssen, T
Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. It is characterised by a chronic progressive course with far reaching implications on the patient's private and professional life. Based on the current literature, employment status is analysed in relation to disease-specific, therapeutic, psychosocial, and socioeconomic factors. A special emphasis is placed on the vocational status of MS patients in Germany. According national and international studies, around 40 % of all MS patients are currently unemployed. Main reasons for early retirement are disease-specific factors such as impaired mobility, disability in the upper extremities, fatigue, and cognitive impairment. According to the German Multiple Sclerosis Registry (GMSR), these symptoms are still insufficiently treated. In patients with minor motoric impairment (EDSS ≤ 3.0), depressive symptoms seem to have a major impact on employment status. Disease progression, older age at diagnosis, and hard physical work are negative predictors in terms of employment situation. The lack of flexible working hours, the inability to have flexible resting times at work, a lack of understanding from colleagues and employers as well as the personal attitude were main non-disease-specific reasons for early retirement. The current knowledge on the vocational status in MS is mainly based on international studies (e. g., Scandinavia, England, USA, Australia, MSIF Survey). For Germany, only the GMSR supports significant information on the employment status of MS patients. According to the GMSR, ataxia, fatigue and cognitive dysfunction are still insufficiently treated - a situation that is at least partly due to insufficient treatment options. Comprehensive studies that focus on a broad range of possible influencing factors on vocational status of German MS patients are currently lacking. © Georg Thieme Verlag KG Stuttgart · New York.
Teixeira-Poit, Stephanie; Kane, Heather L.; Frost, A. Corey; Keating, Michael; Olmsted, Murrey
Background: Although detailed knowledge regarding treatment options for multiple sclerosis (MS) patients is largely limited to neurologists, shortages in the neurologist workforce, including MS subspecialists, are predicted. Thus, MS patients may have difficulties in gaining access to appropriate care. No systematic evaluation has yet been performed of the number of neurology residents planning to pursue MS subspecialization. This study identifies factors affecting interest in providing MS patient care or MS subspecialization among current neurology residents. Methods: We randomly selected half of all Accreditation Council of Graduate Medical Education–certified neurology residency programs in the continental United States to receive the neurology resident survey. Completed surveys were received from 218 residents. Results: Residents were significantly more likely to have increased interest in MS care when they participated in MS research, were interested in teaching, and indicated that the “ability to improve patient outcomes and quality of life” was a positive factor influencing their desire to provide MS patient care. Residents who were interested in providing MS care, interested in teaching, and indicated that “research opportunities” was a positive factor for providing MS patient care were significantly more likely to express interest in MS subspecialization. Conclusions: Increasing opportunities to interact with MS patients, learn about MS care, and participate in MS research may increase interest in MS care and subspecialization among neurology residents. Opportunities to educate residents regarding MS patient care may affect residents’ attitudes. PMID:24688352
Clanet, Michel C; Wolinsky, Jerry S; Ashton, Raymond J; Hartung, Hans-Peter; Reingold, Stephen C
Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks. The objective of this review is to discuss risk assessment in MS therapeutics based on an international workshop and comprehensive literature search and recommend strategies for risk assessment/monitoring. Assessment and perception of therapeutic risks vary between patients, doctors and regulators. Acceptability of risk depends on the magnitude of risk and the demonstrated clinical benefits of any agent. Safety signals must be distinguishable from chance occurrences in a clinical trial and in long-term use of medications. Post-marketing research is crucial for assessing longer-term safety in large patient cohorts. Reporting of adverse events is becoming more proactive, allowing more rapid identification of risks. Communication about therapeutic risks and their relationship to clinical benefit must involve patients in shared decision making. It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions. © The Author(s) 2013.
Minden, Sarah L.; Feinstein, Anthony; Kalb, Rosalind C.; Miller, Deborah; Mohr, David C.; Patten, Scott B.; Bever, Christopher; Schiffer, Randolph B.; Gronseth, Gary S.; Narayanaswami, Pushpa
Objective: To make evidence-based recommendations for screening, diagnosing, and treating psychiatric disorders in individuals with multiple sclerosis (MS). Methods: We reviewed the literature (1950 to August 2011) and evaluated the available evidence. Results and recommendations: Clinicians may consider using the Center for Neurologic Study Emotional Lability Scale to screen for pseudobulbar affect (Level C). Clinicians may consider the Beck Depression Inventory and a 2-question tool to screen for depressive disorders and the General Health Questionnaire to screen for broadly defined emotional disturbances (Level C). Evidence is insufficient to support/refute the use of other screening tools, the possibility that somatic/neurovegetative symptoms affect these tools' accuracy, or the use of diagnostic instruments or clinical evaluation procedures for identifying psychiatric disorders in MS (Level U). Clinicians may consider a telephone-administered cognitive behavioral therapy program for treating depressive symptoms (Level C). Although pharmacologic and nonpharmacologic therapies are widely used to treat depressive and anxiety disorders in individuals with MS, evidence is insufficient to support/refute the use of the antidepressants and individual and group therapies reviewed herein (Level U). For pseudobulbar affect, a combination of dextromethorphan and quinidine may be considered (Level C). Evidence is insufficient to determine the psychiatric effects in individuals with MS of disease-modifying and symptomatic therapies and corticosteroids; risk factors for suicide; and treatment of psychotic disorders (Level U). Research is needed on the effectiveness in individuals with MS of pharmacologic and nonpharmacologic treatments frequently used in the non-MS population. PMID:24376275
Adriani, Marsilio; Nytrova, Petra; Mbogning, Cyprien; Hässler, Signe; Medek, Karel; Jensen, Poul Erik H; Creeke, Paul; Warnke, Clemens; Ingenhoven, Kathleen; Hemmer, Bernhard; Sievers, Claudia; Lindberg Gasser, Raija Lp; Fissolo, Nicolas; Deisenhammer, Florian; Bocskei, Zsolt; Mikol, Vincent; Fogdell-Hahn, Anna; Kubala Havrdova, Eva; Broët, Philippe; Dönnes, Pierre; Mauri, Claudia; Jury, Elizabeth C
Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β is an established treatment for MS; however, up to 30% of IFN-β-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immunogenicity remain uncertain, and reliable biomarkers to predict immunogenicity development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14+ monocytes and increased frequency of proinflammatory monocyte subsets were identified as baseline predictors of nADA development in MS patients treated with IFN-β. The association of this monocyte profile with nADA development was validated in 2 independent cross-sectional MS patient cohorts and a prospective cohort followed before and after IFN-β administration. Reduced monocyte NOTCH2 expression in nADA+ MS patients was associated with NOTCH2 activation measured by increased expression of Notch-responsive genes, polarization of monocytes toward a nonclassical phenotype, and increased proinflammatory IL-6 production. NOTCH2 activation was T cell dependent and was only triggered in the presence of serum from nADA+ patients. Thus, nADA development was driven by a proinflammatory environment that triggered activation of the NOTCH2 signaling pathway prior to first IFN-β administration.
Sandvig, Inger; Barlinn, Jon; Nedregaard, Bård; Skjeldal, Ola H
Multiple sclerosis (MS) has traditionally been considered a disease of adults. However, in recent years, there have been numerous reports about the disease occurring in childhood and adolescence. The purpose of this article is to document Norwegian experience of this population based on clinical observations and neuroradiological findings. Children and adolescents diagnosed with MS at the Department of Child Neurology, Oslo University Hospital, between 1 January 2004 and 1 May 2012 were included. Gender, previous diseases, age, symptoms at first attack, spinal fluid findings and cerebral magnetic resonance tomography (MRI) findings were recorded. The course of the disease, treatment and sequelae was noted. The study includes 18 patients who received MS diagnosis. Median age at onset was 10 years and six months. The presenting symptoms and MRI findings varied. Almost all patients were treated with steroids in the acute phase and later with interferon-beta. Some patients were treated with natalizumab when there was lack of efficiency of interferon-beta. Seven patients developed permanent, moderate sequelae in terms of motor, sensory, or cerebellar symptoms. Nine patients had cognitive difficulties and 11 specified increased fatigability. MS in children and adolescents is a disease with varying acute neurological symptoms and findings. The patients were treated with the same medicines as adults with MS and tolerated it well. We found that cognitive sequelae and fatigue were common also in this young age group. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Minagar, Alireza; Barnett, Michael H.; Benedict, Ralph H.B.; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott
The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. PMID:23296131
... MS can affect your work, your relationships, your sleep, your diet and your ability to exercise. All of these factors contribute to your mood and mental health. Talking with a trained therapist can help you learn ...
Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac
The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.
Garcia-Martin, Elena; Pueyo, Victoria; Almarcegui, Carmen; Martin, Jesus; Ara, Jose R; Sancho, Eva; Pablo, Luis E; Dolz, Isabel; Fernandez, Javier
To quantify structural and functional degeneration in the retinal nerve fibre layer (RNFL) of patients with multiple sclerosis (MS) over a 2-year time period, and to analyse the effect of prior optic neuritis (ON) as well as the duration and incidence of MS relapses. 166 MS patients and 120 healthy controls underwent assessment of visual acuity and colour vision, visual field examination, optical coherence tomography, scanning laser polarimetry and visual evoked potentials (VEPs). All subjects were re-evaluated after a period of 12 and 24 months. Changes in the optic nerve were detected by structural measurements but not by functional assessments. Changes registered in MS patients were greater than changes in healthy controls (p<0.05). Eyes with previous ON showed a greater reduction of parameters in the baseline evaluation, but RNFL atrophy was not significantly greater in the longitudinal study. Patients with MS relapses showed a greater reduction of RNFL thickness and VEP amplitude compared with non-relapsing cases. Patients with and without treatment showed similar measurement reduction, but the non-treated group had a significantly higher increase in Expanded Disability Status Scale (p=0.029). MS causes progressive axonal loss in the optic nerve, regardless of a history of ON. This ganglion cell atrophy occurs in all eyes but is more marked in MS eyes than in healthy eyes.
Brenton, J Nicholas; Goldman, Myla D
Modifiable risk factors for multiple sclerosis (MS), including obesity and the gut microbiome, have been studied and have been found to be potentially relevant. Given this, there is a growing interest in diet modification as a means of impacting MS risk and disease course. The aim of this study was to determine the current behaviors, level of interest, and relevant factors surrounding modification of diet in MS patients. A total of 601 MS patients were mailed a dietary modification survey containing questions regarding subject demographics, disease course, and diet-related questions. Of the 199 survey responders, 17% admitted to currently attempting a diet for their MS and 91.5% were interested in diet modification as a means of benefiting their disease. Willingness to attempt diet therapy was not affected by demographic features or an individual's disease course. Over 85% of these patients were willing to attempt diet therapy for 3 months or longer. The majority of survey responders expressed interest in diet modification in attempts to improve or treat their MS. Our data demonstrate the feasibility of patient recruitment for future studies assessing therapeutic intervention by way of diet modification for MS disease. Copyright © 2016 Elsevier B.V. All rights reserved.
Gu, S-G; Wang, C-J; Zhao, G; Li, G-Y
Multiple sclerosis (MS) is an autoimmune disease that results with a damaged myelin sheath as a result, there is an impairment of nerve impulse conduction. The medication for MS is able to delay its progression, but complete recovery is impossible. Recent studies with neural stem cells have promising results in treating as well as to recover the damaged nerves, but research on in vivo model system is limited in this aspect. Here we are able to successfully establish an MS mice model by injecting with myelin basic protein and we studied the neural stem cell response in supplement with vitamin D. Through histology we provide strong evidence that the MS pathogenesis is reverted on response to vitamin D. We also identified through immunohistochemistry and western blotting that the vitamin D has the ability to trigger neural stem cells, and thereby it assist in recovery from MS. Further, their roles in preventing as well as delaying the MS development are also proven. The role of vitamin D has also cross checked with the help of tunnel assay. Overall, our results conclude that the lesion associated apoptotic signals are reduced on administrated with vitamin D. The present data help to design a new therapeutic intervention to cure MS.
Amor, Sandra; van der Star, Baukje J; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; Watchorn, Jonathan; Kuhle, Jens; Giovannoni, Gavin; Baker, David; Malaspina, Andrea; Puentes, Fabiola
Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (p<0.001). NF-L antibody levels were lower in natalizumab treated than in untreated patients (p<0.001). In the longitudinal series, NF-L antibody levels decreased over time and a significant difference was found following 24 months of treatment compared with baseline measurements (p=0.001). Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS. © The Author(s) 2014.
Virtanen, JO; Wohler, J; Fenton, K; Reich, DS; Jacobson, S
Background Two human herpesviruses, human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV), have been repeatedly linked to multiple sclerosis (MS). Objective The aim of this study was to investigate HHV-6 and EBV reactive oligoclonal bands (OCBs), and viral DNA in the intrathecal compartment in MS. Methods The reactivity of OCBs in cerebrospinal fluid (CSF) for EBV and HHV-6 antigens and stability of virus reactive OCBs over time were studied in a well-characterized MS patient cohort. Associations between virus reactive OCBs and viral DNA in CSF (and any clinical and/or radiological findings) were investigated. Results Of patients with MS, 38% had OCBs reactive to either one of the viruses studied, compared to none in the patients with other inflammatory neurological diseases (p=0.005). The banding pattern of virus reactive OCBs remained the same over time. Furthermore, MS patients with viral DNA in CSF had more contrast enhancing lesions (CELs). Conclusion The stable presence of herpesvirus reactive OCBs in CSF further strengthens the association of MS with these viruses. The finding that herpesviruses might be linked to the appearance of active lesions warrants investigation of new therapeutic strategies to treat these viruses in MS. PMID:23722324
Kraft, George H
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.
Rose, Anita; van de Vis, Wim; Engelbrecht, Jannie; Pirard, Michelle; Lau, Stefanie; Heesen, Christoph; Köpke, Sascha
Objective Sexual dysfunction in multiple sclerosis (MS) is a significant, but often underestimated and overlooked suffering. Interventions to treat sexual dysfunction in MS are rare. The relation between sexual dysfunction in MS and psychological as well as neuropsychological aspects is evident. However, this field of research remains markedly underdeveloped in this severe chronic illness. The aim of this scoping review is to describe the relevant knowledge in this area and to identify psychological interventions to treat sexual dysfunctions in MS. Methods A scoping review was conducted to answer the following questions: (1) Which psychological and neuropsychological factors impact on sexual dysfunction in MS and vice versa? (2) What kind of psychological interventions aiming to improve sexual dysfunctions in MS are available? A comprehensive search and review of MEDLINE, PsycINFO, and CINAHL was completed by using a recent methodological framework for scoping reviews. Results 23 publications covering a total of 13,259 people with MS and 532 healthy controls were identified. Sexual dysfunction was found to be very common in MS and there is an obvious relation to psychological disorders as e.g. depression and anxiety and also to psychological aspects as partner relationship and quality of life. The relation between sexual dysfunction in MS and neuropsychological impairment has only rarely been studied and no clear results were found. Only two studies were identified, assessing the effectiveness of psychological intervention studies on sexual dysfunction in people with MS, and a third study presenting a secondary analysis of a study targeting depression. All three studies reported significant improvements in sexual dysfunction as well as partly in psychological variables. Conclusions There is a pressing need for the development and adequate evaluation of psychological interventions for sexual dysfunctions in MS. In addition, sexual dysfunction and its impact on
Pöttgen, Jana; Rose, Anita; van de Vis, Wim; Engelbrecht, Jannie; Pirard, Michelle; Lau, Stefanie; Heesen, Christoph; Köpke, Sascha
Sexual dysfunction in multiple sclerosis (MS) is a significant, but often underestimated and overlooked suffering. Interventions to treat sexual dysfunction in MS are rare. The relation between sexual dysfunction in MS and psychological as well as neuropsychological aspects is evident. However, this field of research remains markedly underdeveloped in this severe chronic illness. The aim of this scoping review is to describe the relevant knowledge in this area and to identify psychological interventions to treat sexual dysfunctions in MS. A scoping review was conducted to answer the following questions: (1) Which psychological and neuropsychological factors impact on sexual dysfunction in MS and vice versa? (2) What kind of psychological interventions aiming to improve sexual dysfunctions in MS are available? A comprehensive search and review of MEDLINE, PsycINFO, and CINAHL was completed by using a recent methodological framework for scoping reviews. 23 publications covering a total of 13,259 people with MS and 532 healthy controls were identified. Sexual dysfunction was found to be very common in MS and there is an obvious relation to psychological disorders as e.g. depression and anxiety and also to psychological aspects as partner relationship and quality of life. The relation between sexual dysfunction in MS and neuropsychological impairment has only rarely been studied and no clear results were found. Only two studies were identified, assessing the effectiveness of psychological intervention studies on sexual dysfunction in people with MS, and a third study presenting a secondary analysis of a study targeting depression. All three studies reported significant improvements in sexual dysfunction as well as partly in psychological variables. There is a pressing need for the development and adequate evaluation of psychological interventions for sexual dysfunctions in MS. In addition, sexual dysfunction and its impact on psychological wellbeing should be more
Olsson, Malin; Lexell, Jan; Söderberg, Siv
We conducted a qualitative inquiry in order to describe the meaning of women's experiences of living with multiple sclerosis (MS). Multiple sclerosis is a chronic autoimmune disease of the central nervous system. The majority of persons living with MS are women. Living with MS has been described as difficult because of the uncertainty of the illness. Ten women with MS were interviewed and the interviews were analyzed with a phenomenological hermeneutic interpretation. In this study, we suggest that the meaning of living with MS for women can be understood as trying to maintain power and living with an unrecognizable body. The bodies of women with MS serve as hindrances in everyday life. Bodily changes evident to others impose feelings of being met in a different way, which can be understood as an expression of a violated dignity. At the same time, the women with MS struggle to protect their dignity.
Quig, Mary Elizabeth; Tyry, Tuula; Marrie, Ruth Ann; Cutter, Gary; Shearin, Edward; Johnson, Kamau; Simsarian, James
Background: Caring for someone with multiple sclerosis (MS) can be a stressful experience that requires clinical attention. We investigated the impact of caregiver stress on the emotional well-being and physical health of the MS care partner using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Methods: Care partners of NARCOMS participants were invited to complete an online questionnaire that captured demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact of caregiving on employment. Results: Of 1446 care partners who agreed to participate, 1333 had complete data. Most were men (n = 825, 61.9%), with a mean (SD) age of 51.1 (11.2) years. The mean (SD) Zarit total score was 24.6 (15.1), placing the overall group in the mild caregiver burden range. Compared with male care partners, female care partners reported higher levels of burden and stress and more medication use for stress/anxiety and mood disorders. Male care partners were more likely to report physical concerns. Care partners of people with primary progressive MS reported greater perceived burden than did partners of people with secondary progressive MS and relapsing-remitting MS. More than 40% of care partners (559 of 1288) had missed work during the past year owing to caregiving responsibilities. Conclusions: Care partners of people with MS have substantial physical and psychological health concerns and experience an adverse impact on employment. Future research should evaluate how to mitigate the adverse effects of caregiving and evaluate positive aspects of the role. PMID:26664330
Pseudobulbar affect (PBA), a condition involving involuntary and uncontrollable episodes of crying and/or laughing, occurs frequently in patients with a variety of neurological disorders, including amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, dementia including Alzheimer's disease, and multiple sclerosis (MS). Although PBA results in considerable distress for patients and caretakers, it is underrecognized and undertreated. Agents used to treat psychiatric disorders--particularly tricyclic antidepressants and selective serotonin reuptake inhibitors--are useful in alleviating PBA, but act on diffuse neural networks rather than targeting those involved in emotional motor expression. As a result of their nonspecific activity, these agents are associated with a range of unwanted effects that preclude many patients from using them. Dextromethorphan, a common cough suppressant, specifically targets sigma(1) receptors concentrated in the brainstem and cerebellum, thus providing the possibility of targeting regions implicated in emotional expression. When administered in a fixed combination with quinidine, dextromethorphan is effective in treating PBA in patients with ALS, and preliminary results suggest that this therapy also is effective in treating MS-related PBA.
Alghwiri, Alia A; Khalil, Hanan; Al-Sharman, Alham; El-Salem, Khalid
Balance impairments are common and multifactorial among people with multiple sclerosis (MS). Depression is the most common psychological disorder in MS population and is strongly correlated with MS disease. Depression might be one of the factors that contribute to balance deficits in this population. However, the relationship between depression and balance impairments has not been explored in people with MS. To investigate the association between depression and balance impairments in people with MS. Cross sectional design was used in patients with MS. The Activities-specific Balance Confidence scale (ABC) and Berg Balance Scale (BBS) was used to assess balance. Beck Depression Inventory (BDI-II) was used to quantify depression and Kurtizki Expanded Disability Status Scale (EDSS) was utilized for the evaluation of MS disability severity. Pearson correlation coefficient was used to examine the association between depression and balance measurements. Multiple linear stepwise regressions were also conducted to find out if depression is a potential predictor for balance deficits. Seventy-five individuals with MS (Female = 69%) with a mean age (SD) of 38.8 (10) and a mean (SD) EDSS score of 3.0 (1.4) were recruited in this study. Depression was present in 53% of the patients. Depression was significantly correlated with balance measurements and EDSS. However, multiple linear stepwise regressions found that only depression and age significantly predict balance. Depression and balance were found frequent and associated in people with MS. Importantly depression was a significant predictor for balance impairments in individuals with MS. Balance rehabilitation may be hindered by depression. Therefore, depression should be evaluated and treated properly in individuals with MS. Copyright © 2018 Elsevier B.V. All rights reserved.
Lee, Seung-Yup; Min, Jung-Ah; Lee, In Goo; Kim, Jung Jin
Tuberous sclerosis is not as rare as once thought and has high psychiatric comorbidities. However, bipolar or psychotic features associated with tuberous sclerosis have been rarely reported. This report first presents a tuberous sclerosis patient, resembling a schizoaffective disorder of bipolar type. A patient with known tuberous sclerosis displayed mood fluctuation and psychotic features. Her symptoms did not remit along with several psychiatric medications. After hospitalization, the patient responded well with lamotrigine and aripiprazole without exacerbation. As demonstrated in this case, tuberous sclerosis may also encompass bipolar affective or psychotic features. We would like to point out the necessity to consider bipolarity in evaluating and treating tuberous sclerosis.
Melendez-Torres, G J; Auguste, Peter; Armoiry, Xavier; Maheswaran, Hendramoorthy; Court, Rachel; Madan, Jason; Kan, Alan; Lin, Stephanie; Counsell, Carl; Patterson, Jacoby; Rodrigues, Jeremy; Ciccarelli, Olga; Fraser, Hannah; Clarke, Aileen
At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health's risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. In total, 6420 publications were identified, of which 63 relating to 35 randomised
AWARD NUMBER: W81XWH-13-1-0053 TITLE: Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological...2015 Final 1 May 2013 - 30 Apr 2015 Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in...FDA-approved drug, Memantine , an uncompetitive/fast off-rate antagonist of the Nmethyl-D-aspartate-type glutamate receptor, and its improved
Roessler, Richard T.; Rumrill, Phillip D.; Fitzgerald, Shawn M.
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).…
Fjeldstad, Cecilie; Pardo, Gabriel; Bemben, Debra; Bemben, Michael
To evaluate balance in women with multiple sclerosis (MS) who have low disability and minimal clinical impairments as measured by the Expanded Disability Status Scale (EDSS), and compare them with healthy age-matched controls. Patients were aged between 18 and 64 years; 67 individuals with MS (mu = 44.0 plus or minus 1.2 years) and 45 healthy…
ABSTRACT Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease . Epstein - Barr virus (EBV) infection is associated with MS...factors such as Epstein - Barr virus (EBV) infections. EBV is a herpesvirus that infects many cell types and associated with other autoimmune diseases . The...AD_________________ Award Number: W81XWH-12-1-0225 TITLE: Epstein Barr virus and
Brook, Richard A; Rajagopalan, Krithika; Kleinman, Nathan L; Melkonian, Arthur K
The purpose of this analysis was to assess the differences in lost time and health-benefit costs (HBCs) among employees treated with disease modifying treatments (DMTs) for multiple sclerosis (MS). Employees with an MS diagnostic code (ICD-9 340.xx) and a DMT prescription claim (1/1/2001-6/30/2007) were identified from the HCMS Research Reference Database and assigned to DMT cohorts. The first prescription for the DMT was used as each person's index date. One-year outcomes included HBCs and absenteeism (lost time, comprising sick leave [SL], short- and long-term disability [STD/LTD], and workers' compensation). Demographics were compared using t-tests for continuous variables and chi-square tests for discrete variables. Two-part multivariate regression modeling (logistic regression combined with generalized linear regression) was used to determine annual HBCs and absenteeism for each cohort controlling for age, gender, job-related variables, and Charlson Comorbidity Score. All cost variables were inflated to US$2007. Annual ranges among the DMTs were: HBCs $17,953-26,970 and absenteeism 7.33-20.67 days. Compared with glatiramer acetate ('C'), IFN-beta1a IM ('A') users had lower SL ($445, p = 0.0469) and STD ($969, p = 0.0164) costs; and IFN-beta1b ('B') users had lower medical costs ($2143, p = 0.0091). In addition, those treated with 'A' had 4.2 fewer SL days (p = 0.0101) compared with those treated with 'C'. Patients treated with 'A' reported significantly lower SL costs, SL days, and STD costs than patients treated with 'C', suggestive of greater real world benefits with 'A'. Despite small sample sizes and the retrospective nature, the study provides interesting insights into the use of DMTs in MS. The study also revealed important areas of future research, specifically the need for development of methods to determine which MS patient groups respond best to which DMT treatments.
In 1930 there were many conflicting views on the cause, incidence, precipitating factors, inheritance and treatment of multiple sclerosis (MS). A young, London neurologist summarized the state of understanding of the disease with his personal view of many of the uncertain areas, and clarified the thinking for the neurological community at that time. Although his later career was influential in many fields of medicine, and his personal influence was extraordinary in many areas as an author, educator, administrator, opinion leader and historian, his review was an important milestone in the history of MS.
Grigoriadis, Nikolaos; Linnebank, Michael; Alexandri, Nektaria; Muehl, Sarah; Hofbauer, Günther F L
As management of multiple sclerosis (MS) requires life-long treatment with disease-modifying agents, any risks associated with long-term use should be considered when evaluating therapeutic options. Immune cells of the innate and adaptive immune systems play various roles in the pathogenesis of MS. MS therapies affect the immune system, each with a unique mode of action, and consequently possess different long-term safety profiles. Rare, but serious safety concerns, including an increased risk of infection and cancer, have been associated with immunosuppressant use. The risks associated with newer immunosuppressive agents, which target specific elements of MS disease pathophysiology, are not yet fully established as the duration of clinical trials is relatively short and post-marketing experience is limited. Non-immunosuppressants used to treat MS have well-defined safety profiles established over a large number of patient-years demonstrating them to be well-tolerated long-term treatment options. When considering the long-term use of disease-modifying agents for treating MS, classification as immunosuppressants or non-immunosuppressants can be useful when evaluating potential risks associated with chronic use. A successful therapeutic strategy for any serious, chronic disease such as MS should weigh effectiveness versus long-term safety of available treatments.
Lorente Fernández, L; Monte Boquet, E; Pérez-Miralles, F; Gil Gómez, I; Escutia Roig, M; Boscá Blasco, I; Poveda Andrés, J L; Casanova-Estruch, B
Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS. Retrospective observational study with patients treated with inhaled THC/CBD between April 2008 and March 2012. Descriptive patient and treatment variables were collected. Therapeutic response was evaluated based on the doctor's analysis and overall impression. Of the 56 patients who started treatment with THC/CBD, 6 were excluded because of missing data. We evaluated 50 patients (42% male) with a median age 47.8 years (25.6-76.8); 38% were diagnosed with primary progressive MS, 44% with secondary progressive MS, and 18% with relapsing-remitting MS. The reason for prescribing the drug was spasticity (44%), pain (10%), or both (46%). Treatment was discontinued in 16 patients because of ineffectiveness (7 patients), withdrawal (4), and adverse effects (5). The median exposure time in patients whose treatment was discontinued was 30 days vs 174 days in those whose treatment continued at the end of the study. THC/CBD was effective in 80% of patients at a median dose of 5 (2-10) inhalations/day. The adverse event profile consisted of dizziness (11 patients), somnolence (6), muscle weakness (7), oral discomfort (2), diarrhoea (3), dry mouth (2), blurred vision (2), agitation (1), nausea (1), and paranoid ideation (1). THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.
Akcali, Aylin; Bal, Berrin; Erbagci, Binnur
Improving the proficiency of oligodendrocytes in their ability to repair myelin damage is one of the major goals of multiple sclerosis treatment. Insulin-like growth factor-1 (IGF-1) is one of several polypeptides that are considered to have potential benefits in that sense. In the present study, we aimed to determine serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3), thyroid stimulating hormone (TSH) and growth hormone (GH) among treated and non-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and a healthy control group. The study enrolled 100 RRMS patients and 100 age- and sex-matched control subjects diagnosed with definite multiple sclerosis (MS). Serum GH, IGF-1, IGFBP-3, and TSH levels were studied. The number of relapses and Expanded Disability Status Scale were negatively correlated and IGFBP-3 and GH were positively correlated with IGF-1. A statistically significant difference was not observed when patients were divided into two subgroups as patients treated with a MS-specific therapy (n = 54) and non-treated patients (n = 46). TSH and IGFBP-3 values were significantly lower in patient group vs. While no difference was determined with in IGF-1 levels, low levels of IGF-1 was in correlation with the least levels of IGFBP-3. To understand the relation between IGF-1 and IGFBP-3, the role of low levels of IGFBP-3 and TSH may be studied with clinic isolated syndrome patients and the evolution of these patients to definite MS.
... Brain tumors can be treated with medicines called mTOR inhibitors (sirolimus, everolimus). Kidney tumors are treated with ... the blood supply using special x-ray techniques. mTOR inhibitors are being studied as another treatment for ...
Trebst, C; Stangel, M
For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies. Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS. Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS. Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms. Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties. However, results from clinical trials do not allow the recommendation for the general use of cannabinoids in MS. This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS.
Puthenparampil, Marco; Poggiali, Davide; Causin, Francesco; Rolma, Giuseppe; Rinaldi, Francesca; Perini, Paola; Gallo, Paolo
Multiple sclerosis (MS) is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in patients with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described. We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) patients who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke's aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms. Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS. © The Author(s), 2015.
Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie; Nielsen, Jørgen Erik; Vinther-Jensen, Tua; Hjermind, Lena Elisabeth; von Essen, Marina; Ratzer, Rikke Lenhard; Soelberg Sørensen, Per; Romme Christensen, Jeppe
It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria. Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary ( n = 26) and secondary progressive MS ( n = 26) and healthy controls ( n = 24). Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations. Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.
Case series Patient: Male, 42 • Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue • weakness in limbs Medication: — Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. Case Report: Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients’ conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). Conclusions: Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD. PMID:27956736
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
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.
Akbiyik, Derya Iren; Sumbuloglu, Vildan; Guney, Zafer; Armutlu, Kadriye; Korkmaz, Nilufer; Keser, Ilke; Yuksel, Muazzez Merve; Karabudak, Rana
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…
BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.
Labiano-Fontcuberta, Andrés; Mitchell, Alex J; Moreno-García, Sara; Puertas-Martín, Verónica; Benito-León, Julián
There is evidence of the presence of a disturbed pattern of anger in multiple sclerosis (MS). Emotion changes, including anger, are thought to influence health-related quality of life (HRQoL). However, although deleterious consequences of anger on physical health have been well reported, there are no studies that have analysed the effects of anger on the HRQoL in patients with MS. Our purpose was to assess the extent to which anger impacts on the HRQoL of a cohort of MS patients. One hundred and fifty-seven consecutive MS patients were enrolled in the study. Participants were administered affective trait measures (Beck Depression Inventory, Beck Anxiety Inventory) and anger measures (the Spanish adapted version of the State-Trait Anger Expression Inventory-2). HRQoL was quantified using the Functional Assessment of MS. Linear regression analyses revealed that even after controlling for socio-demographic and clinical variables, higher levels of anger expression-in (tendency to handle anger by keeping it inside) independently predicted worse overall HRQoL of MS patients (β = -0.15, p = 0.04). We further found that this relationship was moderated by gender, showing that anger expression-in is a more influential predictor of the HRQoL in women with MS. The present study provides evidence that anger negatively affects the HRQoL of MS patients. Our results may have implications for those involved in treating emotional complications of MS and especially regarding psychotherapeutic interventions to improve HRQoL of MS patients. © The Author(s), 2014.
Multiple sclerosis (MS) is an autoimmune neurological disease characterized by inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought as autoreactive Th1 and Th17 cell-mediated diseases. CD4(+) CD25(+) FoxP3(+) regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and tolerogenic dendritic cells (DCreg) drive the development of inducible Treg cells. Thus, a dysfunction in the development of Treg and DCreg leads to the development of autoimmune diseases. However, the factors that regulate Treg and DCreg are largely unknown. We recently showed that removal of midkine (MK) suppressed EAE due to an expansion of the Treg cell population as well as a decrease in the numbers of autoreactive Th1 and Th17 cells. MK decreased the Treg cell population by suppressing the phosphorylation of STAT5, which is essential for the expression of Foxp3, the master transcriptional factor of Treg cell differentiation. Furthermore, MK reduces the DCreg cell population by inhibiting the phosphorylation of STAT3, which is critical for DCreg development. Blockade of MK signalling by a specific RNA aptamer significantly elevated the population of DCreg and Treg cells and ameliorated EAE without detectable adverse effects. Therefore, the inhibition of MK may provide an effective therapeutic strategy against autoimmune diseases including MS. This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4. © 2013 The British Pharmacological Society.
Multiple sclerosis (MS) is an autoimmune neurological disease characterized by inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought as autoreactive Th1 and Th17 cell-mediated diseases. CD4+CD25+FoxP3+ regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and tolerogenic dendritic cells (DCreg) drive the development of inducible Treg cells. Thus, a dysfunction in the development of Treg and DCreg leads to the development of autoimmune diseases. However, the factors that regulate Treg and DCreg are largely unknown. We recently showed that removal of midkine (MK) suppressed EAE due to an expansion of the Treg cell population as well as a decrease in the numbers of autoreactive Th1 and Th17 cells. MK decreased the Treg cell population by suppressing the phosphorylation of STAT5, which is essential for the expression of Foxp3, the master transcriptional factor of Treg cell differentiation. Furthermore, MK reduces the DCreg cell population by inhibiting the phosphorylation of STAT3, which is critical for DCreg development. Blockade of MK signalling by a specific RNA aptamer significantly elevated the population of DCreg and Treg cells and ameliorated EAE without detectable adverse effects. Therefore, the inhibition of MK may provide an effective therapeutic strategy against autoimmune diseases including MS. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24460675
Zhu, Chaozhe; Jiang, Tianzi
In this work, T1-, T2- and PD-weighted MR images of multiple sclerosis (MS) patients, providing information on the properties of tissues from different aspects, are treated as three independent information sources for the detection and segmentation of MS lesions. Based on information fusion theory, a knowledge guided information fusion framework is proposed to accomplish 3-D segmentation of MS lesions. This framework consists of three parts: (1) information extraction, (2) information fusion, and (3) decision. Information provided by different spectral images is extracted and modeled separately in each spectrum using fuzzy sets, aiming at managing the uncertainty and ambiguity in the images due to noise and partial volume effect. In the second part, the possible fuzzy map of MS lesions in each spectral image is constructed from the extracted information under the guidance of experts' knowledge, and then the final fuzzy map of MS lesions is constructed through the fusion of the fuzzy maps obtained from different spectrum. Finally, 3-D segmentation of MS lesions is derived from the final fuzzy map. Experimental results show that this method is fast and accurate.
Alroughani, R; Ahmed, S F; Behbehani, R; Al-Hashel, J
Post-marketing studies are important to confirm what was established in clinical trials, and to assess the intermediate and long-term efficacy and safety. To assess efficacy and safety of fingolimod in multiple sclerosis (MS) in Kuwait. We retrospectively evaluated MS patients using the MS registries in 3 MS clinics. Relapsing remitting MS patients according to revised 2010 McDonald criteria who had been treated with fingolimod for at least 12 months were included. Primary endpoint was proportion of relapse-free patients at last follow-up. Secondary endpoints were mean change in EDSS and proportion of patients with MRI activity (gadolinium-enhancing or new/enlarging T2 lesions). 76 patients met the inclusion criteria. Mean age and mean disease duration were 34.43 and 7.82 years respectively. Mean duration of exposure to fingolimod was 18.50 months. Proportion of relapse-free patients was 77.6% at last follow-up. Mean EDSS score significantly improved (2.93 versus 1.95; p<0.0001) while 17.1% of patients continued to have MRI activity versus 77.6% at baseline (p<0.0001). Four patients stopped fingolimod due to disease breakthrough (n=3) and lymphadenitis (n=1). Fingolimod is safe and effective in reducing clinical and radiological disease activity in relapsing remitting MS patients. Our results are comparable to reported results of phase III studies. Copyright © 2014 Elsevier B.V. All rights reserved.
Buchanan, Robert J; Radin, Dagmar; Huang, Chunfeng
Caregiver burden is a multidimensional response to many factors associated with providing assistance to people with multiple sclerosis (MS), including physical, psychological, emotional, and social stressors. The aim of this analysis was to identify the characteristics of male informal caregivers, the assistance provided, and the people receiving assistance who were associated with the burden of care. Data were collected from a national survey (which included the Mental Component Summary of the SF-8 Health Survey) of informal caregivers and analyzed using an ordered logistic regression model to identify characteristics associated with burden among male informal caregivers. Greater burden among male caregivers was associated with significantly greater hours per week providing assistance (P = 0.009) and significantly greater restriction on the caregiver's ability to perform daily activities (P < 0.001) due to assisting the person with MS. We found a strong association between the perception of burden and the mental health status of the male caregiver (P < 0.001). Our findings highlight the strong association of caregiver burden and the Mental Component Summary of the SF-8. Reducing burden may improve the mental health of informal caregivers. Health professionals treating either male caregivers or people with MS should be sensitive to the impact that providing assistance has on the mental health of informal caregivers. Copyright Â© 2010. Published by EM Inc USA.
Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).
KhorshidAhmad, Tina; Acosta, Crystal; Cortes, Claudia; Lakowski, Ted M; Gangadaran, Surendiran; Namaka, Michael
Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.
Waldman, Amy; Ness, Jayne; Pohl, Daniela; Simone, Isabella Laura; Anlar, Banu; Amato, Maria Pia; Ghezzi, Angelo
Multiple sclerosis (MS) in children manifests with a relapsing-remitting MS (RRMS) disease course. Acute relapses consist of new neurologic deficits persisting greater than 24 hours, in the absence of intercurrent illness, and occur with a higher frequency early in the disease as compared to adult-onset RRMS. Most pediatric patients with MS recover well from these early relapses, and cumulative physical disability is rare in the first 10 years of disease. Brainstem attacks, poor recovery from a single attack, and a higher frequency of attacks portend a greater likelihood of future disability. Although prospective pediatric-onset MS cohorts have been established in recent years, there remains very limited prospective data detailing the longer-term clinical outcome of pediatric-onset MS into adulthood. Whether the advent of MS therapies, and the largely off-label access to such therapies in pediatric MS, has improved prognosis is unknown. MS onset during the key formative academic years, concurrent with active cognitive maturation, is an important determinant of long-term outcome, and is discussed in detail in another article in this supplement. Finally, increasing recognition of pediatric MS worldwide, recent launch of phase III trials for new agents in the pediatric MS population, and the clear imperative to more fully appreciate health-related quality of life in pediatric MS through adulthood highlight the need for standardized, validated, and robust outcome measures. © 2016 American Academy of Neurology.
Arnett, Peter A.
Several etiologic theories have been proposed to explain depression in the general population. Studying these models and modifying them for use in the multiple sclerosis (MS) population may allow us to better understand depression in MS. According to the reformulated learned helplessness (LH) theory, individuals who attribute negative events to internal, stable, and global causes are more vulnerable to depression. This study differentiated attributional style that was or was not related to MS in 52 patients with MS to test the LH theory in this population and to determine possible differences between illness-related and non-illness-related attributions. Patients were administered measures of attributional style, daily stressors, disability, and depressive symptoms. Participants were more likely to list non-MS-related than MS-related causes of negative events on the Attributional Style Questionnaire (ASQ), and more-disabled participants listed significantly more MS-related causes than did less-disabled individuals. Non-MS-related attributional style correlated with stress and depressive symptoms, but MS-related attributional style did not correlate with disability or depressive symptoms. Stress mediated the effect of non-MS-related attributional style on depressive symptoms. These results suggest that, although attributional style appears to be an important construct in MS, it does not seem to be related directly to depressive symptoms; rather, it is related to more perceived stress, which in turn is related to increased depressive symptoms. PMID:24453767
Fadil, Halim; Kelley, Roger E; Gonzalez-Toledo, Eduardo
There are a number of illnesses that can mimic multiple sclerosis (MS). This pretty much includes any pathological process that can reflect injury to the central nervous system either in a transient or progressive basis. Typically, MS presents itself in individuals in their teens up to their late 30s. On occasion, however, one can see MS present in patients in their 60s. However, in retrospect, many of these patients might have had subtle manifestations of MS in their younger years. Visual obscuration or visual loss can be a manifestation of retinal ischemia, retinal migraine, or optic neuritis which might or might not evolve into a clinical picture compatible with MS. Cranial neuropathy, long tract signs, sensory disturbance, and/or gait ataxia can be related to a number of different processes such as illicit drug use, neurosarcoidosis, neuro-Behcet's disease, neuroborreliosis, HIV-related disease, neurosyphilis, vascular occlusive disease including vasculitis, connective tissue disorders, acute disseminated encephalomyelitis (ADEM), idiopathic transverse myelitis, neuromyelitis optica (NMO), or tropical spastic paraparesis. In addition, a constellation of symptoms, with questionable objective findings, along with normal MRI imaging, normal CSF results, and normal evoked response testing, when indicated, might identify a conversion disorder or possibly malingering. There are now established criteria for the diagnosis of MS, but initial presentations can be less than "textbook" in nature. With the advent of immunomodulating therapy, it has become more important to diagnose MS more effectively earlier on in the course of the illness. Prior to specific therapy for MS, astute clinicians did not necessarily move with alacrity to establish the diagnosis in patients with subtle or transient manifestations. This was in recognition of the fact that little could be offered to alter the course of the illness and a number of patients might never experience further problems if
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.
English, Clayton; Aloi, Joseph J
Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients
Background: Specialist certification among interdisciplinary multiple sclerosis (MS) team members provides formal recognition of a specialized body of knowledge felt to be necessary to provide optimal care to individuals and families living with MS. Multiple sclerosis specialist certification (MS Certified Specialist, or MSCS) first became available in 2004 for MS interdisciplinary team members, but prior to the present study had not been evaluated for its perceived value, challenges, and satisfaction. Methods: A sample consisting of 67 currently certified MS specialists and 20 lapsed-certification MS specialists completed the following instruments: Perceived Value of Certification Tool (PVCT), Perceived Challenges and Barriers to Certification Scale (PCBCS), Overall Satisfaction with Certification Scale, and a demographic data form. Results: Satisfactory reliability was shown for the total scale and four factored subscales of the PVCT and for two of the three factored PCBCS subscales. Currently certified MS specialists perceived significantly greater value and satisfaction than lapsed-certification MS specialists in terms of employer and peer recognition, validation of MS knowledge, and empowering MS patients. Lapsed-certification MS specialists reported increased confidence and caring for MS patients using evidence-based practice. Both currently certified and lapsed-certification groups reported dissatisfaction with MSCS recognition and pay/salary rewards. Conclusions: The results of this study can be used in efforts to encourage initial certification and recertification of interdisciplinary MS team members. PMID:25061432
Harlow, Danielle E; Honce, Justin M; Miravalle, Augusto A
Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high-throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in preclinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients.
Farinotti, Mariangela; Vacchi, Laura; Simi, Silvana; Di Pietrantonj, Carlo; Brait, Lorenzo; Filippini, Graziella
Clinical and experimental data suggest that certain dietary regimens, particularly those including polyunsaturated fatty acids (PUFAs) and vitamins, might improve outcomes in people with multiple sclerosis (MS). Diets and dietary supplements are much used by people with MS in the belief that they might improve disease outcomes and overcome the effectiveness limits of conventional treatments.This is an update of the Cochrane review "Dietary intervention for multiple sclerosis" (first published on The Cochrane Library 2007, Issue 1). To answer MS patients' questions regarding the efficacy and safety of dietary regimens for MS. Can changes in dietary habits be an effective intervention for MS patients? Are the potential side effects of these interventions known, and have they been measured? Are potential interactions between dietary interventions and other curative or symptomatic treatments known and have they been studied? We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (November 2011), CENTRAL (The Cochrane Library 2011, Issue 4), MEDLINE (PubMed) (1966 to November 2011), EMBASE (embase.com) (1974 to November 2011) and reference lists of papers found. All controlled trials (randomised controlled trials (RCTs) and controlled clinical trials (CCTs)) on a specific dietary intervention, diet plan or dietary supplementation, except for vitamin D supplementation, compared to no dietary modification or placebo were eligible. Two review authors independently selected articles, assessed trial quality and extracted data. Data were entered and analysed in RevMan.Dichotomous data were summarised as relative risks (RR) with 95% confidence intervals (95% CI) using a random-effects model in the presence of heterogeneity (I² > 60%). Continuous data were analysed using weighted mean differences, determined by the difference between the pre- and post-intervention changes in the treatment and control groups. Six
Bagnato, Francesca; Hametner, Simon; Welch, Edward Brian
Magnetic resonance imaging (MRI) protocols that are designed to be sensitive to iron typically take advantage of (1) iron effects on the relaxation of water protons and/or (2) iron-induced local magnetic field susceptibility changes. Increasing evidence sustains the notion that imaging iron in brain of patients with multiple sclerosis (MS) may add some specificity toward the identification of the disease pathology. The present review summarizes currently reported in vivo and post mortem MRI evidence of (1) iron detection in white matter and grey matter of MS brains, (2) pathological and physiological correlates of iron as disclosed by imaging and (3) relations between iron accumulation and disease progression as measured by clinical metrics. PMID:23347601
Ardeshiry lajimi, Abdolreza; Hagh, Majid Farshdousti; Saki, Najmaldin; Mortaz, Esmaeil; Soleimani, Masoud; Rahim, Fakher
Multiple Sclerosis is an inflammatory disease of the central nervous system in which T cells experience a second phase of activation, which ultimately leads to axonal demyelination and neurological disability. The recent advances in stem cell therapies may serve as potential treatments for neurological disorders. There are broad types of stem cells such as neural, embryonic, mesenchymal and hematopoietic stem cells with unprecedented hope in treating many debilitating diseases. In this paper we will review the substantial literature regarding experimental and clinical use of these stem cells and possible mechanisms in the treatment of MS. These results may pave the road for the utilization of stem cells for the treatment of MS. PMID:24505515
Gay, Marie-Claire; Bungener, Catherine; Thomas, Sarah; Vrignaud, Pierre; Thomas, Peter W; Baker, Roger; Montel, Sébastien; Heinzlef, Olivier; Papeix, Caroline; Assouad, Rana; Montreuil, Michèle
Despite the high comorbidity of anxiety and depression in people with multiple sclerosis (MS), little is known about their inter-relationships. Both involve emotional perturbations and the way in which emotions are processed is likely central to both. The aim of the current study was to explore relationships between the domains of mood, emotional processing and coping and to analyse how anxiety affects coping, emotional processing, emotional balance and depression in people with MS. A cross-sectional questionnaire study involving 189 people with MS with a confirmed diagnosis of MS recruited from three French hospitals. Study participants completed a battery of questionnaires encompassing the following domains: i. anxiety and depression (Hospital Anxiety and Depression Scale (HADS)); ii. emotional processing (Emotional Processing Scale (EPS-25)); iii. positive and negative emotions (Positive and Negative Emotionality Scale (EPN-31)); iv. alexithymia (Bermond-Vorst Alexithymia Questionnaire) and v. coping (Coping with Health Injuries and Problems-Neuro (CHIP-Neuro) questionnaire. Relationships between these domains were explored using path analysis. Anxiety was a strong predictor of depression, in both a direct and indirect way, and our model explained 48% of the variance of depression. Gender and functional status (measured by the Expanded Disability Status Scale) played a modest role. Non-depressed people with MS reported high levels of negative emotions and low levels of positive emotions. Anxiety also had an indirect impact on depression via one of the subscales of the Emotional Processing Scale ("Unregulated Emotion") and via negative emotions (EPN-31). This research confirms that anxiety is a vulnerability factor for depression via both direct and indirect pathways. Anxiety symptoms should therefore be assessed systematically and treated in order to lessen the likelihood of depression symptoms.
Motl, Robert W; Sandroff, Brian M
Exercise training represents a behavioral approach for safely managing many of the functional, symptomatic, and quality of life consequences of multiple sclerosis (MS). This topical review paper summarizes evidence from literature reviews and meta-analyses, supplemented by recent individual studies, indicating that exercise training can yield small but important improvements in walking, balance, cognition, fatigue, depression, and quality of life in MS. The paper highlights limitations of research on exercise training and its consequences and future research directions and provides an overview for promotion of exercise training in MS based on recent prescriptive guidelines. Collectively, the evidence for the benefits of exercise training in MS suggests that the time is ripe for the promotion of exercise by healthcare providers, particularly neurologists as a central part of the clinical care and management of MS patients.
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.
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
Dargahi, Narges; Katsara, Maria; Tselios, Theodore; Androutsou, Maria-Eleni; Matsoukas, John
The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. PMID:28686222
Freedman, Mark S; Selchen, Daniel; Arnold, Douglas L; Prat, Alexandre; Banwell, Brenda; Yeung, Michael; Morgenthau, David; Lapierre, Yves
The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical recommendations in 2004 to assist clinicians in optimizing the use of disease-modifying therapies (DMT) in patients with relapsing multiple sclerosis. The CMSWG convened to review how disease activity is assessed, propose a more current approach for assessing suboptimal response, and to suggest a scheme for switching or escalating treatment. Practical criteria for relapses, Expanded Disability Status Scale (EDSS) progression and MRI were developed to classify the clinical level of concern as Low, Medium and High. The group concluded that a change in treatment may be considered in any RRMS patient if there is a high level of concern in any one domain (relapses, progression or MRI), a medium level of concern in any two domains, or a low level of concern in all three domains. These recommendations for assessing treatment response should assist clinicians in making more rational choices in their management of relapsing MS patients.
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.
Ahbeddou, N; Ait Ben Haddou, E; Hammi, S; Slimani, C; Regragui, W; Benomar, A; Yahyaoui, M
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.
Background Despite the commonly known benefits of exercise and physical activity evidence shows that persons Multiple Sclerosis (MS) are relatively inactive yet physical activity may be even more important in a population facing functional deterioration. No exercise is effective if it is not done and people with MS face unique barriers to exercise engagement which need to be overcome. We have developed and pilot tested a Multiple Sclerosis Tailored Exercise Program (MSTEP) and it is ready to be tested against general guidelines for superiority and ultimately for its impact on MS relevant outcomes. The primary research question is to what extent does an MS Tailored Exercise Program (MSTEP) result in greater improvements in exercise capacity and related outcomes over a one year period in comparison to a program based on general guidelines for exercise among people with MS who are sedentary and wish to engage in exercise as part of MS self-management. Methods/Design The proposed study is an assessor-blind, parallel-group, randomized controlled trial (RCT). The duration of the intervention will be one year with follow-up to year two. The targeted outcomes are exercise capacity, functional ambulation, strength, and components of quality of life including frequency and intensity of fatigue symptoms, mood, global physical function, health perception, and objective measures of activity level. Logistic regression will be used to test the main hypothesis related to the superiority of the MSTEP program based on a greater proportion of people making a clinically relevant gain in exercise capacity at 1 year and at 2 years, using an intention-to-treat approach. Sample size will be 240 (120 per group). Discussion The MS community is clearly looking for interventions to help alleviate the disabling sequelae of MS and promote health. Exercise is a well-known intervention which has known benefits to all, yet few exercise regularly. For people with MS, the role of exercise in MS
Amato, Maria Pia; Morra, Vincenzo Brescia; Falautano, Monica; Ghezzi, Angelo; Goretti, Benedetta; Patti, Francesco; Riccardi, Alice; Mattioli, Flavia
The aim of this consensus paper was to define the state of the art on cognitive assessment of persons with multiple sclerosis (PwMS), with the purpose of providing recommendations for the Italian centers involved in MS management. While there are no formal guidelines published regarding the assessment of cognitive function in MS, on the basis of an expert opinion meeting, held in Milan (Italy) on July 4, 2016, we report the recommendations of a panel of Italian experts including MS neurologists and neuropsychologists for the assessment and follow-up of cognitive function in adult MS subjects.
Stenager, E N; Stenager, E; Koch-Henriksen, N; Brønnum-Hansen, H; Hyllested, K; Jensen, K; Bille-Brahe, U
In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males and for patients with onset of MS before the age of 30 years and those diagnosed before the age of 40. The SMR was highest within the first five years after diagnosis. PMID:1640228
Messer, Michael M; Haller, Irina V
Objective: Depression is a common condition among patients with multiple sclerosis and often becomes resistant to oral antidepressants. We report a patient with multiple sclerosis who developed severe treatment-resistant depression and who was successfully treated with intravenous ketamine over the period of two years. Methods: Ketamine treatment protocol included an initial series of six treatments administered every other day, followed by a maintenance schedule. Ketamine was administered intravenously at 0.5mg/kg of ideal body weight over 40 minutes. Depression symptoms were measured using Beck Depression Index. Results: The patient's Beck Depression Index score prior to initiating ketamine treatment was 38, corresponding to severe depression. Response to treatment, defined as 50-percent reduction in Beck Depression Index score, was observed after five treatments. For this patient, the maintenance schedule ranged from a weekly treatment to one treatment every three weeks. During the two-year observation period, this patient was able to maintain a stable non-depressed mood and had no worsening of her MS symptoms. Conclusion: Ketamine may be an alternative treatment for resistant depression and may have a special use in patients with multiple sclerosis.
Sharma, Kanchan; Ballham, Samantha A; Inglis, Kirsty E A; Renowden, Shelley; Cottrell, David A
This report presents the 4th documented case worldwide of herpes simplex encephalitis in multiple sclerosis (MS) patients treated with natalizumab and the first case in the UK. Natalizumab is licensed for relapsing remitting multiple sclerosis in patients with high disease activity despite treatment with interferon-beta and patients with rapidly evolving severe, multiple sclerosis. Natalizumab is a monoclonal antibody targeted against alpha-4 integrin. Its proposed mechanism is attenuation of the migration of immune cells into the central nervous system. Reactivation of the JC virus causing progressive multifocal leucoencephalopathy (PML) and its association with natalizumab is well documented. This case adds support to the suggestion that natalizumab also increases the reactivation risk of CNS herpes simplex infection. A 34 year old woman was admitted with a generalized tonic-clonic seizure, fever and confusion following her 40th infusion of natalizumab. MRI demonstrated increased signal in the medial temporal lobes and EEG showed focal sharp waves over the temporal lobe. CSF PCR later confirmed herpes simplex virus. The patient made an eventual excellent recovery following 21 days of intravenous acyclovir therapy followed by 14 days of oral treatment. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.
Epstein-Barr virus (EBV) is a human DNA herpesvirus infecting more than 90% of the world's population. EBV is the etiological agent of infectious mononucleosis (Pfeiffer's disease). Furthermore, diverse malignancies such as Burkitt and Hodgkin lymphoma have been associated with EBV. More recently, a possible role for EBV has been suggested in chronic inflammatory/autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus as well as in multiple sclerosis (MS). MS is currently regarded as a disease with multifactorial etiology, EBV being one possible factor in MS manifestation: Infectious mononucleosis has been shown to increase the risk of developing MS later in life. EBV seroprevalence rates are higher in MS as compared to controls, in adult as well as in pediatric MS patients. Moreover, EBV antibody titres and EBV specific T-cells are increased in MS patients as compared to healthy individuals. Recently, CNS B-cells of MS patients have been reported to harbour EBV. However, there is still controversy whether EBV could be a causative agent as opposed to an innocent bystander in the pathogenesis of MS. This review summarizes current knowledge on the association of EBV and MS including a critical discussion of equivocal findings.
Zajicek, John Peter; Hobart, Jeremy C; Slade, Anita; Barnes, David; Mattison, Paul G
Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies. Patients with stable MS at 22 UK centres were randomised to oral cannabis extract (CE) (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medication. This double blind, placebo controlled, phase III study had a screening period, a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase. The primary outcome measure was a category rating scale (CRS) measuring patient reported change in muscle stiffness from baseline. Further CRSs assessed body pain, spasms and sleep quality. Three validated MS specific patient reported outcome measures assessed aspects of spasticity, physical and psychological impact, and walking ability. The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo (29.4% vs. 15.7%; OR 2.26; 95% CI 1.24 to 4.13; p=0.004, one sided). Similar results were found after 4 weeks and 8 weeks, and also for all further CRSs. Results from the MS scales supported these findings. The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed. NCT00552604.
Buchanan, Robert J.; Wang, Suojin; Zhu,Li; Kim, MyungSuk
Multiple sclerosis (MS) is the most common neurologic disease that disables younger adults, affecting as many as 350,000 Americans. Purpose: The objectives of this study are to develop profiles of nursing home residents with MS from rural areas and compare them to residents with MS who lived in urban areas, suburban areas, and large towns.…
Hansen, Madison R; Okuda, Darin T
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.
He, Dian; Guo, Rui; Zhang, Fubo; Zhang, Chao; Dong, Shuai; Zhou, Hongyu
This is an update of the Cochrane review "Rituximab for relapsing-remitting multiple sclerosis" (first published in The Cochrane Library 2011, Issue 12).More than 80% of individuals with multiple sclerosis (MS) experience a relapsing-remitting disease course. Approximately 10 years after disease onset, an estimated 50% of individuals with relapsing-remitting MS (RRMS) convert to secondary progressive MS. MS causes a major socioeconomic burden for the individual patient and for society. Effective treatment that reduces relapse frequency and prevents progression could impact both costs and quality of life and help to reduce the socioeconomic burden of MS. Alternative and more effective MS treatments with new modes of action and good safety are needed to expand the current treatment repertoire. It has been shown that B lymphocytes are involved in the pathophysiology of MS and rituximab lyses B-cells via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Current clinical trials are evaluating the role of rituximab as a B-cell depletion therapy in the treatment of RRMS. The safety and effectiveness of rituximab, as monotherapy or combination therapy, versus placebo or approved disease-modifying drugs (DMDs) (interferon-β (IFN-β), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab) to reduce disease activity for people with RRMS were assessed. The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (9 August 2013). We checked the references in identified trials and manually searched the reports (2004 to August 2013) from neurological associations and MS societies in Europe and America. We also communicated with researchers who were participating in trials on rituximab and contacted Genentech, BiogenIdec and Roche. All randomised, double-blind, controlled parallel group clinical trials with a length
Cohen, Jeffrey A.; Fox, Edward J.; Giovannoni, Gavin; Hartung, Hans-Peter; Havrdova, Eva; Schippling, Sven; Selmaj, Krzysztof W.; Traboulsee, Anthony; Compston, D. Alastair S.; Margolin, David H.; Thangavelu, Karthinathan; Chirieac, Madalina C.; Jody, Darlene; Xenopoulos, Panos; Hogan, Richard J.; Panzara, Michael A.; Arnold, Douglas L.
Objective: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy. Methods: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed. Results: Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3–5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1–5: −0.48%, −0.22%, −0.10%, −0.19%, −0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter. Conclusions: Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment. Classification of evidence: This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years. PMID:28835403
Miller, Robert C.; Lachance, Daniel H.; Lucchinetti, Claudia F.
Purpose: The aim of this study was a retrospective assessment of neurotoxicity in patients with multiple sclerosis (MS) receiving external beam radiotherapy (EBRT) to the brain. Methods and Materials: We studied 15 consecutively treated patients with MS who received brain EBRT. Neurologic toxicity was assessed with the Common Toxicity Criteria v.3.0. Results: Median follow-up for the 5 living patients was 6.0 years (range, 3.3-27.4 years). No exacerbation of MS occurred in any patient during EBRT. Five patients had Grade 4 neurologic toxicity and 1 had possible Grade 5 toxicity. Kaplan-Meier estimated risk of neurotoxicity greater than Grade 4 at 5more » years was 57% (95% confidence interval, 27%-82%). Toxicity occurred at 37.5 to 54.0 Gy at a median of 1.0 year (range, 0.2-4.3 years) after EBRT. Univariate analysis showed an association between opposed-field irradiation of the temporal lobes, central white matter, and brainstem and increased risk of neurotoxicity (p < 0.04). Three of 6 cases of toxicity occurred in patients treated before 1986. Conclusions: External beam radiotherapy of the brain in patients with MS may be associated with an increased risk of neurotoxicity compared with patients without demyelinating illnesses. However, this risk is associated with treatment techniques that may not be comparable to modern, conformal radiotherapy.« less
Frau, Jessica; Villar, Luisa Maria; Sardu, Claudia; Secci, Maria Antonietta; Schirru, Lucia; Ferraro, Diana; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Bedin, Roberta; Sola, Patrizia; Marrosu, Maria Giovanna; Cocco, Eleonora
Oligoclonal IgM (OCMB) and IgG (OCGB) bands were found to be associated with poor multiple sclerosis (MS) prognosis. We aimed to evaluate the prognostic value of OCMB/OCGB in a cohort of Sardinian MS patients. We recruited patients from the University of Cagliari. They underwent lumbar puncture for diagnostic purposes. Demographic and the following clinical data were recorded: clinical course; time to reach EDSS 3 and 6; EDSS at last follow-up; and MS treatments. The influence of gender, clinical course, age at onset, treatments, and OCGB/OCMB on reaching EDSS 3 was analysed using Cox regression. Kaplan-Meier curves were used to study the time to reach EDSS 3 considering OCMB/OCGB and therapies. The enrolled number of subjects was 503. The variables influencing the achievement of EDSS 3.0 were: male gender (p = 0.005); progressive course (p = 0.001); age at onset (p < 0.001); and disease-modifying drugs (p < 0.001). The OCGB/OCMB status was not significant. Kaplan-Meier analysis showed no difference in time to reach EDSS 3 for patients with and without OCGB or OCMB in both treated and non-treated groups. Our study did not confirm the poor prognostic value of OCMB/OCGB. These results may be influenced by the peculiar genetic background associated with the risk of MS in Sardinians.
Sarah, S A; Faradalila, W N; Salwani, M S; Amin, I; Karsani, S A; Sazili, A Q
The purpose of this study was to identify porcine-specific peptide markers from thermally processed meat that could differentiate pork from beef, chevon and chicken meat. In the initial stage, markers from tryptic digested protein of chilled, boiled and autoclaved pork were identified using LC-QTOF-MS. An MRM method was then established for verification. A thorough investigation of LC-QTOF-MS data showed that only seven porcine-specific peptides were consistently detected. Among these peptides, two were derived from lactate dehydrogenase, one from creatine kinase, and four from serum albumin protein. However, MRM could only detect four peptides (EVTEFAK, LVVITAGAR, FVIER and TVLGNFAAFVQK) that were consistently present in pork samples. In conclusion, meat species determination through a tandem mass spectrometry platform shows high potential in providing scientifically valid and reliable results even at peptide level. Besides, the specificity and selectivity offered by the proteomics approach also provide a robust platform for Halal authentication. Copyright © 2015 Elsevier Ltd. All rights reserved.
da Silva Frozza, Caroline O; da Silva Brum, Emyle; Alving, Anjali; Moura, Sidnei; Henriques, João A P; Roesch-Ely, Mariana
Red propolis, an exclusive variety of propolis found in the northeast of Brazil has shown to present antitumour activity, among several other biological properties. This article aimed to help to evaluate the underlying molecular mechanisms of the potential anticancer effects of red propolis on tumour, Hep-2, and non-tumour cells, Hek-293. Differentially expressed proteins in human cell lines were identified through label-free quantitative MS-based proteomic platform, and cells were stained with Giemsa to show morphological changes. A total of 1336 and 773 proteins were identified for Hep-2 and Hek-293, respectively. Among the proteins here identified, 16 were regulated in the Hep-2 cell line and 04 proteins in the Hek-293 line. Over a total of 2000 proteins were identified under MS analysis, and approximately 1% presented differential expression patterns. The GO annotation using Protein Analysis THrough Evolutionary Relationships classification system revealed predominant molecular function of catalytic activity, and among the biological processes, the most prominent was associated to cell metabolism. The proteomic profile here presented should help to elucidate further molecular mechanisms involved in inhibition of cancer cell proliferation by red propolis, which remain unclear to date. © 2016 Royal Pharmaceutical Society.
... Multiple Sclerosis: Symptoms, Diagnosis, Treatment and Latest NIH Research Past Issues / Spring 2012 Table of Contents Symptoms ... my MS will ever go away? Latest NIH Research Scientists continue their extensive efforts to create new ...
Blikman, Lyan Jm; van Meeteren, Jetty; Twisk, Jos Wr; de Laat, Fred Aj; de Groot, Vincent; Beckerman, Heleen; Stam, Henk J; Bussmann, Johannes Bj
Fatigue is a frequently reported and disabling symptom in multiple sclerosis (MS). To investigate the effectiveness of an individual energy conservation management (ECM) intervention on fatigue and participation in persons with primary MS-related fatigue. A total of 86 severely fatigued and ambulatory adults with a definite diagnosis of MS were randomized in a single-blind, two-parallel-arm randomized clinical trial to the ECM group or the information-only control group in outpatient rehabilitation departments. Blinded assessments were carried out at baseline and at 8, 16, 26 and 52 weeks after randomization. Primary outcomes were fatigue (fatigue subscale of Checklist Individual Strength - CIS20r) and participation (Impact on Participation and Autonomy scale - IPA). Modified intention-to-treat analysis was based on 76 randomized patients (ECM, n = 36; MS nurse, n=40). No significant ECM effects were found for fatigue (overall difference CIS20r between the groups = -0.81; 95% confidence interval (CI), -3.71 to 2.11) or for four out of five IPA domains. An overall unfavourable effect was found in the ECM group for the IPA domain social relations (difference between the groups = 0.19; 95% CI, 0.03 to 0.35). The individual ECM format used in this study did not reduce MS-related fatigue and restrictions in participation more than an information-only control condition.
Razazian, Nazanin; Yavari, Zeinab; Farnia, Vahid; Azizi, Akram; Kordavani, Laleh; Bahmani, Dena Sadeghi; Holsboer-Trachsler, Edith; Brand, Serge
Multiple sclerosis (MS) is a chronic progressive autoimmune disease impacting both body and mind. Typically, patients with MS report fatigue, depression, and paresthesia. Standard treatment consists of immune modulatory medication, though there is growing evidence that exercising programs have a positive influence on fatigue and psychological symptoms such as depression. We tested the hypothesis that, in addition to the standard immune regulatory medication, either yoga or aquatic exercise can ameliorate both fatigue and depression, and we examined whether these interventions also influence paresthesia compared with a nonexercise control condition. Fifty-four women with MS (mean age: M = 33.94 yr, SD = 6.92) were randomly assigned to one of the following conditions: yoga, aquatic exercise, or nonexercise control. Their existing immune modulatory therapy remained unchanged. Participants completed questionnaires covering symptoms of fatigue, depression, and paresthesia, both at baseline and on completion of the study 8 wk later. Compared with the nonexercise control condition and over time, fatigue, depression, and paresthesia decreased significantly in the yoga and aquatic exercise groups. On study completion, the likelihood of reporting moderate to severe depression was 35-fold higher in the nonexercise control condition than in the intervention conditions (yoga and aquatic exercising values collapsed). The pattern of results suggests that for females with MS and treated with standard immune regulatory medication, exercise training programs such as yoga and aquatic exercising positively impact on core symptoms of MS, namely, fatigue, depression, and paresthesia. Exercise training programs should be considered in the future as possible complements to standard treatments.
Escribano, Begoña M; Medina-Fernández, Francisco J; Aguilar-Luque, Macarena; Agüera, Eduardo; Feijoo, Montserrat; Garcia-Maceira, Fe I; Lillo, Rafael; Vieyra-Reyes, Patricia; Giraldo, Ana I; Luque, Evelio; Drucker-Colín, René; Túnez, Isaac
Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord. For this purpose, samples obtained from EAE rats and relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the clinical variables of the disease, i.e. oxidative damage and LBP, were established. Although the conclusions of this research are indeed relevant, further investigation would be necessary to establish the intrinsic mechanisms of the MS-oxidative stress-microbiota relationship.
Ren, Jinma; Ni, Huijuan; Kim, Minchul; Cooley, Kimberly L; Valenzuela, Reuben M; Asche, Carl V
The associations between allergies, antibiotics use, and multiple sclerosis (MS) remain controversial and their mediating or moderating effects have not yet been examined. We aimed to assess the direct and indirect influences of allergies and antibiotics use on MS development, and their interactions. A 1:3 matched case-control study was performed using the National Ambulatory Medical Care Survey database from 2006 to 2013 in the USA. Multiple sclerosis was identified based on the ICD-9 code (340.0) in any position. Cases were matched to their controls based on survey year, age, gender, race, payer type, region, and tobacco use. Allergy diseases and antibiotics prescriptions were extracted by ICD-9 code and drug classification code, respectively. Both generalized structural equation model and MacArthur approach were used to examine their intrinsic relationships. The weighted prevalence of MS was 133.7 per 100,000 visits. A total of 829 MS patients and 2441 controls were matched. Both respiratory tract allergies (OR = 0.29, 95% CI: 0.18, 0.49) and other allergies (OR = 0.38, 95% CI: 0.19, 0.77) were associated with a reduction of the risk of MS. Patients with respiratory tract allergies were more likely to use penicillin (OR = 8.73, 95% CI: 4.12, 18.53) and other antibiotics (OR = 3.77, 95% CI: 2.72, 5.21), and those with other allergies had a higher likelihood of penicillin use (OR = 4.15, 95% CI: 1.27, 13.54); however, the link between antibiotics use and MS was not confirmed although penicillin use might mediate the relationship between allergies and MS. The findings supported allergy as a protective factor for MS development. We also suggest antibiotics use might not be a suitable indicator of bacterial infection to investigate the cause of MS.
Vidal-Jordana, Angela; Montalban, Xavier
Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.
Miljković, Djordje; Spasojević, Ivan
Abstract The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286–2334. PMID:23473637
The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness. PMID:25694551
Grasso, Maria Grazia; Broccoli, Marco; Casillo, Paolo; Catani, Sheila; Pace, Luca; Pompa, Alessandra; Rizzi, Francesco; Troisi, Elio
The aim of this study was to evaluate the effectiveness of cognitive rehabilitation in a group of multiple sclerosis (MS) patients. Thirty-four patients were included in this study and randomly allocated either to treatment with multidisciplinary rehabilitation plus cognitive training or to treatment with multidisciplinary rehabilitation alone. After 3 months of cognitive treatment, the patients assigned to the rehabilitation plus cognitive training group displayed an improvement in the cognitive test of executive function and a marked improvement in quality of life (QoL). The patients treated with multidisciplinary rehabilitation without cognitive training improved in the physical composite score alone. Both groups of patients displayed an improvement in depression, though the improvement was confirmed at the 6-month follow-up examination (p = 0.036) only in patients treated with multidisciplinary rehabilitation plus cognitive training. Our results indicate that the multidisciplinary rehabilitation treatment is the best approach to treat MS. The specific effect of each treatment needs to be assessed to be able to determine its role within a multidisciplinary approach. Cognitive rehabilitation is an important aspect of this multidisciplinary approach insofar as it may improve the QoL of MS people. © 2017 S. Karger AG, Basel.
Zeqiraj, Kamber; Kruja, Jera; Kabashi, Serbeze; Muçaj, Sefedin
Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female--male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5), 14.9% (4-6.5), 6.8% (7-9).
Zeqiraj, Kamber; Kruja, Jera; Kabashi, Serbeze; Muçaj, Sefedin
Background and objectives: Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. Materials and methods: Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. Results: From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003–2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female – male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0–3.5), 14.9% (4–6.5), 6.8% (7–9). PMID:25568528
Zeqiraj, Kamber; Kruja, Jera; Kabashi, Serbeze; Muçaj, Sefedin
Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female - male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5), 14.9% (4-6.5), 6.8% (7-9).
Rosiak, Katarzyna; Zagożdżon, Paweł
Quality of life and needforsocial support in persons diagnosed with multiple sclerosis (MS) are to a large extent determined by the degree of their disability. The aim of the study was to analyze an association between specific forms of MS, subjectively perceived quality of life and social support. The study included subjects with established diagnosis of MS, treated at rehabilitation centers, hospitals and in a home setting, as well as the members of patient organizations. After being informed about objectives of the study, type of included tasks and way to complete them, each participant was handed out a set of questionnaires: Berlin Social Support Scales (Łuszczyńska, Kowalska, Schwarzer, Schulz), Quality of Life Questionnaire (WHOQOLBREF), as well as a survey developed specifically for the purposes of this project. The results were subjected to statistical analysis with STATA 12 package. The study included a total of 110 persons (67 women and 43 men). Quality of life overall, as well in physical, psychological, social relationships and environmental health domains, turned out to be particularly important in patients with primary-progressive MS. Irrespective of MS type, social support overall did not play a significant role on univariate analysis. However, subgroup analysis according to sex demonstrated that men with MS received social support four times less often than women. Quality of life in individuals with primary-progressive MS is significantly lower than in patients presenting with other types of this disease. Men with MS are more likely to present with worse scores for social support overall. They are less likely both to acknowledge the need for support and to realize the availability of support they actually need.
Milo, Ron; Kahana, Esther
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system characterized by relapses and remissions. The risk of acquiring this complex disease is associated with exposure to environmental factors in genetically susceptible individuals. The epidemiology of MS has been extensively studied. We review the geographic epidemiology of the disease, the influence of immigration, age at immigration, clustering and epidemics. Various presumptive risk factors are discussed such as ultraviolet radiation, vitamin D, Epstein-Barr virus and infectious mononucleosis, other infectious agents and non-infectious factors. Two different hypotheses, the hygiene hypothesis and the prevalence hypothesis, were proposed to explain these environmental risk factors for MS. The epidemiological data, combined with pathological and immunological data, may contribute to the debate whether MS is an autoimmune disease, a latent or persistent viral disease, or a neurodegenerative disease. 2009 Elsevier B.V. All rights reserved.
Shih, Tiffany; Wakeford, Craig; Meletiche, Dennis; Sussell, Jesse; Chung, Adrienne; Liu, Yanmei; Shim, Jin Joo; Lakdawalla, Darius
To illustrate a more comprehensive view of value associated with medicines treating a highly severe illness and to apply these insights to estimate the costs and benefits of 3 treatments for multiple sclerosis (MS): Avonex, Tysabri, and Tecfidera. Retrospective study spanning 2002 to 2013. We used economic theory to derive the value of therapy to patients with MS and to individuals who face the risk of contracting MS in the future, under the alternative assumptions that therapies were fully insured or paid for out of pocket. Models were parameterized through secondary data analysis and targeted literature review. Estimates of individual value were aggregated to the societal level using therapy-specific treatment prevalence rates. Aggregate consumer value was compared with manufacturer revenue. In the baseline model, Avonex, Tysabri, and Tecfidera generated $46.2 billion of total value to consumers, almost one-third of which accrued to those without MS. The total value to consumers was double manufacturer revenue. Results were qualitatively robust to the use of alternate epidemiological and economic parameters. We found that value to the healthy is positively related to disease severity, and that value to both the sick and the healthy are larger when costs are shared via health insurance. Theory predicts that treatments for severe disease provide "peace of mind" value to the healthy. Avonex, Tysabri, and Tecfidera have generated significant social value, a large majority of which accrues to consumers. Future economic valuations of medical technology should consider both the potential value to the healthy and the effects of insurance.
Šabanagić-Hajrić, Selma; Alajbegović, Azra
To evaluate the impacts of education level and employment status on health-related quality of life (HRQoL) in multiple sclerosis patients. This study included 100 multiple sclerosis patients treated at the Department of Neurology, Clinical Center of the University of Sarajevo. Inclusion criteria were the Expanded Disability Status Scale (EDSS) score between 1.0 and 6.5, age between 18 and 65 years, stable disease on enrollment. Quality of life (QoL) was evaluated by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Mann-Whitney and Kruskal-Wallis test were used for comparisons. Linear regression analyses were performed to evaluate prediction value of educational level and employment status in predicting MSQOL-54 physical and mental composite scores. Full employment status had positive impact on physical health (54.85 vs. 37.90; p les than 0.001) and mental health (59.55 vs. 45.90; p les than 0.001) composite scores. Employment status retained its independent predictability for both physical (r(2)=0.105) and mental (r(2)=0.076) composite scores in linear regression analysis. Patients with college degree had slightly higher median value of physical (49.36 vs. 45.30) and mental health composite score (66.74 vs. 55.62) comparing to others, without statistically significant difference. Employment proved to be an important factor in predicting quality of life in multiple sclerosis patients. Higher education level may determine better QOL but without significant predictive value. Sustained employment and development of vocational rehabilitation programs for MS patients living in the country with high unemployment level is an important factor in improving both physical and mental health outcomes in MS patients.
Hirotani, Makoto; Niino, Masaaki; Fukazawa, Toshiyuki; Yaguchi, Hiroaki; Nakamura, Masakazu; Kikuchi, Seiji; Sasaki, Hidenao
Type I interferons (IFNs), represented by IFN-α and β, activate immune effector cells belonging to the innate and adaptive immune systems. Plasmacytoid dendritic cells (pDCs) produce IFN-α in response to CpG DNA. We aimed to examine the impact of pDC-produced IFN-α on the adaptive immune system in Multiple Sclerosis (MS). Our results demonstrated that CpG DNA-induced IFN-α production was significantly decreased in PBMCs from MS patients. Decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were found in CpG DNA-treated PBMCs of healthy subjects unlike in those from MS patients. In samples pre-treated with IFN-α and IFN-β, decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were detected in PBMCs from MS patients. These results suggest that CpG DNA-induced decreased IFN-α production causes pro-inflammatory cytokine secretion, and either IFN-α or IFN-β induces anti-inflammatory cytokine secretion in the adaptive immune system in MS. Copyright © 2012 Elsevier Inc. All rights reserved.
Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh
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.
Dressler, Dirk; Bhidayasiri, Roongroj; Bohlega, Saeed; Chahidi, Abderrahmane; Chung, Tae Mo; Ebke, Markus; Jacinto, L Jorge; Kaji, Ryuji; Koçer, Serdar; Kanovsky, Petr; Micheli, Federico; Orlova, Olga; Paus, Sebastian; Pirtosek, Zvezdan; Relja, Maja; Rosales, Raymond L; Sagástegui-Rodríguez, José Alberto; Schoenle, Paul W; Shahidi, Gholam Ali; Timerbaeva, Sofia; Walter, Uwe; Saberi, Fereshte Adib
Botulinum toxin (BT) therapy is an established treatment of spasticity due to stroke. For multiple sclerosis (MS) spasticity this is not the case. IAB-Interdisciplinary Working Group for Movement Disorders formed a task force to explore the use of BT therapy for treatment of MS spasticity. A formalised PubMed literature search produced 55 publications (3 randomised controlled trials, 3 interventional studies, 11 observational studies, 2 case studies, 35 reviews, 1 guideline) all unanimously favouring the use of BT therapy for MS spasticity. There is no reason to believe that BT should be less effective and safe in MS spasticity than it is in stroke spasticity. Recommendations include an update of the current prevalence of MS spasticity and its clinical features according to classifications used in movement disorders. Immunological data on MS patients already treated should be analysed with respect to frequencies of MS relapses and BT antibody formation. Registration authorities should expand registration of BT therapy for spasticity regardless of its aetiology. MS specialists should consider BT therapy for symptomatic treatment of spasticity.
Spasticity is a prevalent and troublesome symptom for people with multiple sclerosis (MS). Common instruments to measure MS spasticity include the clinician-rated (modified) Ashworth scale and the patient-rated 0-10 spasticity Numerical Rating Scale (NRS). Current opinion is that measurement of MS spasticity should incorporate the patient's perspective. Other instruments to assess spasticity-associated symptoms such as the Penn spasms frequency scale, sleep quality NRS and pain NRS can assist in tracking MS spasticity evolution and inform management choices. Worsening spasticity reduces patient autonomy, impacts negatively on quality of life and increases health resource utilization and costs. Despite the wide range of issues associated with MS spasticity, undertreatment is common and standard treatment options (physiotherapy and classical oral therapies) often fail to provide adequate symptomatic control.
Gross, Catharina C.; Schulte-Mecklenbeck, Andreas; Rünzi, Anna; Kuhlmann, Tanja; Posevitz-Fejfár, Anita; Schwab, Nicholas; Schneider-Hohendorf, Tilman; Herich, Sebastian; Held, Kathrin; Konjević, Matea; Hartwig, Marvin; Dornmair, Klaus; Hohlfeld, Reinhard; Ziemssen, Tjalf; Klotz, Luisa; Meuth, Sven G.; Wiendl, Heinz
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) resulting from a breakdown in peripheral immune tolerance. Although a beneficial role of natural killer (NK)-cell immune-regulatory function has been proposed, it still needs to be elucidated whether NK cells are functionally impaired as part of the disease. We observed NK cells in active MS lesions in close proximity to T cells. In accordance with a higher migratory capacity across the blood–brain barrier, CD56bright NK cells represent the major intrathecal NK-cell subset in both MS patients and healthy individuals. Investigating the peripheral blood and cerebrospinal fluid of MS patients treated with natalizumab revealed that transmigration of this subset depends on the α4β1 integrin very late antigen (VLA)-4. Although no MS-related changes in the migratory capacity of NK cells were observed, NK cells derived from patients with MS exhibit a reduced cytolytic activity in response to antigen-activated CD4+ T cells. Defective NK-mediated immune regulation in MS is mainly attributable to a CD4+ T-cell evasion caused by an impaired DNAX accessory molecule (DNAM)-1/CD155 interaction. Both the expression of the activating NK-cell receptor DNAM-1, a genetic alteration consistently found in MS-association studies, and up-regulation of the receptor’s ligand CD155 on CD4+ T cells are reduced in MS. Therapeutic immune modulation of IL-2 receptor restores impaired immune regulation in MS by increasing the proportion of CD155-expressing CD4+ T cells and the cytolytic activity of NK cells. PMID:27162345
Tietjen, Kiira; Wilson, Marian; Amiri, Solmaz; Dietz, Jeremy
The goals of the study were to evaluate participant engagement and effects of an Internet-based, self-directed program for depressive symptoms. We compared outcomes of adults with multiple sclerosis (MS) with those of adults with other chronic diseases. This was a secondary analysis of a randomized controlled pilot study. Data were explored for differences between people diagnosed with MS and those with other chronic disease diagnoses. Data were obtained from 47 participants who participated in the original parent study (11 had MS). Participants with at least a moderate preexisting depressive symptom burden on the Patient Health Questionnaire (PHQ) were randomly divided into either a control group or the 8-week "Think Clearly About Depression" online depression self-management program. Study tools were administered at baseline, week 4, and week 8 to evaluate whether the online program improved depressive symptom self-management. Analysis examined differences between participants with and without an MS diagnosis in the treatment and control groups. Average baseline depressive symptom burdens were severe for those with MS and those without MS as measured by the PHQ. Number needed to treat analysis indicated that 1 in every 2 treatment group participants with MS found clinically significant reductions in depressive symptoms by week 8. All participants with MS completed all online program modules. When compared with those with other chronic diseases, participants with MS showed a trend toward greater improvements in the PHQ and health distress scores in addition to self-efficacy in exercising regularly, social/recreational activities, and controlling/managing depression at the end of 8 weeks. An online depressive symptom self-management program is acceptable to people with MS and may be helpful to address undertreated depressive symptoms. The number of participants limits available statistics and ability to generalize results.
Goodwin, Richard J A; Nilsson, Anna; Borg, Daniel; Langridge-Smith, Pat R R; Harrison, David J; Mackay, C Logan; Iverson, Suzanne L; Andrén, Per E
Analysis of whole animal tissue sections by MALDI MS imaging (MSI) requires effective sample collection and transfer methods to allow the highest quality of in situ analysis of small or hard to dissect tissues. We report on the use of double-sided adhesive conductive carbon tape during whole adult rat tissue sectioning of carboxymethyl cellulose (CMC) embedded animals, with samples mounted onto large format conductive glass and conductive plastic MALDI targets, enabling MSI analysis to be performed on both TOF and FT-ICR MALDI mass spectrometers. We show that mounting does not unduly affect small molecule MSI detection by analyzing tiotropium abundance and distribution in rat lung tissues, with direct on-tissue quantitation achieved. Significantly, we use the adhesive tape to provide support to embedded delicate heat-stabilized tissues, enabling sectioning and mounting to be performed that maintained tissue integrity on samples that had previously been impossible to adequately prepare section for MSI analysis. The mapping of larger peptidomic molecules was not hindered by tape mounting samples and we demonstrate this by mapping the distribution of PEP-19 in both native and heat-stabilized rat brains. Furthermore, we show that without heat stabilization PEP-19 degradation fragments can detected and identified directly by MALDI MSI analysis. Copyright © 2012 Elsevier B.V. All rights reserved.
Koda, Toru; Namba, Akiko; Nakatsuji, Yuji; Niino, Masaaki; Miyazaki, Yusei; Sugimoto, Tomoyuki; Kinoshita, Makoto; Takata, Kazushiro; Yamashita, Kazuya; Shimizu, Mikito; Fukazawa, Toshiyuki; Kumanogoh, Atsushi; Mochizuki, Hideki; Okuno, Tatsusada
We previously demonstrated that patients with multiple sclerosis (MS) of high serum Sema4A levels are resistant to IFN-β therapy. To further elucidate the role of serum Sema4A as a biomarker for therapeutic stratification in MS patients, it is important to clarify the efficacy of other disease-modifying drugs (DMD) in those with high serum Sema4A levels. Thus, in this study we investigated whether fingolimod has beneficial effects on MS patients with high Sema4A levels. We retrospectively analyzed annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) change in 56 relapsing-remitting multiple sclerosis (RRMS) patients who had been treated with fingolimod, including those who switched from IFN-β therapy. The levels of Sema4A in the sera were measured by sandwich ELISA. The implications of Sema4A on the efficacy of fingolimod were investigated by administering recombinant Sema4A-Fc and fingolimod to mice with experimental autoimmune encephalomyelitis (EAE). Retrospective analysis of MS cohort (17 high Sema4A and 39 low Sema4A) demonstrated the effectiveness of fingolimod in those with high serum Sema4A levels, showing reduction of ARR (from 1.21 to 0.12) and EDSS progression (from 0.50 to 0.04). Consistent with this observation, improvement in the disease severity of EAE mice receiving recombinant Sema4A-Fc was also observed after fingolimod treatment. These data suggest that fingolimod could serve as a candidate DMD for managing the disease activity of MS patients with high Sema4A levels.
Li, S; Clements, R; Sulak, M; Gregory, R; Freeman, E; McDonough, J
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids.
Li, S.; Clements, R.; Sulak, M.; Gregory, R.; Freeman, E.; McDonough, J.
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids. PMID:24078261
Rahmanzadeh, Reza; Brück, Wolfgang; Minagar, Alireza; Sahraian, Mohammad Ali
Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.
Ganesh, Aravind; Apel, Sabrina; Metz, Luanne; Patten, Scott
Given that vitamin D has a role in immunomodulation, and its levels appear to correlate with the development of Multiple Sclerosis (MS), it is conceivable that vitamin D may also influence disease activity in MS patients. In this regard, we conducted a systematic review investigating the evidence for: (1) the role of vitamin D in disease activity in MS, and (2) the therapeutic supplementation of vitamin D in MS. A comprehensive search of Medline, Embase, Pubmed, clinical trials registries, and conference proceedings, followed by screening and application of inclusion and exclusion criteria, yielded 57 studies for detailed appraisal. Following careful data extraction, studies addressing the role of vitamin D in disease activity were appraised on the basis of common epidemiological principles, while those involving vitamin D supplementation were assessed for potential bias using Cochrane guidelines. The overall evidence was interpreted in the context of the Bradford-Hill criteria of causation, and the number needed to treat (NNT) to prevent one patient from relapsing over a year was calculated for each supplementation study examining relapse rate. Both cross-sectional and longitudinal studies have fairly consistently demonstrated a strong positive correlation between vitamin D deficiency and subsequent relapse and/or disability in patients with MS. As well, there appears to be a negative correlation between vitamin D levels and inflammatory markers in MS patients, suggesting that vitamin D modifies serum cytokines to a more anti-inflammatory profile. Therefore, vitamin D fulfills the Bradford-Hill criteria for strong and consistent association, biological plausibility, and coherence. However, the criteria of temporality, dose-response, and experimental evidence are yet to be adequately met, although there is preliminary evidence from longitudinal studies and randomized clinical trials (RCTs) of supplementation that vitamin D can attenuate the autoimmune response in
Roeing, Kathleen L; Wajda, Douglas A; Motl, Robert W; Sosnoff, Jacob J
Despite the ubiquitous nature of gait impairment in multiple sclerosis (MS), there is limited information concerning the control of gait termination in individuals with MS. The purpose of this investigation was to examine planned gait termination in individuals with MS and healthy controls with and without cognitive distractors. Individuals with MS and age matched controls completed a series of gait termination tasks over a pressure sensitive walkway under non-distracting and cognitively distracting conditions. As expected the MS group had a lower velocity (89.9±33.3 cm/s) than controls (142.8±22.4 cm/s) and there was a significant reduction in velocity in both groups under the cognitive distracting conditions (MS: 73.9±30.7 cm/s; control: 120.0±25.9 cm/s). Although individuals with MS walked slower, there was no difference between groups in the rate a participant failed to stop at the target (i.e. failure rate). Overall failure rate had a 10-fold increase in the cognitively distracting condition across groups. Individuals with MS were more unstable during termination. Future research examining the neuromuscular mechanisms contributing to gait termination is warranted. Copyright © 2015 Elsevier B.V. All rights reserved.
Lucas, R M; Hughes, A M; Lay, M-L J; Ponsonby, A-L; Dwyer, D E; Taylor, B V; Pender, M P
This review of the considerable evidence linking Epstein-Barr virus (EBV) infection to risk and disease progression in multiple sclerosis (MS) builds on the background to the virus and its interactions with the human host available in the online supplement (see supplement, available online only). The evidence for a similarity in the geographic patterns of occurrence of MS and EBV infection (with infectious mononucleosis or EBV specific serology used as surrogate markers), when reviewed critically, is very limited. There is strong evidence however that people with MS are more likely to report a past history of infectious mononucleosis (thought to represent initial EBV infection at an older age), and higher titres of EBV specific antibodies are associated with an increased risk of developing MS. Elevated levels of the latter are apparent many years before MS onset (compared with non-MS controls) and there is a dose-response relationship between MS risk and antibody titre, with antibodies to the EBV nuclear antigen-1 particularly important. The evidence in relation to EBV DNA load in blood or CSF is conflicting, as is that in relation to T cell responses to EBV. Several hypotheses that have been proposed to explain the links between EBV and MS risk are reviewed and gaps requiring further research are identified.
Zahoor, Insha; Haq, Ehtishamul
Multiple sclerosis (MS) 1 is a chronic neurodegenerative disease involving destruction of the myelin sheath around axons of the brain, spinal cord and optic nerve. There has been a tremendous transformation in its perspective across globe. In recent years, its prevalence has changed dramatically worldwide and India is no exception. Initially, MS was believed to be more common in the Caucasians of Northern Europe and United States; however, it has been found to be present in Indian subcontinent as well. There has been a considerable shift in MS prevalence in India and this has really changed the notion of considering India as a low risk zone for MS. In this review, a concise overview and latest update on changing scenario of MS in India is presented along with some major challenges regarding it persisting across globe even today. In India, remarkable upsurge is needed in carrying out large scale population-based epidemiological studies to get an idea about the true incidence and prevalence rates of MS viz a viz disease burden. Through this review, we have probably tried to identify the actual picture of MS prevalence in India and this could serve as harbinger for upcoming research and at the same time it would definitely aid in working out future strategies for MS management in the country. Copyright © 2017 Elsevier B.V. All rights reserved.
Raggi, Alberto; Covelli, Venusia; Schiavolin, Silvia; Scaratti, Chiara; Leonardi, Matilde; Willems, Michelle
To explore which variables are associated to or determinants of work-related difficulties or unemployment in persons with multiple sclerosis (MS). Papers published between 1993 and February 2015 were included. Quality was judged as poor, acceptable, good or excellent. Determinants were extracted from prospective and retrospective data, associated variables from cross-sectional data; variables were grouped by similarity. Evidence was judged as strong if there were at least two good studies reporting the same results; limited if there was only one good and some acceptable studies. Forty-two papers were selected, for a total of 31,192 patients (75% females). Work-related difficulties were referred as unemployment, lower amount of worked hours or job cessation. Strong evidence of impact over work-related difficulties was found for a core set of variables, i.e., expanded disability status scale, MS duration, patients' age, fatigue and walking problems. Little evidence exists on the impact of contextual factors. Most of the variables identified as associated to or determinants of work-related difficulties can be treated through rehabilitative interventions. It is important that future research addresses not only unemployment issues in MS, but also the amount and severity of problems affecting work-related tasks relying on specific assessment instruments. Multiple sclerosis (MS) affects young persons of working age and limitation in work activities is part of MS-related disability, but they are not consistently addressed in MS research: EDSS, MS duration, patients' age, fatigue, walking problems, cognitive and neuropsychological impairments were the factors most commonly found as associated to or determinant of difficulties with work. Evidence exists that rehabilitation interventions are effective for fatigue, cognitive impairment, mobility and walking difficulties. However, research did not address the impact of rehabilitation programmes on vocational outcomes
Brichetto, Giampaolo; Spallarossa, Patricio; de Carvalho, Maria L Lopes; Battaglia, Mario A
Improvement of sensory strategies is a relevant part of balance rehabilitation in multiple sclerosis (MS). This study aimed to Assess the effectiveness of visual-feedback exercises in improving balance in MS. We divided 36 patients into Wii and control-treated groups that underwent balance rehabilitation. Outcomes were obtained for Berg Balance Scale (BBS), Modified Fatigue Impact Scale, and sway area under conditions of opened and closed eyes. BBS showed a statistically significant improvement (from 49.6 to 54.6 points, p < 0.05) in the Wii group. Interactive visual-feedback exercises such as Wii could be more effective than the current standard protocol in improving balance disorders in MS.
Mateen, Farrah J; Manalo, Natalie C; Grundy, Sara J; Houghton, Melissa A; Hotan, Gladia C; Erickson, Hans; Videnovic, Aleksandar
Fatigue is the most commonly reported symptom among multiple sclerosis (MS) patients, more than a quarter of whom consider fatigue to be their most disabling symptom. However, there are few effective treatment options for fatigue. We aim to investigate whether supplemental exposure to bright white light will reduce MS-associated fatigue. Eligible participants will have clinically confirmed multiple sclerosis based on the revised McDonald criteria (2010) and a score ≥36 on the Fatigue Severity Scale (FSS). Participants will be randomized 1:1 to bright white light (10,000 lux; active condition) or dim red light (<300 lux; control condition) self-administered for 1 hour twice daily. The study will include a 2-week baseline period, a 4-week treatment period, and a 4-week washout period. Participants will record their sleep duration, exercise, caffeine, and medication intake daily. Participants will record their fatigue using the Visual Analogue Fatigue Scale (VAFS) 4 times every third day, providing snapshots of their fatigue level at different times of day. Participants will self-report their fatigue severity using FSS on 3 separate visits: at baseline (week 0), following completion of the treatment phase (week 6), and at study completion (week 10). The primary outcome will be the change in the average FSS score after light therapy. We will perform an intention-to-treat analysis, comparing the active and control groups to assess the postintervention difference in fatigue levels reported on FSS. Secondary outcome measures include change in global VAFS scores during the light therapy and self-reported quality of life in the Multiple Sclerosis Quality of Life-54. We present a study design and rationale for randomizing a nonpharmacological intervention for MS-associated fatigue, using bright light therapy. The study limitations relate to the logistical issues of a self-administered intervention requiring frequent participant self-report in a relapsing condition
Weigel, Kelsey J.; Lynch, Sharon G.; LeVine, Steven M.
Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen. PMID:24397846
Kelleher, Kevin John; Spence, William; Solomonidis, Stephan; Apatsidis, Dimitrios
Multiple sclerosis (MS) is an autoimmunogenic disease involving demyelination within the central nervous system. Many of the typical impairments associated with MS can affect gait patterns. With walking ability being one of the most decisive factors when assessing quality of life and independent living, this review focuses on matters, which are considered of significance for maintaining and supporting ambulation. This article is an attempt to describe current research and available interventions that the caring healthcare professional can avail of and to review the present trends in research to further these available options. Evidence-based rehabilitation techniques are of interest in the care of patients with MS, given the various existing modalities of treatment. In this review, we summarise the primary factors affecting ambulation and highlight available treatment methods. We review studies that have attempted to characterise gait deficits within this patient population. Finally, as ambulatory rehabilitation requires multidisciplinary interventions, we examine approaches, which may serve to support and maintain ambulation within this patient group for as long as possible.
Flachenecker, Peter; Khil, Laura; Bergmann, Sverrir; Kowalewski, Mariusz; Pascu, Ion; Pérez-Miralles, Francisco; Sastre-Garriga, Jaume; Zwingers, Thomas
The MS-ID (Multiple Sclerosis Information Dividend) project was initiated by the European Multiple Sclerosis Platform (EMSP) in 2007 in order to identify and address major inequalities of MS treatment and care and thus eliminate disparities across the EU. One major approach to reach these goals in the longer term is the implementation of a European MS register for MS. The feasibility of an EU MS register was piloted among five countries (Germany, Iceland, Poland, Romania and Spain). Each country liaised with one documentation centre. Countries and test centres were both chosen in a way that a heterogeneous health care structure was provided. After reaching consensus about the data set, comprehension and acceptability of the two questionnaires-representing both the physician's and the patient's perspective-were tested with 20 MS patients in each country. In a 6-month data collection period, data from 547 patients were recorded. Most sections of the questionnaires were available for more than 90% of patients. The results obtained from the pilot phase of the European MS register indicate that it is feasible to collect standardized data across Europe. Thus, the European MS register may be a valuable instrument to compare treatment and care of MS across countries, estimate the cost of MS in Europe and monitor the implementation of and adherence to guidelines. It may help to reduce the disparities in MS care and treatment throughout Europe and eventually improve the quality of life of people with MS.
Minden, Sarah L; Feinstein, Anthony; Kalb, Rosalind C; Miller, Deborah; Mohr, David C; Patten, Scott B; Bever, Christopher; Schiffer, Randolph B; Gronseth, Gary S; Narayanaswami, Pushpa
To make evidence-based recommendations for screening, diagnosing, and treating psychiatric disorders in individuals with multiple sclerosis (MS). We reviewed the literature (1950 to August 2011) and evaluated the available evidence. Clinicians may consider using the Center for Neurologic Study Emotional Lability Scale to screen for pseudobulbar affect (Level C). Clinicians may consider the Beck Depression Inventory and a 2-question tool to screen for depressive disorders and the General Health Questionnaire to screen for broadly defined emotional disturbances (Level C). Evidence is insufficient to support/refute the use of other screening tools, the possibility that somatic/neurovegetative symptoms affect these tools' accuracy, or the use of diagnostic instruments or clinical evaluation procedures for identifying psychiatric disorders in MS (Level U). Clinicians may consider a telephone-administered cognitive behavioral therapy program for treating depressive symptoms (Level C). Although pharmacologic and nonpharmacologic therapies are widely used to treat depressive and anxiety disorders in individuals with MS, evidence is insufficient to support/refute the use of the antidepressants and individual and group therapies reviewed herein (Level U). For pseudobulbar affect, a combination of dextromethorphan and quinidine may be considered (Level C). Evidence is insufficient to determine the psychiatric effects in individuals with MS of disease-modifying and symptomatic therapies and corticosteroids; risk factors for suicide; and treatment of psychotic disorders (Level U). Research is needed on the effectiveness in individuals with MS of pharmacologic and nonpharmacologic treatments frequently used in the non-MS population.
Krupp, L B; Christodoulou, C; Melville, P; Scherl, W F; MacAllister, W S; Elkins, L E
To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS). This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change. Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010). Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.
Ludwig, Michael D; Zagon, Ian S; McLaughlin, Patricia J
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
Sabanciogullari, Vedat; Cevik, Seyda; Karacan, Kezban; Bolayir, Ertugrul; Cimen, Mehmet
Objective: To examine dermatoglyphic features to clarify implicated genetic predisposition in the etiology of multiple sclerosis (MS). Methods: The study was conducted between January and December 2013 in the Departments of Anatomy, and Neurology, Cumhuriyet University School of Medicine, Sivas, Turkey. The dermatoglyphic data of 61 patients, and a control group consisting of 62 healthy adults obtained with a digital scanner were transferred to a computer environment. The ImageJ program was used, and atd, dat, adt angles, a-b ridge count, sample types of all fingers, and ridge counts were calculated. Results: In both hands of the patients with MS, the a-b ridge count and ridge counts in all fingers increased, and the differences in these values were statistically significant. There was also a statistically significant increase in the dat angle in both hands of the MS patients. On the contrary, there was no statistically significant difference between the groups in terms of dermal ridge samples, and the most frequent sample in both groups was the ulnar loop. Conclusions: Aberrations in the distribution of dermatoglyphic samples support the genetic predisposition in MS etiology. Multiple sclerosis susceptible individuals may be determined by analyzing dermatoglyphic samples. PMID:25274586
Lau, Stephanie; Penner, Iris; Heesen, Christoph; Moritz, Steffen
Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system of potential autoimmune origin that is frequently associated with psychological disorders and cognitive deficits, as well as with fatigue, stress, and psychosocial burden. These factors often cause decreased quality of life, social withdrawal, and unemployment. We describe the development of a cognitive-behavioral group intervention based on the concept of metacognition and evaluation of the feasibility and acceptance of the program as a rehabilitation tool. Methods: Metacognitive Training in MS (MaTiMS) consists of six modules, each 90 minutes in duration. We tested acceptance and design of the program in six focus groups (entire sample, n = 27). Framework analysis of transcripts was used to identify key topics and categories. Program modules were revised in accordance with appropriate recommendations of focus group members. We subsequently evaluated MaTiMS in two groups (n = 5, n = 6) in a rehabilitation center. Neuropsychological functioning as well as coping self-efficacy, depression, stress, perceived cognitive deficit, fatigue, and quality of life were assessed. Acceptance of MaTiMS from the patient perspective was also studied. Results: The modules were highly accepted by patients. Pre-post assessments showed significant improvements in the Coping Self Efficacy Scale (P = .007), the Würzburger Fatigue Inventory for MS Score (P = .028), and the Hamburg Quality of Life Questionnaire in Multiple Sclerosis Mood subscale (P = .046). Conclusions: These preliminary results suggest that MaTiMS represents a feasible psychological group training program that may foster improvements in self-efficacy, fatigue, and mood. The next step will be an evaluation of the program in a randomized controlled trial. PMID:26052258
Garcia, J R; Rodriguez, S; Sosa Henriquez, M; Batista, E; Corujo, E; Font de Mora Turon, A; Hernandez Hernandez, D; Betancor Leon, P
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.
Giacobbi, Peter R., Jr.; Dietrich, Frederick; Larson, Rebecca; White, Lesley J.
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…
Roessler, Richard T.; Fitzgerald, Shawn M.; Rumrill, Phillip D.; Koch, Lynn C.
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…
Dwyer, Michael G; Bergsland, Niels; Ramasamy, Deepa P; Jakimovski, Dejan; Weinstock-Guttman, Bianca; Zivadinov, Robert
Lesion accrual in multiple sclerosis (MS) is an important and clinically relevant measure, used extensively as an imaging trial endpoint. However, lesions may also shrink or disappear entirely due to atrophy. Although generally ignored or treated as a nuisance, this phenomenon may actually be an important stand-alone imaging biomarker. Therefore, we investigated the rate of brain lesion loss due to atrophy (atrophied lesion volume) in MS subtypes compared to baseline lesion volume and to new and enlarging lesion volumes, and evaluated the independent predictive value of this phenomenon for clinical disability. A total of 192 patients (18 clinically isolated syndrome, 126 relapsing-remitting MS, and 48 progressive) received 3T magnetic resonance imaging at baseline and 5 years. Lesions were quantified at baseline, and new/enlarging lesion volumes were calculated over the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived cerebrospinal fluid partial volume maps. Measures were compared between disease subgroups, and correlations with disability change (Expanded Disability Status Scale [EDSS]) were evaluated. Hierarchical regression was employed to determine the unique additive value of atrophied lesion volume. Atrophied lesion volume was different between MS subtypes (P = .02), and exceeded new lesion volume accumulation in progressive MS (298.1 vs. 75.5 mm 3 ). Atrophied lesion volume was the only significant correlate of EDSS change (r = .192 relapsing, r = .317 progressive, P < .05), and explained significant additional variance when controlling for brain atrophy and new/enlarging lesion volume (R 2 .092 vs. .045, P = .003). Atrophied lesion volume is a unique and clinically relevant imaging marker in MS, with particular promise in progressive MS. Copyright © 2018 by the American Society of Neuroimaging.
Alali, Dalal; Ballard, Kirrie; Bogaardt, Hans
Dysphagia or swallowing difficulties have been reported to be a concern in adults with multiple sclerosis (MS). This problem can result in several complications including aspiration pneumonia, reduced quality of life and an increase in mortality rate. No previous systematic reviews on treatment effects for dysphagia in MS have been published. The main objective of this study is to summarise and qualitatively analyse published studies on treatment effects for dysphagia in MS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied to conduct a systematic search of seven databases, using relevant key words, and subsequent analysis of the identified studies. The studies were required to meet all three inclusion criteria of including a statement on intention to treat, or measure the effects of treatment for dysphagia in adults with MS and data on treatment outcomes for at least one adult diagnosed with MS. Retained studies were evaluated by two independent reviewers using a critical appraisal tool. This study has not been registered. A total of 563 studies were identified from the database searches. After screening and assessment of full articles for eligibility, five studies were included in the review. Three examined electrical stimulation and two examined the use of botulinum toxin. One study testing electrical stimulation was a randomised controlled trial, two were well-designed case series and two were case series lacking experimental control. All studies reported some positive effects on dysphagia; however, treatments that involved the use of electrical stimulation showed larger effect sizes. There is a paucity of evidence to guide treatment of dysphagia in MS, with only electrical stimulation and botulinum toxin treatment represented in the literature search conducted here. While both treatments show initial promise for reducing the swallowing impairment, they require further research using well-controlled experimental
Cree, Bruce A C; Stuart, William H; Tornatore, Carlo S; Jeffery, Douglas R; Pace, Amy L; Cha, Choon H
Patients with multiple sclerosis (MS) who are of African descent experience a more aggressive disease course than patients who are of white race/ethnicity. In phase 3 clinical trials (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]), natalizumab use significantly improved clinical and magnetic resonance imaging outcomes over 2 years in patients with relapsing MS. Because patients of African descent may be less responsive to interferon beta treatment than patients of white race/ethnicity, the efficacy of natalizumab therapy in this population is clinically important. To evaluate the efficacy of natalizumab use in patients of African descent with relapsing MS. Post hoc analysis. Academic research. Patients of African descent with relapsing MS who received natalizumab or placebo in the phase 3 AFFIRM study and those who received natalizumab plus intramuscular interferon beta-1a or placebo plus intramuscular interferon beta-1a in the phase 3 SENTINEL study. Efficacy of natalizumab use in patients of African descent with relapsing MS who participated in the AFFIRM or SENTINEL trial. Forty-nine patients of African descent participated in AFFIRM (n = 10) or SENTINEL (n = 39). Demographic and baseline disease characteristics were similar between patients treated with natalizumab (n = 21) or placebo (n = 28). Natalizumab therapy significantly reduced the annualized MS relapse rate by 60% (0.21 vs 0.53 in the placebo group, P = .02). Compared with placebo use, natalizumab therapy also significantly reduced the accumulation of lesions observed on magnetic resonance imaging over 2 years: the mean number of gadolinium-enhancing lesions was reduced by 79% (0.19 vs 0.91, P = .03), and the mean number of new or enlarged T2-weighted lesions was reduced by 90% (0.88 vs 8.52, P = .008). Natalizumab therapy
Shimizu, Yoshibumi; Ishikawa, Masaki; Gotoh, Mari; Fukasawa, Keiko; Yamamoto, Shinji; Iwasa, Kensuke; Yoshikawa, Keisuke; Murakami-Murofushi, Kimiko
Cyclic phosphatidic acid (cPA), an analog of lysophosphatidic acid, is involved in the regulation of many cellular processes. A sensitive and specific method to quantify the molecular species of cPA is important for studying the physiological and pathophysiological roles of cPA. Here, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantification method for the simultaneous detection of cPA species having various fatty acids (16:0, 18:0, 18:1, and 18:2) as well as 2-carba-cPA, a chemically synthesized analog of cPA. Chromatography was performed using a reversed-phase C18 column. cPA species were detected using a triple quadrupole mass spectrometer. cPA 17:0 was used as an internal standard. Intra- and interday precision values (CV%) were within 10%. The linear range of detection for each cPA species was 0.01 μg/mL to 5 μg/mL, with correlation coefficients of 0.998 or higher. The developed method was applied to the quantification of cPA species in mouse plasma and organs. The concentrations of cPA 16:0, 18:0, and 18:1 were revealed to be significantly reduced in the brains of cuprizone-treated mice, a model of multiple sclerosis, compared with control mice. These findings could be important for understanding the roles of cPA in the neurodegenerative processes associated with multiple sclerosis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Postlethwaite, Arnold E.; Harris, L. Jeff; Raza, Syed H.; Kodura, Swapna; Akhigbe, Titilola
Importance of the field Systemic-sclerosis (SSc) is an uncommon autoimmune disease with variable degrees of fibroproliferation in blood vessels and certain organs of the body. Presently, there is no cure for SSc. The purpose of this article is to review the current literature regarding pathogenesis and treatment of complications of SSc. Areas covered in this review All available articles regarding research related to SSc pathogenesis and treatment listed in the PubMed.gov database were searched, relevant articles were then reviewed and used as sources of information for this review. What the reader will gain This review attempts for the reader to highlight some current thought regarding mechanisms of SSc pathogenesis and how autoimmunity relates to vascular changes and fibrogenesis of the disease plus provide a review of results of completed clinical trials and current on-going clinical trials that address organ specific or global therapies for this disease which can aid physicians who provide medical care for patients with SSc. Take home message SSc is a complex autoimmune disease, the pathogenesis of which although not completely understood is under active study, and new insights into pathogenesis are continuously being discovered. Although there is no effective disease modifying treatment for patients with SSc, quality of life, morbidity and mortality can be improved by using targeted therapy directed at affecting the consequences of damage to lungs, blood vessels, kidneys and the gastrointestinal tract. Innovative approaches to treating SSc are under intense investigation. PMID:20210685
Kargarfard, Mehdi; Etemadifar, Masoud; Baker, Peter; Mehrabi, Maryam; Hayatbakhsh, Reza
To examine the effectiveness of aquatic exercise training on fatigue and health-related quality of life (HRQOL) in women with multiple sclerosis (MS). Randomized controlled trial, 4-week and 8-week follow-up. Referral center of a multiple sclerosis society. Women (N=32) diagnosed with relapsing-remitting MS (mean age ± SD, 32.6±8.0y) were recruited into this study. After undergoing baseline testing by a neurologist, participants were randomly assigned to either an intervention (aquatic exercise) or a control group. The intervention consisted of 8 weeks supervised aquatic exercise in a swimming pool (3 times a week, each session lasting 60min). At baseline, 4 weeks, and 8 weeks, fatigue and HRQOL were assessed by a blind assessor using the Modified Fatigue Impact Scale and the Multiple Sclerosis Quality of Life-54 questionnaire, respectively. A mixed-model approach to repeated-measures analysis of variance was used to detect within- and between-subject effects. Findings are based on 21 patients (10 from the exercise group and 11 from the control group) who had data available on outcomes. There was no significant difference between the 2 groups at the baseline. Patients in the aquatic exercise group showed significant improvements in fatigue and subscores of HRQOL after 4 and 8 weeks compared with the control group. Results obtained from the intention-to-treat analysis were consistent with those of per-protocol analysis. The findings suggest that aquatic exercise training can effectively improve fatigue and HRQOL of patients with MS and should be considered in the management of this relatively common public health problem. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Fraser, Robert; Ehde, Dawn; Amtmann, Dagmar; Johnson, Kurt L.; Johnson, Erica; Kraft, George H.
People with multiple sclerosis (MS) must manage the day-to-day effects of the disease on their lives. Self-management interventions may be helpful in this challenge. An international, multidisciplinary consensus conference was held on November 15, 2010, by the University of Washington's Rehabilitation Research and Training Center for Multiple Sclerosis (MS RRTC), with funding from the Consortium of Multiple Sclerosis Centers (CMSC) and the National Institute on Disability and Rehabilitation Research (NIDRR), to discuss the concept of self-management for people with MS. The specific goals of the consensus conference were as follows: 1) review the current research on self-management and related issues in chronic disability and specifically in MS; 2) review optimal research methodologies, outcome measurement tools, program planning frameworks, and dissemination strategies for self-management research; and 3) establish recommendations on the next steps necessary to develop, adapt, and test self-management interventions for people with MS. The consensus conference and this document are the initial steps toward achieving the stated goals. Participants in the consensus conference concluded that it is necessary to: 1) define an empirically based conceptual model of self-management for people with MS; 2) establish reliable and valid self-management outcome measures; 3) use best practices to validate models of self-management interventions; and 4) plan dissemination and knowledge translation of interventions once their effectiveness is established. PMID:24453769
Valvano, Abbey K; Rollock, Michael J D; Hudson, William H; Goodworth, Marie-Christine Rutter; Lopez, Eliot; Stepleman, Lara
This study sought to explore relationships between sexual satisfaction, sexual communication and relationship satisfaction in people living with multiple sclerosis (MS). Specifically, sexual satisfaction was evaluated as a moderator between sexual communication and relationship satisfaction. Individuals diagnosed with MS and being treated in a hospital-based MS clinic in the southeastern United States (n = 58) completed measures of sexual satisfaction, sexual communication, sexual dysfunction, relationship quality, depression, level of disability, and frequency of sex-related communication and behaviors in a cross-sectional survey design. Sexual satisfaction moderated the relationship between quality of sexual communication and relationship quality, controlling for depression and frequency of sexual behavior and sexual communication. Directionality was examined in a 2nd regression analysis, in which the predictor and outcome variables were switched, which was also significant. Additionally, depression most strongly predicted relationship dissatisfaction. Findings help to establish sexual satisfaction as a moderator between sexual communication and relationship satisfaction, although directionality cannot be supported. Results also highlight the role of depression in overall relationship functioning and support the biopsychosocial model of care for treatment of sexual dysfunction in people living with MS. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Bellini, Tiziana; Trentini, Alessandro; Delbue, Serena; Elia, Francesca; Gastaldi, Matteo; Franciotta, Diego; Bergamaschi, Roberto; Manfrinato, Maria Cristina; Volta, Carlo Alberto; Granieri, Enrico; Fainardi, Enrico
Background. Natalizumab is a highly effective treatment approved for multiple sclerosis (MS). The opening of the blood-brain barrier mediated by matrix metalloproteinases (MMPs) is considered a crucial step in MS pathogenesis. Our goal was to verify the utility of serum levels of active MMP-2 and MMP-9 as biomarkers in twenty MS patients treated with Natalizumab. Methods. Serum levels of active MMP-2 and MMP-9 and of specific tissue inhibitors TIMP-1 and TIMP-2 were determined before treatment and for 21 months of therapy. Results. Serum levels of active MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 did not differ during the treatment. The ratio between MMP-9 and MMP-2 was increased at the 15th month compared with the 3rd, 6th, and 9th months, greater at the 18th month than at the 3rd and 6th months, and higher at the 21st than at the 3rd and 6th months. Discussion. Our data indicate that an imbalance between active MMP-9 and active MMP-2 can occur in MS patients after 15 months of Natalizumab therapy; however, they do not support the use of serum active MMP-2 and active MMP-9 and TIMP-1 and TIMP-2 levels as biomarkers for monitoring therapeutic response to Natalizumab. PMID:27340316
Metz, Luanne M; Greenfield, Jamie; Marrie, Ruth Ann; Jette, Nathalie; Blevins, Gregg; Svenson, Lawrence W; Alikhani, Katayoun; Wall, Winona; Dhaliwal, Raveena; Suchowersky, Oksana
Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non-evidence-based medical tourism for CCSVI procedures. We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI. A convenience sample of all Albertans with MS was recruited between July 2011 and March 2013. In total, 868 individuals enrolled; 704 were included in this cross-sectional, baseline analysis. Of these, 128 (18.2%) participants retrospectively reported having procedures for CCSVI between April 2010 and September 2012. The proportion of participants reporting CCSVI procedures declined from 80 (62.5%) in 2010, to 40 (31.1%) in 2011, and 8 (6.3%) in 2012. In multivariable logistic regression analysis, CCSVI procedures were independently associated with longer disease duration, secondary progressive clinical course, and greater disability status. Although all types of people with MS pursued procedures for CCSVI, a major driver of participation was greater disability. This highlights that those with the greatest disability are the most vulnerable to unproven experimental procedures. Participation in CCSVI procedures waned over time possibly reflecting unmet expectations of treated patients, decreased media attention, or that individuals who wanted procedures had them soon after the CCSVI hypothesis was widely publicized.
Nomura, Shohei; Shimakawa, Shuichi; Kashiwagi, Mitsuru; Tanabe, Takuya; Fukui, Miho; Tamai, Hiroshi
Multiple sclerosis (MS) is a syndrome characterized by complex neurological symptoms resulting from demyelinating lesions in the central nervous system. We report a child with a relapse of MS whose only presenting symptom was severe abdominal pain. Dysfunctional intestinal mobility was assessed by abdominal computed tomography. Findings resembled paralytic ileus resulting from peritonitis. However, the patient demonstrated no other symptoms of peritonitis. A T2-weighted magnetic resonance image revealed a new demyelinating lesion localized to thoracic segments T4-T12. The lesion presumably affected autonomic efferents involved in intestinal mobility. Treatment with a pulse of methylprednisolone reduced both abdominal pain and lesion size. To our knowledge, this is the first reported case of a pediatric MS patient with a demyelinating lesion associated with an autonomic symptom of altered intestinal mobility in the absence of neurological symptoms. This atypical presentation of MS highlights the need for physicians' vigilance when treating this patient population. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Murray, Cynthia L.; Ploughman, Michelle; Harris, Chelsea; Hogan, Stephen; Murdoch, Michelle; Stefanelli, Mark
Despite the absence of scientific evidence demonstrating the efficacy of the “liberation procedure” in treating multiple sclerosis (MS), thousands of MS patients worldwide have undergone the procedure. The study objective was to explore the experience of liberation procedure decision making for individuals with MS. Fifteen adults in Newfoundland and Labrador, Canada, each participated in an in-depth interview. The data analysis revealed three groups of people: “waiters,” “early embracers,” and “late embracers.” Using van Manen’s hermeneutic phenomenological approach, we identified three themes each in the stories of the early and late embracers and four themes in the waiters’ stories. A characteristic of the late embracers and waiters was skepticism, whereas desperation set the embracers apart from the waiters. With a deeper understanding of the experience, nurses can be more attuned to the perspectives of MS patients while helping them make informed decisions about undergoing the liberation procedure. PMID:28462292
Hedayatfar, Alireza; Falavarjani, Khalil Ghasemi; Soheilian, Masoud; Elmi Sadr, Navid; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Rohani, Mohammad; Almasi, Mostafa; Chee, Soon-Phaik
To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.
Budhram, Adrian; Parvathy, Seema; Kremenchutzky, Marcelo; Silverman, Michael
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.
Tejera-Alhambra, Marta; Casrouge, Armanda; de Andrés, Clara; Seyfferth, Ansgar; Ramos-Medina, Rocío; Alonso, Bárbara; Vega, Janet; Fernández-Paredes, Lidia; Albert, Matthew L.; Sánchez-Ramón, Silvia
Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients. PMID:26039252
Abdelrahman, Hisham S; Selim, Heba S; Hashish, Mona H; Sultan, Lobna I
Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. Many diseases are associated with Epstein-Barr virus (EBV) infection, such as infectious mononucleosis and many types of malignancies, and it is thought to be related to some diseases of autoimmune origin, such as rheumatoid arthritis, systemic lupus erythematosis, and others. The present study aimed to assess EBV in patients with MS. This case-control study was conducted from October 2012 to September 2013 on 75 MS patients and non-MS controls. Both were tested quantitatively for immunoglobulin G (IgG) antibodies against Epstein-Barr nuclear antigen-1 (EBNA1) and viral capsid antigen (VCA) using the enzyme linked immunosorbent assay technique. Seventy MS patients (93.3%) were positive for EBNA1 IgG compared with 68 controls (90.7%). In MS patients, the mean EBNA1 IgG serum level was 310.91 (±131.05) U/ml; meanwhile, among controls the mean serum EBNA IgG level was 177.81 (±104.98) U/ml.All patients with MS were positive for VCA IgG, whereas only 60 (80.0%) controls were positive. In the MS group, the VCA IgG mean level was 302.19 (±152.11) U/ml compared with 167.94 (±111.79) U/ml in controls. The differences in the serum levels of both markers between the two groups were statistically significant (P<0.001). EBV proved to have a unique immunological pattern in MS patients when compared with non-MS controls. Further studies for more confirmation of the relation between EBV and MS on a large scale are recommended.
Dobson, Ruth; Ramagopalan, Sreeram; Topping, Joanne; Smith, Paul; Solanky, Bhavana; Schmierer, Klaus; Chard, Declan; Giovannoni, Gavin
Multiple sclerosis (MS) develops as a result of environmental influences on the genetically susceptible. Siblings of people with MS have an increased risk of both MS and demonstrating asymptomatic changes in keeping with MS. We set out to develop an MS risk score integrating both genetic and environmental risk factors. We used this score to identify siblings at extremes of MS risk and attempted to validate the score using brain MRI. 78 probands with MS, 121 of their unaffected siblings and 103 healthy controls were studied. Personal history was taken, and serological and genetic analysis using the illumina immunochip was performed. Odds ratios for MS associated with each risk factor were derived from existing literature, and the log values of the odds ratios from each of the risk factors were combined in an additive model to provide an overall score. Scores were initially calculated using log odds ratio from the HLA-DRB1*1501 allele only, secondly using data from all MS-associated SNPs identified in the 2011 GWAS. Subjects with extreme risk scores underwent validation studies. MRI was performed on selected individuals. There was a significant difference in the both risk scores between people with MS, their unaffected siblings and healthy controls (p<0.0005). Unaffected siblings had a risk score intermediate to people with MS and controls (p<0.0005). The best performing risk score generated an AUC of 0.82 (95%CI 0.75-0.88). The risk score demonstrates an AUC on the threshold for clinical utility. Our score enables the identification of a high-risk sibling group to inform pre-symptomatic longitudinal studies.
Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia
Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O'Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl
Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment.
Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O’Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl
Background Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Conclusion Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment. PMID:28053511
Foley, Frederick W; Portnoy, Jeffrey G
The goal of this paper is to describe the role of the neuropsychologist in a Multiple Sclerosis clinic setting. A brief overview of the pathophysiology and neuropsychological deficits in MS is presented. Practical details regarding relations with the neurology team, and the neuropsychologist's focus on assessment are described. Recommendations regarding necessary training and skills, as well as typical clinical practice routines are described. The neuropsychologist's communication with internal and external providers and family members in order to assist implementation of recommendations is described.
Zahoor, Insha; Haq, Ehtishamul; Asimi, Ravouf
Multiple sclerosis (MS) is a disabling neurological disorder commonly diagnosed in young adults. Its causes still remain inexplicable and presently it can only be managed by different drug treatments. There has been a remarkable shift in MS perspective across world. One of its peculiar attribute is unstable (changing) prevalence rate across different parts of the world. Earlier MS was believed to be less prevalent in India, however, there has been growing evidence suggesting its increasing prevalence which has changed its perspective from being less prevalent to more prevalent. There is a complete lack of data on the prevalence rate and epidemiological basis of MS in Kashmir Valley of India. By and large MS research in this region seems to be hampered due to lack of proper research infrastructure, absence of MS registry, inadequate funding and more importantly by absence of active local and foreign collaborations between scientists and clinicians. This review tries to raise some key issues encountered while conducting MS research in Kashmir and at the same time highlighting the measures to be adopted for carrying out a large scale molecular epidemiological study. Copyright © 2016 Elsevier B.V. All rights reserved.
Toro, Jaime; Blanco, Luisa; Orozco-Cabal, Luis Felipe; Díaz, Camilo; Reyes, Saúl; Burbano, Lisseth; Cuéllar-Giraldo, David Felipe; Duque, Alejandra; Patiño, Jorge; Cortés, Fabián
Multiple sclerosis (MS) is a demyelinating disease with a lifetime prevalence of 4.41/100000 in Bogota, Colombia. It is known that it can be related with neuropsychiatric disorders, increasing by a factor of three the prevalence of depression in MS patients compared to general population. However, less attention has been given to the association between MS and impulsive behavior. This cross-sectional study compared the levels of impulsivity controlling for the presence of MS. 60 patients with MS and 60 sex- and age-matched subjects without MS were included. In order to assess depression and impulsivity, participants completed the 13-item short form of the Beck Depression Inventory (BDI-SF), the self-report Barratt Impulsiveness Scale version 11 (BIS-11) and the Immediate and Delayed Memory Tasks (IMT-DMT) as an objective measure of impulsive behavior. Total scores, motor and cognitive subscales on the BIS-11 were significantly higher in the MS group. However, median BDI-SF score was also higher in MS patients than in subjects without MS (p < 0.001). To rule out depression as a confounding factor, stratification was performed using the BDI-SF score. In the subgroup of individuals with a BDI-SF< 8, the BIS-11 cognitive subscale scores were significantly higher in patients with MS than in subjects without MS (p = 0.041). In the IMT/DMT test, subjects with MS had a fewer number of correct detections than did subjects without MS, after controlling for BDI-SF score (p = 0.0001/p = 0.003). The ratio of commission errors to correct detections in the IMT was significantly higher in the MS group (p = 0.011). Patients with MS showed higher levels of cognitive impulsivity than subjects without MS. Objective measures for impulsiveness further support this finding. Impulsiveness scales scores might be biased by depression, which should be considered when assessing impulsivity in MS. Copyright © 2018 Elsevier B.V. All rights reserved.
Abolhassani, Shahla; Yazdannik, Ahmadreza; Taleghani, Fariba; Zamani, Ahmadreza
This study aimed to determine the social aspects of multiple sclerosis (MS) in the Iranian individuals. A qualitative case study approach was used for this study, which is a part of a larger qualitative study about health care delivery system of MS. Participants were selected on the basis of purposive sampling method. Semi-structured interviews regarding the social aspects of MS were conducted with 18 MS patients, 6 family members and 7 health care providers. Besides interviews with the participants, documents related to the aim of the study, including weblogs, MS magazines, special websites of individuals with MS and news agencies. Data analysis was performed using the qualitative content analysis technique. Data obtained has been categorised into five main categories, including confronting stigma symbols, the outcome of stigma, walling-in due to stigma, disturbance in normal life and concern about job. There are multiple social effects of MS on the afflicted individuals, which affect various dimensions of their life. Policy makers and health care providers must also consider these effects of MS on other dimensions of the individuals' life. Implications for Rehabilitation Multiple sclerosis (MS) is a disease which restricts social life for patients, in addition to physical impacts. Individuals with MS experienced stigma as well as problems with employment and marital life, due to improper information about MS in society. We recommend that health care workers offer proper information about MS to patients and their family members to minimise the social problems faced by them. We recommend that mass media offers proper information about MS to people in society to disseminate the correct picture of MS. We recommend that the rehabilitation team offers psychological support to patients and their families for their empowerment, to facilitate dealing with the impacts of the disease. We recommend that health care providers teach the family members about patient support and
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.
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
Bishop, Malachy; Chan, Fong; Rumrill, Phillip D., Jr.; Frain, Michael P.; Tansey, Timothy N.; Chiu, Chung-Yi; Strauser, David; Umeasiegbu, Veronica I.
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…
Tansey, Timothy N.; Strauser, David; Frain, Michael P.; Bishop, Malachy; Chiu, Chung-Yi; Kaya, Cahit; Chan, Fong
The experience of living with multiple sclerosis (MS) can have a profound effect on employment. The impact of MS is a complex interaction of personal, medical, functional, financial, and psychosocial variables that ultimately results in up to 80% of persons with MS leaving their jobs within 10 years of their diagnosis. The aim of this study was to…
Tomassini, Valentina; Matthews, Paul M.; Thompson, Alan J.; Fuglø, Daniel; Geurts, Jeroen J.; Johansen-Berg, Heidi; Jones, Derek K.; Rocca, Maria A.; Wise, Richard G.; Barkhof, Frederik; Palace, Jacqueline
The development of therapeutic strategies that promote functional recovery is a major goal of multiple sclerosis (MS) research. Neuroscientific and methodological advances have improved our understanding of the brain’s recovery from damage, generating novel hypotheses for potential targets or modes of intervention and laying the foundation for the development of scientifically informed strategies promoting recovery in interventional studies. This Review aims to encourage the transition from characterization of recovery mechanisms to the development of strategies that promote recovery in MS. We discuss current evidence for functional reorganization that underlies recovery and its implications for development of new recovery-oriented strategies in MS. Promotion of functional recovery requires an improved understanding of recovery mechanisms modulated by interventions and the development of reliable measures of therapeutic effects. As imaging methods can be used to measure functional and structural alterations associated with recovery, this Review discusses their use as reliable markers to measure the effects of interventions. PMID:22986429
Miljković, Djordje; Timotijević, Gordana; Mostarica Stojković, Marija
Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well as numerous immunity-related actions that these cells are capable of, imply that astrocytes should have a prominent role in neuroinflammatory disorders, such as multiple sclerosis (MS). The role of astrocytes in MS is rather ambiguous, as they have the capacity to both stimulate and restrain neuroinflammation and tissue destruction. In this paper we present some of the proved and the proposed functions of astrocytes in neuroinflammation and discuss the effect of MS therapeutics on astrocytes. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Koppenaal, David W.; Barinaga, Charles J.; Denton, M Bonner B.
Good eyesight is often taken for granted, a situation that everyone appreciates once vision begins to fade with age. New eyeglasses or contact lenses are traditional ways to improve vision, but recent new technology, i.e. LASIK laser eye surgery, provides a new and exciting means for