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Sample records for aggressive multiple sclerosis

  1. Natalizumab in aggressive multiple sclerosis after haematopoietic stem cell transplantation.

    PubMed

    Capobianco, Marco; Motuzova, Y; Frau, J; Cocco, E; Mamusa, E; Marrosu, M G; Bertolotto, A

    2012-08-01

    High-dose cyclophosphamide followed by autologous haematopoietic stem cell transplantation (HDC-AHSCT) is a treatment option for aggressive and refractory multiple sclerosis (MS). Natalizumab is a monoclonal antibody approved for relapsing-remitting (RR) MS unresponsive to immunomodulating drugs. Nothing is known about the use of natalizumab in patients after HDC-AHSCT. We describe five female RR-MS patients with incomplete response to HDC-AHSCT. Natalizumab was then administered with abolition of both MRI and clinical activity. No severe adverse events, in particular opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML), were observed. Our results suggest that the use of natalizumab in aggressive RR-MS after HDC-AHSCT could be effective and safe. The very long-term risk of adverse events due to sequential aggressive immunosuppression has to be established.

  2. Multiple Sclerosis

    MedlinePlus

    Multiple sclerosis Overview By Mayo Clinic Staff Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective ...

  3. Multiple Sclerosis

    MedlinePlus

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

  4. Multiple sclerosis - resources

    MedlinePlus

    Resources - multiple sclerosis ... The following organizations provide information on multiple sclerosis : Multiple Sclerosis Foundation -- www.msfocus.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/multiple_sclerosis National ...

  5. Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

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

  6. Multiple sclerosis.

    PubMed

    Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

    2015-06-01

    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.

  7. Multiple sclerosis - discharge

    MedlinePlus

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

  8. Vision and multiple sclerosis.

    PubMed

    Hickman, Simon J; Raoof, Naz; McLean, Rebecca J; Gottlob, Irene

    2014-01-01

    Multiple sclerosis can affect vision in many ways, including optic neuritis, chronic optic neuropathy, retrochiasmal visual field defects, higher order cortical processing, double vision, nystagmus and also by related ocular conditions such as uveitis. There are also side effects from recently introduced multiple sclerosis treatments that can affect vision. This review will discuss all these aspects and how they come together to cause visual symptoms. It will then focus on practical aspects of how to recognise when there is a vision problem in a multiple sclerosis patient and on what treatments are available to improve vision.

  9. Genetics Home Reference: multiple sclerosis

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions multiple sclerosis multiple sclerosis Enable ...

  10. Stem Cell Transplants May Help Some with Multiple Sclerosis

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163677.html Stem Cell Transplants May Help Some With Multiple Sclerosis Review ... 20, 2017 MONDAY, Feb. 20, 2017 (HealthDay News) -- Stem cell transplants may halt the progression of aggressive multiple ...

  11. Multiple sclerosis and pregnancy.

    PubMed

    Popescu, C D

    2014-01-01

    Multiple sclerosis is one of the main reasons for invalidation of young adults of both sexes. The disease is more common in women than in men. The illness begins most frequently in patients between the ages of 20 and 40 years, which is also the most fertile period for women. MS is an immune-mediated disease with chronic evolution marked by exacerbations and remissions that amplify the degree of disability. The most common clinical picture is the one with relapse and remission whose evolution is greatly improved after immunomodulatory treatment. We have revised the literature together with the data from the national multiple sclerosis society and the cases that are in the National Programme of Multiple Sclerosis, mainly the ones that are assigned to the regional center of Iaşi, at the Neurology Clinic inside the Clinical Rehabilitation Hospital Iaşi. Pregnancy is quite frequent in female patients with MS. Certain risks are present during pregnancy, birth and breastfeeding and certain protocols must be applied, such as interrupting the immunomodulatory treatment before the conception. Child delivery must be closely monitored and it must take into consideration the dysfunction that the patient has and be adapted to the existing deficits. There are some methods that may be used during delivery for female patients with multiple sclerosis in order to make this process smooth and reduce the risk of postpartum complications. Multiple sclerosis is an invalidating disease, with a high prevalence in women. Pregnancy in patients with MS is not such a natural phenomenon as in a healthy female and it requires a multidisciplinary team in order to ensure the safety of both the mother and the newborn.

  12. [Future challenges in multiple sclerosis].

    PubMed

    Fernández, Óscar

    2014-12-01

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

  13. Ambulation and multiple sclerosis.

    PubMed

    Motl, Robert W

    2013-05-01

    Walking impairment is a common consequence of multiple sclerosis (MS) that can result in substantial limitations of daily activities and compromised quality of life. Walking impairment is often monitored as an indicator of disease and neurologic disability progression. The worsening of walking performance while undertaking a cognitive task underscores the role of nonmotor impairments in ambulation limitations. Walking impairment has ubiquitous and life-altering consequences, underscoring the importance of continued efforts to identify approaches to prevent and forestall this event, and to restore walking ability in persons with MS.

  14. Multiple Sclerosis: An Update.

    PubMed

    Faguy, Kathryn

    2016-05-01

    Multiple sclerosis (MS) is the most common disabling neurologic condition in young adults and imposes high financial and quality of life costs on patients, their families, and society. Yet, developments in the battle against MS include new treatments to slow its progression and updated diagnostic criteria that can accelerate diagnosis and effective treatment. This article offers a review and update on the disease, focusing on risk factors and possible causes, symptoms, forms of MS, diagnostic criteria and tools, and the expanding array of approved treatments. It also reports on the skyrocketing cost of MS drugs, misdiagnosis, and special patient populations with MS.

  15. Symptomatic therapy in multiple sclerosis

    PubMed Central

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

    2011-01-01

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

  16. Rickettsial Antibodies in Multiple Sclerosis

    PubMed Central

    Field, E. J.; Chambers, Mavis

    1970-01-01

    The serum of subjects with multiple sclerosis or other degenerative neurological diseases and that of normal controls does not differ significantly in its content of antibodies to several rickettsial antigens. There is no evidence for a rickettsial aetiology of multiple sclerosis, and no grounds for an extended clinical trial of Le Gac's full method of treatment with antibiotics. PMID:4983591

  17. Electroconvulsive Therapy in Multiple Sclerosis.

    PubMed

    Steen, Katie; Narang, Puneet; Lippmann, Steven

    2015-01-01

    We performed a literature search regarding the safety and efficacy of electroconvulsive therapy in patients with multiple sclerosis and comorbid psychiatric symptoms. Literature review was conducted via PubMed databases. Of the cases we reviewed, most subjects with multiple sclerosis reported significant psychiatric symptom relief, with only a handful reporting neurologic deterioration. There was some evidence that active white matter lesions may be predictive of neurologic deterioration when electroconvulsive therapy is used in patients with multiple sclerosis. A brief description of the pathophysiology and effects of depression in patients with multiple sclerosis is also provided. Although no clinical recommendations or meaningful conclusions can be drawn without further investigation, the literature suggests that electroconvulsive therapy for treatment of psychiatric illnesses in patients with multiple sclerosis is safe and efficacious.

  18. Tremor in multiple sclerosis

    PubMed Central

    Mostert, Jop; Heersema, Dorothea; De Keyser, Jacques

    2007-01-01

    Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide some relief, but published evidence of effectiveness is very limited. Most trials were of small size and of short duration. Cannabinoids appear ineffective. Tremor reduction can be obtained with stereotactic thalamotomy or thalamic stimulation. However, the studies were small and information on long-term functional outcome is scarce. Physiotherapy, tremor reducing orthoses, and limb cooling can achieve some functional improvement. Tremor in MS remains a significant challenge and unmet need, requiring further basic and clinical research. PMID:17318714

  19. Vaccines in Multiple Sclerosis.

    PubMed

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  20. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

  1. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-04-12

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.

  2. Management of multiple sclerosis.

    PubMed

    Perrin Ross, Amy

    2013-11-01

    Patients with multiple sclerosis (MS), a disease of the central nervous system that disrupts signals within the brain and also the signals between the brain and body, will likely experience symptoms that may negatively impact their quality of life (QOL). Due to the complexity of MS and its disease burden, multidisciplinary management that combines pharmacologic and nonpharmacologic strategies with patient education is necessary. Diagnosing relapses of MS in clinical practice can be difficult due to the multiple subtypes of MS, variations of symptomatology, and pseudo-relapses. Managing relapses also presents its own set of challenges, for example, evaluating if treatment is appropriate and determining which agent would be most effective for a patient if treatment is recommended. Patient education is essential for achieving optimal outcomes for patients with MS and improving patient QOL, and should increase awareness of: (1) the disease itself and its progression; (2) the signs and symptoms of MS; (3) current treatment strategies and plan of care; (4) the recognition and management of relapses; (5) the value of treatment adherence and impact of nonadherence; and (6) hope for the future. The management of active MS may be further complicated by the complex variety of pharmacotherapeutic options, and in some instances, by having to switch between agents and drug classes. Newer agents in development (eg, alemtuzumab, ocrelizumab, laquinimod) offer the opportunity to expand the therapeutic armamentarium, although further long-term data are required to evaluate any safety concerns associated with newer agents.

  3. Chronic hypothermia in multiple sclerosis.

    PubMed Central

    Sullivan, F; Hutchinson, M; Bahandeka, S; Moore, R E

    1987-01-01

    Two patients with clinically definite multiple sclerosis presented with acute hypothermia and on recovery were found to be chronically hypothermic. Thermoregulatory studies indicated a central, hypothalamic defect which is presumed to be due to a plaque of demyelination. PMID:3612161

  4. [Current therapy of multiple sclerosis].

    PubMed

    Antonio García Merino, J

    2014-12-01

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

  5. Therapeutics for multiple sclerosis symptoms.

    PubMed

    Ben-Zacharia, Aliza Bitton

    2011-01-01

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

  6. Fatigue and multiple sclerosis.

    PubMed

    Béthoux, F

    2006-07-01

    Even if the definition and pathophysiology of fatigue in multiple sclerosis (MS) are still debated, and despite the scarcity of objective markers correlated with the subjective sensation of fatigue, a review of the literature shows the importance of its detection and management, and allows one to propose therapeutic strategies. Fatigue is not only the most frequently reported symptom in MS, but also a frequent source of activity and participation limitations, psychological distress, and impairment of quality of life. Its management, which must be initiated early, is based on a comprehensive evaluation of its characteristics and consequences (sometimes with the use of scales such as the Fatigue Severity Scale and the Modified Fatigue Impact Scale), and on the identification of many potential contributing factors (psychological disorders, sleep disturbances, pain, infections and other comorbidities, medications, and deconditioning). Rehabilitative interventions are essential to the treatment of fatigue. Beyond the traditional energy conservation strategies and cooling techniques, several randomized controlled studies have demonstrated the positive impact of aerobic exercise. Medications are partially beneficial, and with the exception of amantadine, their efficacy has not been confirmed by randomized double-blind trials.

  7. Progressive multiple sclerosis

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.

    2015-01-01

    Purpose to Review To highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS). To highlight results of clinical trial experience to date and review ongoing clinical trials and perspective new treatment options. Explain the challenges of clinical trial design in PMS. Recent Findings MS has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms. The classification of the course of PMS has been re-organized into categories of active vs. inactive inflammatory disease and the presence vs. absence of gradual disease progression. This differentiation allows clearer conceptualization of PMS and possibly even more efficient recruitment of PMS subjects into clinical trials. Clinical trial experience to date in PMS has been negative with anti-inflammatory medications used in relapsing MS. Simvastatin was recently tested in a phase II trial and showed a 43% reduction on annualized atrophy progression in secondary progressive MS. Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod, and anti-B-cell therapy ocrelizumab. Several efforts for development of outcome measures in PMS are ongoing. Summary PMS represents a significant challenge, as the pathogenesis of the disease is not well understood, no validated outcome metrics have been established, and clinical trial experience to date has been disappointing. Advances in the understanding of the disease and lessons learned in previous clinical trials are paving the way for successful development of disease modifying agents for this disease. PMID:25887766

  8. Multiple sclerosis and behavior.

    PubMed

    Pinkston, James B; Kablinger, Anita; Alekseeva, Nadejda

    2007-01-01

    Multiple sclerosis (MS) is one of the most frequently seen neurological causes of progressive disability in early to middle adulthood. The disease is variable in its presentation and course, affects roughly 100-300 per 100,000 persons within the United States alone, and is slightly more common among females than males. MS places substantial burdens on patients, families, and caregivers. It negatively affects cognitive abilities and psychiatric functioning, and can add a notably deleterious effect on a patient's quality of life. This chapter reviews the recent literature on the behavioral manifestations of MS. Cognitive domains discussed include executive functioning, processing speed, attention, learning and memory, language functioning, and visual spatial processing. Some attention will also be paid to differential diagnosis and the cognitive effects of treatment. Psychiatric manifestations are also discussed, including symptoms of depression, bipolar disorder, euphoria, pathological laughter and crying, and psychosis, as well as maladaptive personality traits. Finally, the chapter concludes with a discussion of the effects of MS on quality of life including such areas as fatigue, sexual dysfunction, pain, employment, and cognitive functioning.

  9. Clinical neurophysiology of multiple sclerosis.

    PubMed

    Leocani, Letizia; Comi, Giancarlo

    2014-01-01

    The availability of new treatments able to modify the natural course of multiple sclerosis (MS) has generated interest in paraclinical measures to monitor disease evolution. Among these, neurophysiologic measures, mainly evoked potentials (EPs), are used in the functional assessment of central sensorimotor and cognitive networks affected by MS. EP abnormalities may reveal subclinical lesions, objectivate the involvement of sensory and motor pathways in the presence of vague disturbances, and provide indications of the demyelinating nature of the disease process. However, their diagnostic value is much lower than that of magnetic resonance imaging, and is more sensitive to brain and cervical spinal cord lesions. The application of EPs in assessing disease severity and monitoring the evolution of nervous damage is more promising, thanks to their good correlation with disability in cross-sectional and longitudinal studies, and potential use as paraclinical endpoints in clinical trials. Recent evidence indicates that EPs performed early in the disease may help to predict a worse future progression in the long term. If confirmed, these data suggest the possible usefulness of EPs in the early identification of patients who are more likely to develop future disability, thus requiring more frequent monitoring or being potential candidates for more aggressive disease-modifying treatments.

  10. Rituximab in multiple sclerosis

    PubMed Central

    Svenningsson, Rasmus; Alping, Peter; Novakova, Lenka; Björck, Anna; Fink, Katharina; Islam-Jakobsson, Protik; Malmeström, Clas; Axelsson, Markus; Vågberg, Mattias; Sundström, Peter; Lycke, Jan; Piehl, Fredrik; Svenningsson, Anders

    2016-01-01

    Objective: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). Methods: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2–5 according to the Common Terminology Criteria for Adverse Events were recorded. Results: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS). At baseline, 26.2% had contrast-enhancing lesions (CELs). Patients were treated with 500 or 1,000 mg rituximab IV every 6–12 months, during a mean 21.8 (SD 14.3) months. During treatment, the annualized relapse rates were 0.044 (RRMS), 0.038 (SPMS), and 0.015 (PPMS), and 4.6% of patients displayed CELs. Median Expanded Disability Status Scale remained unchanged in RRMS (p = 0.42) and increased by 0.5 and 1.0 in SPMS and PPMS, respectively (p = 0.10 and 0.25). Infusion-related AEs occurred during 7.8% of infusions and most were mild. A total of 89 AEs grades ≥2 (of which 76 infections) were recorded in 72 patients. No case of progressive multifocal leukoencephalopathy was detected. Conclusions: This is the largest cohort of patients with MS treated with rituximab reported so far. The safety, clinical, and MRI findings in this heterogeneous real-world cohort treated with different doses of rituximab were similar to those reported in previous randomized controlled trials on B-cell depletion therapy in MS. Classification of evidence: This study provides Class IV evidence that for patients with MS, rituximab is safe and effective. PMID:27760868

  11. Multiple sclerosis update.

    PubMed

    Markowitz, Clyde E

    2013-11-01

    Multiple sclerosis (MS) is a chronic but incurable disease of the central nervous system (CNS) that is often diagnosed in the second or third decade of life. It is more common among women than men, significantly impairs patient quality of life, and is associated with substantial costs to patients, healthcare systems, and society. Of the approximately 2.3 million individuals worldwide that have MS, more than 400,000 reside in the United States. Although the etiology of MS is not completely understood, a great deal of evidence suggests a complex relationship between environmental and genetic factors. The pathophysiology of MS involves an aberrant attack by the host immune system on oligodendrocytes, which synthesize and maintain myelin sheaths in the CNS. There are 4 identified disease courses in MS, and approximately 85% of people with MS present with relapsing-remitting MS, which is characterized by discrete acute attacks followed by periods of remission. Signs and symptoms of MS are dependent on the demyelinated area(s) of the CNS and often involve sensory disturbances, limb weakness, fatigue, and increased body temperature. The criteria for a diagnosis of MS include evidence of damage in at least 2 separate areas of the CNS, evidence that the damage occurred at different time points, and the ruling out of other possible diagnoses. Diseasemodifying drugs (DMDs) that reduce the frequency of relapses, development of brain lesions, and progression of disability are the standard of care for relapsing forms of MS, and the use of DMDs should be initiated as early as possible.

  12. [Current description of multiple sclerosis].

    PubMed

    Río, Jordi; Montalbán, Xavier

    2014-12-01

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

  13. Multiple Sclerosis and its Management

    PubMed Central

    Weinshenker, Brian

    1992-01-01

    Multiple sclerosis, the most common disabling disease of the central nervous system affecting young adults, is diagnosed primarily from a history of typical relapsing and remitting white matter symptoms supported by objective signs. Multiple sclerosis may present in more insidious ways or may be mimicked by other diseases, which seemingly satisfy the diagnostic criteria of dissemination in time and space. Patients need psychological support to deal with an uncertain future. A multidisciplinary team approach can best manage both acute temporary disability and, often later, progressive physical and occasionally mental disability. ImagesFigures 1-3 PMID:21221279

  14. Body composition in multiple sclerosis

    PubMed Central

    Dionyssiotis, Y

    2013-01-01

    Multiple sclerosis affects central nervous system leading to disability. Among other complications the deterioration of body composition is usually neglected and increases the risk for diseases such as coronary heart disease, non-insulin dependent diabetes mellitus, lipid abnormalities and bone loss leading to fractures in this population. Body mass index values, the effect of spasticity, the increased number of drugs used and the relationship between skeletal muscle and bone which interacts with impaired motor function leading to body composition alterations in multiple sclerosis are reviewed. PMID:23935336

  15. Emotional Disorders in People with Multiple Sclerosis

    MedlinePlus

    ... and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on emotional disorders in multiple sclerosis (MS) and summarizes the main findings of a ...

  16. Accelerated Cure Project for Multiple Sclerosis

    MedlinePlus

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

  17. Multiple Sclerosis: Can It Cause Seizures?

    MedlinePlus

    ... it cause seizures? Is there any connection between multiple sclerosis and epilepsy? Answers from B Mark Keegan, M. ... seizures are more common in people who have multiple sclerosis (MS) than in those who don't have ...

  18. Epidemiology of multiple sclerosis.

    PubMed

    Leray, E; Moreau, T; Fromont, A; Edan, G

    2016-01-01

    Multiple sclerosis (MS) is the most frequently seen demyelinating disease, with a prevalence that varies considerably, from high levels in North America and Europe (>100/100,000 inhabitants) to low rates in Eastern Asia and sub-Saharan Africa (2/100,000 population). Knowledge of the geographical distribution of the disease and its survival data, and a better understanding of the natural history of the disease, have improved our understanding of the respective roles of endogenous and exogenous causes of MS. Concerning mortality, in a large French cohort of 27,603 patients, there was no difference between MS patients and controls in the first 20 years of the disease, although life expectancy was reduced by 6-7 years in MS patients. In 2004, the prevalence of MS in France was 94.7/100,000 population, according to data from the French National Health Insurance Agency for Salaried Workers (Caisse nationale d'assurance maladie des travailleurs Salariés [CNAM-TS]), which insures 87% of the French population. This prevalence was higher in the North and East of France. In several countries, including France, the gender ratio for MS incidence (women/men) went from 2/1 to 3/1 from the 1950s to the 2000s, but only for the relapsing-remitting form. As for risk factors of MS, the most pertinent environmental factors are infection with Epstein-Barr virus (EBV), especially if it arises after childhood and is symptomatic. The role of smoking in MS risk has been confirmed, but is modest. In contrast, vaccines, stress, traumatic events and allergies have not been identified as risk factors, while the involvement of vitamin D has yet to be confirmed. From a genetic point of view, the association between HLA-DRB1*15:01 and a high risk of MS has been known for decades. More recently, immunogenetic markers have been identified (IL2RA, IL7RA) and, in particular thanks to studies of genome-wide associations, more than 100 genetic variants have been reported. Most of these are involved in

  19. Childhood Multiple Sclerosis: A Review

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  20. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  1. Vitamin D Levels Predict Multiple Sclerosis Progression

    MedlinePlus

    ... Research Matters NIH Research Matters February 3, 2014 Vitamin D Levels Predict Multiple Sclerosis Progression Among people ... sclerosis (MS), those with higher blood levels of vitamin D had better outcomes during 5 years of ...

  2. Treating multiple sclerosis with natalizumab.

    PubMed

    Iaffaldano, Pietro; Lucchese, Guglielmo; Trojano, Maria

    2011-12-01

    Natalizumab is the first monoclonal antibody approved for the treatment of relapsing multiple sclerosis. Pivotal trials demonstrated the efficacy of natalizumab on clinical and paraclinical measures of disease activity and disability progression. Although a direct comparison has not been performed yet, natalizumab seems to be more efficacious than the currently available immunomodulant drugs, such as IFN-β and glatiramer acetate. Despite its efficacy, the occurrence of an increased risk of progressive multifocal leukoencephalopathy with the treatment, raises concerns about its widespread use in multiple sclerosis patients. This paper provides an overview of the most relevant results from the Phase I-IV studies on natalizumab and highlights the challenges addressed to minimize and manage its adverse events in clinical practice.

  3. Tolerogenic vaccines for Multiple sclerosis.

    PubMed

    Mannie, Mark D; Curtis, Alan D

    2013-05-01

    Tolerogenic vaccines represent a new class of vaccine designed to re-establish immunological tolerance, restore immune homeostasis, and thereby reverse autoimmune disease. Tolerogenic vaccines induce long-term, antigen-specific, inhibitory memory that blocks pathogenic T cell responses via loss of effector T cells and gain of regulatory T cell function. Substantial advances have been realized in the generation of tolerogenic vaccines that inhibit experimental autoimmune encephalomyelitis in a preclinical setting, and these vaccines may be a prequel of the tolerogenic vaccines that may have therapeutic benefit in Multiple Sclerosis. The purpose here is to provide a snapshot of the current concepts and future prospects of tolerogenic vaccination for Multiple Sclerosis, along with the central challenges to clinical application.

  4. Multiple sclerosis - New treatment modalities

    PubMed Central

    Totaro, Rocco; Di Carmine, Caterina; Marini, Carmine; Carolei, Antonio

    2015-01-01

    Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability. The place in therapy of newer treatment implies careful balancing of risk-benefit profile as well as accurate patient selection. Hence the widening of therapeutic arsenal provides greater opportunity for personalized therapy but also entails a complex trade-off between efficacy, tolerability, safety and eventually patient preference. PMID:26831413

  5. Multiple Sclerosis Epidemiology in Europe.

    PubMed

    Bezzini, Daiana; Battaglia, Mario A

    2017-01-01

    Multiple sclerosis is characterized by a non-homogeneous distribution around the world. Some authors in past described a latitude gradient, with increasing risk from the equator to North and South Poles, but this theory is still controversial. Regarding Europe, there are many articles in the literature concerning the epidemiology of this disease but, unfortunately, they are not always comparable due to different methodologies, they do not cover all countries in the continent, and most of them reported data of small areas and rarely at a national level. In 2012 there were 20 national registries that could help to describe the epidemiology of the disease and, in addition, there is an European Register for Multiple Sclerosis that collect data from already existing national or regional MS registries and databases. Another valid alternative to obtain epidemiological data, also at national level, in a routinely and cost-saving way is through administrative data that are of increasing interest in the last years.

  6. [Special cases of multiple sclerosis].

    PubMed

    Mendibe Bilbao, Mar

    2014-12-01

    Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions.

  7. Bipolar disorder and multiple sclerosis.

    PubMed

    Ybarra, Mariana Inés; Moreira, Marcos Aurélio; Araújo, Carolina Reis; Lana-Peixoto, Marco Aurélio; Teixeira, Antonio Lucio

    2007-12-01

    Bipolar disorder may be overrepresented in multiple sclerosis (MS) patients. Although research in this area is limited, studies assessing the nature of this association have focused on genetic aspects, adverse reaction to drugs and brain demyelinating lesions. Herein we report three patients with MS that also presented bipolar disorder. The coexistence of neurological and psychiatric symptoms in most MS relapses highlights the relevance of biological factors in the emergence of mood disorders in these patients.

  8. [Multiple sclerosis: current immunological aspects].

    PubMed

    Cuevas-García, Carlos

    2017-01-01

    Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments' main purpose is to modulate aspects related to the adaptive immune response (B and T cells). The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes) and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

  9. Evoked potentials in multiple sclerosis.

    PubMed

    Kraft, George H

    2013-11-01

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

  10. [Smoking and multiple sclerosis].

    PubMed

    Arruti, Maialen; Castillo-Triviño, Tamara; Egüés, Nerea; Olascoaga, Javier

    2015-02-16

    Introduccion. La esclerosis multiple (EM) es una enfermedad autoinmune de etiologia compleja, hoy por hoy desconocida, en la que factores geneticos y ambientales determinan la susceptibilidad. En los ultimos años, el efecto del tabaco ha sido uno de los factores ambientales que ha emergido en la EM, y se ha asociado tanto a un aumento de la susceptibilidad como a un aumento de la progresion. Objetivo. Revisar la evidencia actual sobre el papel del tabaco en la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados que han analizado distintos aspectos del tabaco en la EM: vias patogenicas implicadas, asociacion del tabaco y riesgo de EM, interaccion con otros factores de riesgo y efecto del tabaco en el curso de la enfermedad. Conclusiones. Los estudios observacionales demuestran que el tabaquismo incrementa de forma significativa el riesgo de EM (odds ratio ~ 1,5) y es un factor de riesgo independiente. Sin embargo, la EM es una enfermedad compleja y el aumento de riesgo por el tabaco puede diferir en funcion de la interaccion con otros factores geneticos y ambientales. El papel del tabaco como factor de progresion es mas controvertido, con resultados contradictorios y estudios de gran variabilidad, lo que dificulta establecer una conclusion firme. Los mecanismos por los que el tabaquismo modifica el riesgo y posiblemente la progresion de la enfermedad no son aun conocidos.

  11. [Diet and multiple sclerosis].

    PubMed

    Pozuelo-Moyano, Beatriz; Benito-León, Julián

    2014-05-16

    Introduccion. El tipo de dieta se ha relacionado con el proceso inflamatorio que forma parte de la esclerosis multiple (EM). En los ultimos años, distintas lineas de investigacion han generado una gran cantidad de conocimiento sobre la participacion de la dieta en la patogenesis de la EM. Objetivo. Elucidar de modo critico las evidencias que relacionan distintos tipos de dietas y alimentos con la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados mas significativos que han analizado el papel de la dieta en la patogenesis y en el tratamiento de la EM. Para explorar la asociacion entre la dieta y el riesgo de EM se ha revisado la evidencia disponible hasta el momento, pasando por estudios observacionales hasta terminar con estudios de intervencion. Conclusiones. Se necesita mas investigacion sobre la nutricion como factor de riesgo, ya que podria tener relacion con la enfermedad, y el control de esta podria llevar a una disminucion significativa de la incidencia o progresion de la patologia.

  12. Symptomatic management in multiple sclerosis

    PubMed Central

    Shah, Pushkar

    2015-01-01

    Multiple sclerosis (MS) is the commonest cause of disability in young adults. While there is increasing choice and better treatments available for delaying disease progression, there are still, very few, effective symptomatic treatments. For many patients such as those with primary progressive MS (PPMS) and those that inevitably become secondary progressive, symptom management is the only treatment available. MS related symptoms are complex, interrelated, and can be interdependent. It requires good understanding of the condition, a holistic multidisciplinary approach, and above all, patient education and empowerment. PMID:26538847

  13. [Driving ability with multiple sclerosis].

    PubMed

    Küst, J; Dettmers, C

    2014-07-01

    Driving is an important issue for young patients, especially for those whose walking capacity is impaired. Driving might support the patient's social and vocational participation. The question as to whether a patient with multiple sclerosis (MS) is restricted in the ability to drive a car depends on neurological and neuropsychological deficits, self-awareness, insight into deficits and ability to compensate for loss of function. Because of the enormous variability of symptoms in MS the question is highly individualized. A practical driving test under supervision of a driving instructor (possibly accompanied by a neuropsychologist) might be helpful in providing both patient and relatives adequate feedback on driving abilities.

  14. Spasticity management in multiple sclerosis.

    PubMed

    Hughes, Christina; Howard, Ileana M

    2013-11-01

    Spasticity is a prevalent and potentially disabling symptom common in individuals with multiple sclerosis. Adequate evaluation and management of spasticity requires a careful assessment of the patient's history to determine functional impact of spasticity and potential exacerbating factors, and physical examination to determine the extent of the condition and culpable muscles. A host of options for spasticity management are available: therapeutic exercise, physical modalities, complementary/alternative medicine interventions, oral medications, chemodenervation, and implantation of an intrathecal baclofen pump. Choice of treatment hinges on a combination of the extent of symptoms, patient preference, and availability of services.

  15. Demyelination of subcortical nuclei in multiple sclerosis

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  16. Interhemispheric disconnection effects in multiple sclerosis.

    PubMed Central

    Lindeboom, J; ter Horst, R

    1988-01-01

    Patients with multiple sclerosis reported less left ear numbers but more right ear numbers than controls in a dichotic listening test. The multiple sclerosis patients were also relatively impaired on three learning tasks; one of these, a test for paired-associate learning of names and faces, correlated with left ear findings; the results are interpreted as supporting a hypothesised disconnection mechanism. PMID:3236021

  17. Multiple sclerosis beyond EDSS: depression and fatigue.

    PubMed

    Ziemssen, Tjalf

    2009-02-01

    Depression and fatigue are common symptoms of multiple sclerosis and are the primary determinants of impaired quality of life in this demyelinating neurological disease. The twelve-month prevalence of major depression in patients with multiple sclerosis is around 15%. Untreated depression is associated with suicidal ideation, impaired cognitive function and poor adherence to immunomodulatory treatment. For these reasons, systematic screening and management of depressive symptoms is recommended for all patients with multiple sclerosis. There is some evidence that interferon-beta treatment may exacerbate depressive symptoms and a switch to glatiramer acetate can be envisaged in patients treated with an interferon-beta in whom depressive symptoms become an issue. Fatigue is present in over three-quarters of patients with multiple sclerosis. It is considered the most debilitating symptom of the disease and is a major reason for work absenteeism. There is growing evidence that immunomodulatory treatments, in particular glatiramer acetate, improve fatigue symptoms in patients with multiple sclerosis.

  18. Hughes syndrome and multiple sclerosis.

    PubMed

    Uthman, I; Noureldine, M H A; Berjawi, A; Skaf, M; Haydar, A A; Merashli, M; Hughes, G R V

    2015-02-01

    Multiple sclerosis (MS) and antiphospholipid syndrome (APS) share common clinical, laboratory and radiological features. We reviewed all the English papers on MS and APS published in the literature from 1965 to 2014 using PubMed and Google Scholar. We found that APS can mimic antiphospholipid antibodies (aPL)-positive MS in many ways in its clinical presentation. Nevertheless, APS diagnosis, clinical manifestations and management differ from those of MS. aPL were found in MS patients with titers ranging from 2% to 88%. The distribution and volume of lesions on magnetic resonance imaging (MRI) may help to differentiate MS from primary APS. In addition, atypical MS presentation can guide physicians toward an alternative diagnosis, especially when features of thrombosis and/or history of connective tissue disease are present. In that case, an anticoagulation trial could be worthwhile.

  19. Autonomic Dysregulation in Multiple Sclerosis

    PubMed Central

    Pintér, Alexandra; Cseh, Domonkos; Sárközi, Adrienn; Illigens, Ben M.; Siepmann, Timo

    2015-01-01

    Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment. PMID:26213927

  20. Multiple sclerosis, a treatable disease.

    PubMed

    Doshi, Anisha; Chataway, Jeremy

    2016-12-01

    This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is often diverse; however, there are key features that can be useful in the clinic. We comment on the diagnostic criteria and review the main subtypes of MS, including clinically isolated syndrome, relapsing remitting MS, secondary progressive MS and primary progressive MS. Although the underlying aetiology of MS is still not known, we summarise those with most evidence of association. Finally, we aim to present treatment strategies for managing the acute relapse, disease-modifying therapies and MS symptoms. This review highlights that progressive MS is an area where there is currently a paucity of available disease-modifying treatments and this will be a major focus for future development.

  1. Intensive immunosuppression in multiple sclerosis.

    PubMed

    Zaffaroni, M; Ghezzi, A; Comi, G

    2006-03-01

    Immunosuppressive drugs have been used out of label in multiple sclerosis (MS) for over 30 years and around 10% of patients are actually under immunosuppressive treatment. The rationale for immunosuppression in MS lies in the hypothesis that MS is an inflammatory immune-mediated disease that can take advantage of strong anti-inflammatory activity. Azathioprine, methotrexate, cyclophosphamide and mitoxantrone are the most utilised agents, but only the latter has been approved for clinically active MS. Many of them are safe in combination with interferon-beta and are under investigation in controlled trials. Plasma exchange is limited to catastrophic attacks in refractory MS whilst bone marrow transplantation is considered in patients with an extremely severe, active disease as the final option in escalation therapy. Although immunosuppressants are best effective in induction therapy, their use is limited by toxicity and potential long-term risk.

  2. Painful and involuntary Multiple Sclerosis

    PubMed Central

    Bagnato, Francesca; Centonze, Diego; Galgani, Simonetta; Grasso, Maria Grazia; Haggiag, Shalom; Strano, Stefano

    2010-01-01

    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

  3. Epigenetic Drugs for Multiple Sclerosis.

    PubMed

    Peedicayil, Jacob

    2016-01-01

    There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS.

  4. Class II HLA antigens in multiple sclerosis.

    PubMed Central

    Miller, D H; Hornabrook, R W; Dagger, J; Fong, R

    1989-01-01

    HLA typing in Wellington revealed a stronger association of multiple sclerosis with DR2 than with DQw1. The association with DQw1 appeared to be due to linkage disequilibrium of this antigen with DR2. These results, when considered in conjunction with other studies, are most easily explained by the hypothesis that susceptibility to multiple sclerosis is influenced by multiple risk factors, with DR2 being an important risk factor in Caucasoid populations. PMID:2732726

  5. [Standartization of MRI studies in multiple sclerosis].

    PubMed

    Bryukhov, V V; Krotenkova, I A; Morozova, S N; Krotenkova, M V

    2016-01-01

    The use of magnetic resonance imaging (MRI) in patients with multiple sclerosis has markedly increased in recent years. The main task of the MRI studies after the diagnosis of multiple sclerosis is to assess the dynamics of MRI for determining disease progression and monitoring the efficacy of therapy. In this regard, it is very important to obtain the most identical baseline and follow-up MRI that is possible when a single standard protocol is used. This article presents the protocol of brain MRI and spinal cord MRI and interpretation of MRI studies in patients with multiple sclerosis.

  6. Multiple sclerosis and sexual dysfunction

    PubMed Central

    Guo, Zhen-Ni; He, Si-Yuan; Zhang, Hong-Liang; Wu, Jiang; Yang, Yi

    2012-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by episodic and progressive neurologic dysfunction resulting from inflammatory and autoimmune reactions. The underlying pathogenesis of MS remains largely unclear. However, it is currently accepted as a T cell-mediated autoimmune disease. Among other clinical manifestations, sexual dysfunction (SD) is a painful but still underreported and underdiagnosed symptom of the disorder. SD in MS patients may result from a complex set of conditions and may be associated with multiple anatomic, physiologic, biologic, medical and psychological factors. SD arises primarily from lesions affecting the neural pathways involved in physiologic function. In addition, psychological factors, the side effects of medications and physical symptoms such as fatigue, muscular weakness, menstrual changes, pain and concerns about bladder and bowel incontinence may also be involved. Since MS primarily affects young people, SD secondary to MS may have a great impact on quality of life. Thus, maintaining a healthy sexual life with MS is an important priority. The treatment of SD requires multidisciplinary teamwork and cooperation among specialists, individual patients, partners and the society. PMID:22447199

  7. Association between polyneuritis and multiple sclerosis.

    PubMed Central

    Forrester, C; Lascelles, R G

    1979-01-01

    We report two cases in which multiple sclerosis and inflammatory polyneuritis occurred separately, and suggest that this association supports the idea that the two conditions may have an aetiological link. PMID:228012

  8. Multiple sclerosis: Experimental and clinical aspects

    SciTech Connect

    Scheinberg, L.; Raine, C.S.

    1984-01-01

    This book discusses the experimental and clinical aspects of multiple sclerosis. Specifically discussed are - Association of Epstein Barr Virus with pathology of central nervous system; immunology of viruses; and immunosuppression.

  9. Multiple sclerosis associated with water intoxication.

    PubMed Central

    D'Costa, D. F.; Weston, P.; Millac, P. A.

    1990-01-01

    We present a case of well documented multiple sclerosis which presented with the syndrome of inappropriate antidiuretic hormone secretion, following an exacerbation of the disease. This is a poorly documented association. PMID:2217038

  10. Epidemiology in multiple sclerosis: a pilgrim's progress.

    PubMed

    Kurtzke, John F

    2013-09-01

    There was more neurology taught under Harold G. Wolff at Cornell University Medical College in New York than perhaps anywhere else in the country when I attended from 1948 to 1952. I took my residency at the Veterans Administration Hospital in the Bronx, New York, a teaching hospital of Cornell, with Wolff as my Director of Training. While a resident, we thought we had found a treatment for multiple sclerosis. To test our conclusion, the first Class 1 treatment trial ever conducted for multiple sclerosis was performed. This showed no effect, but the participants began investigating multiple sclerosis among the 16 million persons at prime age for symptom onset who had served in the military in World War II. This led me to study its epidemiology worldwide, beginning with a detailed review of all published population-based estimates of frequency. Among these were nationwide surveys from Sweden, Denmark, Switzerland and later Norway and Finland, which showed in each country a concentration of the significantly high regions into contiguous areas forming a single 'focus' in each land, maximal in Denmark under the age of 15 years. The primary locus of high frequency multiple sclerosis seemed to be in the south-central inland lake region of Sweden, with spread to its contiguous neighbours. These concentrations in time and space indicated that multiple sclerosis was a disease probably acquired in early adolescence. Migration studies supported this: moves from high to low showed retention of birthplace risk only for those aged >15 years, whereas opposite moves indicated susceptibility limited to some 11-45 year olds. Epidemics of multiple sclerosis would suggest the disease is not only acquired but also infectious. If an infectious origin were true, transmission would have to occur before clinical onset, and would have to involve a much greater number of subjects than clinically involved. I believe there have been epidemics in Iceland, Shetland-Orkney and the Faroe Islands

  11. Disease Modifying Therapy in Multiple Sclerosis

    PubMed Central

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

    2014-01-01

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

  12. Neuroendocrine Immunoregulation in Multiple Sclerosis

    PubMed Central

    Lee, Wai-Ping; Berneman, Zwi N.

    2013-01-01

    Currently, it is generally accepted that multiple sclerosis (MS) is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases. PMID:24382974

  13. Fibronectin in multiple sclerosis lesions.

    PubMed Central

    Sobel, R. A.; Mitchell, M. E.

    1989-01-01

    Cryostat sections of central nervous system (CNS) tissues of patients with multiple sclerosis (MS) and other CNS diseases were stained with antibodies to fibronectin, a macrophage fibronectin receptor component, fibrin/fibrinogen, and albumin using immunoperoxidase. In active, but not inactive, MS plaques vessel fibronectin was increased (to approximately 57% of Factor VIII+ vessels) over uninvolved MS and normal control white matter (P less than 0.001 for both). Fibronectin was primarily localized to vessel walls and amount of staining correlated with degree of inflammation. Active plaques and necrotic lesions also had extracellular fibronectin and fibrin/ogen. These molecules and the fibronectin receptor were found on macrophages. Albumin was more widely and diffusely distributed in lesions than fibronectin. Thus, in addition to extravasation from damaged vessels, fibronectin may be deposited on or synthesized by endothelial cells and macrophages in the CNS. Fibronectin could facilitate monocyte adhesion to endothelial cell luminal surfaces, promote migration of mononuclear cells, and enhance myelin phagocytosis in MS lesions. Images Figure 1 Figure 2 PMID:2528301

  14. Islamic fasting and multiple sclerosis

    PubMed Central

    2014-01-01

    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

  15. [Oral treatments in multiple sclerosis].

    PubMed

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

    2014-12-01

    The development of new disease-modifying drugs (DMD) in relapsing-remitting multiple sclerosis (RRMS), which share the common denominator of oral administration, considerably improves patient expectations in terms of effectiveness, tolerability and treatment adherence compared with currently available drugs. However, the common route of administration of these drugs does not mean that they are equivalent, since the heading of "oral route" encompasses drugs with distinct indications and mechanisms of action, as well as heterogeneous results in terms of efficacy and safety, allowing treatment to be personalized according to the each patient' s characteristics. Currently, four oral DMD are available or in an advanced stage of clinical development: fingolimod, teriflunomide, dimethyl fumarate and laquinimod. In pivotal trials versus placebo, these molecules reduced the annualized rate of exacerbations versus placebo by 54%, 31%, 53% and 23%, respectively, the risk of progression of disability by 31%, 30%, 38% and 36%, and the number of active lesions showing contrast uptake on magnetic resonance imaging by 82%, 80%, 90% and 37%, respectively. Based on the risk/benefit ratio, fingolimod is indicated in patients with suboptimal response to initial DMD or in severe rapidly progressing RRMS, while the remaining drugs can be used as first-line options. Clinical experience with these treatments will provide new data on safety and effectiveness, which will be determinant when establishing therapeutic algorithms.

  16. Are cannabinoids effective in multiple sclerosis?

    PubMed

    Meza, Rodrigo; Peña, Javier; García, Karen; Corsi, Oscar; Rada, Gabriel

    2017-03-10

    Multiple beneficial effects have been proposed lately for cannabinoids in different clinical situations. Among them, it has been postulated they would control symptoms of multiple sclerosis. However, there is no consensus about their real clinical role. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 25 systematic reviews including 35 studies overall, of which 26 were randomized trials. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded cannabinoids in multiple sclerosis do not reduce spasticity or pain, and are probably associated to frequent adverse effects.

  17. Defective immunoregulation in multiple sclerosis.

    PubMed

    Goust, J M; Hoffman, P M; Pryjma, J; Hogan, E L; Fudenberg, H H

    1980-11-01

    Imbalances in T cell subpopulations have been reported in multiple sclerosis (MS). In the present study of 31 MS patients, the percentage of T cells with Fc receptors for IgG (Tg) was found to be increased in patients with chronic progressive disease, and another T cell subset binding to the Raji B lymphoid cell line was decreased. An inverse correlation (r = -0.675; < 95% confidence limit) was found between these two subsets, suggesting that they vary inversely in MS. The mitogenic responses of MS mononuclear cells, isolated T cells, and recombinet T and non-T cells to the lectins phytohemagglutinin and pokeweek mitogen (PWM) did not differ from those of normal cells. However, more immunoglobulin (Ig)-producing cells were generated in a PWM-driven system with cells from MS patients than with cells from age-matched controls (p < 0.05). Autologous recombination of separated T and non-T cells did not significantly modify these results. T cells from MS patients added to B cells from normal controls exerted an effect that was related to their percentage of Tg cells; that is, values above 15% were associated with a suppression of Ig production, whereas for Tg values below 12%, a helper effect or no modification was observed. These results suggest that changes in T cell subsets in MS are related to changes in functional ability to modulate Ig production by normal B cells. However, MS B cells partly escape regulation by their own T cells, suggesting an associated B cell hyperactivity.

  18. Nutrition Facts in Multiple Sclerosis

    PubMed Central

    Rossano, Rocco

    2015-01-01

    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

  19. [Hypothalamic involvement in multiple sclerosis].

    PubMed

    Darlix, A; Mathey, G; Monin, M-L; Sauvée, M; Braun, M; Schaff, J-L; Debouverie, M

    2012-05-01

    Hypothalamic involvement is a rare condition in patients with multiple sclerosis (MS). We report two patients with a long history of MS who presented with severe acute hypothermia with associated thrombocytopenia and elevated transaminase levels. Several cases of hypothermia or hyperthermia in patients with MS have been reported in the literature. They could be linked with hypothalamic lesions, in particular in the pre-optic area. However, other anatomical locations seem to be involved in thermoregulation and can be affected by MS. Besides, some cases of syndrome of inappropriate antidiuretic hormone secretion have been reported in patients with MS. Finally, some sleep disorders, particularly hypersomnia or narcolepsy, could be related to hypothalamic lesions, through the fall in hypocretin-1 in the cerebrospinal fluid. Hypocretin-1 is a neuropeptide that is secreted by some hypothalamic cells. It plays a role in the sleep-awake rhythm. We report one patient with narcolepsy and cataplexy before the first symptoms of MS appeared. Hypothalamic signs are rare in MS. However, several series of autopsies have shown a high frequency of demyelinating lesions in the hypothalamic area. Among these lesions, the proportion of active lesions seems elevated. Yet only few of them have a clinical or biological translation such as thermoregulation dysfunction, sleep disorders or natremia abnormalities. Thus, it seems unlikely that inflammatory hypothalamic lesions alone, even when bilateral, could be the explanation of these signs. A sufficient number of inflammatory demyelinating lesions, which we can observe in patients with a long history of MS and an already severe disability, is probably necessary to develop such a rare symptomatology. Hypothalamic signs might be a factor of poor prognosis for the disease course and progression of the disability.

  20. Social cognition in multiple sclerosis

    PubMed Central

    Firth, Joseph; Enzinger, Christian; Kontopantelis, Evangelos; Yung, Alison R.; Elliott, Rebecca; Drake, Richard J.

    2016-01-01

    Objective: To quantify the magnitude of deficits in theory of mind (ToM) and facial emotion recognition among patients with multiple sclerosis (MS) relative to healthy controls. Methods: An electronic database search of Ovid MEDLINE, PsycINFO, and Embase was conducted from inception to April 1, 2016. Eligible studies were original research articles published in peer-reviewed journals that examined ToM or facial emotion recognition among patients with a diagnosis of MS and a healthy control comparison group. Data were independently extracted by 2 authors. Effect sizes were calculated using Hedges g. Results: Twenty-one eligible studies were identified assessing ToM (12 studies) and/or facial emotion recognition (13 studies) among 722 patients with MS and 635 controls. Deficits in both ToM (g = −0.71, 95% confidence interval [CI] −0.88 to −0.55, p < 0.001) and facial emotion recognition (g = −0.64, 95% CI −0.81 to −0.47, p < 0.001) were identified among patients with MS relative to healthy controls. The largest deficits were observed for visual ToM tasks and for the recognition of negative facial emotional expressions. Older age predicted larger emotion recognition deficits. Other cognitive domains were inconsistently associated with social cognitive performance. Conclusions: Social cognitive deficits are an overlooked but potentially important aspect of cognitive impairment in MS with potential prognostic significance for social functioning and quality of life. Further research is required to clarify the longitudinal course of social cognitive dysfunction, its association with MS disease characteristics and neurocognitive impairment, and the MS-specific neurologic damage underlying these deficits. PMID:27655736

  1. Nutrition facts in multiple sclerosis.

    PubMed

    Riccio, Paolo; Rossano, Rocco

    2015-01-01

    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.

  2. Iron chelation and multiple sclerosis

    PubMed Central

    Weigel, Kelsey J.; Lynch, Sharon G.; LeVine, Steven M.

    2014-01-01

    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

  3. Impaired neurosteroid synthesis in multiple sclerosis.

    PubMed

    Noorbakhsh, Farshid; Ellestad, Kristofor K; Maingat, Ferdinand; Warren, Kenneth G; Han, May H; Steinman, Lawrence; Baker, Glen B; Power, Christopher

    2011-09-01

    High-throughput technologies have led to advances in the recognition of disease pathways and their underlying mechanisms. To investigate the impact of micro-RNAs on the disease process in multiple sclerosis, a prototypic inflammatory neurological disorder, we examined cerebral white matter from patients with or without the disease by micro-RNA profiling, together with confirmatory reverse transcription-polymerase chain reaction analysis, immunoblotting and gas chromatography-mass spectrometry. These observations were verified using the in vivo multiple sclerosis model, experimental autoimmune encephalomyelitis. Brains of patients with or without multiple sclerosis demonstrated differential expression of multiple micro-RNAs, but expression of three neurosteroid synthesis enzyme-specific micro-RNAs (miR-338, miR-155 and miR-491) showed a bias towards induction in patients with multiple sclerosis (P < 0.05). Analysis of the neurosteroidogenic pathways targeted by micro-RNAs revealed suppression of enzyme transcript and protein levels in the white matter of patients with multiple sclerosis (P < 0.05). This was confirmed by firefly/Renilla luciferase micro-RNA target knockdown experiments (P < 0.05) and detection of specific micro-RNAs by in situ hybridization in the brains of patients with or without multiple sclerosis. Levels of important neurosteroids, including allopregnanolone, were suppressed in the white matter of patients with multiple sclerosis (P < 0.05). Induction of the murine micro-RNAs, miR-338 and miR-155, accompanied by diminished expression of neurosteroidogenic enzymes and allopregnanolone, was also observed in the brains of mice with experimental autoimmune encephalomyelitis (P < 0.05). Allopregnanolone treatment of the experimental autoimmune encephalomyelitis mouse model limited the associated neuropathology, including neuroinflammation, myelin and axonal injury and reduced neurobehavioral deficits (P < 0.05). These multi-platform studies point to

  4. The range of multiple sclerosis associated with neurofibromatosis type 1

    PubMed Central

    Perini, P; Gallo, P

    2001-01-01

    Multiple sclerosis associated with neurofibromatosis type 1 (NF1) is a very rare event. Seven patients with multiple sclerosis and NF1 are described in the literature, and all were reported to have the primary progressive form of multiple sclerosis. Three new patients with NF1 that developed multiple sclerosis are described and it is shown that the range of multiple sclerosis associated with NF1 includes the relapsing forms of the disease. The risk of having both NF1 and multiple sclerosis in north east Italy is higher than would be expected based on the prevalence rates of the two diseases.

 PMID:11606684

  5. Anti-integrin therapy for multiple sclerosis.

    PubMed

    Kawamoto, Eiji; Nakahashi, Susumu; Okamoto, Takayuki; Imai, Hiroshi; Shimaoka, Motomu

    2012-01-01

    Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.

  6. Role of Chlamydia in Multiple Sclerosis.

    PubMed

    Ivanova, M V; Kolkova, N I; Morgunova, E Yu; Pashko, Yu P; Zigangirova, N A; Zakharova, M N

    2015-09-01

    Chlamydia and antibodies to them were detected by serological, molecular biological, and culture methods in the sera and cerebrospinal fluid of patients with multiple sclerosis and in the reference groups of subjects without neurological diseases. Correlations between the agent presence in the biological fluids of patients and clinical characteristics of the disease were analyzed. C. pneumoniae were more incident in the biological liquids of patients with multiple sclerosis than in healthy volunteers. On the other hand, the incidence of the agent in the patients was not high and its presence did not correlate with the clinical manifestations. C. trachomatis was equally rare in the patients and volunteers. The studies indicated the existence of a group of patients infected by C. pneumoniae in the cohort of patients with multiple sclerosis, but the impact of this agent for the disease course remains unclear.

  7. Multiple Sclerosis, Personal Stories | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Multiple Sclerosis Personal Stories: Nicole Lemelle, Iris Young, Michael Anthony, ... something quite different for a person living with multiple sclerosis, such as his girlfriend's brother, Chuy. The more ...

  8. Ocrevus Approved to Treat Severe Form of Multiple Sclerosis

    MedlinePlus

    ... html Ocrevus Approved to Treat Severe Form of Multiple Sclerosis First drug sanctioned in U.S. for primary progressive ... Drug Administration to treat adults with primary progressive multiple sclerosis (PPMS) and relapsing forms of the disease, the ...

  9. Development of a Novel Microfluidic Platform for Multiple Sclerosis Study

    DTIC Science & Technology

    2012-08-01

    Platform for Multiple Sclerosis Study PRINCIPAL INVESTIGATOR: In Hong Yang CONTRACTING ORGANIZATION: Johns Hopkins University...COVERED 15 Jul 2011 - 14 Jul 2012 4. TITLE AND SUBTITLE Development of a Novel Microfluidic Platform for Multiple Sclerosis Study 5a. CONTRACT NUMBER...NSC in the pathology and therapy of neurodegenerative disorders including multiple sclerosis (MS) [1-2]. Evidence suggests that NSC proliferation

  10. Magnetic resonance sees lesions of multiple sclerosis

    SciTech Connect

    Ziporyn, T.

    1985-02-15

    The value of nuclear magnetic resonance imaging in the diagnosis and quantitation of the progression of multiple sclerosis is discussed. Magnetic resonance imaging generates images that reflect differential density and velocity of hydrogen nuclei between cerebral gray and white matter, as well as between white matter and pathological lesions of the disease.

  11. Cognitive and depressive disorders in multiple sclerosis.

    PubMed

    Alajbegović, Azra; Loga, Natasa; Tiro, Naida; Alajbegović, Salem; Cindro, Veselin; Hozo, Izet

    2009-03-01

    Among other symptoms, multiple sclerosis can also produce symptoms of affective and cognitive disorders. The majority of patients have certain cognitive dysfunctions, and the' most common affective disorder is reactive depression. The aim of the study was to determine the correlation of the Mini-Mental State (MMS) and Beck Depression Inventory (BDI) scale scores with the Expanded Disability Status Scale (EDSS) score in patients with multiple sclerosis treated at University Department of Neurology, Sarajevo University Clinical Center in Sarajevo. We evaluated 50 randomly selected patients with various types of multiple sclerosis using the MMS, BDI and EDSS instruments. The study included 33 women and 17 men (66% : 34%), mean age 40.74 years (SD 9.236). The mean value of EDSS score was 3.98, ranging from 1.0 to 8.5 in women and from 1.0 to 6.5 in men. BDI scale scores showed a mean value of 12.56. The mean MMS score in baseline sample was 26.88. Statistically significant positive correlation was found between age and EDSS score, and negative correlation between EDSS and MMS, as well as between BDI and MMS. Study results indicated older patients with multiple sclerosis to have a higher EDSS score with more pronounced cognitive disturbances. There was no statistically significant correlation between EDSS score and depression.

  12. Therapeutic strategies in multiple sclerosis. I. Immunotherapy.

    PubMed Central

    Hohlfeld, R

    1999-01-01

    This review first addresses several general aspects of the immunotherapy of multiple sclerosis. Next, two approved immunomodulatory treatments, interferon-beta and copolymer-1 (glatiramer acetate), are reviewed in more detail. Finally, other immunosuppressive therapies and experimental strategies are briefly discussed. PMID:10603621

  13. Lung Volume Recruitment in Multiple Sclerosis

    PubMed Central

    Srour, Nadim; LeBlanc, Carole; King, Judy; McKim, Douglas A.

    2013-01-01

    Introduction Pulmonary function abnormalities have been described in multiple sclerosis including reductions in forced vital capacity (FVC) and cough but the time course of this impairment is unknown. Peak cough flow (PCF) is an important parameter for patients with respiratory muscle weakness and a reduced PCF has a direct impact on airway clearance and may therefore increase the risk of respiratory tract infections. Lung volume recruitment is a technique that improves PCF by inflating the lungs to their maximal insufflation capacity. Objectives Our goals were to describe the rate of decline of pulmonary function and PCF in patients with multiple sclerosis and describe the use of lung volume recruitment in this population. Methods We reviewed all patients with multiple sclerosis referred to a respiratory neuromuscular rehabilitation clinic from February 1999 until December 2010. Lung volume recruitment was attempted in patients with FVC <80% predicted. Regular twice daily lung volume recruitment was prescribed if it resulted in a significant improvement in the laboratory. Results There were 79 patients included, 35 of whom were seen more than once. A baseline FVC <80% predicted was present in 82% of patients and 80% of patients had a PCF insufficient for airway clearance. There was a significant decline in FVC (122.6 mL/y, 95% CI 54.9–190.3) and PCF (192 mL/s/y, 95% 72–311) over a median follow-up time of 13.4 months. Lung volume recruitment was associated with a slower decline in FVC (p<0.0001) and PCF (p = 0.042). Conclusion Pulmonary function and cough decline significantly over time in selected patients with multiple sclerosis and lung volume recruitment is associated with a slower rate of decline in lung function and peak cough flow. Given design limitations, additional studies are needed to assess the role of lung volume recruitment in patients with multiple sclerosis. PMID:23383293

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

    PubMed

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

    2017-04-10

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

  15. Anal sphincter dysfunction in multiple sclerosis: an observation manometric study.

    PubMed

    Marola, Silvia; Ferrarese, Alessia; Gibin, Enrico; Capobianco, Marco; Bertolotto, Antonio; Enrico, Stefano; Solej, Mario; Martino, Valter; Destefano, Ines; Nano, Mario

    2016-01-01

    Constipation, obstructed defecation, and fecal incontinence are frequent complaints in multiple sclerosis. The literature on the pathophysiological mechanisms underlying these disorders is scant. Using anorectal manometry, we compared the anorectal function in patients with and without multiple sclerosis. 136 patients referred from our Center for Multiple Sclerosis to the Coloproctology Outpatient Clinic, between January 2005 and December 2011, were enrolled. The patients were divided into four groups: multiple sclerosis patients with constipation (group A); multiple sclerosis patients with fecal incontinence (group B); non-multiple sclerosis patients with constipation (group C); non-multiple sclerosis patients with fecal incontinence (group D). Anorectal manometry was performed to measure: resting anal pressure; maximum squeeze pressure; rectoanal inhibitory reflex; filling pressure and urge pressure. The difference between resting anal pressure before and after maximum squeeze maneuvers was defined as the change in resting anal pressure calculated for each patient.

  16. Mining Gene Expression Data of Multiple Sclerosis

    PubMed Central

    Zhu, Zhenli; Huang, Zhengliang; Li, Ke

    2014-01-01

    Objectives Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example. Materials and methods Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control) were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models’ performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined. Results An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score. Conclusions The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases. PMID:24932510

  17. [Potential pathogens in multiple sclerosis (MS)].

    PubMed

    Zawada, Mariola

    2012-10-22

     Multiple sclerosis is a neuroimmunological disease in which etiologic agents have not been identified yet. The etiology of MS is complex in its nature and may involve many different agents acting simultaneously or in a cascade manner leading to the development of the disease. The causes of MS development were sought among the factors associated with HLA and TCR genes and human endogenous retroviruses (HERV). Environmental factors such as bacterial, fungal and viral infections as well as potential participation of vitamin D in the pathogenesis of the disease have also been examined. The current state of knowledge concerning potential factors participating in the etiopathogenesis of multiple sclerosis has been reviewed in this paper.

  18. Teriflunomide in relapsing multiple sclerosis: therapeutic utility.

    PubMed

    Freedman, Mark S

    2013-09-01

    Teriflunomide is an oral, once-daily disease-modifying therapy (DMT) approved in the USA, Australia, and Argentina for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide reversibly limits the expansion of activated T and B cells associated with the inflammatory process purportedly involved in multiple sclerosis pathogenesis, while preserving lymphocytes for routine immune surveillance. In an extensive clinical development program, teriflunomide demonstrated consistent benefits on both clinical and magnetic resonance imaging outcomes. In long-term studies, teriflunomide treatment was associated with low rates of relapse and disability progression for up to 8 years. The safety profile of teriflunomide has been well characterized, with adverse events generally mild to moderate in nature and infrequently leading to permanent treatment discontinuation. The evidence reviewed here indicates that teriflunomide is an effective addition to the current DMTs used to treat RMS.

  19. Monoclonal Antibodies for Multiple Sclerosis Treatment.

    PubMed

    Palavra, Filipe

    2015-01-01

    Since their introduction in medical therapy, in the last quarter of the 20th century, monoclonal antibodies have gained an increasing importance in the treatment of various diseases. Neurology has been one of the medical specialties benefiting of the therapeutic potential of these monoclonal antibodies and certain neurological conditions may now contain such drugs in their therapeutic algorithms. Multiple sclerosis is one of these diseases and, in addition to the monoclonal antibodies already licensed for clinical use, several others are in development for future utilization in this specific area. The future will certainly pass through this kind of drugs and, in this article, a review of the most relevant data related to monoclonal antibodies already in use and also in clinical development for multiple sclerosis treatment will be performed.

  20. The Diagnostic Challenge of Multiple Sclerosis

    PubMed Central

    Seland, T. Peter

    1984-01-01

    Multiple sclerosis is a common cause of many neurological complaints and disabilities among young, adult Canadians. In the absence of a reliable and specific laboratory test for the disease, the diagnosis is established primarily by clinical criteria, which are outlined in this article. Recent advances in immunology, neurophysiology and neuroimaging have provided techniques to improve diagnostic confidence, particularly in early or atypical cases. PMID:21278960

  1. Paroxysmal ataxia and dysarthria in multiple sclerosis.

    PubMed

    Iorio, R; Capone, F; Plantone, D; Batocchi, A P

    2014-01-01

    Paroxysmal ataxia and dysarthria are part of the spectrum of transient neurological disturbances that can be frequently encountered in multiple sclerosis (MS). Prompt recognition of these symptoms is important because they can be the only manifestation of a MS relapse and symptomatic therapy is often beneficial. We report a patient who developed paroxysmal ataxia and dysarthria, documented by video imaging, while he was recovering from a MS relapse. Treatment with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and dysarthria.

  2. Oxidative damage in multiple sclerosis lesions.

    PubMed

    Haider, Lukas; Fischer, Marie T; Frischer, Josa M; Bauer, Jan; Höftberger, Romana; Botond, Gergö; Esterbauer, Harald; Binder, Christoph J; Witztum, Joseph L; Lassmann, Hans

    2011-07-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are currently poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Since mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, we analysed by immunocytochemistry the presence and cellular location of oxidized lipids and oxidized DNA in lesions and in normal-appearing white matter of 30 patients with multiple sclerosis and 24 control patients without neurological disease or brain lesions. As reported before in biochemical studies, oxidized lipids and DNA were highly enriched in active multiple sclerosis plaques, predominantly in areas that are defined as initial or 'prephagocytic' lesions. Oxidized DNA was mainly seen in oligodendrocyte nuclei, which in part showed signs of apoptosis. In addition, a small number of reactive astrocytes revealed nuclear expression of 8-hydroxy-d-guanosine. Similarly, lipid peroxidation-derived structures (malondialdehyde and oxidized phospholipid epitopes) were seen in the cytoplasm of oligodendrocytes and some astrocytes. In addition, oxidized phospholipids were massively accumulated in a fraction of axonal spheroids with disturbed fast axonal transport as well as in neurons within grey matter lesions. Neurons stained for oxidized phospholipids frequently revealed signs of degeneration with fragmentation of their dendritic processes. The extent of lipid and DNA oxidation correlated significantly with inflammation, determined by the number of CD3 positive T cells and human leucocyte antigen-D expressing macrophages and microglia in the lesions. Our data suggest profound oxidative injury of oligodendrocytes and neurons to be associated with active demyelination and axonal or neuronal injury in multiple sclerosis.

  3. Matrix Metalloproteinases, Synaptic Injury, and Multiple Sclerosis

    PubMed Central

    Szklarczyk, Arek; Conant, Katherine

    2010-01-01

    Multiple sclerosis (MS) is a disease of the central nervous system in which immune mediated damage to myelin is characteristic. For an overview of this condition and its pathophysiology, please refer to one of many excellent published reviews (Sorensen and Ransohoff, 1998; Weiner, 2009). To follow, is a discussion focused on the possibility that synaptic injury occurs in at least a subset of patients, and that matrix metalloproteinases (MMPs) play a role in such. PMID:21423441

  4. [Management of neuropathic bladder in multiple sclerosis].

    PubMed

    Pappalardo, A; Patti, F; Reggio, A

    2004-05-01

    It is estimated that almost 70% of patients affected by multiple sclerosis (MS) suffer from urinary symptoms, with devastant impact on Quality of Life (QoL). The major aims of management should be to ameliorate the patients quality of life and to prevent the frequent complications of bladder dysfunction such as infention and renal damage. Therapy can usually eliminate or reduce the symptoms of neuropathic bladder. In the following pages is discussed the complex management of urinary symptoms in MS patients.

  5. Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

    PubMed

    Pryce, Gareth; Baker, David

    2015-01-01

    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.

  6. Registers of multiple sclerosis in Denmark.

    PubMed

    Koch-Henriksen, N; Magyari, M; Laursen, B

    2015-01-01

    There are two nationwide population-based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier in life that may affect the risk of MS. This register has no systematic follow-up data except for survival. The DMSR has over the years published nationwide incidence- and prevalence data from Denmark and has been involved in a number of 'historical prospective' studies to elucidate the association between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow-up register for all patients who have received disease-modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS.

  7. Acute Optic Neuritis: Prognosis for the Development of Multiple Sclerosis.

    DTIC Science & Technology

    1979-12-01

    The literature was reviewed in regard to acute optic neuritis: prognosis for the development of multiple sclerosis , with specific reference to our...series, was preselected and not prospective, causing a higher incidence of later multiple sclerosis . The second factor was the definition of multiple ...development of multiple sclerosis in patients affected with acute optic neuritis. This finding leads us to conclude that an incidence of 13% to 17

  8. Genes and Environment in Multiple Sclerosis project: A platform to investigate multiple sclerosis risk.

    PubMed

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

    2016-02-01

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

  9. Spinal cord lesions and disability in Hispanics with multiple sclerosis

    PubMed Central

    Amezcua, L.; Lerner, A.; Ledezma, K.; Conti, D.; Law, M.; Weiner, L.; Langer-Gould, A.

    2013-01-01

    Background Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. Objective To describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. Methods Cross-sectional study of 164 patients with complete MRIs. Spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale ≥4.0) was adjusted for age, disease duration and sex using logistic regression. Results 125/164(73%) MS patients had spinal cord lesions (sSCLs, 57%; LESCLs, 19%) but only 11(7%) had OSMS. LESCLs were associated with disability (p<0.0001), longer disease duration (p<0.0001) and MS (n=21 vs. n=10 OSMS; p<0.0001). LESCLs was associated with the greatest risk to disability (OR 7.3, 95% CIs1.9-26.5; p=0.003; sSCLs OR 2.5, 95% CIs0.9-7.1; p=0.09) compared with noSCLs. Conclusion LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population. PMID:23912723

  10. Peripheral blood lymphocyte phenotype and function in multiple sclerosis.

    PubMed Central

    Hughes, P J; Compston, D A

    1988-01-01

    T suppressor cell function and phenotype are abnormal in patients with multiple sclerosis, especially during the chronic progressive phase but the sub-populations defined by mitogen stimulation and serological methods may not be identical. In this study, involving 45 patients with multiple sclerosis and 33 controls, there was no correlation between T suppressor function and CD8 cell phenotype in patients with multiple sclerosis or in controls. These phenotypic and functional studies cannot therefore be used interchangeably in the assessment of patients with multiple sclerosis since they provide different information about lymphocyte subpopulations. PMID:2976082

  11. Exercise Training in Progressive Multiple Sclerosis

    PubMed Central

    Paulseth, John E.; Dove, Carin; Jiang, Shucui; Rathbone, Michel P.; Hicks, Audrey L.

    2016-01-01

    Background: There is evidence of the benefits of exercise training in multiple sclerosis (MS); however, few studies have been conducted in individuals with progressive MS and severe mobility impairment. A potential exercise rehabilitation approach is total-body recumbent stepper training (TBRST). We evaluated the safety and participant-reported experience of TBRST in people with progressive MS and compared the efficacy of TBRST with that of body weight–supported treadmill training (BWSTT) on outcomes of function, fatigue, and health-related quality of life (HRQOL). Methods: Twelve participants with progressive MS (Expanded Disability Status Scale scores, 6.0–8.0) were randomized to receive TBRST or BWSTT. Participants completed three weekly sessions (30 minutes) of exercise training for 12 weeks. Primary outcomes included safety assessed as adverse events and patient-reported exercise experience assessed as postexercise response and evaluation of exercise equipment. Secondary outcomes included the Multiple Sclerosis Functional Composite, the Modified Fatigue Impact Scale, and the Multiple Sclerosis Quality of Life–54 questionnaire scores. Assessments were conducted at baseline and after 12 weeks. Results: Safety was confirmed in both exercise groups. Participants reported enjoying both exercise modalities; however, TBRST was reviewed more favorably. Both interventions reduced fatigue and improved HRQOL (P ≤ .05); there were no changes in function. Conclusions: Both TBRST and BWSTT seem to be safe, well tolerated, and enjoyable for participants with progressive MS with severe disability. Both interventions may also be efficacious for reducing fatigue and improving HRQOL. TBRST should be further explored as an exercise rehabilitation tool for patients with progressive MS. PMID:27803637

  12. Evaluating Walking in Patients with Multiple Sclerosis

    PubMed Central

    Bennett, Susan

    2011-01-01

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

  13. Evoked potentials in monitoring multiple sclerosis.

    PubMed

    Leocani, L; Medaglini, S; Comi, G

    2000-01-01

    The usefulness of evoked potentials (EPs) in the diagnosis of multiple sclerosis is limited by its relatively low sensitivity to subclinical lesions. However, they are still a good tool to assess the integrity of afferent and efferent pathways and to quantify the severity of white matter involvement. Transversal and longitudinal studies have demonstrated good correlation between EP abnormalities and disability, suggesting that multimodal evoked potentials could be useful in monitoring the disease evolution in single patients and as surrogate end points in clinical trials.

  14. [Risk of affective disorder in multiple sclerosis].

    PubMed

    Stenager, Elsebeth Nylev; Stage, Kurt Bjerregaard; Stenager, Egon

    2011-01-10

    An increased risk for depression has been found in multiple sclerosis (MS). The purpose of the present study has been to give suggestions to guidelines for diagnosis and treatment of depression in MS in Denmark based on the international literature and recommendations. The method was a review of the relevant literature. The study recommends assessment of all MS patients for depression. Treatment of depression with serotonin reuptake inhibitors and/or cognitive behavioural therapy is recommended, depending on the severity of the illness. Caution is recommended in patients receiving beta interferon treatment.

  15. Heterogeneity versus homogeneity of multiple sclerosis

    PubMed Central

    Sato, Fumitaka; Martinez, Nicholas E; Omura, Seiichi; Tsunoda, Ikuo

    2011-01-01

    The 10th International Congress of Neuroimmunology, including the 10th European School of Neuroimmunology Course, was held by the International Society of Neuroimmunology in Sitges (Barcelona, Spain) on 26–30 October 2010. The conference covered a wide spectrum of issues and challenges in both basic science and clinical aspects of neuroimmunology. Data and ideas were shared through a variety of programs, including review talks and poster sessions. One of the topics of the congress was whether multiple sclerosis is a homogenous or heterogenous disease, clinically and pathologically, throughout its course. PMID:21426254

  16. Monthly distribution of multiple sclerosis patients' births

    NASA Astrophysics Data System (ADS)

    Bharanidharan, Padmanabhan

    As part of an integrated geographical and environmental epidemiological study of multiple sclerosis (MS) in Budapest's Pesterzsébet district, many biometeorological variables were specifically examined. Also, the monthly distribution of birthdates of MS patients resident in the district was plotted. Patients reliably diagnosed with MS were found to have been born in greater numbers in the months of April and October, precisely 6 months apart. This finding indicates the presence of natural non-genetic factors in the creation of MS susceptibility, affecting the nervous system at the crucial time of myelination.

  17. New oral drugs for multiple sclerosis.

    PubMed

    Gasperini, Claudio; Ruggieri, S

    2009-10-01

    Disease-modifying treatments are now available in relapsing-remitting and secondary progressive multiple sclerosis (MS), and their beneficial effects have been shown in several clinical studies. However, as these treatments are only partially effective in halting the MS disease process and are frequently associated with side effects and suboptimal patient adherence, new oral therapeutic approaches are warranted. This review focuses on advances in current and novel oral treatment approaches for MS. Several pivotal reports have provided promising results for new oral therapies evaluating the safety and efficacy of new agents including fingolimod, fumaric acid, cladribine, teriflunomide and laquinimod.

  18. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    PubMed

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis.

  19. Dermatoglyphic features in patients with multiple sclerosis

    PubMed Central

    Sabanciogullari, Vedat; Cevik, Seyda; Karacan, Kezban; Bolayir, Ertugrul; Cimen, Mehmet

    2014-01-01

    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

  20. The Danish Multiple Sclerosis Treatment Register

    PubMed Central

    Magyari, Melinda; Koch-Henriksen, Nils; Sørensen, Per Soelberg

    2016-01-01

    Aim of the database The Danish Multiple Sclerosis Treatment Register (DMSTR) serves as a clinical quality register, enabling the health authorities to monitor the quality of the disease-modifying treatment, and it is an important data source for epidemiological research. Study population The DMSTR includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main variables Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start, and thereafter every 6 months. The longitudinally collected information about the disease activity and side effects made it possible to investigate the clinical efficacy and adverse events of different disease-modifying therapies. Conclusion The database contributed to a certain harmonization of treatment procedures in Denmark and will continue to be a major factor in terms of quality in clinical praxis, research and monitoring of adverse events, and plays an important role in research. PMID:27822098

  1. Suicide and multiple sclerosis: an epidemiological investigation.

    PubMed Central

    Stenager, E N; Stenager, E; Koch-Henriksen, N; Brønnum-Hansen, H; Hyllested, K; Jensen, K; Bille-Brahe, U

    1992-01-01

    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

  2. Symptom management in patients with multiple sclerosis.

    PubMed

    Ziemssen, Tjalf

    2011-12-01

    Multiple sclerosis is a complex disease associated with a wide variety of different symptoms that can affect the ability of multiple sclerosis patients to carry out normal activities of daily living. Although a myriad of symptoms can afflict these patients, the most commonly reported include fatigue, mood disorders, changes in cognitive function or memory, sensory changes (numbness, pain, vibrations), motor changes (loss of balance, poor coordination, muscle weakness or stiffness), vision changes (double vision, blurred vision, loss of vision) and bladder or bowel dysfunction. Treatments are available that can help minimise some of these symptoms and relieve patient distress. After the diagnosis has been established and a decision taken regarding initiation of immunomodulatory treatments, the majority of management decisions with which the physician will be confronted will concern symptom management. Whereas some symptoms are relatively easily treated, others are more difficult to manage. Management involves rehabilitation, pharmacological treatments and surgical procedures. Successful symptom management is a key determinant of quality of life for the patient and is the basis for improving physical and psychological function.

  3. Cellular immune response in multiple sclerosis plaques.

    PubMed Central

    Boyle, E. A.; McGeer, P. L.

    1990-01-01

    Multiple sclerosis plaques were immunohistochemically stained to exhibit cells expressing immune-system antigens. Human leukocyte antigen (HLA)-DR-positive cells formed dense rings around all plaque regions. The majority were reactive microglia/macrophages. Counterstaining with oil red O revealed heavy myelin debris within these cells. They were distinct from astrocytes, which were identified with an antibody to glial fibrillary acidic protein (GFAP) and which did not contain oil red O myelin debris. Numerous leukocytes and microglia were stained with antibody to leukocyte common antigen (LCA). Lymphocytes in cuffs around vessels, along the margins of capillary walls, and, sparingly, in the tissue matrix of affected areas, were stained with antibodies to CD4 (T-helper/inducer) and CD8 (T-cytotoxic/suppressor). In experimental allergic encephalomyelitis (EAE) induced in Lewis rats, a similar proliferation of Ia-positive (OX6, OX17) cells displaying reactive microglia/macrophage morphology was observed. These Ia-positive cells also were easily distinguished from GFAP-positive astrocytes. The results suggest that macrophages/reactive microglia, and not astrocytes, express class II MHC antigens in multiple sclerosis and EAE plaques. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:1698025

  4. Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  5. Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

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

    2004-01-01

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

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

    SciTech Connect

    Ingalls, T.H. )

    1989-09-01

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

  7. [Current aspects of therapy conversion for multiple sclerosis].

    PubMed

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

    2015-10-01

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

  8. Sleep and Cognitive Function in Multiple Sclerosis

    PubMed Central

    Braley, Tiffany J.; Kratz, Anna L.; Kaplish, Neeraj; Chervin, Ronald D.

    2016-01-01

    Study Objectives: To examine associations between cognitive performance and polysomnographic measures of obstructive sleep apnea in patients with multiple sclerosis (MS). Methods: Participants underwent a comprehensive MS-specific cognitive testing battery (the Minimal Assessment of Cognitive Function in MS, or MACFIMS) and in-laboratory overnight PSG. Results: In adjusted linear regression models, the oxygen desaturation index (ODI) and minimum oxygen saturation (MinO2) were significantly associated with performance on multiple MACFIMS measures, including the Paced Auditory Serial Addition Test (PASAT; 2-sec and 3-sec versions), which assesses working memory, processing speed, and attention, and on the Brief Visuospatial Memory Test-Revised, a test of delayed visual memory. The respiratory disturbance index (RDI) was also significantly associated with PASAT-3 scores as well as the California Verbal Learning Test-II (CVLT-II) Discriminability Index, a test of verbal memory and response inhibition. Among these associations, apnea severity measures accounted for between 12% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation (as reflected by the total arousal index) and total sleep time also showed significant associations with a component of the CVLT-II that assesses response inhibition, explaining 18% and 27% of the variance in performance. Conclusions: Among patients with MS, obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function (as reflected by response inhibition), attention, processing speed, and working memory. If sleep disorders degrade these cognitive functions, effective treatment could offer new opportunities to improve cognitive functioning in patients with MS. Commentary: A commentary on this article appears in this issue on page 1489. Citation: Braley TJ, Kratz AL, Kaplish N, Chervin RD. Sleep and cognitive function

  9. Leg spasticity and ambulation in multiple sclerosis.

    PubMed

    Balantrapu, Swathi; Sosnoff, Jacob J; Pula, John H; Sandroff, Brian M; Motl, Robert W

    2014-01-01

    Background. Spasticity of the legs is common in multiple sclerosis (MS), but there has been limited research examining its association with ambulatory outcomes. Objective. This study examined spasticity of the legs and its association with multiple measures of ambulation in persons with MS. Methods. The sample included 84 patients with MS. Spasticity of the legs was measured using a 5-point rating scale ranging between 0 (normal) and 4 (contracted). Patients completed the 6-minute walk (6 MW), timed 25 foot walk (T25FW), and timed up-and-go (TUG), and O2 cost of walking was measured during the 6 MW. The patients undertook two walking trials on a GAITRite (CIR systems, Inc.) for measuring spatial and temporal parameters of gait. The patients completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and wore an accelerometer over a seven-day period. Results. 52% (n = 44) of the sample presented with spasticity of the legs. Those with leg spasticity had significantly worse ambulation as measured by 6 MW (P = 0.0001, d = -0.86), T25FW (P = 0.003, d = 0.72), TUG (P = 0.001, d = 0.84), MSWS-12 (P = 0.0001, d = 1.09), O2 cost of walking (P = 0.001, d = 0.75), average steps/day (P < 0.05, d = -0.45), and walking velocity (P < 0.05, d = -0.53) and cadence (P < 0.05, d = -0.46). Conclusion. Leg spasticity was associated with impairments in ambulation, including alterations in spatiotemporal parameters and free-living walking.

  10. Leg Spasticity and Ambulation in Multiple Sclerosis

    PubMed Central

    Balantrapu, Swathi; Sosnoff, Jacob J.; Pula, John H.; Sandroff, Brian M.; Motl, Robert W.

    2014-01-01

    Background. Spasticity of the legs is common in multiple sclerosis (MS), but there has been limited research examining its association with ambulatory outcomes. Objective. This study examined spasticity of the legs and its association with multiple measures of ambulation in persons with MS. Methods. The sample included 84 patients with MS. Spasticity of the legs was measured using a 5-point rating scale ranging between 0 (normal) and 4 (contracted). Patients completed the 6-minute walk (6 MW), timed 25 foot walk (T25FW), and timed up-and-go (TUG), and O2 cost of walking was measured during the 6 MW. The patients undertook two walking trials on a GAITRite (CIR systems, Inc.) for measuring spatial and temporal parameters of gait. The patients completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and wore an accelerometer over a seven-day period. Results. 52% (n = 44) of the sample presented with spasticity of the legs. Those with leg spasticity had significantly worse ambulation as measured by 6 MW (P = 0.0001, d = −0.86), T25FW (P = 0.003, d = 0.72), TUG (P = 0.001, d = 0.84), MSWS-12 (P = 0.0001, d = 1.09), O2 cost of walking (P = 0.001, d = 0.75), average steps/day (P < 0.05, d = −0.45), and walking velocity (P < 0.05, d = −0.53) and cadence (P < 0.05, d = −0.46). Conclusion. Leg spasticity was associated with impairments in ambulation, including alterations in spatiotemporal parameters and free-living walking. PMID:24999434

  11. Rehabilitation of multiple sclerosis patients in India

    PubMed Central

    Surya, Nirmal

    2015-01-01

    Multiple sclerosis (MS) is a chronic progressive disease which is one of the leading causes of handicap in young subjects. The large range of symptoms associated with MS lead to continuing decline in neurologic status and quality of life. The coexistence of physical and cognitive impairments, together with the imprevisible evolution of the disease makes MS rehabilitation very challenging. The main objective of rehabilitation is, therefore, to ease the burden of symptoms by improving self-performance and independence. Inpatient, outpatient and Home rehabilitation with multidisciplinary team has been shown to be beneficial in improving disability. Individualized programs elaborated by a multidisciplinary team of experts are the key to success of rehabilitation. Family plays a big role and Family Based Rehabilitation will be important in long term rehab program in MS. PMID:26538848

  12. Evolution of diagnostic criteria for multiple sclerosis.

    PubMed

    Przybek, Joanna; Gniatkowska, Inga; Mirowska-Guzel, Dagmara; Członkowska, Anna

    2015-01-01

    Multiple sclerosis is a chronic demyelinating disease of the central nervous system that occurs primarily in young adults. There is no single diagnostic test to recognize the disease. The diagnostic criteria, based on clinical examination and laboratory tests, have changed considerably over time. The first guidelines involved only the results of the patient's neurological examination. The diagnostic criteria developed by Poser in 1983 were based largely on the results of additional tests, including visual evoked potentials and analysis of cerebrospinal fluid. The McDonald criteria, developed in 2001 and updated in 2005 and 2010, reflected the diagnostic breakthrough caused by widespread use of magnetic resonance imaging (MRI). Currently, the diagnosis depends largely on the results of the MRI examination. An early diagnosis is particularly important for starting disease-modifying treatments.

  13. Low dose naltrexone therapy in multiple sclerosis.

    PubMed

    Agrawal, Y P

    2005-01-01

    The use of low doses of naltrexone for the treatment of multiple sclerosis (MS) enjoys a worldwide following amongst MS patients. There is overwhelming anecdotal evidence, that in low doses naltrexone not only prevents relapses in MS but also reduces the progression of the disease. It is proposed that naltrexone acts by reducing apoptosis of oligodendrocytes. It does this by reducing inducible nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevent the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and oligodendrocytes via activation of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid class of glutamate receptor is prevented. It is crucial that the medical community respond to patient needs and investigate this drug in a clinical trial.

  14. Neurobehavioral burden of multiple sclerosis with nanotheranostics

    PubMed Central

    Sriramoju, Bhasker; Kanwar, Rupinder K; Kanwar, Jagat R

    2015-01-01

    Multiple sclerosis (MS) is a chronic demyelinating neurological disorder affecting people worldwide; women are affected more than men. MS results in serious neurological deficits along with behavioral compromise, the mechanisms of which still remain unclear. Behavioral disturbances such as depression, anxiety, cognitive impairment, psychosis, euphoria, sleep disturbances, and fatigue affect the quality of life in MS patients. Among these, depression and psychosis are more common than any other neurological disorders. In addition, depression is associated with other comorbidities. Although anxiety is often misdiagnosed in MS patients, it can induce suicidal ideation if it coexists with depression. An interrelation between sleep abnormalities and fatigue is also reported among MS patients. In addition, therapeutics for MS is always a challenge because of the presence of the blood–brain barrier, adding to the lack of detailed understanding of the disease pathology. In this review, we tried to summarize various behavioral pathologies and their association with MS, followed by its conventional treatment and nanotheranostics. PMID:26508863

  15. Proton magnetic resonance spectroscopy in multiple sclerosis

    SciTech Connect

    Wolinsky, J.S.; Narayana, P.A.; Fenstermacher, M.J. )

    1990-11-01

    Regional in vivo proton magnetic resonance spectroscopy provides quantitative data on selected chemical constituents of brain. We imaged 16 volunteers with clinically definite multiple sclerosis on a 1.5 tesla magnetic resonance scanner to define plaque-containing volumes of interest, and obtained localized water-suppressed proton spectra using a stimulated echo sequence. Twenty-five of 40 plaque-containing regions provided spectra of adequate quality. Of these, 8 spectra from 6 subjects were consistent with the presence of cholesterol or fatty acids; the remainder were similar to those obtained from white matter of normal volunteers. This early experience with regional proton spectroscopy suggests that individual plaques are distinct. These differences likely reflect dynamic stages of the evolution of the demyelinative process not previously accessible to in vivo investigation.

  16. Benefits of Exercise Training in Multiple Sclerosis.

    PubMed

    Motl, Robert W; Sandroff, Brian M

    2015-09-01

    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.

  17. Diagnostic criteria for pediatric multiple sclerosis.

    PubMed

    Rubin, Jennifer P; Kuntz, Nancy L

    2013-06-01

    An estimated 2 % to 5 % of all persons with multiple sclerosis (MS) have onset of symptoms before 16 years of age Krupp and Hertz (Neurology 68(Suppl 2), 2007). As in adults, the diagnosis of pediatric MS is a clinical one, requiring recurrent episodes of CNS demyelination with supportive paraclinical data (MRI findings, CSF characteristics) in the absence of another plausible diagnosis. The differential diagnosis is broad and, the more atypical the case and the younger the child, the more consideration is necessary before making a diagnosis of MS. MS must be differentiated from acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica (NMO). After initial presentation with a CNS demyelinating event or clinically isolated syndrome (CIS), children can meet the diagnostic criteria for MS if serial changes are noted on MRI and other disorders are excluded. Accurate diagnosis of pediatric MS is critical because of the implications of the diagnosis, including the need for long-term disease modifying therapy.

  18. Multiple sclerosis genetics: leaving no stone unturned.

    PubMed

    Oksenberg, J R; Barcellos, L F

    2005-08-01

    Compelling epidemiologic and molecular data indicate that genes play a primary role in determining who is at risk for developing multiple sclerosis (MS), how the disease progresses, and how someone responds to therapy. The genetic component of MS etiology is believed to result from the action of allelic variants in several genes. Their incomplete penetrance and moderate individual effect probably reflects epistatic interactions, post-transcriptional regulatory mechanisms, and significant environmental influences. Equally significant, it is also likely that locus heterogeneity exists, whereby specific genes influence susceptibility and pathogenesis in some individuals but not in others. With the aid of novel analytical algorithms, the combined study of genomic, transcriptional, proteomic, and phenotypic information in well-controlled study groups will define a useful conceptual model of pathogenesis and a framework for understanding the mechanisms of action of existing therapies for this disorder, as well as the rationale for novel curative strategies.

  19. Multiple sclerosis in India: An overview

    PubMed Central

    Singhal, Bhim S.; Advani, Hemali

    2015-01-01

    Multiple sclerosis (MS) is being increasingly diagnosed in India mainly due to increase in the number of practicing neurologists and easy and affordable availability of magnetic resonance imaging (MRI). The clinical features and course are largely similar to those seen in the West. The term optico-spinal MS (Asian MS) was coined in the pre-MRI days. Many such patients turn out to be cases of neuromyelitis optica — a distinct disorder and not a variant of MS. Others have shown the classical features of MS on MRI scan. Several of the disease-modifying agents, not all, are now available in India. Their use, however, has been limited in view of the high cost. PMID:26538844

  20. Monoclonal antibodies in treatment of multiple sclerosis

    PubMed Central

    Rommer, P S; Dudesek, A; Stüve, O; Zettl, UK

    2014-01-01

    Monoclonal antibodies (mAbs) are used as therapeutics in a number of disciplines in medicine, such as oncology, rheumatology, gastroenterology, dermatology and transplant rejection prevention. Since the introduction and reintroduction of the anti-alpha4-integrin mAb natalizumab in 2004 and 2006, mAbs have gained relevance in the treatment of multiple sclerosis (MS). At present, numerous mAbs have been tested in clinical trials in relapsing–remitting MS, and in progressive forms of MS. One of the agents that might soon be approved for very active forms of relapsing–remitting MS is alemtuzumab, a humanized mAb against CD52. This review provides insights into clinical studies with the mAbs natalizumab, alemtuzumab, daclizumab, rituximab, ocrelizumab and ofatumumab. PMID:24001305

  1. Is multiple sclerosis a mitochondrial disease?

    PubMed Central

    Mao, Peizhong; Reddy, P. Hemachandra

    2009-01-01

    Multiple sclerosis (MS) is a relatively common and etiologically unknown disease with no cure treatment. It is the leading cause of neurological disability in young adults, affecting over two million people worldwide. Traditionally, MS has been considered a chronic, inflammatory disorder of the central white matter in which ensuing demyelination results in physical disability. Recently, MS has become increasingly viewed as a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system lead to permanent neurological and clinical disability. In this article, we discuss the latest developments on MS research, including etiology, pathology, genetic association, EAE animal models, mechanisms of neuronal injury and axonal transport and therapeutics. In this article, we also focus on the mechanisms of mitochondrial dysfunction that are involved in MS, including mitochondrial DNA defects, and mitochondrial structural/functional changes. PMID:19607913

  2. [Vision aids for multiple sclerosis patients].

    PubMed

    Frieling, E; Kornhuber, H H; Nissl, K

    1986-02-07

    Optical or electronic vision aids enabled 35 of 39 visually handicapped multiple sclerosis patients to read. Six patients had an uncorrected ametropia. 15 could read again with the help of magnifying optical aids and 11 with the help of an electronic television system. An electronic television reader was useful when visual acuities were below 0.1 and in patients with oscillating nystagmus or tremor capitis. Contact lenses helped 3 patients who had a neurogenous visual defect and oscillating nystagmus. Although acquired oscillating nystagmus disappears on eyelid closure and only reappears again on fixation, its amplitude, when unable to read, is greater. On overcoming the neurogenous visual defect with vision aids it becomes smaller.

  3. [Treatment of multiple sclerosis symptoms and exacerbations].

    PubMed

    Prieto González, José María

    2014-12-01

    In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis.

  4. Mitochondrial haplogroups in Basque multiple sclerosis patients.

    PubMed

    Otaegui, D; Sáenz, A; Martínez-Zabaleta, M; Villoslada, P; Fernández-Manchola, I; Alvarez de Arcaya, A; Emparanza, J I; López de Munain, A

    2004-10-01

    Previous studies have suggested that mitochondrial metabolism and/or mitochondrial DNA (mtDNA) could be, in conjunction with other genetic or environmental factors, a risk factor for the development of multiple sclerosis (MS). One of these studies establishes that mitochondrial haplogroup JT is a risk factor for developing the disease, in particular the visual manifestations [optic neuritis (ON)]. Nevertheless, as distribution of these haplogroups varies between populations, the observed association may be due to a slanted sample with no physiopathological value. This hypothesis was checked with MS patients, originals from Basque country (this population has peculiar genetic characteristics) and from other Spanish regions. We concluded that such an association does not exist. By contrast, a decrease could be seen in the frequency of the JT haplogroup in the ON group and in the MS-Basque group. That trend could be a protective effect, which needs to be verified in further investigations.

  5. Innovative Monoclonal Antibody Therapies in Multiple Sclerosis

    PubMed Central

    Kieseier, Bernd C.

    2008-01-01

    The recent years have witnessed great efforts in establishing new therapeutic options for multiple sclerosis (MS), especially for relapsing–remitting disease courses. In particular, the application of monoclonal antibodies provide innovative approaches allowing for blocking or depleting specific molecular targets, which are of interest in the pathogenesis of MS. While natalizumab received approval by the US Food and Drug Administration and the European Medicines Agency in 2006 as the first monoclonal antibody in MS therapy, rituximab, alemtuzumab, and daclizumab were successfully tested for relapsing-remitting MS in small cohorts in the meantime. Here, we review the data available from these recent phase II trials and at the same time critically discuss possible pitfalls which may be relevant for clinical practice. The results of these studies may not only broaden our therapeutic options in the near future, but also provide new insights into disease pathogenesis. PMID:21180564

  6. Natalizumab in the Treatment of Multiple Sclerosis

    PubMed Central

    Yaldizli, Özgür

    2009-01-01

    Natalizumab reduced the rate of clinical relapse at one year by 68% and the risk of sustained progression of disability by 42-54% over 2 years in its pivotal phase III trial (AFFIRM) in relapsing-remitting multiple sclerosis (RRMS). Natalizumab is generally well tolerated, but due to rare and potentially fatal side-effects, it was approved with a restricted-distribution format in 2006. Expert statements and the European Medical Agency recommend the use of natalizumab after failure of first-line disease-modifying therapies in patients with relapsing forms of MS. As part of the risk management plan, worldwide extensive safety programmes aim to provide more data on natalizumab safety in clinical practice. At the end of September 2008, 48 000 patients have received natalizumab and 18000 patients are on treatment for at least 1 year. The assessment of risk and benefit is still ongoing. PMID:21180646

  7. Malignancies after mitoxantrone for multiple sclerosis

    PubMed Central

    Seuffert, Linda; Mäder, Uwe; Toyka, Klaus V.

    2016-01-01

    Objective: To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis. Methods: This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence. Results: Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8–11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m2 (interquartile range 50.8–102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval [CI] 1.05–2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20–6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39–24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs ≤75 mg/m2) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes. Conclusions: While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable. PMID:27170571

  8. Total lymphoid irradiation for multiple sclerosis

    SciTech Connect

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    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 inferior 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.

  9. Managing Neuropsychological Impairment in Multiple Sclerosis

    PubMed Central

    Lau, Stephanie; Penner, Iris; Heesen, Christoph; Moritz, Steffen

    2015-01-01

    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

  10. The management of multiple sclerosis in children: a European view.

    PubMed

    Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey; Amato, Maria Pia; Anlar, Banu; Blinkenberg, Morten; Boon, Maartje; Filippi, Massimo; Jozwiak, Sergiusz; Ketelslegers, Immy; Kornek, Barbara; Lim, Ming; Lindstrom, Eva; Nadj, Congor; Neuteboom, Rinze; Rocca, Maria A; Rostasy, Kevin; Tardieu, Marc; Wassmer, Evangeline; Catsman-Berrevoets, Coriene; Hintzen, Rogier

    2010-10-01

    About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce in paediatric multiple sclerosis. Nevertheless, expertise in this field has grown thanks to recent open-label trials and experience generated in specialized centres. In spring 2009, a first meeting was held in Rotterdam with clinicians from 11 European countries (one from Canada) that are all active in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.

  11. Gluten sensitivity in multiple sclerosis: experimental myth or clinical truth?

    PubMed

    Shor, Dana Ben-Ami; Barzilai, Ori; Ram, Maya; Izhaky, David; Porat-Katz, Bat Sheva; Chapman, Joab; Blank, Miri; Anaya, Juan-Manuel; Shoenfeld, Yehuda

    2009-09-01

    Patients with neurological disease of unknown etiology sometimes present with antigliadin and antitissue transglutaminase antibodies. The association between these antibodies and multiple sclerosis has been previously suggested. The purpose of this study was to determine the prevalence of these antibodies in multiple sclerosis patients. We determined the level of serum immunoglobulin A and immunoglobulin G antigliadin and antitissue transglutaminase antibodies in 98 patients with multiple sclerosis. We found a highly significant increase in titers of immunoglobulin G antibodies against gliadin and tissue transglutaminase in the multiple sclerosis patients. Seven patients had a positive IgG AGA, whereas only 2 controls presented positive titers (P = 0.03). Four patients had positive IgG anti-tTG while all the controls tested negative (P = 0.02). However, immunoglobulin A antibodies against gliadin and tissue transglutaminase were not statistically higher in the multiple sclerosis group in comparison to the control group. Our findings support the associations between antibodies against gliadin and tissue transglutaminase to multiple sclerosis. The specific role of these antibodies in the pathogenesis of multiple sclerosis remains uncertain and requires additional research. A gluten free diet should be considered in specific cases of patients who present with gluten antibodies.

  12. Spinal cord lesions and disability in Hispanics with multiple sclerosis.

    PubMed

    Amezcua, L; Lerner, A; Ledezma, K; Conti, D; Law, M; Weiner, L; Langer-Gould, A

    2013-11-01

    Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. The purpose of this study is to describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. A cross-sectional study of 164 patients with complete MRIs was used. In each case the spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale ≥4.0) was adjusted for age, disease duration and sex using logistic regression. A total of 125/164 (73 %) MS patients had spinal cord lesions (sSCLs, 57 %; LESCLs, 19 %), but only 11 (7 %) had OSMS. LESCLs were associated with disability (p < 0.0001), longer disease duration (p < 0.0001) and MS (n = 21 vs. n = 10 OSMS; p < 0.0001). LESCLs were also associated with the greatest risk to disability (OR 7.3, 95 % CIs 1.9-26.5; p = 0.003; sSCLs OR 2.5, 95 % CIs 0.9-7.1; p = 0.09) compared with noSCLs. LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.

  13. Role of pathogens in multiple sclerosis.

    PubMed

    Libbey, Jane E; Cusick, Matthew F; Fujinami, Robert S

    2014-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS). Although the etiology of MS is unknown, genetic and environmental factors play a role. Infectious pathogens are the likely environmental factors involved in the development of MS. Pathogens associated with the development or exacerbation of MS include bacteria, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, the Staphylococcus aureus-produced enterotoxins that function as superantigens, viruses of the herpes virus (Epstein-Barr virus and human herpesvirus 6) and human endogenous retrovirus (HERV) families and the protozoa Acanthamoeba castellanii. Evidence, from studies with humans and animal models, supporting the association of these various pathogens with the development and/or exacerbation of MS will be discussed along with the potential mechanisms including molecular mimicry, epitope spreading and bystander activation. In contrast, infection with certain parasites such as helminthes (Schistosoma mansoni, Fasciola hepatica, Hymenolepis nana, Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercolaris, Enterobius vermicularis) appears to protect against the development or exacerbation of MS. Evidence supporting the ability of parasitic infections to protect against disease will be discussed along with a brief summary of a recent Phase I clinical trial testing the ability of Trichuris suis ova treatment to improve the clinical course of MS. A complex interaction between the CNS (including the blood-brain barrier), multiple infections with various infectious agents (occurring in the periphery or within the CNS), and the immune response to those various infections may have to be deciphered before the etiology of MS can be fully understood.

  14. Mimicry between mitochondrial disorder and multiple sclerosis.

    PubMed

    Finsterer, Josef; Höftberger, Romana; Stöllberger, Claudia; Rolinski, Boris

    2012-06-01

    Under certain conditions or at certain stages of the disease course, multiple sclerosis (MS) and mitochondrial disorder (MID) may be differential diagnoses and thus may be confused with each other. In a 30 years old female MS was diagnosed at age 16 year upon recurrent sensory disturbances of the right lower leg, an "inflammatory" cerebrospinal fluid, and a cerebral MRI with multiple non-enhancing white matter lesions. Steroids were repeatedly given but because of rapid deterioration treatment was switched to interferon and mitoxantrone, without improvement. Fourteen years after onset the patient additionally presented with a history of rhabdomyolysis, hypothyroidism, ophthalmoparesis, anarthria, tetraspasticity, tetraparesis, and joint contractures. After MID had been diagnosed in her mother she was re-evaluated and elevated resting lactate, axonal polyneuropathy, and empty sella were additionally found. Muscle biopsy revealed myophagy, fat deposition, and type-II predominance, and biochemical investigations showed a deficiency of complex I and IV of the respiratory chain. MID was diagnosed also in the index patient. It is concluded that even if CSF investigations or imaging studies suggest MS, differentials such as MIDs need to be excluded before prescribing medication possibly toxic to a MID. An "inflammatory CSF" may also occur in MIDs.

  15. The symptomatic management of multiple sclerosis

    PubMed Central

    Schapiro, Randall T.

    2009-01-01

    The management of multiple sclerosis (MS) revolves around disease management, symptom management, and person management. Of these, symptom management takes up the bulk of the time of the practicing physician. Some symptoms are easily managed whereas others are more difficult. Decisions have often to be made on whether to treat or to wait and watch. This article discusses the varied symptoms of MS and the approaches to management, which involves rehabilitation, pharmacological treatments, and surgical procedures. The skilled physician managing MS should be familiar with the multiple approaches to improving the quality of life of those with MS. After the diagnosis has been established and the decisions regarding treatment approaches have been made, the talk in a typical office appointment for MS usually turns to symptom management. Thus, the majority of management decisions made by the clinician revolve around that important topic. It is symptom management that will determine quality of life for those with MS, It is the basis for improving function, and, up until twenty years ago, it was the only basis for treating MS. Now, however, we can approach treatment by disease management, symptom management, and person management. The MS specialist must be well versed in all three areas. PMID:20182577

  16. Bone health in patients with multiple sclerosis.

    PubMed

    Zikan, Vit

    2011-01-01

    Multiple sclerosis (MS) is a gait disorder characterized by acute episodes of neurological defects leading to progressive disability. Patients with MS have multiple risk factors for osteoporotic fractures, such as progressive immobilization, long-term glucocorticoids (GCs) treatment or vitamin D deficiency. The duration of motor disability appears to be a major contributor to the reduction of bone strength. The long term immobilization causes a marked imbalance between bone formation and resorption with depressed bone formation and a marked disruption of mechanosensory network of tightly connected osteocytes due to increase of osteocyte apoptosis. Patients with higher level of disability have also higher risk of falls that combined with a bone loss increases the frequency of bone fractures. There are currently no recommendations how to best prevent and treat osteoporosis in patients with MS. However, devastating effect of immobilization on the skeleton in patients with MS underscores the importance of adequate mechanical stimuli for maintaining the bone structure and its mechanical competence. The physical as well as pharmacological interventions which can counteract the bone remodeling imbalance, particularly osteocyte apoptosis, will be promising for prevention and treatment of osteoporosis in patients with MS.

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

    ERIC Educational Resources Information Center

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

    2000-01-01

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

  18. Jaw, blink and corneal reflex latencies in multiple sclerosis.

    PubMed Central

    Sanders, E A; Ongerboer de Visser, B W; Barendswaard, E C; Arts, R J

    1985-01-01

    Jaw, blink and corneal reflexes, which all involve the trigeminal system, were recorded in 54 patients with multiple sclerosis; thirty-seven of these patients were classified as having definite multiple sclerosis and 17 as indefinite multiple sclerosis, according to Schumacher's criteria. The jaw reflex was abnormal less frequently than either of the other two reflexes, but in four cases it was the only abnormal reflex found. Testing a combination of two or three trigeminal reflexes did not yield a higher incidence of abnormalities than testing the blink or corneal reflex alone. Nine patients showed abnormal reflexes which were unexpected on the basis of clinical symptoms. The combined recordings demonstrate at least one abnormal reflex in 74% of the patients. The various types of reflex abnormalities reflect major damage to different parts of the trigeminal system and may therefore make an important contribution to the diagnosis of multiple sclerosis. PMID:4087004

  19. Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis.

    PubMed Central

    Pandey, J P; Goust, J M; Salier, J P; Fudenberg, H H

    1981-01-01

    Serum samples from 70 Caucasian patients with multiple sclerosis were typed for nine Gm markers. Significant association was found with the Gm 1,17;21 phenotype, and the relative risk for individuals with this phenotype was calculated at 3.6. The data indicate that Caucasians positive for Gm 1,17;21 are almost four times more likely to develop multiple sclerosis than those without this phenotype. PMID:6787085

  20. Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis.

    PubMed

    Pandey, J P; Goust, J M; Salier, J P; Fudenberg, H H

    1981-06-01

    Serum samples from 70 Caucasian patients with multiple sclerosis were typed for nine Gm markers. Significant association was found with the Gm 1,17;21 phenotype, and the relative risk for individuals with this phenotype was calculated at 3.6. The data indicate that Caucasians positive for Gm 1,17;21 are almost four times more likely to develop multiple sclerosis than those without this phenotype.

  1. Co-occurring depression and pain in multiple sclerosis.

    PubMed

    Alschuler, Kevin N; Ehde, Dawn M; Jensen, Mark P

    2013-11-01

    Depression and pain are highly prevalent among individuals with multiple sclerosis, and they often co-occur. The purpose of this article is to summarize the literature and theory related to the comorbidity of pain and depression and describe how their presence can impact individuals with multiple sclerosis. Additionally, the article discusses how existing treatments of pain and depression could be adapted to address shared mechanisms and overcome barriers to treatment utilization.

  2. Epstein Barr Virus and Blood Brain Barrier in Multiple Sclerosis

    DTIC Science & Technology

    2014-01-01

    brain-barrier, Epstein-Barr virus; EBV ; BBB; MS, Multiple sclerosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...ABSTRACT Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease. Epstein-Barr virus ( EBV ) infection is associated with MS...pathogenesis. However, mechanism for the EBV -MS connection is unclear. The blood– brain barrier (BBB) is a separation of circulating blood and the brain

  3. Anal sphincter dysfunction in multiple sclerosis: an observation manometric study

    PubMed Central

    Marola, Silvia; Gibin, Enrico; Capobianco, Marco; Bertolotto, Antonio; Enrico, Stefano; Solej, Mario; Martino, Valter; Destefano, Ines; Nano, Mario

    2016-01-01

    Abstract Constipation, obstructed defecation, and fecal incontinence are frequent complaints in multiple sclerosis. The literature on the pathophysiological mechanisms underlying these disorders is scant. Using anorectal manometry, we compared the anorectal function in patients with and without multiple sclerosis. 136 patients referred from our Center for Multiple Sclerosis to the Coloproctology Outpatient Clinic, between January 2005 and December 2011, were enrolled. The patients were divided into four groups: multiple sclerosis patients with constipation (group A); multiple sclerosis patients with fecal incontinence (group B); non-multiple sclerosis patients with constipation (group C); non-multiple sclerosis patients with fecal incontinence (group D). Anorectal manometry was performed to measure: resting anal pressure; maximum squeeze pressure; rectoanal inhibitory reflex; filling pressure and urge pressure. The difference between resting anal pressure before and after maximum squeeze maneuvers was defined as the change in resting anal pressure calculated for each patient. Results Group A patients were noted to have greater sphincter hypotonia at rest and during contraction compared with those in group C (p=0.02); the rectal sensitivity threshold was lower in group B than in group D patients (p=0.02). No voluntary postcontraction sphincter relaxation was observed in either group A or group B patients (p=0.891 and p=0.939, respectively). Conclusions The decrease in the difference in resting anal pressure before and after maximum squeeze maneuvers suggests post-contraction sphincter spasticity, indicating impaired pelvic floor coordination in multiple sclerosis patients. A knowledge of manometric alterations in such patients may be clinically relevant in the selection of patients for appropriate treatments and for planning targeted rehabilitation therapy. PMID:28352843

  4. Natalizumab therapy of multiple sclerosis: recommendations of the Multiple Sclerosis Study Group--Italian Neurological Society.

    PubMed

    Ghezzi, A; Grimaldi, L M E; Marrosu, M G; Pozzilli, C; Comi, G; Bertolotto, A; Trojano, M; Gallo, P; Capra, R; Centonze, D; Millefiorini, E; Sotgiu, S; Brescia Morra, V; Amato, M P; Lugaresi, A; Mancardi, G; Caputo, D; Montanari, E; Provinciali, L; Durelli, L; Bergamaschi, R; Bellantonio, P; Tola, M R; Cottone, S; Savettieri, G; Tedeschi, G

    2011-04-01

    Three years after the introduction of natalizumab (NA) therapy for the second line treatment of relapsing-remitting multiple sclerosis (MS), Italian MS centers critically reviewed the scientific literature and their own clinical experience. Natalizumab was shown to be highly efficacious in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. This article summarizes the MS-SIN Study Group recommendations on the use of NA in MS, with particular reference to the appropriate selection and monitoring of patients as well as to the management of adverse events.

  5. A study of oligoclonal band negative multiple sclerosis.

    PubMed Central

    Zeman, A Z; Kidd, D; McLean, B N; Kelly, M A; Francis, D A; Miller, D H; Kendall, B E; Rudge, P; Thompson, E J; McDonald, W I

    1996-01-01

    OBJECTIVES--To determine whether oligoclonal band (OCB) negative multiple sclerosis is a reliable diagnosis and, if so, whether it has a distinctive prognosis. METHODS--Retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite multiple sclerosis with and without intrathecal synthesis of oligoclonal IgG. RESULTS--Thirty four patients were identified with apparent OCB negative clinically definite multiple sclerosis. The results of oligoclonal banding proved to have been equivocal in 14 of 34; the clinical diagnosis of multiple sclerosis was questionable in 8 of 34. The remaining 12 patients with "true" OCB negative multiple sclerosis were significantly less disabled than matched OCB positive controls. Re-examination of CSF-serum pairs from six OCB negative patients showed that three remained OCB negative while three showed evidence of intrathecal synthesis of OCBs. CONCLUSIONS--OCB negative clinically definite multiple sclerosis is rare and should be diagnosed with caution; in unequivocal cases it seems to have a relatively benign prognosis. PMID:8558146

  6. The Ocular Manifestations of Drugs Used to Treat Multiple Sclerosis.

    PubMed

    Heath, Gregory; Airody, Archana; Gale, Richard Peter

    2017-03-01

    Recent times have seen an increase in the number of options to treat multiple sclerosis. Ocular manifestations of multiple sclerosis are well known to treating physicians; however, the medications used to treat multiple sclerosis can also have ocular side effects. This review article focuses on the ocular manifestations of corticosteroids and disease-modifying agents such as interferon, fingolomod, natalizumab, alemtuzumab and mitoxantron used to treat the disease. The ocular manifestations of multiple sclerosis treatments can be varied depending on the drug used, and include retinopathy, chronic central serous chorioretinopathy, macular oedema, Graves' ophthalmopathy and cortical blindness. These effects may be specific to the drug or secondary to their immunosuppressive effect. The association of macular oedema with fingolomod is clear and merits ocular screening for toxicity. The immunosuppressive nature of the treatments makes patients prone to acquired infections. Hence, if a patient with multiple sclerosis presents with vision loss, infectious and drug-induced aetiology should be considered alongside relapses of multiple sclerosis itself as a cause.

  7. Therapeutic Yoga: Symptom Management for Multiple Sclerosis

    PubMed Central

    MacDonald, Megan

    2015-01-01

    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

  8. Relapses in multiple sclerosis: Relationship to disability.

    PubMed

    Goodin, Douglas S; Reder, Anthony T; Bermel, Robert A; Cutter, Gary R; Fox, Robert J; John, Gareth R; Lublin, Fred D; Lucchinetti, Claudia F; Miller, Aaron E; Pelletier, Daniel; Racke, Michael K; Trapp, Bruce D; Vartanian, Timothy; Waubant, Emmanuelle

    2016-03-01

    Multiple sclerosis (MS) is a recurrent inflammatory disease of the central nervous system, which ultimately causes substantial disability in many patients. A key clinical feature of this disease is the occurrence of relapses, consisting of episodes of neurological dysfunction followed by periods of remission. This review considers in detail the importance of the occurrence of relapses to the ultimate course of MS and the impact of relap setreatment (both acutely and prophylactically) on the long-term outcome for individuals. The ultimate goal of therapy in MS is the reduction of long-term disability. Clinical trials in MS, however, typically only extend for a very short time period compared to the time it takes for disability to evolve. Consequently, short-term outcome measures that are associated with, and predict, future disability need to be identified. In this regard, not only are relapses a characteristic feature of MS, they have also been proven to be associated with the occurrence of long-term disability. Moreover, treatments that reduce the number and severity of these attacks improve the long-term prognosis.

  9. Therapeutic Yoga: Symptom Management for Multiple Sclerosis.

    PubMed

    Rogers, Kim A; MacDonald, Megan

    2015-11-01

    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.

  10. Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

    PubMed Central

    Miljković, Djordje; Spasojević, Ivan

    2013-01-01

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

  11. Uphill and Downhill Walking in Multiple Sclerosis

    PubMed Central

    Samaei, Afshin; Hajihasani, Abdolhamid; Fatemi, Elham; Motaharinezhad, Fatemeh

    2016-01-01

    Background: Various exercise protocols have been recommended for patients with multiple sclerosis (MS). We investigated the effects of uphill and downhill walking exercise on mobility, functional activities, and muscle strength in MS patients. Methods: Thirty-four MS patients were randomly allocated to either the downhill or uphill treadmill walking group for 12 sessions (3 times/wk) of 30 minutes' walking on a 10% negative slope (n = 17) or a 10% positive slope (n = 17), respectively. Measurements were taken before and after the intervention and after 4-week follow-up and included fatigue by Modified Fatigue Impact Scale; mobility by Modified Rivermead Mobility Index; disability by Guy's Neurological Disability Scale; functional activities by 2-Minute Walk Test, Timed 25-Foot Walk test, and Timed Up and Go test; balance indices by Biodex Balance System; and quadriceps and hamstring isometric muscles by torque of left and right knee joints. Analysis of variance with repeated measures was used to investigate the intervention effects on the measurements. Results: After the intervention, significant improvement was found in the downhill group versus the uphill group in terms of fatigue, mobility, and disability indices; functional activities; balance indices; and quadriceps isometric torque (P < .05). The results were stable at 4-week follow-up. Conclusions: Downhill walking on a treadmill may improve muscle performance, functional activity, and balance control in MS patients. These findings support the idea of using eccentric exercise training in MS rehabilitation protocols. PMID:26917996

  12. Depression in multiple sclerosis: a review.

    PubMed

    Siegert, R J; Abernethy, D A

    2005-04-01

    Several studies have reported high rates of depression in multiple sclerosis (MS) with a lifetime prevalence of approximately 50% and an annual prevalence of 20% not uncommon. Concern about the potential of new drug treatments to exacerbate or precipitate depression in MS has led to increased interest in the relation between MS and depression. This review on MS and depression identifies the following key issues: How common is depression in people with MS? Is depression in MS associated with lesions in specific regions of the central nervous system? Is there an increased risk of suicide in MS? Is there a higher than expected incidence of anxiety disorders in MS? Are fatigue and depressed mood related in MS? Is there a relation between depression and cognitive impairment in MS? Which psychosocial variables affect the development of depression in MS? Does treatment with interferon increase the risk of depression? How effective are treatments for MS patients with depression? Each of these issues is briefly reviewed with critical commentary, and some priorities for future research are suggested.

  13. Longitudinal study of alexithymia and multiple sclerosis

    PubMed Central

    Chahraoui, Khadija; Duchene, Céline; Rollot, Fabien; Bonin, Bernard; Moreau, Thibault

    2014-01-01

    Objective The aim of this study was to investigate the course of alexithymia and its relation with anxiety and depression in patients with multiple sclerosis (MS), over a period of 5 years. Methods Sixty-two MS patients were examined at two timepoints, 5 years apart, and they answered questionnaires collecting socio-demographic, medical, and psychological data (depression, anxiety, alexithymia). Results Our data show that emotional disorders remain stable over time in patients with MS, particularly as regards alexithymia and anxiety. Conversely, the rate of depression decreased between the two evaluations, falling from 40% to 26%. The two dimensions of alexithymia (i.e., difficulty describing and difficulty identifying feelings) were correlated with anxiety and depression, whereas the third component of alexithymia (externally oriented thinking) was independent, and was the only component to change over time, with a significant fall observed at 5 years. Conclusion Alexithymia was associated with increased severity of anxiety and attack relapses. PMID:24653957

  14. The topographical model of multiple sclerosis

    PubMed Central

    Cook, Karin; De Nino, Scott; Fletcher, Madhuri

    2016-01-01

    Relapses and progression contribute to multiple sclerosis (MS) disease course, but neither the relationship between them nor the spectrum of clinical heterogeneity has been fully characterized. A hypothesis-driven, biologically informed model could build on the clinical phenotypes to encompass the dynamic admixture of factors underlying MS disease course. In this medical hypothesis, we put forth a dynamic model of MS disease course that incorporates localization and other drivers of disability to propose a clinical manifestation framework that visualizes MS in a clinically individualized way. The topographical model encapsulates 5 factors (localization of relapses and causative lesions; relapse frequency, severity, and recovery; and progression rate), visualized utilizing dynamic 3-dimensional renderings. The central hypothesis is that, like symptom recrudescence in Uhthoff phenomenon and pseudoexacerbations, progression clinically recapitulates prior relapse symptoms and unmasks previously silent lesions, incrementally revealing underlying lesion topography. The model uses real-time simulation software to depict disease course archetypes and illuminate several well-described but poorly reconciled phenomena including the clinical/MRI paradox and prognostic significance of lesion location and burden on disease outcomes. Utilization of this model could allow for earlier and more clinically precise identification of progressive MS and predictive implications can be empirically tested. PMID:27648465

  15. Pediatric multiple sclerosis: Cognition and mood.

    PubMed

    Amato, Maria Pia; Krupp, Lauren B; Charvet, Leigh E; Penner, Iris; Till, Christine

    2016-08-30

    In comparison with the large body of evidence on cognitive functioning in adults with multiple sclerosis (MS), there is limited information on cognition in pediatric-onset MS (POMS). Unique vulnerabilities in POMS can derive from having a disease that occurs during key periods of age-expected brain growth, active myelination in the CNS, and maturation of neural networks during the learning curve and key formative years in the academic career of the patient. Therefore, the consequences of MS on developing cognitive faculties can be assessed only in the pediatric population and cannot be simply extrapolated from studies carried on in the adult population. Until the last decade, research in the pediatric population was mainly represented by small clinical series, often limited by the narrow scope of neuropsychological assessment and lack of adequate control groups. Over the last decade, however, cognitive functioning and mood-related difficulties have become an increasing concern as awareness of this population has grown. A few specialized MS centers have begun performing more systematic research in the field in order to assess the prevalence of cognitive impairments and mood-related difficulties in patients with POMS, to better characterize the neuropsychological pattern and determine the functional consequences of these problems. This chapter summarizes our current understanding of cognitive and mood-related difficulties in POMS and highlights perceived gaps in knowledge and priorities for future research.

  16. The Transition to Secondary Progressive Multiple Sclerosis

    PubMed Central

    Wood, Fiona; Brain, Katherine E.; Edwards, Michelle; Jones, Rhiannon; Wallbank, Rachel; Robertson, Neil P.; Edwards, Adrian

    2016-01-01

    Background: Identifying the transition from relapsing-remitting to secondary progressive multiple sclerosis (SPMS) can be challenging for clinicians. Little previous research has explored how professionals experience working with patients during this specific stage of the disease. We explored the experiences of a group of multidisciplinary professionals who support patients in the transition to SPMS to describe this stage from a professional perspective. Methods: This qualitative semistructured interview study included 11 professionals (medical, nursing, and allied health professionals; specialists and generalists) working with patients with MS in South Wales, United Kingdom. Thematic analysis of the interview data was performed. Results: Two overarching themes were identified: the transition and providing support. The transition theme comprised issues related to recognizing and communicating about SPMS. Uncertainty influenced recognizing the transition and knowing how to discuss it with patients. The providing support theme included descriptions of challenging aspects of patient care, providing support for caregivers, using the multidisciplinary team, and working within service constraints. Providing adequate psychological support and engaging patients with self-management approaches were seen as particularly challenging. Conclusions: Caring for patients in the transition to SPMS generates specific challenges for professionals. Further research on health-care interactions and patients'/professionals' experiences regarding the transition phase may help identify strategies for professional development and learning and how to optimize the patient experience at this difficult stage of disease. PMID:27803641

  17. Overview and diagnosis of multiple sclerosis.

    PubMed

    Hunter, Samuel F

    2016-06-01

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

  18. A basic overview of multiple sclerosis immunopathology.

    PubMed

    Grigoriadis, N; van Pesch, V

    2015-10-01

    Multiple sclerosis (MS) is a multi-component disease characterized by inflammation, neurodegeneration and failure of central nervous system (CNS) repair mechanisms. Immune dysregulation appears to originate with dendritic cells (antigen-presenting cells) which have an activated phenotype in individuals with MS. Dendritic cells migrate across the blood-brain barrier and induce differentiation of memory T cells into pro-inflammatory T helper 1 (Th1) and Th17 lymphocytes. In turn, induction of macrophage and microglial activation produces other pro-inflammatory cytokines and oxygen and nitric oxide radicals responsible for the demyelination and axonal loss. Other known mediators of MS pathology include CD8+ T cells and memory B cells within the CNS. Some pathological hallmarks of MS are early axonal degeneration and progressive decline of brain volume in patients with clinically isolated syndromes who progress to clinically definite MS. Many new options to interfere with the course of MS have become available in recent years. To limit inflammatory demyelinating processes and delay disease progression, intervention to control inflammation must begin as early as possible. Each distinct type of immunotherapy (immunomodulation, immunosuppression and immune-selective intervention - blockade type, sequestering type or depleting type) corresponds to a specific underlying immunopathology of MS.

  19. [Medical-social aspects of multiple sclerosis].

    PubMed

    Vermersch, P; Marissal, J P

    2001-09-01

    On a daily basis the quality of life of patients suffering from multiple sclerosis (MS) partially depends on social measures. These are not specific to MS. Patients often need to be helped by hospital or town social services for the numerous and complicated administrative steps to be taken. The information given to a patient is of prime importance concerning his rights, particularly his occupational rights. Many organisations have to be contacted to obtain financial and material aids, even if the latter are considered insufficient in many fields especially for improvements in accommodation. An invalidity card may entitle its holder to certain tax reductions. The competences of the COTOREP are wide-ranging and include the recognition of the handicapped worker, his training and his regarding at work, his orientation and admission into a specialised structure, the degree of his invalidity rate and should his handicap justify it, benefits such as the handicapped adults allowance and the compensatory third person's allowance. It is essential to adopt a multidisciplinary way when dealing with MS in order to provide a better care, experiments in specialised structures and networks are being undertaken. Numerous partners are taking part in these new approaches and patient associations may find their place there. Social aspects have to be taken into account as well in the way the cost of the disease is evaluated in terms of money and humanity.

  20. Epigenetic Modifications and Therapy in Multiple Sclerosis.

    PubMed

    Aslani, Saeed; Jafari, Naser; Javan, Mohammad Reza; Karami, Jafar; Ahmadi, Majid; Jafarnejad, Mahmoud

    2017-03-01

    Breakthroughs in genetic studies, like whole human genome sequencing and genome-wide association studies (GWAS), have richened our knowledge of etiopathology of autoimmune diseases (AID) through discovery of genetic patterns. Nonetheless, the precise etiology of autoimmune diseases remains largely unknown. The lack of complete concordance of autoimmune disease in identical twins suggests that non-genetic factors also play a major role in determining disease susceptibility. Although there is no certain definition, epigenetics has been known as heritable alterations in gene function without changes in the nucleotide sequence. DNA methylation, histone modifications, and microRNA-associated gene expression suppression are the central mechanisms for epigenetic regulations. Multiple sclerosis (MS) is a disorder of the central nervous system (CNS), characterized by both inflammatory and neurodegenerative features. Although studies on epigenetic alterations in MS only began in the past decade, a mounting number of surveys suggest that epigenetic changes may be involved in the initiation and development of MS, probably through bridging the effects of environmental risk factors to genetics. Arming with clear understanding of epigenetic dysregulations underpins development of epigenetic therapies. Identifying agents inhibiting the enzymes controlling epigenetic modifications, particularly DNA methyltransferases and histone deacetylases, will be promising therapeutic tool toward MS. In the article underway, it is aimed to go through the recent progresses, attempting to disclose how epigenetics associates with the pathogenesis of MS and how can be used as therapeutic approach.

  1. Noise in multiple sclerosis: unwanted and necessary

    PubMed Central

    Bordi, Isabella; Ricigliano, Vito A G; Umeton, Renato; Ristori, Giovanni; Grassi, Francesca; Crisanti, Andrea; Sutera, Alfonso; Salvetti, Marco

    2014-01-01

    As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression “noise”) can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy. PMID:25356421

  2. Evidence of platelet activation in multiple sclerosis

    PubMed Central

    Sheremata, William A; Jy, Wenche; Horstman, Lawrence L; Ahn, Yeon S; Alexander, J Steven; Minagar, Alireza

    2008-01-01

    Objective A fatality in one multiple sclerosis (MS) patient due to acute idiopathic thrombocytopenic purpura (ITP) and a near fatality in another stimulated our interest in platelet function abnormalities in MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients. Methods In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation [plasma platelet microparticles (PMP), P-selectin expression (CD62p), circulating platelet microaggragtes (PAg)], as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured. Results Compared to controls, PMP were significantly elevated in MS (p < 0.001) and CD62p expression was also markedly elevated (p < 0.001). Both are markers of platelet activation. Platelet-associated IgM, but not IgG, was marginally elevated in MS (p = 0.01). Protein S in MS patients did not differ significantly from normal values. Conclusion Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted. PMID:18588683

  3. Progressive multiple sclerosis and mood disorders.

    PubMed

    Lorefice, Lorena; Fenu, G; Trincas, G; Moro, M F; Frau, J; Coghe, G C; Cocco, E; Marrosu, M G; Carta, M G

    2015-09-01

    Mood disorders are very common among multiple sclerosis (MS) patients, but their frequency in patients with progressive course (PMS) has not been adequately researched. Our study aimed to determine the frequency of mood disorders among patients with PMS compared with those with relapsing-remitting MS (RMS) and to explore the associations with disability and disease duration. The study included consecutive outpatients affected by MS according the 2010 revised Mc Donald diagnostic criteria. Psychiatric diagnoses were determined according to DSM-IV by psychiatrists using structured interview tools (ANTAS-SCID). Demographic and clinical data of patients were also collected. Disease courses were defined according to the re-examined phenotype descriptions by the Committee and MS Phenotype Group. Intergroup comparisons were performed by Chi-square test, while logistic regression analysis was performed to assess possible factors associated with mood disorders. In total, 240 MS patients (167 women) were enrolled; of these, 18 % (45/240) had PMS. The lifetime DSM-IV major depression diagnosis (MDD) was established in 40 and 23 % of the PMS and RMS patients, respectively. Using logistic regression analysis, the presence of MDD was independent from disease duration and disability and dependent on PMS course (P = 0.02; OR 2.2). Patients with PMS presented with MDD more frequently than those with RMS, independently from disease duration and physical disability. These findings highlight the importance of considering mood disorders, especially MDD, in the management of PMS patients.

  4. Multiple sclerosis and pregnancy: current considerations.

    PubMed

    Buraga, Ioan; Popovici, Roxana-Elena

    2014-01-01

    Multiple sclerosis is the most common neurological disease of young adults that causes major disability. In Romania, it is estimated that this disease has a prevalence of 35-40 per 100,000 inhabitants. It is a disease that begins at the age of 20-40 years and is 2-3 times more common in women than in men. More than half of patients with MS develop the disease in their fertile period of life; therefore, MS patients use contraceptive methods while being under our treatment. Since several therapeutic options have been implemented with good efficiency in the disease stabilization, increasingly more patients begin to wonder about the possibility of having a child and about the possible risks of pregnancy. The evolution during pregnancy and the lactation period has been favorable, with lower relapses and side effects comparable to those in the general population. In addition, babies born to mothers with MS have not had a significantly different mean gestational age or birth weight compared to babies born to healthy mothers.

  5. Pediatric multiple sclerosis: Clinical features and outcome.

    PubMed

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

    2016-08-30

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

  6. Pediatric multiple sclerosis: Escalation and emerging treatments.

    PubMed

    Chitnis, Tanuja; Ghezzi, Angelo; Bajer-Kornek, Barbara; Boyko, Alexey; Giovannoni, Gavin; Pohl, Daniela

    2016-08-30

    Over the last 20 years, there have been significant advances in multiple sclerosis (MS) therapeutics, with regulatory approval for 13 therapies in adults by the European Medicines Agency (EMA) and Food and Drug Administration. However, there is only limited approval for interferon-β and glatiramer acetate use in children 12 years and older by the EMA. Availability of disease-modifying therapies to children and adolescents with MS is variable by region, and is extremely limited in some regions of the world. Up to 30% of children experience breakthrough disease requiring therapies beyond traditional first-line agents. Recent legislation in both the United States and Europe has mandated clinical studies for all new therapeutics applicable to children. Several clinical trials in children are underway that will provide important information regarding the efficacy and safety of newer drugs. This review summarizes the current knowledge of breakthrough disease, escalation, and induction treatment approaches in children with MS, especially pertaining to disease course and disability outcomes in this group of patients. In addition, ongoing clinical trials and approaches and challenges in conducting clinical trials in the pediatric population are discussed.

  7. Therapeutic strategies in childhood multiple sclerosis.

    PubMed

    Ghezzi, Angelo

    2010-07-01

    Multiple sclerosis (MS) in children and adolescents accounts for 3-10% of the whole MS population, and is characterized by a relapsing course in almost all cases. The frequency of relapses is higher than in adult onset MS, at least in the first years of evolution. The objective of treatment is to speed the recovery after a relapse, to prevent the occurrence of relapses, and to prevent disease progression and neurodegeneration. The use of drugs for MS in children and adolescents has not been studied in clinical trials, so their use is mainly based on results from trials in adults and from observational studies. There is a consensus to treat acute relapses with intravenous high-dose corticosteroids. The possibility of preventing relapses and disease progression is based on the use of immunomodulatory agents. Interferon-beta (IFNB) and glatiramer acetate (GA) have been demonstrated to be safe and well tolerated in pediatric MS patients, and also to reduce relapse rate and disease progression. Cyclophosphamide and natalizumab could be offered as second-line treatment in patients with a poor response to IFNB or GA. New oral and injectable drugs will be available in the near future: if safe and well tolerated in the long-term follow up of adults with MS, they could be tested in the pediatric MS population.

  8. Role of Pathogens in Multiple Sclerosis

    PubMed Central

    Libbey, Jane E.; Cusick, Matthew F.; Fujinami, Robert S.

    2015-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS). Although the etiology of MS is unknown, genetic and environmental factors play a role. Infectious pathogens are the likely environmental factors involved in the development of MS. Pathogens associated with the development or exacerbation of MS include bacteria, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, the Staphylococcus aureus-produced enterotoxins that function as superantigens, viruses of the herpes virus (Epstein-Barr virus and human herpesvirus 6) and human endogenous retrovirus (HERV) families and the protozoa Acanthamoeba castellanii. Evidence, from studies with humans and animal models, supporting the association of these various pathogens with the development and/or exacerbation of MS will be discussed along with the potential mechanisms including molecular mimicry, epitope spreading and bystander activation. In contrast, infection with certain parasites such as helminthes (Schistosoma mansoni, Fasciola hepatica, Hymenolepis nana, Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercolaris, Enterobius vermicularis) appears to protect against the development or exacerbation of MS. Evidence supporting the ability of parasitic infections to protect against disease will be discussed along with a brief summary of a recent Phase I clinical trial testing the ability of Trichuris suis ova treatment to improve the clinical course of MS. A complex interaction between the CNS (including the blood-brain barrier), multiple infections with various infectious agents (occurring in the periphery or within the CNS), and the immune response to those various infections may have to be deciphered before the etiology of MS can be fully understood. PMID:24266364

  9. [The Multiple Sclerosis Documentation System MSDS. Discussion of a documentation standard for multiple sclerosis].

    PubMed

    Pette, M; Eulitz, M

    2002-02-01

    The MSDS (multiple sclerosis documentation system) has been developed at the Department of Neurology, Technical University of Dresden, Germany, during the last 4 years. The first version of this database application has been in use since October 2000. The MSDS manages information on MS patients, their treating physicians, patient history (symptoms, other diseases, biographical history, family history, habits, medication), clinical signs, results of laboratory examinations (blood chemistry, autoantibodies, borrelia serology, evoked potentials, cranial and spinal cord magnetic resonance imaging), clinical scores relevant for MS, and biosamples. In principle, MSDS allows online data input and semiautomatically generates reports to all general practitioners and neurologists treating the respective patient. Patient information sheets and internal treatment guidelines are part of the system. During a 3-month evaluation, the first version of MSDS was tested at eight university multiple sclerosis ambulatory care units and one general neurology hospital. The overall judgement was favorable. Suggestions for changes and improvements, as well as practical experiences, were considered when developing MSDS 2.0, which will be available by the end of 2001.

  10. An autopsy case of the Marburg variant of multiple sclerosis (acute multiple sclerosis).

    PubMed

    Suzuki, Makiko; Kawasaki, Hideya; Masaki, Katsuhisa; Suzuki, Satoshi O; Terada, Tatsuhiro; Tsuchida, Takashi; Tokuyama, Tsutomu; Kono, Satoshi; Komori, Takashi; Baba, Satoshi; Kira, Jun-ichi; Miyajima, Hiroaki

    2013-01-01

    We herein report an autopsy case of the Marburg variant of multiple sclerosis (MS). A 29-year-old woman developed acute and progressive neurological symptoms. A diagnosis of MS was suspected based on the patient's clinical background and brain MRI findings and the lack of evidence of malignancy on a brain biopsy. Despite the administration of typical treatment for MS, a fatal outcome occurred three months after disease onset. The autopsy revealed multiple inflammatory demyelinating lesions in the central nervous system. In addition, two noteworthy histopathological features were observed compared with prototypical MS. We evaluate the pathogenic differences between the Marburg type and prototypical MS by discussing the neuropathology and cerebrospinal fluid (CSF) findings of our case.

  11. Fatigue and Comorbidities in Multiple Sclerosis

    PubMed Central

    Fiest, Kirsten M.; Fisk, John D.; Patten, Scott B.; Tremlett, Helen; Wolfson, Christina; Warren, Sharon; McKay, Kyla A.; Berrigan, Lindsay I.

    2016-01-01

    Abstract Background: Fatigue is commonly reported by people with multiple sclerosis (MS). Comorbidity is also common in MS, but its association with the presence of fatigue or fatigue changes over time is poorly understood. Methods: Nine hundred forty-nine people with definite MS were recruited from four Canadian centers. The Fatigue Impact Scale for Daily Use and a validated comorbidity questionnaire were completed at three visits over 2 years. Participants were classified into groups with no fatigue versus any fatigue. Logistic regression was used to determine the relationship between fatigue and each comorbidity at baseline, year 1, year 2, and overall. Results: The incidence of fatigue during the study was 38.8%. The prevalence of fatigue was greater in those who were older (P = .0004), had a longer time since symptom onset (P = .005), and had greater disability (P < .0001). After adjustment, depression (odds ratio [OR], 2.58; 95% confidence interval [CI], 2.03–3.27), irritable bowel syndrome (OR, 1.71; 95% CI, 1.18–2.48), migraine (OR, 1.69; 95% CI, 1.27–2.27), and anxiety (OR, 1.57; 95% CI, 1.15–2.16) were independently associated with fatigue that persisted during the study. There was also an individual-level effect of depression on worsening fatigue (OR, 1.49; 95% CI, 1.08–2.07). Conclusions: Comorbidity is associated with fatigue in MS. Depression is associated with fatigue and with increased risk of worsening fatigue over 2 years. However, other comorbid conditions commonly associated with MS are also associated with persistent fatigue, even after accounting for depression. Further investigation is required to understand the mechanisms by which comorbidities influence fatigue. PMID:27134583

  12. Prevalence of celiac disease in multiple sclerosis

    PubMed Central

    2011-01-01

    Background Celiac disease (CD) is a common systemic disease related to a permanent intolerance to gluten and is often associated with different autoimmune and neurological diseases. Its mean prevalence in the general population is 1-2% worldwide. Our aim was to study the prevalence of celiac disease in a prospective series of Multiple Sclerosis (MS) patients and their first-degree relatives. Methods We analyzed the prevalence of serological, histological and genetic CD markers in a series of 72 MS patients and in their 126 first-degree relatives, compared to 123 healthy controls. Results Tissue IgA-anti-transglutaminase-2 antibodies were positive in 7 MS patients (10%), compared to 3 healthy controls (2.4%) (p < 0.05). OR: 5.33 (CI-95%: 1.074-26.425). No differences were found in HLA-DQ2 markers between MS patients (29%) and controls (26%) (NS). We detected mild or moderate villous atrophy (Marsh III type) in duodenal biopsies, in 8 MS patients (11.1%). We also found a high proportion of CD among first-degree relatives: 23/126 (32%). Several associated diseases were detected, mainly dermatitis 41 (57%) and iron deficiency anemia in 28 (39%) MS patients. We also found in them, an increased frequency of circulating auto-antibodies such as anti-TPO in 19 (26%), ANA in 11 (15%) and AMA in 2 (3%). Conclusions We have found an increased prevalence of CD in 8 of the 72 MS patients (11.1%) and also in their first-degree relatives (23/126 [32%]). Therefore, increased efforts aimed at the early detection and dietary treatment of CD, among antibody-positive MS patients, are advisable. PMID:21385364

  13. Pain in Portuguese Patients with Multiple Sclerosis

    PubMed Central

    Seixas, Daniela; Sá, Maria José; Galhardo, Vasco; Guimarães, Joana; Lima, Deolinda

    2011-01-01

    Early reports often ignored pain as an important symptom in multiple sclerosis (MS). Pain prevalence figures in MS from European countries other than Portugal range between 40 and 65%. To our knowledge there is no published data in English on pain in MS in Portugal. We describe the demographic and clinical characteristics, with an emphasis on pain, of 85 MS patients followed-up in a Portuguese hospital, contributing to pain epidemiology in MS. Patients were interviewed sequentially after their regular appointments at the MS clinic; patients with pain completed The Brief Pain Inventory and The McGill Pain Questionnaire (MPQ). The prevalence of pain found was 34%. Headache and back pain were the most common anatomical sites described, followed by upper and lower limbs. Intensity of pain in an 11-point scale was, for the maximum pain intensity 6.7 ± 1.8, for the minimum pain intensity 2.2 ± 2.0, for the mean pain intensity 4.5 ± 1.5, and for the actual pain intensity 2.4 ± 2.9. Pain interfered significantly with general activity, mood, work, social relations, and enjoyment of life. All MS patients with pain employed words from both the sensory and affective categories of the MPQ to describe it. Patient pain descriptions’ included the word “hot-burning” in 59% of the cases, common in the report of central pain, but neuropathic pain medications were only used by 10% of them. Pain is an important symptom in Portuguese patients with MS, not only because of the high prevalence found, concordant with other European countries, but also because of its interference with quality-of-life. PMID:21503136

  14. Apathy in multiple sclerosis: gender matters.

    PubMed

    Novo, Ana M; Batista, Sonia; Tenente, Joana; Nunes, Carla; Macário, Carmo; Sousa, Lívia; Gonçalves, Freire

    2016-11-01

    Apathy has been recognized as a frequent symptom in multiple sclerosis (MS) but uncertainty remains about its prevalence and clinical correlates. Therefore, the objective of this work was to assess the prevalence of apathy in patients with MS and to identify clinical and demographic correlates. A case-control study with 30 patients and 30 healthy controls matched for age, gender and education was performed. Apathy diagnosis was established using Robert et al.'s criteria. Additionally, apathy was assessed using the 10-item short version of the clinical-rated Apathy Evaluation Scale (AES-C-10). The Beck Depression Inventory (BDI), Modified Fatigue Impact Scale (MFIS), and Montreal Cognitive Assessment (MoCA) were used to evaluate depression, fatigue and cognitive impairment, respectively. Apathy prevalence in MS patients was 43.3%. Patients with MS had higher AES-C-10 scores than controls (13.9 vs. 12.0, p=0.015). Patients with apathy presented a higher proportion of males (53.8% vs. 11.8%, p=0.02), lower educational level (53.8% vs. 11.8% of patients with up to 9years of education), higher scores on cognitive dimension of MFIS (18.0 vs. 8.0, p=0.048) and BDI (13.0 vs. 7.0, p=0.035) and worse performance on MoCA (24.0 vs. 26.0, p=0.028). Gender was the only independent predictor of apathy, with men presenting a higher risk compared to women (OR: 9.62; 95%CI: 1.02-90.61; p=0.048). In conclusion, apathy is a common neuropsychiatric disorder in MS and it is probably underdiagnosed. Male patients seem to have an increased risk of apathy, and this finding may be related to the generally more unfavorable course of MS in men.

  15. A Risk Score for Predicting Multiple Sclerosis

    PubMed Central

    Dobson, Ruth; Ramagopalan, Sreeram; Topping, Joanne; Smith, Paul; Solanky, Bhavana; Schmierer, Klaus; Chard, Declan; Giovannoni, Gavin

    2016-01-01

    Objective 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. Methods 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. Results 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). Interpretations 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. PMID:27802296

  16. Clutter Management for Individuals with Multiple Sclerosis

    PubMed Central

    2014-01-01

    Background: Although there is substantial anecdotal evidence that clutter is common among people with multiple sclerosis (MS), the literature contains no reports of studies on the actual prevalence of the problem or its impact on functional performance in this population. Clutter promotes confusion and places individuals in potentially dangerous situations by increasing their risks of falling, losing medications, and misplacing important documents. In addition, it may negatively affect activities of daily living (ADLs). Many common MS symptoms such as decreased mobility, visual or cognitive changes, fatigue, and depression can exacerbate clutter accumulation, which in turn can have detrimental effects on physical, financial, emotional, cognitive, and social functioning. It is critical for MS clinicians to address clutter management in order to improve patients' overall functional independence and participation. Methods: A clutter reduction protocol was developed and implemented at our institution for individuals with MS. Our group program addresses psychosocial issues preventing organization and offers practical strategies for clutter removal and management to improve performance in ADLs. A clutter questionnaire is administered to individuals before and after their participation in the group program. Results: Anecdotal reports indicate that the intervention helped to reduce clutter, promote a more realistic attitude toward “possessions,” and establish a sense of accomplishment in controlling one's environment. Participants also reported fewer falls, feeling less isolated, increased ease in finding their medications, and a general sense of cognitive clarity in accomplishing ADLs. Outcome assessments are now being developed to objectively measure these effects as well as the prevalence of clutter within the MS population. Conclusions: Clutter management is an important area for MS clinicians to address because it can significantly affect patients' functioning

  17. Effects of diazoxide in multiple sclerosis

    PubMed Central

    Rovira, Alex; Montalban, Xavier; Arroyo, Rafael; Paul, Friedemann; Meca-Lallana, Virginia; Ramo, Cristina; Fernandez, Oscar; Saiz, Albert; Garcia-Merino, Antonio; Ramió-Torrentà, Lluís; Casanova, Bonaventura; Oreja-Guevara, Celia; Muñoz, Delicias; Martinez-Rodriguez, Jose Enrique; Lensch, Eckart; Prieto, Jose Maria; Meuth, Sven G.; Nuñez, Xavier; Campás, Clara; Pugliese, Marco

    2015-01-01

    Objective: The aim of this study was to test the safety of diazoxide and to search for signs of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: In this multicenter, randomized, placebo-controlled, double-blind trial (treatment allocation was concealed), 102 patients with RRMS were randomized to receive a daily oral dose of diazoxide (0.3 and 4 mg/d) or placebo for 24 weeks (NCT01428726). The primary endpoint was the cumulative number of new T1 gadolinium-enhancing lesions per patient, recorded every 4 weeks from week 4 to week 24. Secondary endpoints included brain MRI variables such as the number of new/enlarging T2 lesions and the percentage brain volume change (PBVC); clinical variables such as the percentage of relapse-free patients, relapse rate, and change in the Expanded Disability Status Scale score; and safety and tolerability. Results: Diazoxide was well-tolerated and it produced no serious adverse events other than 1 case of Hashimoto disease. At the 2 doses tested, diazoxide did not improve the primary endpoint or the MRI and clinical variables related to the presence of new lesions or relapses. Patients treated with diazoxide showed reduced PBVC compared with the placebo group, although such changes could be confounded by the higher disease activity of the treated group and the vascular effects of diazoxide. Conclusion: At the doses tested, oral diazoxide did not decrease the appearance of new lesions evident by MRI. The effects in slowing the progression of brain atrophy require further validation. Classification of evidence: This study provides Class I evidence that for patients with RRMS, diazoxide (0.3 and 4 mg/d) does not significantly change the number of new MRI T1 gadolinium-enhancing lesions. PMID:26405686

  18. Pharmacogenomic study in patients with multiple sclerosis

    PubMed Central

    Bustamante, Marta F.; Morcillo-Suárez, Carlos; Malhotra, Sunny; Rio, Jordi; Leyva, Laura; Fernández, Oscar; Zettl, Uwe K.; Killestein, Joep; Brassat, David; García-Merino, Juan Antonio; Sánchez, Antonio J.; Urcelay, Elena; Alvarez-Lafuente, Roberto; Villar, Lusia M.; Alvarez-Cermeño, Jose Carlos; Farré, Xavier; Lechner-Scott, Jeannette; Vandenbroeck, Koen; Rodríguez-Antigüedad, Alfredo; Drulovic, Jelena S.; Martinelli Boneschi, Filippo; Chan, Andrew; Oksenberg, Jorge; Navarro, Arcadi; Montalban, Xavier

    2015-01-01

    Objectives: We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-β treatment in patients with multiple sclerosis (MS). Methods: In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-β responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-β response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-β responders and 274 nonresponders). Results: Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-β response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-β response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). Conclusions: These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-β. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted. PMID:26445728

  19. Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

    PubMed

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

    2017-03-01

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

  20. Glioblastoma following treatment with fingolimod for relapsing-remitting multiple sclerosis.

    PubMed

    Sharim, Justin; Tashjian, Randy; Golzy, Nima; Pouratian, Nader

    2016-08-01

    Glioblastoma is an uncommon and aggressive primary brain tumor with incidence of 3 per 100,000 annually. We report a 50-year-old woman diagnosed with glioblastoma within threeyears of induction of fingolimod therapy for relapsing-remitting multiple sclerosis. Fingolimod, an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis, has also been suggested to impart a cardioprotective role in heart failure and arrhythmia via activation of P21-activated kinase-1 (Pak1). In the brain, Pak1 activation has been shown to correlate with decreased survival time amongst patients with glioblastoma. A molecular mechanism underlying a link between fingolimod use and glioblastoma development may involve activation of Pak1. To our knowledge, this is the first report of a potential association between fingolimod use and glioblastoma development.

  1. Vision and vision-related outcome measures in multiple sclerosis.

    PubMed

    Balcer, Laura J; Miller, David H; Reingold, Stephen C; Cohen, Jeffrey A

    2015-01-01

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

  2. Inflammatory Optic Neuritis: From Multiple Sclerosis to Neuromyelitis Optica.

    PubMed

    de Seze, Jérôme

    2013-01-01

    Inflammatory optic neuritis represents a frequent clinical situation in neurology and ophthalmology. In those parts of the world where multiple sclerosis is common, it is the condition most discussed as the cause of optic neuritis. However, the risk for conversion from optic neuritis to multiple sclerosis is evaluated at only around 50% after 15 years of follow-up. The risk is higher in cases in whom abnormalities typical of multiple sclerosis are found on magnetic resonance imaging of the brain and oligoclonal bands found on cerebrospinal fluid protein electrophoresis with no corresponding bands in serum. When these investigations are normal, optic neuritis is usually considered as "idiopathic" with a suspected viral aetiology, but in some cases, a systemic disease such as sarcoidosis, systemic lupus erythematosis, or Sjögren syndrome may be diagnosed. In rare cases, either recurrent optic neuritis or myelitis may occur without any evidence for multiple sclerosis. In the first case, it corresponds to a recently characterised disorder referred to as chronic relapsing inflammatory optic neuropathy and in the second case to a recently better identified entity, neuromyelitis optica. In the present paper, the differential diagnosis of inflammatory optic neuritis is presented from multiple sclerosis to infectious optic neuritis, systemic disease, and neuromyelitis optica.

  3. How can proteomics elucidate the complexity of multiple sclerosis?

    PubMed

    Farias, Alessandro S; Santos, Leonilda M B

    2015-10-01

    Multiple sclerosis affects more than 2.5 million people worldwide. Although multiple sclerosis was described almost 150 years ago, there are many knowledge gaps regarding its etiology, diagnosis, prognosis, and pathogenesis. Multiple sclerosis is an inflammatory, demyelinating, neurodegenerative disease of the CNS. During the last several decades, experimental models of multiple sclerosis have contributed to our understanding of the inflammatory disease mechanisms and have aided drug testing and development. However, little is known about the neurodegenerative mechanisms that operate during the evolution of the disease. Currently, all therapeutic approaches are primarily based on the inflammatory aspect of the disease. During the last decade, proteomics has emerged as a promising tool for revealing molecular pathways as well as identifying and quantifying differentially expressed proteins. Therefore, proteomics may be used for the discovery of biomarkers, potential drug targets, and new regulatory mechanisms. To date, a considerable number of proteomics studies have been conducted on samples from experimental models and patients with multiple sclerosis. These data form a solid base for further careful analysis and validation.

  4. Symptomatic cranial neuralgias in multiple sclerosis: clinical features and treatment.

    PubMed

    De Santi, Lorenzo; Annunziata, Pasquale

    2012-02-01

    In multiple sclerosis, neuropathic pain is a frequent condition, negatively influencing the overall quality of life. Cranial neuralgias, including trigeminal, glossopharyngeal neuralgias, as well as occipital neuralgia, are typical expression of neuropathic pain. Neuralgias are characterised by paroxysmal painful attacks of electric shock-like sensation, occurring spontaneously or evoked by innocuous stimuli in specific trigger areas. In multiple sclerosis, demyelination in the centrally myelinated part of the cranial nerve roots plays an important role in the origin of neuralgic pain. These painful syndromes arising in multiple sclerosis are therefore considered "symptomatic", in contrast to classic cranial neuralgias, in which no cause other than a neurovascular contact is identified. At this time, the evidence on the management of symptomatic cranial neuralgias in multiple sclerosis is fragmentary and a comprehensive review addressing this topic is still lacking. For that reason, treatment is often based on personal clinical experience as well as on anecdotal reports. The aim of this review is to critically summarise the latest findings regarding the pathogenesis, the diagnosis, the instrumental evaluation and the medical as well as neurosurgical treatment of symptomatic trigeminal, glossopharyngeal and occipital neuralgia in multiple sclerosis, providing useful insights for neurologists and neurosurgeons and a broad range of specialists potentially involved in the treatment of these painful syndromes.

  5. Treatment of multiple sclerosis with the pregnancy hormone estriol.

    PubMed

    Sicotte, Nancy L; Liva, Stephanie M; Klutch, Rochelle; Pfeiffer, Paul; Bouvier, Seth; Odesa, Sylvia; Wu, T C Jackson; Voskuhl, Rhonda R

    2002-10-01

    Multiple sclerosis patients who become pregnant experience a significant decrease in relapses that may be mediated by a shift in immune responses from T helper 1 to T helper 2. Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift. We treated nonpregnant female multiple sclerosis patients with the pregnancy hormone estriol in an attempt to recapitulate the beneficial effect of pregnancy. As compared with pretreatment baseline, relapsing remitting patients treated with oral estriol (8 mg/day) demonstrated significant decreases in delayed type hypersensitivity responses to tetanus, interferon-gamma levels in peripheral blood mononuclear cells, and gadolinium enhancing lesion numbers and volumes on monthly cerebral magnetic resonance images. When estriol treatment was stopped, enhancing lesions increased to pretreatment levels. When estriol treatment was reinstituted, enhancing lesions again were significantly decreased. Based on these results, a larger, placebo-controlled trial of estriol is warranted in women with relapsing remitting multiple sclerosis. This novel treatment strategy of using pregnancy doses of estriol in multiple sclerosis has relevance to other autoimmune diseases that also improve during pregnancy.

  6. "Abnormal" illness behaviour in chronic fatigue syndrome and multiple sclerosis.

    PubMed Central

    Trigwell, P.; Hatcher, S.; Johnson, M.; Stanley, P.; House, A.

    1995-01-01

    OBJECTIVE--To investigate the presence of abnormal illness behaviour in patients with a diagnosis of chronic fatigue syndrome. DESIGN--A cross sectional descriptive study using the illness behaviour questionnaire to compare illness behaviour scores and illness behaviour profiles of patients with chronic fatigue syndrome and patients with multiple sclerosis. SETTING--A multidisciplinary fatigue clinic and a teaching hospital neurology outpatient clinic. SUBJECTS--98 patients satisfying the Oxford criteria for chronic fatigue syndrome and 78 patients with a diagnosis of multiple sclerosis. MAIN OUTCOME MEASURE--Responses to the 62 item illness behaviour questionnaire. RESULTS--90 (92%) patients in the chronic fatigue syndrome group and 70 (90%) in the multiple sclerosis group completed the illness behaviour questionnaire. Both groups had significantly high scores on the general hypochondriasis and disease conviction subscales and significantly low scores on the psychological versus somatic concern subscale, as measured in relation to normative data. There were, however, no significant differences in the subscale scores between the two groups and the two groups had identical illness behaviour profiles. CONCLUSION--Scores on the illness behaviour questionnaire cannot be taken as evidence that chronic fatigue syndrome is a variety of abnormal illness behaviour, because the same profile occurs in multiple sclerosis. Neither can they be taken as evidence that chronic fatigue and multiple sclerosis share an aetiology. More needs to be known about the origins of illness beliefs in chronic fatigue syndrome, especially as they are important in determining outcome. PMID:7613314

  7. Vision and vision-related outcome measures in multiple sclerosis

    PubMed Central

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

    2015-01-01

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

  8. Natural killer cells and their receptors in multiple sclerosis.

    PubMed

    Kaur, Gurman; Trowsdale, John; Fugger, Lars

    2013-09-01

    The immune system has crucial roles in the pathogenesis of multiple sclerosis. While the adaptive immune cell subsets, T and B cells, have been the main focus of immunological research in multiple sclerosis, it is now important to realize that the innate immune system also has a key involvement in regulating autoimmune responses in the central nervous system. Natural killer cells are innate lymphocytes that play vital roles in a diverse range of infections. There is evidence that they influence a number of autoimmune conditions. Recent studies in multiple sclerosis and its murine model, experimental autoimmune encephalomyelitis, are starting to provide some understanding of the role of natural killer cells in regulating inflammation in the central nervous system. Natural killer cells express a diverse range of polymorphic cell surface receptors, which interact with polymorphic ligands; this interaction controls the function and the activation status of the natural killer cell. In this review, we discuss evidence for the role of natural killer cells in multiple sclerosis and experimental autoimmune encephalomyelitis. We consider how a change in the balance of signals received by the natural killer cell influences its involvement in the ensuing immune response, in relation to multiple sclerosis.

  9. Binaural auditory processing in multiple sclerosis subjects.

    PubMed

    Levine, R A; Gardner, J C; Stufflebeam, S M; Fullerton, B C; Carlisle, E W; Furst, M; Rosen, B R; Kiang, N Y

    1993-06-01

    In order to relate human auditory processing to physiological and anatomical experimental animal data, we have examined the interrelationships between behavioral, electrophysiological and anatomical data obtained from human subjects with focal brainstem lesions. Thirty-eight subjects with multiple sclerosis were studied with tests of interaural time and level discrimination (just noticeable differences or jnds), brainstem auditory evoked potentials and magnetic resonance (MR) imaging. Interaural testing used two types of stimuli, high-pass (> 4000 Hz) and low-pass (< 1000 Hz) noise bursts. Abnormal time jnds (Tjnd) were far more common than abnormal level jnds (70% vs 11%); especially for the high-pass (Hp) noise (70% abnormal vs 40% abnormal for low-pass (Lp) noise). The HpTjnd could be abnormal with no other abnormalities; however, whenever the BAEPs, LpTjnd and/or level jnds were abnormal HpTjnd was always abnormal. Abnormal wave III amplitude was associated with abnormalities in both time jnds, but abnormal wave III latency with only abnormal HpTjnds. Abnormal wave V amplitude, when unilateral, was associated with a major HpTjnd abnormality, and, when bilateral, with both HpTjnd and LpTjnd major abnormalities. Sixteen of the subjects had their MR scans obtained with a uniform protocol and could be analyzed with objective criteria. In all four subjects with lesions involving the pontine auditory pathway, the BAEPs and both time jnds were abnormal. Of the twelve subjects with no lesions involving the pontine auditory pathway, all had normal BAEPs and level jnds, ten had normal LpTjnds, but only five had normal HpTjnds. We conclude that interaural time discrimination is closely related to the BAEPs and is dependent upon the stimulus spectrum. Redundant encoding of low-frequency sounds in the discharge patterns of auditory neurons, may explain why the HpTjnd is a better indicator of neural desynchrony than the LpTjnd. Encroachment of MS lesions upon the pontine

  10. Defining reliable disability outcomes in multiple sclerosis.

    PubMed

    Kalincik, Tomas; Cutter, Gary; Spelman, Tim; Jokubaitis, Vilija; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, Francois; Grammond, Pierre; Hupperts, Raymond; Oreja-Guevara, Celia; Boz, Cavit; Pucci, Eugenio; Bergamaschi, Roberto; Lechner-Scott, Jeannette; Alroughani, Raed; Van Pesch, Vincent; Iuliano, Gerardo; Fernandez-Bolaños, Ricardo; Ramo, Cristina; Terzi, Murat; Slee, Mark; Spitaleri, Daniele; Verheul, Freek; Cristiano, Edgardo; Sánchez-Menoyo, José Luis; Fiol, Marcela; Gray, Orla; Cabrera-Gomez, Jose Antonio; Barnett, Michael; Butzkueven, Helmut

    2015-11-01

    Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common

  11. Dopamine, T cells and multiple sclerosis (MS).

    PubMed

    Levite, Mia; Marino, Franca; Cosentino, Marco

    2017-03-10

    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

  12. Self-injury and aggression in tuberous sclerosis complex: cross syndrome comparison and associated risk markers

    PubMed Central

    2014-01-01

    Background Research reporting prevalence rates of self-injurious and aggressive behaviour in people with tuberous sclerosis complex (TSC) is limited. No studies have compared rates of these behaviours in TSC with those in other syndrome groups matched for degree of disability or investigated risk markers for these behaviours in TSC. Methods Data from the Challenging Behaviour Questionnaire were collected for 37 children, aged 4 to 15 years, with TSC. Odds ratios were used to compare rates of self-injury and aggression in children with TSC with children with idiopathic autism spectrum disorder (ASD), fragile X, Cornelia de Lange and Down syndromes. Characteristics were measured using the Mood Interest and Pleasure Questionnaire, the Activity Questionnaire, the Social Communication Questionnaire, the Repetitive Behaviour Questionnaire, the Wessex Behaviour Schedule and the revised Non-communicating Children Pain Checklist. Mann-Whitney U analyses were used to compare characteristics between individuals with self-injury and aggression and those not showing these behaviours. Results Rates of self-injury and aggression in TSC were 27% and 50%, respectively. These are high but not significantly different from rates in children with Down syndrome or other syndrome groups. Both self-injury and aggression were associated with stereotyped and pain-related behaviours, low mood, hyperactivity, impulsivity and repetitive use of language. Children who engaged in self-injury also had lower levels of interest and pleasure and showed a greater degree of ‘insistence on sameness’ than children who did not self-injure. Aggression was associated with repetitive behaviour. The majority of these associations remained significant when the association with level of adaptive functioning was controlled for. Conclusions Behavioural profiles can be used to identify those most at risk of developing self-injury and aggression. Further research is warranted to understand the influence of

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

    PubMed

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

    2012-01-01

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

  14. Adherence of adolescents to multiple sclerosis disease-modifying therapy.

    PubMed

    Thannhauser, Jennifer E; Mah, Jean K; Metz, Luanne M

    2009-08-01

    In this mixed-methods study, utilization data for disease-modifying therapies were reviewed to determine the adherence rate among our pediatric multiple sclerosis cohort. Adolescents were interviewed to explore their experiences with multiple sclerosis and the impact of peer relationships on adherence to treatment. Seventeen adolescents (6 male, 11 female) started interferon beta or glatiramer acetate before age 18. The mean age at first drug start date was 15.8 years. Eight of the adolescents (47%) discontinued treatment after a median duration of 20 months. Many of the adolescents struggled to integrate the injections into their daily lives, with peers either facilitating or impeding this transition. In conclusion, adolescents in this cohort had difficulty adhering to disease-modifying therapies, and peers played an important role in mediating their adjustment to multiple sclerosis. Specific strategies are required to improve adolescents' adherence to treatment, including less intrusive options and enhancing peer support.

  15. Stem cell therapy in multiple sclerosis: promise and controversy.

    PubMed

    Duncan, I D; Goldman, S; Macklin, W B; Rao, M; Weiner, L P; Reingold, S C

    2008-05-01

    Stem cells offer the potential for regeneration of lost tissue in neurological disease, including multiple sclerosis (MS). Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on "Stem Cells & MS: Prospects and Strategies" Participants reviewed the current state of knowledge about the potential use of stem and progenitor cells in MS and other degenerative neurological disorders and outlined a series of urgent fundamental and applied clinical research priorities that should allow the potential of regeneration of damaged tissue in MS to be assessed and pursued.

  16. Remyelination strategies in multiple sclerosis: a critical reflection.

    PubMed

    Kipp, Markus

    2016-01-01

    Remyelination is the natural repair mechanism of demyelination and can be a highly efficient process in multiple sclerosis. However, in the majority of lesions, this regenerative approach is incomplete or fails. It is believed that remyelination protects against progressive axonal damage and thus long-term disability in patients with multiple sclerosis. For this reason, therapeutic promotion of remyelination represents an attractive option for preventing disease progression. In this editorial we casts a critical eye over the most frequently used experimental settings which aim to uncover potential remyelination promoting drugs. This article reflects upon the personal opinion of the author who currently used animal models allow to assess the potency of pharmacological interventions to accelerate, but not to induce myelin repair. Furthermore, it is discussed how remyelination and neuroprotection might well be two separate entities. Thus, induction of remyelination does not necessarily prevent disease progression in multiple sclerosis patients.

  17. Devic's neuromyelitis optica and Schilder's myelinoclastic diffuse sclerosis

    PubMed Central

    Hainfellner, J A; Schmidbauer, M; Schmutzhard, E; Maier, H; Budka, H

    1992-01-01

    An adult patient developed both Devic's neuromyelitis optica and Schilder's myelinoclastic diffuse sclerosis, suggesting that these entities represent rare topographical and aggressive variants within the spectrum of multiple sclerosis. Images PMID:1343820

  18. Secondary and tertiary treatments for multiple sclerosis patients with urinary symptoms

    PubMed Central

    Tracey, James M.

    2016-01-01

    Multiple sclerosis patients with refractory urinary symptoms after treatment with behavioral therapy and medications still have treatment options. Prior to starting treatments, baseline symptoms should be assessed and treatment goals thoroughly discussed. Catheterization, botulinum toxin, and reconstructive surgery all can play a role in improving both safety and quality of life for these patients. Newer modalities, such as neuromodulation, may also have an increasing role in the future as more data develop regarding efficacy. Risks need to be weighed against any perceived benefit and disease status before more aggressive therapy is initiated. PMID:27847911

  19. Induction and add-on therapy with mitoxantrone and interferon beta in multiple sclerosis.

    PubMed

    Zaffaroni, Mauro; Rizzo, Annalisa; Baldini, Silvana Maria; Ghezzi, Angelo; Comi, Giancarlo

    2008-09-01

    We retrospectively analyzed data from 70 multiple sclerosis (MS) patients treated with mitoxantrone (MX) before Interferon-beta (IFN-beta) because of clinically and MRI very active isolated syndrome (CIS) or relapsing-remitting MS (induction therapy) or due to breakthrough/persistently active disease in spite of IFN-beta (add-on/combination therapy), or for increased disability suggesting a secondary progression (rescue therapy). After almost 2-year follow-up, relapse rate and disability decreased very significantly in the two former groups while MX was essentially ineffective as rescue therapy. Induction therapy is a valid option for very aggressive/active CIS and MS at onset.

  20. Multiple sclerosis treatment and infectious issues: update 2013

    PubMed Central

    Winkelmann, A; Loebermann, M; Reisinger, E C; Zettl, U K

    2014-01-01

    Immunomodulation and immunosuppression are generally linked to an increased risk of infection. In the growing field of new and potent drugs for multiple sclerosis (MS), we review the current data concerning infections and prevention of infectious diseases. This is of importance for recently licensed and future MS treatment options, but also for long-term established therapies for MS. Some of the disease-modifying therapies (DMT) go along with threats of specific severe infections or complications, which require a more intensive long-term monitoring and multi-disciplinary surveillance. We update the existing warning notices and infectious issues which have to be considered using drugs for multiple sclerosis. PMID:24134716

  1. Management of Fatigue in Persons with Multiple Sclerosis

    PubMed Central

    Khan, Fary; Amatya, Bhasker; Galea, Mary

    2014-01-01

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

  2. Multiple Sclerosis: Hope Through Research | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Multiple Sclerosis Hope Through Research Past Issues / Spring 2012 Table ... that television journalist Neil Cavuto was diagnosed with multiple sclerosis (MS) more than 15 years ago. And that ...

  3. Drugs in development for relapsing multiple sclerosis.

    PubMed

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    Drug development for multiple sclerosis (MS), as with any other neurological disease, faces numerous challenges, with many drugs failing at various stages of development. The disease-modifying therapies (DMTs) first introduced for MS are only moderately effective, but given the lack of competition, they have been widely accepted in clinical practice. Although safety and efficacy continue to be the two main metrics by which drugs will be judged, the newer agents in the market also face challenges of a more comparative nature-are they more efficacious than the currently available drugs on the market? Are they safer or better tolerated? Do they offer any practical advantages over current treatments? Fingolimod represented a milestone following its approval as an oral drug for MS in 2010, offering patients a far more convenient administration route. However, association with cardiovascular complications has led to a more cautious approach in its initial prescribing, now requiring cardiac monitoring for the first 6 h as well as subsequent monitoring of blood pressure and for macular oedema. Natalizumab, amongst licensed drugs, represents the current benchmark for efficacy. The risk of progressive multifocal leukoencephalopathy during natalizumab treatment is now more quantifiable. Other monoclonal antibodies are in various phases of development. Marketing authorisation for alemtuzumab has been filed, and whilst trial data suggest that its efficacy outperforms both licensed drugs and others in development, there is a significant risk of secondary autoimmunity. Its once-yearly administration, however, seems particularly advantageous. Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. Daclizumab is also moderately efficacious but may struggle to establish itself given its monthly subcutaneous dosing. There are new oral

  4. Vaccines for multiple sclerosis: progress to date.

    PubMed

    Correale, Jorge; Farez, Mauricio; Gilmore, Wendy

    2008-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS, characterized pathologically by a perivascular infiltrate consisting predominantly of T cells and macrophages. Although its aetiology remains unknown, several lines of evidence support the hypothesis that autoimmune mechanisms play a major role in the development of the disease. Several widely used disease-modifying agents are approved for the treatment of MS. However, these agents are only partially effective and their ability to attenuate the more progressive phases of the disease is not clear at this time. Therefore, there is a need to develop improved treatment options for MS. This article reviews the role of several novel, selective vaccine strategies that are currently under investigation, including: (i) T-cell vaccination (TCV); (ii) T-cell receptor (TCR) peptide vaccination; (iii) DNA vaccination; and (iv) altered peptide ligand (APL) vaccination. The administration of attenuated autoreactive T cells induces regulatory networks to specifically suppress pathogenic T cells in MS, a strategy named TCV. The concept of TCV was based on the experience of vaccination against aetiological agents of infectious diseases in which individuals are purposely exposed to an attenuated microbial pathogen, which then instructs the immune system to recognize and neutralize it in its virulent form. In regard to TCV, attenuated, pathogenic T cells are similarly used to instruct the immune system to recognize and neutralize disease-inducing T cells. In experimental allergic encephalomyelitis (EAE), an animal model for MS, pathogenic T cells use a strikingly limited number of variable-region elements (V region) to form TCR specific for defined autoantigens. Thus, vaccination with peptides directed against these TCR structures may induce immunoregulatory mechanisms, thereby preventing EAE. However, unlike EAE, myelin-reactive T cells derived from MS patients utilize a broad range of different V regions

  5. Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis

    PubMed Central

    Hou, Zong-liu; Liu, Ying; Mao, Xi-Hong; Wei, Chuan-yu; Meng, Ming-yao; Liu, Yun-hong; Zhuyun Yang, Zara; Zhu, Hongmei; Short, Martin; Bernard, Claude; Xiao, Zhi-cheng

    2013-01-01

    There is currently great interest in the use of mesenchymal stem cells as a therapy for multiple sclerosis with potential to both ameliorate inflammatory processes as well as improve regeneration and repair. Although most clinical studies have used autologous bone marrow-derived mesenchymal stem cells, other sources such as allogeneic umbilical cord-derived cells may provide a more accessible and practical supply of cells for transplantation. In this case report we present the treatment of aggressive multiple sclerosis with multiple allogenic human umbilical cord-derived mesenchymal stem cell and autologous bone marrow-derived mesenchymal stem cells over a 4 y period. The treatments were tolerated well with no significant adverse events. Clinical and radiological disease appeared to be suppressed following the treatments and support the expansion of mesenchymal stem cell transplantation into clinical trials as a potential novel therapy for patients with aggressive multiple sclerosis. PMID:24192520

  6. [Structure of peripheral blood platelets surface in patients with amyotrophic lateral sclerosis and multiple sclerosis].

    PubMed

    Kiktenko, A I; Zlobina, G P; Brusov, O S; Zakharova, M N

    2005-01-01

    Using scanning electronic microscopy of peripheral blood platelets in 32 patients with amyotrophic lateral sclerosis (ALS) and 6 patients with multiple sclerosis (MS), platelets activation, emerging in pseudopodiums formation, aggregation and lysis, was found. Platelets activation was more pronounced in ALS than in MS. It was most markedly seen for quantitative evaluation of the above traits. The features of platelet activation found in the study support the evidence for considering ALS as a systemic disorder being characterized by a broad spectrum of alterations of biological processes.

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

    ERIC Educational Resources Information Center

    Mackenzie, Catherine; Green, Jan

    2009-01-01

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

  8. Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis

    PubMed Central

    Motta, Caterina; Palermo, Eduardo; Studer, Valeria; Germanotta, Marco; Germani, Giorgio; Centonze, Diego; Cappa, Paolo

    2016-01-01

    Background The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. Objective To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. Methods A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. Results We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Conclusions Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis. PMID:26863109

  9. The mystery of the origin of multiple sclerosis.

    PubMed Central

    McDonald, W I

    1986-01-01

    Our present understanding of the aetiology and pathogenesis of multiple sclerosis is discussed in relation to the views of Sir William Gowers. He perceived that both environmental and genetic factors might be implicated in the aetiology of the disease. Evidence for the former was first reported in 1903, but has become convincing only in the past 20 years; the nature of the environmental factor remains obscure. Evidence for a genetic influence on susceptibility has accumulated since the 1930s, the most compelling coming from the recent Canadian twin study. The number and mode of operation of the genetic factors is still uncertain, but there is evidence for the implication of genetically controlled cellular immune mechanisms in the pathogenesis of the disease. The precise relationship between transient changes in immunological status and the development of new lesions has yet to be defined; magnetic resonance imaging (MRI) promises to play a significant role in this analysis because of its sensitivity in detecting abnormalities in multiple sclerosis. MRI is not in itself specific; it is probable that the similar appearances in multiple sclerosis and cerebral vascular disease both derive at least in part from the influence of astrocytic gliosis on proton content and distribution. The significance of the gliosis is uncertain. Gowers believed that the primary defect in multiple sclerosis lay in the astrocyte. Recent observations on the immunological functions of this cell in vitro suggest that it could be involved early in the pathogenesis of the lesion. Images PMID:2936869

  10. Predictors of Employment Status for People with Multiple Sclerosis

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  11. Determinants of Employment Status among People with Multiple Sclerosis.

    ERIC Educational Resources Information Center

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

    2001-01-01

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

  12. Evaluating Functional Decline in Patients with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Rosenblum, Sara; Weiss, Patrice L.

    2010-01-01

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

  13. Exercise and Quality of Life in Women with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Giacobbi, Peter R., Jr.; Dietrich, Frederick; Larson, Rebecca; White, Lesley J.

    2012-01-01

    The purpose of this study was to evaluate perceptions of quality of life after a 4-month progressive resistance training program for individuals with multiple sclerosis (MS). A second purpose was to examine participants' views about factors that facilitated or impeded exercise behavior. Qualitative interviews were conducted with eight females…

  14. Decreased Postural Balance in Multiple Sclerosis Patients with Low Disability

    ERIC Educational Resources Information Center

    Fjeldstad, Cecilie; Pardo, Gabriel; Bemben, Debra; Bemben, Michael

    2011-01-01

    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…

  15. Economic Status of Families Living with Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Catanzaro, Marci; Weinert, Clarann

    1992-01-01

    A nationwide survey of 604 families living with multiple sclerosis found average duration of the disease was 10 years; family income was above the national median; in 28 percent of the families, health insurance was inadequate to cover illness costs; and, overall, factors other than income and amount of health insurance determined the economic…

  16. Biophysical mechanisms of MRI signal frequency contrast in multiple sclerosis

    PubMed Central

    Yablonskiy, Dmitriy A.; Luo, Jie; Sukstanskii, Alexander L.; Iyer, Aditi; Cross, Anne H.

    2012-01-01

    Phase images obtained with gradient echo MRI provide image contrast distinct from T1- and T2-weighted images. It is commonly assumed that the local contribution to MRI signal phase directly relates to local bulk tissue magnetic susceptibility. Here, we use Maxwell’s equations and Monte Carlo simulations to provide theoretical background to the hypothesis that the local contribution to MRI signal phase does not depend on tissue bulk magnetic susceptibility but tissue magnetic architecture—distribution of magnetic susceptibility inclusions (lipids, proteins, iron, etc.) at the cellular and subcellular levels. Specifically, we show that the regular longitudinal structures forming cylindrical axons (myelin sheaths and neurofilaments) can be locally invisible in phase images. Contrary to an expectation that the phase contrast in multiple sclerosis lesions should always increase in degree along with worsening of lesion severity (which happens for all known MR magnitude-based contrast mechanisms), we show that phase contrast can actually disappear with extreme tissue destruction. We also show that the phase contrast in multiple sclerosis lesions could be altered without loss of nervous system tissue, which happens in mild injury to the myelin sheaths or axonal neurofilaments. Moreover, we predict that the sign of phase contrast in multiple sclerosis lesions indicates the predominant type of tissue injury—myelin damage (positive sign) vs. axonal neurofilament damage (negative sign). Therefore, our theoretical and experimental results shed light on understanding the relationship between gradient echo MRI signal phase and multiple sclerosis pathology. PMID:22891307

  17. Characteristics of diadochokinesis in Parkinson's Disease and Multiple Sclerosis

    NASA Astrophysics Data System (ADS)

    Tjaden, Kris; Watling, Elizabeth

    2002-05-01

    The current study applies a quantitative, acoustic analysis procedure for the study of rapid syllable productions outlined by Kent and colleagues [R. D. Kent et al., J. Med. Sp. Lang. Path. 7, 83-90 (1999)] to syllables produced by speakers with Parkinson's Disease and Multiple Sclerosis. Neurologically healthy talkers will be studied for comparison purposes. Acoustic measures will be reported for syllable repetitions of /p schwa/, /t schwa/, and /k schwa/. Temporal measures will include syllable duration, syllable rate, and stop gap duration. The energy envelope of syllable repetitions will be quantified using measures of rms amplitude minima and maxima. Acoustic measures will be contrasted to determine the extent to which acoustic profiles of diadochokinesis distinguish hypokinetic dysarthria associated with Parkinson's Disease, ataxic dysarthria secondary to Multiple Sclerosis, and spastic dysarthria secondary to Multiple Sclerosis. It also is of interest to determine whether speakers with Parkinson's Disease and Multiple Sclerosis judged to be nondysarthric via perceptual analyses also demonstrate objective, acoustic profiles of diadochokinesis that are within normal limits. [Work supported by NIH.

  18. Physical activity and irreversible disability in multiple sclerosis.

    PubMed

    Motl, Robert W

    2010-10-01

    Multiple sclerosis (MS) is a neurological disease that may result in the progressive worsening of disability. Recent research has identified physical activity as a behavioral correlate of disability in MS. The current review highlights that previous research has generally included samples with minimal disability and provides a rationale for considering physical activity as an influence of disability in the second stage of MS.

  19. Amyotrophic lateral sclerosis: one or multiple causes?

    PubMed Central

    Bastos, Aline Furtado; Orsini, Marco; Machado, Dionis; Mello, Mariana Pimentel; Nader, Sergio; Silva, Júlio Guilherme; da Silva Catharino, Antonio M.; de Freitas, Marcos R.G.; Pereira, Alessandra; Pessoa, Luciane Lacerda; Sztajnbok, Flavio R.; Leite, Marco Araújo; Nascimento, Osvaldo J.M.; Bastos, Victor Hugo

    2011-01-01

    The Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1), certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients. PMID:21785676

  20. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis?

    PubMed Central

    Stenager, Egon

    2012-01-01

    It has been suggested that exercise (or physical activity) might have the potential to have an impact on multiple sclerosis (MS) pathology and thereby slow down the disease process in MS patients. The objective of this literature review was to identify the literature linking physical exercise (or activity) and MS disease progression. A systematic literature search was conducted in the following databases: PubMed, SweMed+, Embase, Cochrane Library, PEDro, SPORTDiscus and ISI Web of Science. Different methodological approaches to the problem have been applied including (1) longitudinal exercise studies evaluating the effects on clinical outcome measures, (2) cross-sectional studies evaluating the relationship between fitness status and MRI findings, (3) cross-sectional and longitudinal studies evaluating the relationship between exercise/physical activity and disability/relapse rate and, finally, (4) longitudinal exercise studies applying the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Data from intervention studies evaluating disease progression by clinical measures (1) do not support a disease-modifying effect of exercise; however, MRI data (2), patient-reported data (3) and data from the EAE model (4) indicate a possible disease-modifying effect of exercise, but the strength of the evidence limits definite conclusions. It was concluded that some evidence supports the possibility of a disease-modifying potential of exercise (or physical activity) in MS patients, but future studies using better methodologies are needed to confirm this. PMID:22435073

  1. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis?

    PubMed

    Dalgas, Ulrik; Stenager, Egon

    2012-03-01

    It has been suggested that exercise (or physical activity) might have the potential to have an impact on multiple sclerosis (MS) pathology and thereby slow down the disease process in MS patients. The objective of this literature review was to identify the literature linking physical exercise (or activity) and MS disease progression. A systematic literature search was conducted in the following databases: PubMed, SweMed+, Embase, Cochrane Library, PEDro, SPORTDiscus and ISI Web of Science. Different methodological approaches to the problem have been applied including (1) longitudinal exercise studies evaluating the effects on clinical outcome measures, (2) cross-sectional studies evaluating the relationship between fitness status and MRI findings, (3) cross-sectional and longitudinal studies evaluating the relationship between exercise/physical activity and disability/relapse rate and, finally, (4) longitudinal exercise studies applying the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Data from intervention studies evaluating disease progression by clinical measures (1) do not support a disease-modifying effect of exercise; however, MRI data (2), patient-reported data (3) and data from the EAE model (4) indicate a possible disease-modifying effect of exercise, but the strength of the evidence limits definite conclusions. It was concluded that some evidence supports the possibility of a disease-modifying potential of exercise (or physical activity) in MS patients, but future studies using better methodologies are needed to confirm this.

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

    PubMed

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

    2017-04-01

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

  3. Axonal loss in the multiple sclerosis spinal cord revisited.

    PubMed

    Petrova, N; Carassiti, D; Altmann, D R; Baker, D; Schmierer, K

    2017-04-12

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

  4. Theranostic Implications of Nanotechnology in Multiple Sclerosis: A Future Perspective

    PubMed Central

    Singh, Ajay Vikram; Khare, Manish; Gade, W. N.; Zamboni, Paolo

    2012-01-01

    Multiple Sclerosis is a multifactorial disease with several pathogenic mechanisms and pathways. Successful MS management and medical care requires early accurate diagnosis along with specific treatment protocols based upon multifunctional nanotechnology approach. This paper highlights advances in nanotechnology that have enabled the clinician to target the brain and CNS in patient with multiple sclerosis with nanoparticles having therapeutic and imaging components. The multipartite theranostic (thera(py) + (diag)nostics) approach puts forth strong implications for medical care and cure in MS. The current nanotheranostics utilize tamed drug vehicles and contain cargo, targeting ligands, and imaging labels for delivery to specific tissues, cells, or subcellular components. A brief overview of nonsurgical nanorepair advances as future perspective is also described. Considering the potential inflammatory triggers in MS pathogenesis, a multifunctional nanotechnology approach will be needed for the prognosis. PMID:23346386

  5. [A review of multiple sclerosis (2). Diagnosis and treatment].

    PubMed

    Martinez-Altarriba, M C; Ramos-Campoy, O; Luna-Calcaño, I M; Arrieta-Antón, E

    2015-09-01

    Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although there are several hypotheses, such as infections or genetics. In its pathophysiology, it seems that immune activation attacks the myelin sheath, causing a progressive and irreversible axonal degeneration. The disease produces a variety of symptoms, and diagnosis requires fulfilling a number of criteria and the exclusion of other possible causes. The role of neuroimaging is very important, especially Magnetic Resonance Imaging. Despite the availability of disease-modifying drugs, none of them are able to halt its progress, and the most useful drugs are those designed to alleviate the symptoms of outbreaks. Overall, multiple sclerosis requires a significant effort in research to clarify not only why and how it occurs, as well as the development of new measures to improve quality of life of affected patients.

  6. [A review of multiple sclerosis (1). Presentation of a case].

    PubMed

    Martinez-Altarriba, M C; Ramos-Campoy, O; Luna-Calcaño, I M; Arrieta-Antón, E

    2015-01-01

    Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although there are several hypotheses, such as infections or genetics. In its pathophysiology, it seems that immune activation attacks the myelin sheath, causing a progressive and irreversible axonal degeneration. The disease produces a variety of symptoms, and diagnosis requires fulfilling a number of criteria and the exclusion of other possible causes. The role of neuroimaging, especially MRI, is very important. Despite the availability of disease-modifying drugs, none of them are able to halt its progress, and the most useful drugs are those designed to alleviate the symptoms of outbreaks. Overall, multiple sclerosis requires a significant effort in research to clarify not only why and how it occurs, but also to develop of new measures to improve the life of affected patients.

  7. Therapy Insight: bladder dysfunction associated with multiple sclerosis.

    PubMed

    Kalsi, Vinay; Fowler, Clare J

    2005-10-01

    Bladder dysfunction is a common problem for patients with multiple sclerosis. The severity of symptoms often correlate with the degree of spinal cord involvement and, hence, the patient's general level of disability. The emphasis of management is now mainly medical and is increasingly offered by nonurologists. Treatments can be highly effective, relieving patients of what are otherwise very troublesome symptoms that would compound their neurological disability. This article gives an overview of the neural control of the bladder, followed by an explanation of the pathophysiology of detrusor overactivity secondary to neurological disease. A review of methods available for treating bladder dysfunction in multiple sclerosis then follows. The treatment options for this disorder are largely medical and include established first-line measures such as anticholinergics, clean intermittent self-catheterization and the use of desmopressin, as well as potential second-line agents, such as cannabinoids, intravesical vanilloids and intradetrusor botulinum neurotoxin type A. The diminishing role of surgical intervention is also discussed.

  8. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    PubMed

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

    2016-07-01

    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis.

  9. Multiple sclerosis lesions of the auditory pons are not silent.

    PubMed

    Levine, R A; Gardner, J C; Fullerton, B C; Stufflebeam, S M; Furst, M; Rosen, B R

    1994-10-01

    To understand the relationship between brainstem lesions and auditory neurology in patients with multiple sclerosis, we compared behavioural, electrophysiological and imaging data in 38 patients with probable or definite multiple sclerosis and normal or near normal hearing. Behavioural measures included (i) general hearing tests (audiogram, speech discrimination) and (ii) hearing tests likely to be critically dependent upon brainstem processing (masking level difference, interaural time and level discrimination). Brainstem auditory evoked potentials provided the electrophysiological data. Multiplanar high-resolution MRI of the brainstem provided the anatomical data. Interaural time discrimination for high-frequency sounds was by far the most sensitive of all tests with abnormalities in 71% of all subjects. Whenever any other test was abnormal this test was always abnormal. Interaural time discrimination for low-frequency sounds and evoked potentials were closely related and next most sensitive with abnormalities in approximately 40% of all subjects. Interaural level discrimination and masking level difference were least sensitive with abnormalities in < 10% of subjects. Speech discrimination scores correlated significantly with the masking level differences, as well as with interaural time discrimination for high-frequency sounds. Pontine lesions were found in five of the 16 patients, in whom an objective method for detecting magnetic resonance lesions could be applied. All four with lesions involving the pontine auditory pathway had marked abnormalities in interaural time discrimination and evoked potentials. None of the other 12 had evoked potentials abnormalities. We conclude that neurological tests requiring precise neural timing can reveal behavioural deficits for multiple sclerosis lesions of the auditory pons that are otherwise 'silent'. Of all neurological systems the auditory system at the level of the pons is probably the most sensitive to multiple

  10. Peripheral Vasculitis, Intermediate Uveitis and Interferon Use in Multiple Sclerosis

    PubMed Central

    Kinyas, Şeref; Esgin, Haluk

    2016-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. A 40-year-old female patient with a 12-year history of MS was admitted to our clinic with blurred vision and floaters in her right eye for about 1 month. Here, we share the findings and the management of intermediate uveitis and retinal periphlebitis in an MS case being treated with interferon beta-1a for 7 years. PMID:27800257

  11. Postmarketing evidence of disease-modifying drugs in multiple sclerosis.

    PubMed

    Trojano, Maria; Paolicelli, Damiano; Fuiani, Aurora; Pellegrini, Fabio; Iaffaldano, Pietro; Direnzo, Vita; D'Onghia, Mariangela

    2008-09-01

    There is growing interest in the use of observational data to estimate treatment effects in chronic diseases such as multiple sclerosis (MS). The main results derived from postmarketing evaluations, in the last 2 years, of short-and long-term disease modifying drugs (DMDs) effectiveness will be reported in this Review. Moreover, some of the methodological improvements that may be useful to enhance the quality of observational studies will also be discussed.

  12. Major depression and multiple sclerosis - a case report.

    PubMed

    Moore, S

    2013-09-15

    Multiple Sclerosis (MS) is a chronic and disabling disease with a considerable social impact and economic consequences. In Europe, it is the most common cause of non-traumatic disability in young adults. Existing therapies that target immune modulation are largely ineffective in halting the progression of the disease and are fraught with severe side effects. Therefore, managing the comorbidities of MS is of utmost importance for long-term patient care and quality of life.

  13. Vascular comorbidities in multiple sclerosis: a nationwide study from Denmark.

    PubMed

    Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils; Laursen, Bjarne; Sørensen, Per Soelberg

    2016-12-01

    To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case-control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were identified from the Danish Multiple Sclerosis Registry and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique personal identification numbers. To assess the presence of vascular comorbidities before and after MS onset, cases and controls were followed from January 1977 to the index date, and from the index date through December 2012. We used logistic regression to calculate odds ratios (ORs) and Cox regression to calculate hazard ratios (HRs). Before the index date, MS cases had a decreased probability for cerebrovascular comorbidity [OR 0.69 (95 % CI 0.48-0.99, p = 0.043)], and a numerically but not statistically significant decreased probability for cardiovascular comorbidity [OR 0.87 (95 % CI 0.71-1.07, p = 0.188)]. After the index date, MS cases had an increased risk for cerebrovascular comorbidity [HR 1.84 (95 % CI 1.69-2.00, p < 0.0005)], and for cardiovascular comorbidity [HR 1.08 (95 % CI 1.02-1.15, p = 0.013)]. The lower occurrence of cerebrovascular comorbidities in cases prior to MS onset could be due to protective immune mechanisms, while the higher occurrence of vascular comorbidities in cases after MS onset could be because of converging causal pathways of the coexisting diseases. These findings deserve to be studied closer in a broader spectrum of comorbidities in MS.

  14. Dysphagia in multiple sclerosis: from pathogenesis to diagnosis.

    PubMed

    Tassorelli, Cristina; Bergamaschi, Roberto; Buscone, Simona; Bartolo, Michelangelo; Furnari, Anna; Crivelli, Paola; Alfonsi, Enrico; Alberici, Elisa; Bertino, Giulia; Sandrini, Giorgio; Nappi, Giuseppe

    2008-12-01

    Abnormalities of swallowing are commonly encountered in Multiple Sclerosis (MS), especially in the most disabled patients. The disturbances usually involve oral and pharyngeal phases of swallowing, although upper oesophageal sphincter dysfunction has also been detected. MS patients need to be effectively evaluated and managed in order to recognize dysphagia before any medical complications such as aspiration pneumonia appear. An integrated approach is proposed to define the severity of dysphagia and to devise the most appropriate therapeutic/rehabilitative methodology.

  15. Epstein Barr Virus and Blood Brain Barrier in Multiple Sclerosis

    DTIC Science & Technology

    2013-07-01

    of EBV in MS disease. 15. SUBJECT TERMS Blood-brain-barrier, Epstein-Barr virus; EBV ; BBB; MS, Multiple sclerosis 16. SECURITY CLASSIFICATION OF...virus ( EBV ) infection is associated with MS pathogenesis. However, mechanism for the EBV -MS connection is unclear. The blood–brain barrier (BBB) is...astrocytes. Interestingly EBV is able to infect both kinds of cells. Because EBV is able to transfer infection from one cell type to another cell type

  16. Cluster headache-like pain in multiple sclerosis.

    PubMed

    Leandri, M; Cruccu, G; Gottlieb, A

    1999-10-01

    We describe a case with simultaneous occurrence of cluster headache-like pain and multiple sclerosis. Both neuroimaging and neurophysiology (trigeminal evoked potentials) revealed a demyelination plaque in the pons, at the trigeminal root entry zone, on the side of pain. Although that type of lesion is usually associated with trigeminal neuralgia pain, we hypothesize that in this case it may be linked with the concomitant cluster headache, possibly by activation of trigemino-vascular mechanisms.

  17. Grey matter atrophy in patients suffering from multiple sclerosis.

    PubMed

    Kincses, Zsigmond Tamás; Tóth, Eszter; Bankó, Nóra; Veréb, Dániel; Szabó, Nikoletta; Csete, Gergő; Faragó, Péter; Király, András; Bencsik, Krisztina; Vécsei, László

    2014-09-30

    White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.

  18. Can multiple sclerosis as a cognitive disorder influence patients' dreams?

    PubMed

    Moghadasi, Abdorreza Naser; Owji, Mahsa

    2013-01-01

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

  19. Role of statins in the treatment of multiple sclerosis.

    PubMed

    Ciurleo, Rosella; Bramanti, Placido; Marino, Silvia

    2014-09-01

    Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely prescribed for hypercholesterolemia treatment. In the last years, statins have also been shown to exert immunomodulatory and anti-inflammatory effects which appear to be related to inhibition of isoprenylation of small GTP-binding proteins and, at least in part, independent of their cholesterol-lowering effects. These "pleiotropic" effects make statins an attractive treatment option for immune-mediated disorders such as multiple sclerosis. Studies in vitro and in experimental autoimmune encephalomyelitis animal model seem to support not only the efficacy of statins as immunomodulatory agents but also their potential neuroprotective properties, although the exact mechanism with which statins exert these effects has not yet been fully understood. The immunomodulatory, anti-inflammatory and neuroprotective properties of statins provided the incentive for several clinical trials in multiple sclerosis, in which they were tested not only as mono-therapy but also in combination with interferon-β. However, the attempt to translate the results of animal model studies in humans produced conflicting results. Further large, prospective, randomized, double-blind, placebo-controlled trials, designed to evaluate the long-term effects of statins alone or in add-on to other disease-modifying therapies, are needed to support their routine clinical use in multiple sclerosis.

  20. Measles and Other Virus-specific Immunoglobulins in Multiple Sclerosis

    PubMed Central

    Haire, Margaret; Fraser, K. B.; Millar, J. H. D.

    1973-01-01

    Immunoglobulins M and G specific for meales, herpes simplex, and rubella viruses were assayed by the fluorescent antibody method in sera and cerebrospinal fluids (C.S.F.) obtained simultaneously from 30 patients with multiple sclerosis, 30 patients with other neurological diseases, and 30 “normal” control subjects. Sera of 11 out of 30 patients with multiple sclerosis had IgM which reacted specifically with measles virus-infected cells, compared with 2 out of 30 of the patients with other neurological diseases and none of the 30 normal controls. Virus-specific IgM was not found in C.S.F. by this method. The geometric mean titre of measles virus-specific IgG in serum was significantly higher in the multiple sclerosis group than in either control group, and while IgG specific for all three viruses was found in C.S.F., suggesting transfer across the blood-brain barrier, measles IgG predominated. ImagesFIG. 1FIG. 2 PMID:4356870

  1. Measles and other virus-specific immunoglobulins in multiple sclerosis.

    PubMed

    Haire, M; Fraser, K B; Millar, J H

    1973-09-22

    Immunoglobulins M and G specific for meales, herpes simplex, and rubella viruses were assayed by the fluorescent antibody method in sera and cerebrospinal fluids (C.S.F.) obtained simultaneously from 30 patients with multiple sclerosis, 30 patients with other neurological diseases, and 30 "normal" control subjects. Sera of 11 out of 30 patients with multiple sclerosis had IgM which reacted specifically with measles virus-infected cells, compared with 2 out of 30 of the patients with other neurological diseases and none of the 30 normal controls. Virus-specific IgM was not found in C.S.F. by this method.The geometric mean titre of measles virus-specific IgG in serum was significantly higher in the multiple sclerosis group than in either control group, and while IgG specific for all three viruses was found in C.S.F., suggesting transfer across the blood-brain barrier, measles IgG predominated.

  2. Oral health status of a population with multiple sclerosis

    PubMed Central

    Martínez-Pérez, Eva M.; Miegimolle-Herrero, Mónica; Planells-del-Pozo, Paloma

    2012-01-01

    Objective: To determine the oral treatment needs of a sample of patients diagnosed with multiple sclerosis in the Community of Madrid (Spain). Patients and methods: A cross-sectional epidemiological study was carried out with a sample of 64 patients who were aged 25 to 77 years. They were distributed into homogeneous age groups: < 46 years, 46-54 years and > 54 years. In order to evaluate the oral health status and treatment requirements, the parameters and guidelines of the WHO were used. Results: The prevalence of caries was 100%, or very close in all three groups. As age increased, the morbidity rate decreased, but the mortality rate increased considerably. On analyzing gingival health, 65% of patients had calculus, 5% bleeding and 30% were healthy. Conclusions: The DMFT index found provided data that was, in general, very similar to that of the general population in Spain. However, the gingival health status found demonstrated that the population of multiple sclerosis patients requires specific assistance. Key words: Multiple sclerosis, oral health, dentures. PMID:22143682

  3. Autobiographical memory in multiple sclerosis patients: assessment and cognitive facilitation.

    PubMed

    Ernst, A; Blanc, F; Voltzenlogel, V; de Seze, J; Chauvin, B; Manning, L

    2013-01-01

    The multifocal nature of lesions in multiple sclerosis hints at the occurrence of autobiographical memory (AbM) impairment. However, the dearth of studies on AbM in multiple sclerosis is noticeable, notwithstanding the importance of AbM in everyday life. In the first section of this study, 25 multiple sclerosis patients and 35 controls underwent a detailed episodic AbM assessment. Results obtained by means of ANOVA suggested an AbM retrieval deficit in every patient. That pattern of performance paved the way for the second section of the study, in which we followed up 10 out of the 25 patients. Our objective was to assess the effectiveness of a cognitive facilitation programme designed to alleviate AbM retrieval deficits, based on the key role of mental visual imagery on AbM. Statistical group analyses by means of ANOVA and individual analyses using the χ(2) test showed significant differences in AbM test results, in post-facilitation relative to pre-facilitation training, in all 10 patients. Moreover, the patients' comments showed that the positive effects were transferred in their daily life functioning. We would like to suggest that the facilitation programme efficiently enhanced the process of self-centred mental visual imagery, which might have compensated for poor retrieval of personal memories by providing better access to visual details and detailed visual scenes of personal recollections.

  4. Falls and Physical Activity in Persons with Multiple Sclerosis

    PubMed Central

    Sosnoff, J. J.; Sandroff, B. M.; Pula, J. H.; Morrison, S. M.; Motl, R. W.

    2012-01-01

    Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P < .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P > .05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis. PMID:22966459

  5. Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

    PubMed Central

    Lidster, Katie; Jackson, Samuel J.; Ahmed, Zubair; Munro, Peter; Coffey, Pete; Giovannoni, Gavin; Baker, Mark D.; Baker, David

    2013-01-01

    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

  6. Spasticity in multiple sclerosis and role of glatiramer acetate treatment

    PubMed Central

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

    2015-01-01

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

  7. Pregnancy outcome in women with multiple sclerosis: results from a prospective nationwide study in Finland.

    PubMed

    Jalkanen, A; Alanen, A; Airas, L

    2010-08-01

    The majority of individuals obtaining the diagnosis of multiple sclerosis are women of childbearing age. They are naturally concerned as to how multiple sclerosis affects the course of pregnancy and the developing foetus. The objective of this study was to prospectively evaluate the incidence of pregnancy complications and delivery risks, and to follow the natural course of multiple sclerosis during and after pregnancy in a cohort of Finnish patients with multiple sclerosis. Sixty-one patients with multiple sclerosis who became pregnant during the years 2003-2005 were prospectively followed-up from early pregnancy until 6 months postpartum. Multiple sclerosis relapses, Expanded Disability Status Scale rates and obstetric details were recorded. The results were compared with the statistics obtained from Finnish Medical Birth Register from the year 2004. We found that patients with multiple sclerosis were no more likely to experience pregnancy complications than Finnish pregnant women generally, but they had a greater likelihood for a need of artificial insemination (4.9% vs. 0.9%; p = 0.0009). Subjects with multiple sclerosis were more likely to undergo assisted vaginal delivery than the at-large cohort (16.4% vs. 6.5%; p = 0.0017). We conclude that pregnancy does not seem to pose a woman with multiple sclerosis to a greater risk for pregnancy complications when compared with women in general. The potential need for instrumental delivery should, however, be taken into account when planning the delivery of a mother with multiple sclerosis.

  8. Epidemiology of multiple sclerosis in U. S. veterans: 2. Latitude, climate and the risk of multiple sclerosis

    SciTech Connect

    Norman, J.E. Jr.; Kurtzke, J.F.; Beebe, G.W.

    1983-01-01

    An analysis of ten climatic factors and elevation for the counties of birth of 4371 U.S. white male veterans with multiple sclerosis and matched controls has been made in relation to birthplace latitude. The climatic factors include an air pollution index, concentrations of minerals in ground water, measures of annual solar radiation, both in energy per unit area and in hours of sunshine, mean annual periods of high and low temperatures, and measures of annual rainfall and average humidity. These variables all significantly influence the risk of multiple sclerosis when analyzed alone, but when they are adjusted for latitude, their effect is found to be due to their correlation with this variable.

  9. [Multiple sclerosis in literature, cinema and television].

    PubMed

    Collado-Vazquez, S; Carrillo, J M; Cano-de-la-Cuerda, R

    2016-12-16

    Introduccion. En la actualidad, la atencion del paciente con esclerosis multiple y su entorno supone un reto clinico y terapeutico para los profesionales de la salud. El objetivo del presente trabajo es analizar la aparicion de la esclerosis multiple en la literatura, el cine y la television, y reflexionar sobre su imagen en dichos medios. Desarrollo. Se han revisado algunas obras representativas que han abordado la esclerosis multiple, y se ha observado que en muchas de ellas se ofrece una vision muy fidedigna de la enfermedad. Del mismo modo, se han revisado las principales peliculas y series de television que, en ocasiones, son un reflejo cercano al publico general de la vision e impacto de la enfermedad sobre los pacientes o familiares, no exentas de excesos dramaticos y distorsiones de la realidad. Conclusiones. La literatura refleja, en gran medida, la epidemiologia real, los sintomas y la progresion de la enfermedad, mientras que las opciones diagnosticas y terapeuticas parecen estar en un segundo plano. El cine y la television han ofrecido una imagen correcta, pero en ocasiones atendiendo mas a efectos dramaticos. Es importante que la literatura, el cine y la television ofrezcan una vision ajustada a la realidad de esta enfermedad para dar a conocer esta afeccion neurologica y contribuir a disminuir su estigma.

  10. Modeling the Heterogeneity of Multiple Sclerosis in Animals

    PubMed Central

    Simmons, Sarah B.; Pierson, Emily R.; Lee, Sarah Y.; Goverman, Joan M.

    2013-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system manifested with varying clinical course, pathology, and inflammatory patterns. There are multiple animal models that reflect different aspects of this heterogeneity. Collectively, these models reveal a balance between pathogenic and regulatory CD4+ T cells, CD8+ T cells and B cells that influences the incidence, timing, and severity of central nervous system autoimmunity. In this review we discuss experimental autoimmune encephalomyelitis (EAE) models that have been used to study the pathogenic and regulatory roles of these immune cells, models that recapitulate different aspects of the disease seen in patients with MS, and questions remaining for future studies. PMID:23707039

  11. Decline of cognition in multiple sclerosis: dissociable deficits.

    PubMed Central

    Jennekens-Schinkel, A; Sanders, E A

    1986-01-01

    Three female patients (ages 32, 37 and 27 years) developed progressive deficits of cognition in stages of multiple sclerosis in which physical disability ratings were low. Neuropsychological examination revealed severe cognitive impairments in the first two patients. Cognitive functioning was essentially intact in the third patient, although her work pace was significantly slowed. CT scanning of the brain showed cortical atrophy as well as white matter lesions in patients 1 and 2, and multiple lesions and oedema of predominantly white matter in patient 3. The differences of cognitive dysfunction between the third and the first two patients may be related to involvement of different anatomical structures. Images PMID:3806111

  12. Genomic effects of IFN-beta in multiple sclerosis patients.

    PubMed

    Weinstock-Guttman, Bianca; Badgett, Darlene; Patrick, Kara; Hartrich, Laura; Santos, Roseane; Hall, Dennis; Baier, Monika; Feichter, Joan; Ramanathan, Murali

    2003-09-01

    The purpose of this report was to characterize the dynamics of the gene expression cascades induced by an IFN-beta-1a treatment regimen in multiple sclerosis patients and to examine the molecular mechanisms potentially capable of causing heterogeneity in response to therapy. In this open-label pharmacodynamic study design, peripheral blood was obtained from eight relapsing-remitting multiple sclerosis patients just before and at 1, 2, 4, 8, 24, 48, 120, and 168 h after i.m. injection of 30 micro g of IFN-beta-1a. The total RNA was isolated from monocyte-depleted PBL and analyzed using cDNA microarrays containing probes for >4000 known genes. IFN-beta-1a treatment resulted in selective, time-dependent effects on multiple genes. The mRNAs for genes implicated in the anti-viral response, e.g., double-stranded RNA-dependent protein kinase, myxovirus resistance proteins 1 and 2, and guanylate binding proteins 1 and 2 were rapidly induced within 1-4 h of IFN-beta treatment. The mRNAs for several genes involved in IFN-beta signaling, such as IFN-alpha/beta receptor-2 and Stat1, were also increased. The mRNAs for lymphocyte activation markers, such as IFN-induced transmembrane protein 1 (9-27), IFN-induced transmembrane protein 2 (1-8D), beta(2)-microglobulin, and CD69, were also increased in a time-dependent manner. The findings demonstrate that IFN-beta treatment induces specific and time-dependent changes in multiple mRNAs in lymphocytes of multiple sclerosis patients that could provide a framework for rapid monitoring of the response to therapy.

  13. Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

    DTIC Science & Technology

    2015-10-01

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

  14. Plasma Exchange in a Patient with Tumefactive, Corticosteroid-Resistant Multiple Sclerosis

    PubMed Central

    Ikeda, Kristin M.; Lee, Donald H.; Fraser, J. Alexander; Mirsattari, Seyed

    2015-01-01

    Tumefactive multiple sclerosis (MS) is an aggressive form of MS that can be difficult to treat with standard therapies. In severe MS relapses, plasma exchange (PLEX) has shown some benefit, but reports of its use in patients with tumefactive MS are limited. This article describes the successful use of PLEX in a patient with tumefactive MS. A 46-year-old right-handed woman with a recent diagnosis of MS presented with drowsiness, dysarthria, horizontal nystagmus, and quadriparesis. Her brain magnetic resonance images demonstrated multiple tumefactive demyelinating lesions in the medulla, bilateral periventricular white matter, and corona radiata white matter. She was initially treated with a 10-day course of intravenous methylprednisolone without benefit; therefore, PLEX was initiated. After the second exchange, the patient started to improve and was discharged initially to rehabilitation and then home. She was started on disease-modifying therapy with natalizumab and did not experience further relapses but had slow clinical decline during the next year, which led to discontinuation of natalizumab treatment. PLEX may be used as second-line treatment in corticosteroid-resistant MS relapses, but there are limited reports of its use in patients with tumefactive MS. This patient presented with aggressive disease with multiple tumefactive lesions and did not respond to standard treatment with corticosteroids. PLEX was successful in improving her symptoms, allowing her to return home, although the disease progressed during the next year. PMID:26472944

  15. [Affective and psychotic disorders in multiple sclerosis].

    PubMed

    Pozuelo-Moyano, Beatriz; Benito-León, Julián

    2015-12-01

    Introduccion. La esclerosis multiple (EM) es la segunda causa mas importante de discapacidad de origen neurologico en los adultos jovenes. Tanto la sintomatologia fisica como la psiquiatrica (trastornos afectivos y psicoticos) impactan de manera negativa en la calidad de vida relacionada con la salud de los pacientes con EM. Objetivo. Elucidar de modo critico la prevalencia y la patogenia de los sintomas afectivos y psicoticos presentes en la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados mas significativos que han analizado la prevalencia y la patogenia de la sintomatologia afectiva y psicotica en los pacientes con EM. Para explorar la asociacion entre los sintomas afectivos y psicoticos con la EM se ha revisado la evidencia disponible hasta el momento. Conclusiones. La depresion es el trastorno psiquiatrico mas frecuente en la EM. Es necesaria mas investigacion para elucidar los mecanismos subyacentes que pueden provocar sintomas afectivos y psicoticos en la EM. El control de dichos sintomas en los pacientes de EM podria mejorar su calidad de vida relacionada con la salud.

  16. Patterns of Objective and Subjective Burden of Informal Caregivers in Multiple Sclerosis

    PubMed Central

    Bayen, E.; Papeix, C.; Pradat-Diehl, P.; Lubetzki, C.; Joël, M. E.

    2015-01-01

    Background. Home care for patients with Multiple Sclerosis (MS) relies largely on informal caregivers (ICs). Methods. We assessed ICs objective burden (Resource Utilization in Dementia measuring informal care time (ICT)) and ICs subjective burden (Zarit Burden Inventory (ZBI)). Results. ICs (N = 99) were spouses (70%), mean age 52 years, assisting disabled patients with a mean EDSS (Expanded Disability Status Scale) of 5.5, with executive dysfunction (mean DEX (Dysexecutive questionnaire) of 25) and a duration of MS ranging from 1 to 44 years. Objective burden was high (mean ICT = 6.5 hours/day), mostly consisting of supervision time. Subjective burden was moderate (mean ZBI = 27.3). Multivariate analyses showed that both burdens were positively correlated with higher levels of EDSS and DEX, whereas coresidency and IC's female gender correlated with objective burden only and IC's poor mental health status with subjective burden only. When considering MS aggressiveness, it appeared that both burdens were not correlated with a higher duration of MS but rather increased for patients with severe and early dysexecutive function and for patients classified as fast progressors according to the Multiple Sclerosis Severity Score. Conclusion. Evaluation of MS disability course and IC's personal situation is crucial to understand the burden process and to implement adequate interventions in MS. PMID:26078487

  17. Trigeminal root entry zone involvement in neuromyelitis optica and multiple sclerosis.

    PubMed

    Sugiyama, Atsuhiko; Mori, Masahiro; Masuda, Hiroki; Uchida, Tomohiko; Muto, Mayumi; Uzawa, Akiyuki; Ito, Shoichi; Kuwabara, Satoshi

    2015-08-15

    Trigeminal root entry zone abnormality on brain magnetic resonance imaging has been frequently reported in multiple sclerosis patients, but it has not been investigated in neuromyelitis optica patients. Brain magnetic resonance imaging of 128 consecutive multiple sclerosis patients and 46 neuromyelitis optica patients was evaluated. Trigeminal root entry zone abnormality was present in 11 (8.6%) of the multiple sclerosis patients and two (4.3%) of the neuromyelitis optica patients. The pontine trigeminal root entry zone may be involved in both multiple sclerosis and neuromyelitis optica.

  18. [Acquired and developmental Gerstmann syndrome. Illustration from a patient with multiple sclerosis].

    PubMed

    Ehrlé, N; Maarouf, A; Chaunu, M-P; Sabbagh-Peignot, S; Bakchine, S

    2012-11-01

    Gerstmann's syndrome (GS) is defined by a clinical tetrad including acalculia, finger anomia, left-right disorientation and agraphia. In this article, we describe the case of a 42-year-old woman suffering from an aggressive relapsing-remitting multiple sclerosis in which a systematic neuropsychological assessment revealed Gertsmann's syndrome amongst other cognitive disturbances. Brain MRI showed a high concentration of plaques within a left subcortical parietal region that has recently been considered as a crucial node for GS appearance. However, history, taking provided information suggesting that an important part of the GS, may have been present since childhood, evoking a possible neurodevelopmental origin in this patient. This article reviews the role of the GS concept in contemporary literature, with a special attention to pathophysiological hypotheses and to precautions necessary to study such cases.

  19. The Underdiagnosis of Sleep Disorders in Patients with Multiple Sclerosis

    PubMed Central

    Brass, Steven D.; Li, Chin-Shang; Auerbach, Sanford

    2014-01-01

    Study Objectives: To report at a population level the prevalence of restless legs syndrome, insomnia, and the risk of obstructive sleep apnea in multiple sclerosis patients. Sleep patterns and associations with fatigue and daytime sleepiness were identified. Methods: A cross-sectional study was performed using a written survey that was mailed to 11,400 individuals from the Northern California Chapter of the National Multiple Sclerosis (MS) Society Database who self-identified as having MS. The survey included individual questions relating to demographics as well as several standard validated questionnaires related to primary sleep disorders, sleepiness, fatigue severity, and sleep patterns. Results: Among the 11,400 surveys mailed out, 2,810 (24.6%) were returned. Of these, 2,375 (84.5%) met the inclusion criteria. Among the completed surveys, 898 (37.8%) screened positive for obstructive sleep apnea, 746 (31.6%) for moderate to severe insomnia, and 866 (36.8%) for restless legs syndrome. In contrast, only 4%, 11%, and 12% of the cohort reported being diagnosed by a health care provider with obstructive sleep apnea, insomnia, and restless legs syndrome, respectively. Excessive daytime sleepiness was noted in 30% of respondents based on the Epworth Sleepiness Scale. More than 60% of the respondents reported an abnormal level of fatigue based on the Fatigue Severity Scale. Both abnormal fatigue and sleepiness scores were associated with screening positive for obstructive sleep apnea, insomnia, and restless legs syndrome. Conclusion: A significant percentage of MS subjects in our sample screened positive for one or more sleep disorders. The vast majority of these sleep disorders were undiagnosed. Greater attention to sleep problems in this population is warranted, especially in view of fatigue being the most common and disabling symptom of MS. Citation: Brass SD, Li CS, Auerbach S. The underdiagnosis of sleep disorders in patients with multiple sclerosis. J Clin Sleep

  20. The role of information system in multiple sclerosis management.

    PubMed

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-12-01

    Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management.

  1. Patient perceptions of multiple sclerosis and its treatment

    PubMed Central

    de Seze, Jérôme; Borgel, Florent; Brudon, Frédérique

    2012-01-01

    Background In order to improve the treatment outcome in multiple sclerosis, it is important to document the factors that influence adherence to therapy. The purpose of this study was to determine patient perceptions and awareness of multiple sclerosis and its treatment, treatment adherence, and impact on quality of life and daily living. Methods This was a cross-sectional observational study performed in France. Each participating neurologist included the first three patients with relapsing-remitting multiple sclerosis who consulted after the start of the study. Data on clinical features were collected from a physician questionnaire and on disease and treatment perception and on quality of life from a patient autoquestionnaire. Results A total of 175 neurologists entered 202 patients in the study. The mean duration of disease was 8.0 ± 7.0 years, and immunomodulatory treatment had been administered for a mean duration of 3.0 ± 2.0 years. A total of 166 patients (82.2%) were treated with interferon-β preparations and 36 patients (17.8%) with glatiramer acetate. Eighty-five patients (42.1%) reported missing their injections from time to time and 36 patients (17.8%) reported “drug holidays”. The most frequently given reason for nonadherence was forgetfulness (38.7% of cases). Eighty-six patients (42.6%) and 70 patients (34.7%) claimed to be well informed about their disease and treatment, respectively. Adherence was significantly higher in well informed patients (P = 0.035). The majority of patients (176 patients, 87.1%) intended continuing their current treatment and 49.5% considered that their current treatment might reduce relapses. The most frequently reported side effect was muscle pain (124 patients, 61.4%). Conclusion Patient understanding of treatment for disease enhances treatment adherence. Greater patient involvement in disease management requires better communication between physicians and their patients. PMID:22536062

  2. The role of information system in multiple sclerosis management

    PubMed Central

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-01-01

    Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management. PMID:25709660

  3. [Non-medicinal treatments of spasticity in multiple sclerosis].

    PubMed

    Mailhan, L; Papeix, C

    2012-04-01

    Non-medicinal treatments of spasticity may be proposed in patients with multiple sclerosis as either an adjunct to pharmacological treatments or the first line of treatment. Assessment of non-medicinal treatments, whether manual, surgical or with instrumentation, shows it to be beneficial for limb spasticity. Studies also reveal that, contrary to expectations, physical exercise does not increase spasticity. This means that physical exercise may be prioritized and that sports practice should not be forbidden, provided that the patient has an adequate neurological status and takes sufficient breaks to avoid fatigue.

  4. Uhthoff's phenomenon in multiple sclerosis and neuromyelitis optica.

    PubMed

    Park, Kwiyoung; Tanaka, Keiko; Tanaka, Masami

    2014-01-01

    To evaluate and compare the incidence and clinical features of Uhthoff's phenomenon in Japanese patients with neuromyelitis optica (NMO) and those with multiple sclerosis (MS), we asked 135 consecutive patients with MS and an NMO-related disorder (NMOrd) whether they experienced worse neurological symptoms after an increase in body temperature. Responses were obtained from 54 MS and 37 NMOrd patients. Uhthoff's phenomenon was observed in 26 MS (48.1%) and 20 NMOrd patients (54.1%). Motor and sensory symptoms were more frequent than visual symptoms in both diseases. The incidence of Uhthoff's phenomenon was similar in MS and NMOrd.

  5. Multiple sclerosis in children: clinical, diagnostic, and therapeutic aspects.

    PubMed

    Rostásy, Kevin

    2007-01-01

    Multiple sclerosis (MS) is the most common inflammatory disease of human central nervous system (CNS), which is characterized by inflammatory demyelination and neuroaxonal injury/loss. The majority of MS patients are diagnosed in early- to mid-adulthood; however, the onset of MS in childhood is being increasingly recognized. Although adults and children share important aspects of the disease, several features including course of the disease and a broader differential diagnosis are unique to children. This chapter summarizes recent insights and emphasizes that children with MS should be started on immunomodulatory therapies early in order to prevent future disability.

  6. Electroconvulsive therapy in patient with psychotic depression and multiple sclerosis.

    PubMed

    Urban-Kowalczyk, Małgorzata; Rudecki, Tomasz; Wróblewski, Dariusz; Smigielski, Janusz; Kałużyńska, Olga; Rabe-Jabłońska, Jolanta

    2014-08-01

    Safety of electroconvulsive therapy (ECT) in depressive patients with multiple sclerosis (MS) is still discussed and based solely on case reports. This kind of therapy was used in both unipolar depression and depression in bipolar disorder. It was suggested that ECT might cause the deterioration of neurological state (new MS lesions in magnetic resonance imaging). Moreover, there were also data indicating some anesthesiological complications and difficulties in patients with MS. We have presented a case of a patient who was treated with ECT and developed grand mal seizure after 14th electroconvulsive treatment.

  7. Depression and immunity: inflammation and depressive symptoms in multiple sclerosis.

    PubMed

    Gold, Stefan M; Irwin, Michael R

    2009-05-01

    An increasing body of evidence suggests that patients who have major depressive disorder show alterations in immunologic markers including increases in proinflammatory cytokine activity and inflammation. Inflammation of the central nervous system is a pathologic hallmark of multiple sclerosis (MS). Patients affected by this disease also show a high incidence of depression. Accumulating evidence from animal studies suggests that some aspects of depression and fatigue in MS may be linked to inflammatory markers. This article reviews the current knowledge in the field and illustrates how the sickness behavior model may be applied to investigate depressive symptoms in inflammatory neurologic diseases.

  8. GEMS Project: A Platform to Investigate Multiple Sclerosis Risk

    PubMed Central

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

    2015-01-01

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

  9. Neuro-Ophthalmic Syndromes and Processing Speed in Multiple Sclerosis.

    PubMed

    Costa, Silvana L; Gonçalves, Óscar F; Chiaravalloti, Nancy D; DeLuca, John; Almeida, Jorge

    2016-03-01

    The impact of prior neuro-ophthalmic syndromes on the performance on vision-based neuropsychological tasks in patients with multiple sclerosis (MS) is unknown. Two groups of MS participants, one with (Msos+) and the other without (Msos-), a history of neuro-ophthalmic syndromes, underwent neuropsychological assessment and were compared with healthy age- and education-matched controls (HC). Participants with Msos+ performed significantly worse on the symbol digit modalities test than the Msos- (P < 0.03) and the HC groups (P < 0.01) and coding (P < 0.01). A clinical history of neuro-ophthalmic syndromes is associated with reduced performance on visual processing speed tasks.

  10. miRNA in multiple sclerosis: search for novel biomarkers.

    PubMed

    Gandhi, Roopali

    2015-08-01

    A major challenge in multiple sclerosis (MS) is to develop biomarkers that could help in understanding individual MS patients, i.e. whether they are a responder or non-responder to therapy, which medicine is more effective, and the degree to which they may be entering the progressive phase of disease. In the last few years, a lot of attention has been drawn toward identification of diagnostic, prognostic, process-specific, and treatment-related biomarkers for MS. In this review, we will focus on the micro RNAs (miRNAs) as potential candidates for MS biomarkers.

  11. Presentation of multiple sclerosis with comorbid Huntington's disease.

    PubMed

    Maloni, Heidi W; Wallin, Mitchell T

    2015-09-01

    We report a case of Huntington's disease (HD) in a 53-year-old male with multiple sclerosis (MS). The diagnosis of MS met the McDonald criteria and was based on clinical attacks separated in space and time, cerebrospinal fluid, and MRI. The diagnosis of HD was established by DNA testing, family history, and positron emission tomography. While a number of neurologic and autoimmune diseases have been reported with MS, this is the first co-occurrence of HD and MS. Salient features of both disorders are reviewed as well as the importance of obtaining a thorough family history.

  12. Cortical reorganization in multiple sclerosis after intrathecal baclofen therapy.

    PubMed

    Guerrera, S; Morabito, R; Baglieri, A; Corallo, F; Ciurleo, R; De Luca, R; De Salvo, S; Marino, M A; Spadaro, L; Timpano, F; Bramanti, P; Marino, S

    2014-04-01

    Our objective was to assess the role of Intrathecal Baclofen Therapy (ITB) in the cortical reorganization in a patient affected by multiple sclerosis (MS) undergoing physical therapy. We reported a case of a woman affected by MS and severe spasticity, who performed an fMRI examination, before and after the ITB implantation. The subject showed controlateral motor cortex activation after motor task. After a month of ITB implantation, patient showed ipsilateral and controlateral motor cortex activation although with a broader extension. fMRI examination supported the hypothesis of a central influence in patients who undergo physiotherapy and therapy with ITB.

  13. CD24 Ala/Val polymorphism and multiple sclerosis.

    PubMed

    Goris, An; Maranian, Melanie; Walton, Amie; Yeo, Tai Wai; Ban, Maria; Gray, Julia; Dubois, Bénédicte; Compston, Alastair; Sawcer, Stephen

    2006-06-01

    CD24 is expressed on a broad range of cells in the immune and central nervous systems and appears to be required for development of experimental autoimmune encephalomyelitis in mice. Association of a CD24 Ala/Val coding polymorphism with susceptibility to and progression of multiple sclerosis was recently reported. We typed this coding polymorphism in a combined cohort of 1,180 cases and 1,168 unrelated and family-based controls from Belgium and the UK, but were unable to confirm either association. Since the CD24 gene is part of a segmental duplication, special care is required for the identification and genotyping of single nucleotide polymorphisms.

  14. Epilepsy and multiple sclerosis: Increased risk among progressive forms.

    PubMed

    Martínez-Juárez, Iris E; López-Meza, Elmer; González-Aragón, Maria del Carmen Fernández; Ramírez-Bermúdez, Jesús; Corona, Teresa

    2009-04-01

    Multiple sclerosis (MS) patients are at higher risk for epilepsy. Epilepsy was frequent among our MS patients (6.55%). Progressive MS forms were associated with higher incidence of epilepsy (p=0.021). Partial motor seizures were observed in five patients (62.5%) and generalized tonic-clonic in three (37.5%). Electroencephalogram (EEG) revealed epileptic activity in 62.5%. A high percentage of MS patients with epilepsy (37.5%) reported intoxication as the most severe form of adverse effect of antiepileptic therapy.

  15. Abnormal Control of Orbicularis Oculi Reflex Excitability in Multiple Sclerosis

    PubMed Central

    Cabib, Christopher; Llufriu, Sara; Martinez-Heras, Eloy; Saiz, Albert; Valls-Solé, Josep

    2014-01-01

    Brain lesions in patients with multiple sclerosis may lead to abnormal excitability of brainstem reflex circuits because of impairment of descending control pathways. We hypothesized that such abnormality should show in the analysis of blink reflex responses in the form of asymmetries in response size. The study was done in 20 patients with relapsing-remitting multiple sclerosis and 12 matched healthy subjects. We identified first patients with latency abnormalities (AbLat). Then, we analyzed response size by calculating the R2c/R2 ratio to stimulation of either side and the mean area of the R2 responses obtained in the same side. Patients with significantly larger response size with respect to healthy subjects in at least one side were considered to have abnormal response excitability (AbEx). We also examined the blink reflex excitability recovery (BRER) and prepulse inhibition (BRIP) of either side in search for additional indices of asymmetry in response excitability. Neurophysiological data were correlated with MRI-determined brain lesion-load and volume. Eight patients were identified as AbLat (median Expanded Disability Status Scale–EDSS = 2.75) and 7 of them had ponto-medullary lesions. Nine patients were identified as AbEx (EDSS = 1.5) and only 2 of them, who also were AbLat, had ponto-medullary lesions. In AbEx patients, the abnormalities in response size were confined to one side, with a similar tendency in most variables (significantly asymmetric R1 amplitude, BRER index and BRIP percentage). AbEx patients had asymmetric distribution of hemispheral lesions, in contrast with the symmetric pattern observed in AbLat. The brainstem lesion load was significantly lower in AbEx than in AbLat patients (p = 0.04). Asymmetric abnormalities in blink reflex response excitability in patients with multiple sclerosis are associated with lesser disability and lower tissue loss than abnormalities in response latency. Testing response excitability could

  16. Exploring the origins of grey matter damage in multiple sclerosis.

    PubMed

    Calabrese, Massimiliano; Magliozzi, Roberta; Ciccarelli, Olga; Geurts, Jeroen J G; Reynolds, Richard; Martin, Roland

    2015-03-01

    Multiple sclerosis is characterized at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, it is becoming clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage may have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. Histological, immunological and neuroimaging studies have provided new insight in this rapidly expanding field, and form the basis of the most recent hypotheses on the pathogenesis of grey matter damage.

  17. [Plasmapheresis in acute phase of multiple sclerosis and neuromyelitis optica].

    PubMed

    Matsuo, Hidenori

    2014-11-01

    In acute phase of multiple sclerosis (MS) and neuromyelitis optica (NMO), plasmapheresis (PP) should be considered as the 2nd choice treatment when corticosteroid pulse therapy results in unsuccessful. It is believed that the beneficial effects of PP occur through the elimination of pathogenic humoral and plasma factors, including autoantibodies, complement components, and cytokines. In MS, several clinical trials have shown the efficacy. However, there have been no randomized controlled trials that demonstrated the efficacy of PP in NMO. There are three methods of PP, plasma exchange, double filtration plasmapheresis and immunoadsorption plasmapheresis, available in Japan. But the difference of efficacy among these 3 methods has not been fully evaluated.

  18. Nature plus nurture: the triggering of multiple sclerosis.

    PubMed

    Wekerle, Hartmut

    2015-01-01

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

  19. Reliability of gait in multiple sclerosis over 6 months.

    PubMed

    Sosnoff, Jacob J; Klaren, Rachel E; Pilutti, Lara A; Dlugonski, Deirdre; Motl, Robert W

    2015-03-01

    Gait impairment is ubiquitous in multiple sclerosis (MS) and is often characterized by alterations in spatiotemporal parameters of gait. There is limited information concerning reliability of spatiotemporal gait parameters over clinical timescales (e.g. 6 months). The current report provides novel evidence that gait parameters of 74 ambulatory persons with MS with mild-to-moderate disability are reliable over 6-months (ICC's for overall sample range from 0.56 to 0.91) in the absence of any intervention above and beyond standard care. Such data can inform clinical decision-making and power analyses for designing RCTs (i.e., sample size estimates) involving persons with MS.

  20. Exercise in the management of persons with multiple sclerosis

    PubMed Central

    2015-01-01

    For decades, persons with multiple sclerosis (MS) were counseled to avoid excessive physical activity and exercise because of concerns about worsening disease activity. Recent studies indicate that, not only can those with MS tolerate physical exercise, but that it is helpful in managing symptoms, preventing complications and comorbidities, and may possibly have neuroprotective actions. This article reviews previous studies on the effects of different exercise protocols in people with MS, and provides summaries of suggested exercise regimens that may be appropriate and beneficial for this patient population. PMID:25941539

  1. Exercising with multiple sclerosis: insights into meaning and motivation.

    PubMed

    Kasser, Susan

    2009-07-01

    The purpose of this phenomenological study was to explore the meaning of exercise in the lives of individuals with multiple sclerosis (MS) and describe the motivational basis that contributed to their exercise involvement. Twelve adults with MS (10 females, 2 males) between the ages of 32 and 56 years were interviewed. Analysis of transcribed interviews used an inductive approach. Three major themes emerged from thematic analysis of the qualitative data: exercising to maintain function and health, enhanced exercise self-efficacy, and feelings of hope and optimism. Findings were interpreted within the conceptual framework of self-efficacy and a disability-only social context.

  2. Examining the factor structure of the Multiple Sclerosis Impact Scale.

    PubMed

    Fitzgerald, Shawn M; Li, Jian; Rumrill, Phillip D; Merchant, William; Bishop, Malachy

    2014-01-01

    The purpose of this study was to investigate the factor structure of the Multiple Sclerosis Impact Scale (MSIS-29) to assess its suitability for modeling the impact of MS on a nation-wide sample of individuals from the United States. Investigators completed a Confirmatory Factor Analysis (CFA) to examine the two-factor structure proposed by Hobart et al. [17]. Although the original MSIS-29 factor structure did not fit the data exactly, the hypothesized two-factor model was partially supported in the current data. Implications for future instrument development and rehabilitation practice are discussed.

  3. Disability profile of multiple sclerosis in New Zealand.

    PubMed

    Alla, Sridhar; Pearson, John F; Taylor, Bruce V; Miller, David H; Clarke, Glynnis; Richardson, Ann; Willoughby, Ernie; Abernethy, David A; Sabel, Clive E; Mason, Deborah F

    2016-06-01

    New Zealand is a high risk region for multiple sclerosis (MS). The aim of this study was to investigate demographic, clinical and temporal factors associated with disability status in the New Zealand National Multiple Sclerosis Prevalence Study (NZNMSPS) cohort. Data were obtained from the 2006 NZNMSPS with MS diagnosis based on the 2005 McDonald criteria. Disability was assessed using the Expanded Disability Status Scale (EDSS). Disability profiles were generated using multiple linear regression analysis. A total of 2917 persons with MS was identified, of whom disability data were available for 2422 (75% females). The overall disability was EDSS 4.4±standard deviation 2.6. Higher disability was associated with older age, longer disease duration, older and younger ages of onset, spinal cord syndromes with motor involvement at onset, and a progressive onset type. Lower disability was associated with sensory symptoms at onset and a relapsing onset type. Overall, the factors studied explained about one-third of the variation in disability, and of this, about two-thirds was accounted for by age, age of onset and disease duration and one-third by the nature of first symptoms and type of disease onset (progressive or relapsing). Current age, age at onset and disease duration all had independent associations with disability and their effects also interacted in contributing to higher disability levels over the course of the disease.

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

    PubMed

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

    2016-06-01

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

  5. Specialized housing and transportation needs of adults with multiple sclerosis.

    PubMed

    Roessler, Richard T; Bishop, Malachy; Rumrill, Phillip D; Sheppard-Jones, Kathleen; Waletich, Brittany; Umeasiegbu, Veronica; Bishop, Lisa

    2013-01-01

    This study evaluated the specialized housing, transportation, and resource needs and barriers of adults with MS. Information pertaining to barriers and barrier removal strategies related to housing and transportation issues for adults with MS was gathered as part of a national survey of a randomly selected and representative sample of 5082 adults with MS, in cooperation with affiliate chapters of the National Multiple Sclerosis Society (NMSS) and the North American Research Committee on Multiple Sclerosis (NARCOMS). This article presents a qualitative analysis of participants' responses to questions addressing: (a) barriers to obtaining specialized housing and adapted transportation for individuals with MS, (b) factors contributing to maintenance of an independent lifestyle, and (c) information and referral resources pertinent to obtaining specialized housing and adapted transportation. The results provide the first assessment of these issues on a national scale and underscore the need for increased access to professional consultation, financial resources, and housing modification information and resources to enable persons with MS to obtain the specialized housing needed to maintain maximal independent lifestyles.

  6. [Pathogenic mechanisms of neuronal damage in multiple sclerosis].

    PubMed

    Flores-Alvarado, Luis Javier; Gabriel-Ortiz, Genaro; Pacheco-Mois, Fermín P; Bitzer-Quintero, K

    2015-06-01

    Multiple sclerosis is the most common cause of progressive neurological disability in young adults. This disease involves damage to the myelin sheath that normally insulates the electrical activity of nerve fibers. This leads to a wide range of symptoms as specific nerves become injured and lose their function. Epidemiological and experimental studies show that genetic alterations, antioxidant enzyme abnormalities and autoimmunity are risk factors for developing the disease. Recent evidence suggests that inflammation and oxidative stress within the central nervous system are major causes of ongoing tissue damage. Resident central nervous system cells and invading inflammatory cells release several reactive oxygen and nitrogen species which cause the histopathological features of multiple sclerosis: demyelization and axonal damage. The interplay between inflammatory and neurodegenerative processes results in an intermittent neurological disturbance followed by progressive accumulation of disability. Reductions in inflammation and oxidative stress status are important therapeutic strategies to slow or halt the disease processes. Therefore, several drugs are currently in trial in clinical practice to target this mechanism; particularly the use of supplements such as antioxidants and omega-3 polyunsaturated fatty acids, in order to improve the survival and quality of patients' lives.

  7. Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

  8. A Framework of Care in Multiple Sclerosis, Part 2

    PubMed Central

    Aliotta, Philip J.; Bainbridge, Jacquelyn; Bennett, Susan E.; Cutter, Gary; Fenton, Kaylan; Lublin, Fred; Northrop, Dorothy; Rintell, David; Walker, Bryan D.; Weigel, Megan; Zackowski, Kathleen; Jones, David E.

    2017-01-01

    Abstract The Consortium of Multiple Sclerosis Centers (CMSC) convened a Framework Taskforce composed of a multidisciplinary group of clinicians and researchers to examine and evaluate the current models of care in multiple sclerosis (MS). The methodology of this project included analysis of a needs assessment survey and an extensive literature review. The outcome of this work is a two-part continuing education series of articles. Part 1, published previously, covered the updated disease phenotypes of MS along with recommendations for the use of disease-modifying therapies. Part 2, presented herein, reviews the variety of symptoms and potential complications of MS. Mobility impairment, spasticity, pain, fatigue, bladder/bowel/sexual dysfunction, cognitive dysfunction, and neuropsychiatric issues are examined, and both pharmacologic and nonpharmacologic interventions are described. Because bladder and bowel symptoms substantially affect health-related quality of life, detailed information about elimination dysfunction is provided. In addition, a detailed discussion about mental health and cognitive dysfunction in people with MS is presented. Part 2 concludes with a focus on the role of rehabilitation in MS. The goal of this work is to facilitate the highest levels of independence or interdependence, function, and quality of life for people with MS. PMID:28243186

  9. Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

    SciTech Connect

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

    2010-07-23

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

  10. Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

    SciTech Connect

    Habib, A.C.; Zheng, W.; Haacke, E.M.; Webb, S.; Nichol, H.; /SLAC

    2012-07-17

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

  11. Thermal comfort requirements: A study of people with multiple sclerosis

    SciTech Connect

    Webb, L.H.; Parsons, K.C.; Hodder, S.G.

    1999-07-01

    Existing specifications for thermal comfort in built environments are coming under increased criticism for failing to consider the requirements of specific populations. People with physical disabilities are an example of one such population. This paper presents the results of a study on the thermal comfort requirements of 32 people with multiple sclerosis. Subjects were exposed to three conditions: 18.5 C, PMV = {minus}1.5, slightly cool to cool; 23 C, PMV = 0, neutral; 29 C, PMV = +1.5, slightly warm to warm. Results indicate that people with multiple sclerosis have a wide range of responses to the three experimental conditions. The actual percentage dissatisfied was much higher than predicted by Fange's (1970) predicted percentage dissatisfied. Their preferred environment is slightly warmer than 23 C, PMV = 0, neutral. A subgroup of the population prefers an environment that is slightly cooler than 23 C. Further work is needed to qualify if their preferred environments match that of PMV+1 and PMV{minus}1 and to identify if any of the factors such as age, duration of disability, and medication affect the actual mean vote.

  12. Surface markers on lymphocytes of multiple sclerosis patients.

    PubMed Central

    Nowak, J; Wajgt, A

    1975-01-01

    Peripheral blood lymphocytes of twenty-two multiple sclerosis (MS) patients and thirty-five healthy controls were examined for the presence of surface markers characteristic for B lymphocytes (surface immunoglobulin, receptor for C3 (EAC), reporter for Fc (EA) and the spontaneous rosette-forming capacity characteristic of T cells. The results obtained indicate that the number of B and T cells in MS is similar to controls, as evaluated by the presence of surface immunoglobulin and E rosette-forming capacity. However, a statistically significant reduction in the percentage of lymphocytes bearing C3 receptors has been found in MS patients. It might have resulted from a reduction in the lymphocyte population bearing C3 receptor but no surface immunoglobulin. The EA rosette test revealed the greatest difference between the groups. The difference indicated a reduction in the density of the receptor for 7S Fc on lymphocytes from MS patients. The results obtained are consistent with the hypothesis of an immune deficit in multiple sclerosis. PMID:1102165

  13. Biomarkers in multiple sclerosis: an update for 2014.

    PubMed

    Fernandez, Oscar; Martin, Roland; Rovira, Alex; Llufriu, Sara; Vidal-Jordana, Angela; Fernandez-Sanchez, Victoria E; Alvarez-Cermeno, José C; Izquierdo, Guillermo; Arroyo-Gonzalez, Rafael; Rodriguez-Antiguedad, Alfredo; Casanova-Estruch, Bonaventura; Montalban, Xavier

    2014-06-16

    Multiple sclerosis is a chronic, demyelinating and inflammatory disease of the central nervous system that mainly affects young adults. It is characterised by processes involving inflammation, demyelination and axonal destruction, and as a result the pathogenic aspects and response to treatment of the disease vary widely. It is therefore difficult to establish a prognosis for these patients or to determine the effectiveness of the different drugs that are employed. Current clinical research into the development of new biomarkers has advanced a great deal in recent years, especially in the early stages of the disease. Yet, it is essential to further our knowledge about novel markers of the disease, and not only in the more advanced stages, so as to be able to stop disability from progressing and to establish new therapy regimens in these patients. This review presents an update on the information available about the biomarkers that are currently validated and used in multiple sclerosis, together with the possible candidates for utilisation in routine clinical practice.

  14. Selecting Rehabilitation Outcome Measures for People with Multiple Sclerosis

    PubMed Central

    Potter, Kirsten; Allen, Diane D.; Bennett, Susan E.; Brandfass, Kathi G.; Widener, Gail L.; Yorke, Amy M.

    2015-01-01

    Despite the well-known benefits of using standardized outcome measures (OMs) in clinical practice, a variety of barriers interfere with their use. In particular, rehabilitation therapists lack sufficient knowledge in selecting appropriate OMs. The challenge is compounded when working with people with multiple sclerosis (MS) owing to heterogeneity of the patient population and symptom variability in individual patients. To help overcome these barriers, the American Physical Therapy Association appointed the Multiple Sclerosis Outcome Measures Task Force to review and make evidence-based recommendations for OM use in clinical practice, education, and research specific to people with MS. Sixty-three OMs were reviewed based on their clinical utility, psychometric properties, and a consensus evaluation of the appropriateness of use for people with MS. We sought to illustrate use of the recommendations for two cases. The first case involves a 43-year-old man with new-onset problems after an exacerbation. The second case pertains to an outpatient clinic interested in assessing the effectiveness of their MS rehabilitation program. For each case, clinicians identified areas that were important to assess and various factors deemed important for OM selection. Criteria were established and used to assist in OM selection. In both cases, the described processes narrowed the selection of OMs and assisted with choosing the most appropriate ones. The recommendations, in addition to the processes described in these two cases, can be used by clinicians in any setting working with patients with MS across the disability spectrum. PMID:26300704

  15. Relapsing-Remitting Multiple Sclerosis Patients' Experience with Natalizumab

    PubMed Central

    Miller, Colleen E.; Jezewski, Mary Ann

    2012-01-01

    This phenomenological investigation was undertaken to gain a better understanding of multiple sclerosis (MS) patients' experience with natalizumab (Tysabri; Biogen Idec Inc, Cambridge, MA) treatment and its impact on their quality of life (QOL). Twenty MS patients who were receiving natalizumab treatment were recruited by the physicians, nurse practitioners, nurses, and social worker of the William C. Baird Multiple Sclerosis Center in Buffalo, New York, between March 2009 and November 2009. Patients were invited to participate if they had relapsing-remitting MS, had received at least six treatments of natalizumab, and could articulate their experience. An interviewer obtained informed consent, gathered basic demographic information, and then tape-recorded the participants' accounts of their experience with natalizumab. The audio-recorded interviews were transcribed and de-identified before being submitted to the investigators for analysis. The Atlas.ti qualitative data analysis program (Scolari, Berlin, Germany) was used to manage the data. Patients found natalizumab easy to tolerate and effective; moreover, they described improvement in their QOL. Patients must weigh the benefits of control of their MS against the increased risk of developing progressive multifocal leukoencephalopathy with natalizumab treatment. Information from this study will be used to educate professionals involved in MS patient care as well as patients and families considering treatment with natalizumab. PMID:24453731

  16. Treatment of Multiple Sclerosis With Chinese Scalp Acupuncture

    PubMed Central

    Cheng, Wei; Liu, Ming; Li, He; Lü, Xiaolin; Sun, Zhongren

    2013-01-01

    Chinese scalp acupuncture is a contemporary acupuncture technique with just 40 years of history. It integrates traditional Chinese needling methods with Western medical knowledge of the cerebral cortex and has been proven to be a very effective technique for treating multiple sclerosis (MS) and other central nervous system disorders. A 65-year-old male patient who had had MS for 20 years was treated with Chinese scalp acupuncture. The motor area, sensory area, foot motor and sensory area, balance area, hearing and dizziness area, and tremor area were stimulated once a week for 10 weeks, then once a month for six sessions. After the 16 treatments, the patient showed remarkable improvements. He was able to stand and walk without any problems. The numbness and tingling in his limbs did not bother him anymore. He had more energy and had not experienced incontinence of urine or dizziness after the first treatment. He was able to return to work full time. At this writing, the patient has been in remission for 26 months. This case demonstrates that Chinese scalp acupuncture can be a very effective treatment for patients with MS. Chinese scalp acupuncture holds the potential to expand treatment options for MS in both conventional and complementary or integrative therapies. It can not only relieve symptoms, increase the patient's quality of life, and slow and reverse the progression of physical disability but also reduce the number of relapses and help patients with multiple sclerosis to remain in remission. PMID:24278838

  17. ADC evaluation of the corticospinal tract in multiple sclerosis.

    PubMed

    Inal, Mikail; Unal, Birsen; Kala, Ibrahim; Turkel, Yakup; Bilgili, Yasemin Karadeniz

    2015-06-01

    Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MR imaging (DWI) provide important information about tissues. The goal of this study was to evaluate the ADC values in the corticospinal tract regions in multiple sclerosis (MS). The ADC values of 42 patients with multiple sclerosis and 46 healthy people were measured. The ADC values in the corticospinal tract at the capsula interna posterior crus from six points and mesencephalon from three points bilaterally in MS patients were compared with those of controls. An ANOVA post hoc test was used to analyse the differences in mean ADC values between the MS and control groups. The mean ADC values of the right (p = 0.008) and left internal capsules (p = 0.000) and right (p = 0.002) and left mesencephalons (p = 0.044) in MS patients were significantly lower than in the control group. There was no significant difference between the right and left side ADC values in MS (p = 0.313 vs. p = 0.223) and control groups (p = 0.756 vs. p = 0.105), respectively. The mean ADC values of the corticospinal tract in MS patients were significantly lower than in the control group. This decreased diffusion may be the result of cellular infiltration due to inflammation, cytotoxic oedema, demyelination or remyelination processes.

  18. Myasthenia Gravis Development and Crisis Subsequent to Multiple Sclerosis

    PubMed Central

    Gharagozli, Kurosh; Shojaei, Maziar; Harandi, Ali Amini; Akbari, Nayyereh; Ilkhani, Manouchehr

    2011-01-01

    During the last decade, sporadic combination of multiple sclerosis (MS) and myasthenia gravis (MG) has been reported repeatedly. Although these are anecdotal, they are important enough to raise concerns about co-occurrence of MG and MS. Here, we present a case of an MS patient who developed an MG crisis. She had received interferon for relapsing remitting MS. Interestingly, she developed an MG crisis 4 years after the diagnosis of MS. MS and MG have relatively the same distribution for age, corresponding to the younger peak of the bimodal age distribution in MG. They also share some HLA typing characteristics. Furthermore, some evidences support the role of systemic immune dysregulation due to a genetic susceptibility that is common to these two diseases. The association may be underdiagnosed because of the possible overlap of symptoms especially bulbar manifestations in which either MG or MS can mimic each other, leading to underestimating incidence of the combination. The evidence warrants physicians, especially neurologists, to always consider the possibility of the other disease when encountering any patients either with MS or MG. Anecdotal and sporadic reports of combination of multiple sclerosis (MS) and myasthenia gravis (MG) have been raised concerns about co-occurrence of them. PMID:21629802

  19. Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

    PubMed

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies.

  20. Epidemiology and genetic aspects of multiple sclerosis in India.

    PubMed

    Bhatia, Rohit; Bali, Prerna; Chaudhari, Rima M

    2015-09-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a complex pathophysiology. Considered a rare disease in India in the past, studies over time suggest an increase in subjects with MS in India, although the observations are limited by the lack of formally conducted epidemiological studies and the absence of a nationwide registry. The current World Health Organization (WHO) Multiple Sclerosis International Federation (MSIF) "Atlas of MS" 2013 estimates a prevalence rate of 5-20 per 100,000, which also seems an underestimate. Although there have been reports of phenotypic differences between MS in Indians and the Western counterparts, recent studies report a reasonable similarity in disease types and characteristics. A few studies on the genetics of MS have been reported, including human leukocyte antigen (HLA) associations and non-major histopathology complex (MHC) disease loci. The current review discusses the pivotal studies of the past, newer observations on MS from India, and the need for a national registry.

  1. Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

    PubMed Central

    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

    2015-01-01

    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

  2. Quantifying gait impairment in multiple sclerosis using GAITRite technology.

    PubMed

    Sosnoff, Jacob J; Weikert, Madeline; Dlugonski, Deirdre; Smith, Douglas C; Motl, Robert W

    2011-05-01

    This pilot study investigated the validity of the functional ambulatory profile (FAP) score from the GAITRite electronic pathway in persons with multiple sclerosis (PwMS) who had onset of walking impairment. Thirteen PwMS who had Expanded Disability Status Scale (EDSS) scores of 4.0-6.0 performed four trials on GAITRite™ pathway, and completed a multidimensional walking assessment including performance tests (timed 25 foot walk; T25FW, timed up and go; TUG), self reports of walking ability (Multiple Sclerosis Walking Scale-12; MSWS-12) and function (Late Life Function and Disability Inventory; LL-FDI), and free-living walking behavior (accelerometry). The FAP score correlated strongly with neurological disability (EDSS, ρ=-0.81), walking performance (T25FW, ρ=-0.82; TUG, ρ=-0.88) and self-reported walking function (LL-FDI, ρ=0.81), and moderately with self-reported walking impairment (MSWS-12, ρ=0.49) and free-living walking behavior (accelerometry, ρ=0.52). This suggests that the FAP score is a valid marker of gait impairment in PwMS who have onset of walking impairment.

  3. [Disease-modifying drugs in pediatric patients with multiple sclerosis].

    PubMed

    Bykova, O V; Nankina, I A; Drozdova, I M; Kvasova, O V; Batysheva, T T; Boiko, A N

    2016-01-01

    The vast majority of therapies are being evaluated and introduced for the treatment of adult multiple sclerosis (MS). A role of these drugs in the management of pediatric MS has yet to be defined both in Russia and in the whole world. Despite the fact that today the study of new drugs in the pediatric population have included in routine practices of the big pharmaceutical agencies, such as FDA and EMA, recommendations for the treatment of pediatric patients with MS are based not so much on a long period of systematic clinical research, but on professional consensus of international expert associations, in particular, the International pediatric multiple sclerosis study group (IPMSSG). The clinical trials include the small number of patients which is not comparable to those conducted in adults. Therefore, there is a need for study designs for assessment of efficacy and safety of the drugs for MS treatment in children and adolescents. The authors present the IPMSSG concept on the treatment of pediatric MS taking into account peculiarities of the Russian legislation and experience of national experts.

  4. Multiple sclerosis: Therapeutic applications of advancing drug delivery systems.

    PubMed

    Dolati, Sanam; Babaloo, Zohreh; Jadidi-Niaragh, Farhad; Ayromlou, Hormoz; Sadreddini, Sanam; Yousefi, Mehdi

    2017-02-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, which is accompanying with demyelination, neurodegeneration and sensibility to oxidative stress. In MS, auto-reactive lymphocytes cross the blood-brain barrier (BBB) and reside in the perivenous demyelinating lesions which create various distinct inflammatory demyelinated plaques situated predominantly in the white matter. The current MS-related therapeutic approaches can be classified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs suppress circulating immune cells, inhibit passing the BBB and decrease the inflammatory responses. Recent advances have remarkably delayed disease development and improved the quality of life for numerous patients. In spite of major improvements in therapeutic options, there are some limitations regarding the routes of administration and the necessity for repeated and long-term dosing in which cause to systemic disadvantageous consequences and patient non-compliance. Nanotechnology presents promising approaches to improve autoimmune disease treatment with the capability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we emphasis on nanomedicine-based drug delivery approaches of biological immunomodulatory mediators for the treatment of multiple sclerosis. This comprehensive review details the most successful drugs in MS therapy and also focuses on conceptions and clinical potential of novel nanomedicine attitudes for inducing immunosuppression and immunological tolerance in MS to modulate abnormal and pathologic immune responses.

  5. Profile of the Brazilian scientific production in multiple sclerosis.

    PubMed

    Araujo, C R; Moreira, M A; Lana-Peixoto, M A

    2006-09-01

    This paper analyzes the profile of the Brazilian output in the field of multiple sclerosis from 1981 to 2004. The search was conducted through the MEDLINE and LILACS databases, selecting papers in which the term "multiple sclerosis" was defined as the main topic and "Brazil" or "Brasil" as others. The data were analyzed regarding the themes, the state in Brazil and institution where the papers were produced, the journals where the papers were published, journal's impact factor, and language. The search disclosed 141 documents (91 from MEDLINE and LILACS, and 50 from LILACS only) published in 44 different journals (23 of them MEDLINE-indexed). A total of 111 documents were produced by 17 public universities, 29 by 3 private medical schools and 1 by a non-governmental organization. There were 65 original contributions, 37 case reports, 20 reviews, 6 PhD dissertations, 5 guidelines, 2 validation studies, 2 clinical trials, 2 chapters in textbooks, 1 Master of Science thesis, and 1 patient education handout. The journal impact factor ranged from 0.0217 to 6.039 (median 3.03). Of 91 papers from MEDLINE, 65 were published by Arquivos de Neuro-Psiquiatria. More than 90% of the papers were written in Portuguese. São Paulo was the most productive state in the country, followed by Rio de Janeiro, Minas Gerais and Paraná. Eighty-two percent of the Brazilian output came from the Southeastern region.

  6. Treatment of multiple sclerosis with chinese scalp acupuncture.

    PubMed

    Hao, Jason Jishun; Cheng, Wei; Liu, Ming; Li, He; Lü, Xiaolin; Sun, Zhongren

    2013-01-01

    Chinese scalp acupuncture is a contemporary acupuncture technique with just 40 years of history. It integrates traditional Chinese needling methods with Western medical knowledge of the cerebral cortex and has been proven to be a very effective technique for treating multiple sclerosis (MS) and other central nervous system disorders. A 65-year-old male patient who had had MS for 20 years was treated with Chinese scalp acupuncture. The motor area, sensory area, foot motor and sensory area, balance area, hearing and dizziness area, and tremor area were stimulated once a week for 10 weeks, then once a month for six sessions. After the 16 treatments, the patient showed remarkable improvements. He was able to stand and walk without any problems. The numbness and tingling in his limbs did not bother him anymore. He had more energy and had not experienced incontinence of urine or dizziness after the first treatment. He was able to return to work full time. At this writing, the patient has been in remission for 26 months. This case demonstrates that Chinese scalp acupuncture can be a very effective treatment for patients with MS. Chinese scalp acupuncture holds the potential to expand treatment options for MS in both conventional and complementary or integrative therapies. It can not only relieve symptoms, increase the patient's quality of life, and slow and reverse the progression of physical disability but also reduce the number of relapses and help patients with multiple sclerosis to remain in remission.

  7. Multiple sclerosis: basic knowledge and new insights in perioperative management.

    PubMed

    Makris, Alexandros; Piperopoulos, Alexandros; Karmaniolou, Iosifina

    2014-04-01

    Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system affecting young adults that may lead to significant disability. The clinical course varies among the types of the disease as well as among individuals. Herein we provide a brief review of the recent data concerning the clinical presentation, diagnosis, causes, and pathogenesis of MS as well as medication used, followed by the anesthetic considerations of patients diagnosed with the disease. To accomplish this, we conducted a systematic PubMed literature search for articles, using the terms multiple sclerosis, anesthesia, general, regional, perioperative, and preoperative, and we then manually reviewed the references from each pertinent article. Because randomized controlled trials on the field are rare, most information is derived by case reports and case series. We concluded that the disease itself as well as the treatment modalities may have several implications in the conduct of anesthesia and perioperative management of MS patients. General and regional anesthetic techniques have been successfully used. With thorough preoperative evaluation and in depth knowledge of the disease and its complications, the MS patients can be managed safely.

  8. Cognitive status in patients with multiple sclerosis in Lanzarote

    PubMed Central

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

    2016-01-01

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

  9. Matching and accepting assistive technology in multiple sclerosis: A focus group study with people with multiple sclerosis, carers and occupational therapists.

    PubMed

    Squires, Luke A; Williams, Nefyn; Morrison, Val L

    2016-11-15

    To explore experiences and perceptions of assistive technology, 14 people with multiple sclerosis, 5 carers and 4 occupational therapists participated in focus groups. Transcripts were analysed thematically drawing from illness self-regulation theory. Identified themes are as follows: critical multiple sclerosis events (developing symptoms/disability, delayed diagnosis and coping, public reaction and multiple sclerosis progression to assistive technology), matching assistive technology for continued use (acceptance of multiple sclerosis and assistive technology, realistic expectations, occupational therapist responsiveness, timing is crucial and carers and others) and impact of assistive technology (promoting or losing independence, stigma and embarrassment and redefining the carer). Acceptance and communication among those involved ensures assistive technology matches needs and maximises health and psychosocial outcomes.

  10. Multiple sclerosis-associated virus-related pol sequences found both in multiple sclerosis and healthy donors are more frequently expressed in multiple sclerosis patients.

    PubMed

    Nowak, Jerzy; Januszkiewicz, Danuta; Pernak, Monika; Liweń, Izabela; Zawada, Mariola; Rembowska, Jolanta; Nowicka, Karina; Lewandowski, Krzysztof; Hertmanowska, Hanna; Wender, Mieczyslaw

    2003-02-01

    In the etiopathogenesis of multiple sclerosis (MS), both genetic and environmental factors play an important role. Among environmental factors, viral infections are most likely connected with the etiology of MS. There are many evidence suggesting possible involvement of retroviruses in the development of autoimmune diseases including MS. Multiple sclerosis-associated retrovirus (MSRV) seems to be the important candidate for viral etiology of MS. The aim of the study was to analyze MSRV pol sequences in patients with MS. As control, groups of myasthenia gravis, Parkinson's disease, and migraine patients, and healthy individuals have been studied. The MSRV pol sequences have been analyzed in RNA isolated from the serum and in DNA and RNA of peripheral blood lymphocytes from untreated MS patients and control groups. The MSRV pol sequences have been detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and PCR technique, using specific oligonucleotide primers. In the serum RNA (cDNA), MSRV pol sequences have been identified in 31/32 MS patients. MSRV pol sequences were detected in serum cDNA of 9/17 myasthenia gravis patients, 7/16 Parkinson's disease patients, 10/21 migraine patients, and 13/27 healthy individuals. MSRV pol sequences were observed also in RNA from lymphocytes of all MS patients, 12/17 myasthenia gravis patients, 9/16 Parkinson's disease patients, 14/21 migraine patients, and 18/27 healthy donors. In the DNA from peripheral blood lymphocytes of all studied patients and healthy individuals, MSRV pol sequences have been found. The observed pattern of fiber-fluorescence in situ hybridization (FISH) signals suggests the presence of multiple copies of MSRV pol sequences, most likely tandemly dispersed in the genome. It can be concluded that MSRV pol sequences are endogenous, widespread in lymphocytes DNA, and transcribed into RNA of MS patients as well as of other studied patients and healthy individuals. However, more frequent expression of

  11. Review of methodological issues of clinical trials in multiple sclerosis.

    PubMed

    Montalban, Xavier

    2011-12-01

    There are currently six approved disease-modifying therapies available to the physician for the treatment of multiple sclerosis. Their efficacy on clinical and radiological parameters has been demonstrated in Phase III pivotal clinical trials over the past two decades. Perceptions of the relative potency of these treatments have been driven principally by the response measured relative to a placebo group. However, efficacy comparisons between trials is of limited value because of differences in study methodology, in characteristics of the patient populations included, in the behaviour of the placebo group during the trial and in the time at which the trial was conducted. Moreover, and most importantly, the assumption that the efficacy observed in clinical trial settings is the same as that achievable in everyday clinical practice is inevitably flawed. Impressions of the relative efficacy of two treatments may differ dramatically depending on whether absolute or relative differences with respect to placebo are compared. Randomised direct comparative trials are therefore the only objective way to evaluate the relative efficacy of two therapies. It is clear that between-treatment differences are difficult to quantify in short-term studies and require large numbers of patients. Long-term outcome is increasingly important to monitor in spite of the inherent methodological limitations in order to establish the safety profile of a potentially lifelong treatment. New disease-modifying treatments for multiple sclerosis will soon be available. Although these are eagerly awaited, their risk-benefit profile, and their place in therapy, will only be adequately understood once real-life and long-term use has been documented as well as it has been for current treatments. Over the last two decades, considerable advances have been made in the methodology of clinical trials in multiple sclerosis. Consensual standardised protocols have been designed and validated for Phase II and

  12. Quality of life in multiple sclerosis in France, Germany, and the United Kingdom

    PubMed Central

    Murphy, N; Confavreux, C; Haas, J; Konig, N; Roullet, E; Sailer, M; Swash, M; Young, C; J-L, M.

    1998-01-01

    OBJECTIVE—To assess the quality of life (QoL) of patients with multiple sclerosis in France, Germany, and the United Kingdom with a cross sectional study.
METHODS—Patients were classified into three severity groups according to the expanded disability severity scale (EDSS); stage I, II, and III, corresponding to mild (EDSS 1.0-3.5), moderate (EDSS 4.0-6.0), or severe (EDSS 6.5-8.0) multiple sclerosis respectively. Ninety patients with multiple sclerosis and 30 control patients without multiple sclerosis were recruited in each country. Control patients were matched to the patients with multiple sclerosis according to age and sex. Quality of life was assessed using the functional status questionnaire (FSQ).
RESULTS—The aspects of QoL that were mostly affected in the three countries under study were physical function and general wellbeing. Social role function decreased with increased severity of disease in France and in particular in Germany. Multiple sclerosis did not seem to have an impact on psychological function. The QoL of control patients was systematically higher than that of patients with multiple sclerosis.
CONCLUSIONS—Use of such a generic scale showed that progression of multiple sclerosis is accompanied by a decrease in QoL and suggested that this could be a relevant measurement in assessing the effect of treatment and progression of disease. Variation between countries, however, may be important.

 PMID:9771766

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  15. Impact of psychotherapy on insomnia symptoms in patients with depression and multiple sclerosis.

    PubMed

    Baron, Kelly Glazer; Corden, Marya; Jin, Ling; Mohr, David C

    2011-04-01

    The purpose of the study was to evaluate the prevalence of insomnia in multiple sclerosis patients with comorbid depression, associations between psychological symptoms, multiple sclerosis symptoms and insomnia, and to test effects of a 16-week protocol-based psychotherapy intervention for depression on insomnia symptoms. Participants with multiple sclerosis and depression (n = 127) were randomized to telephone administered cognitive behavioral therapy and telephone administered supportive emotion-focused therapy. Multiple sclerosis functional limitation was measured at baseline. Depression, insomnia, anxiety and quality of life were evaluated at pre treatment, mid treatment (8 weeks), and post treatment (16 weeks). Prevalence of insomnia ≥3 times per week was 78% at pre treatment and 43% at post treatment. Insomnia at baseline was associated with depression, multiple sclerosis related mood symptoms and anxiety. Middle of the night awakenings were associated with swallowing and speech problems. Improvements in insomnia were associated with improvement in depression and anxiety. Participants with residual insomnia were more likely to have major depressive disorder, greater multiple sclerosis severity, elevated anxiety and lower mental components of quality of life. Results demonstrate rates of insomnia in patients with comorbid multiple sclerosis and depression are higher than those reported in the general multiple sclerosis population and additional insomnia treatment is indicated beyond the treatment of comorbid psychological disorders.

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

    ERIC Educational Resources Information Center

    Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

    2010-01-01

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

  17. [Betahistine in the treatment of vestibular and coordination disturbances in multiple sclerosis].

    PubMed

    Popova, N F; Chugunova, M A; Kunel'skaia, N L; Shagaev, A S; Boĭko, A N; Gusev, E I

    2011-01-01

    We present the results of the efficacy trial of betahistine (Vestibo) based on the complex clinical/instrumental examination (stabilometric, vestibulometric) in 40 patients with multiple sclerosis of different severity of vestibular and coordination dysfunction. We demonstrated the clinical efficacy and safety of using this drug as one of the areas of symptomatic therapy in treatment vestibular and coordination disturbances in multiple sclerosis.

  18. How fatigue influences exercise participation in men with multiple sclerosis.

    PubMed

    Smith, Catherine M; Fitzgerald, H Jane M; Whitehead, Lisa

    2015-02-01

    Researchers have suggested that men with multiple sclerosis (MS) experience lower self-efficacy than women with MS and have linked women's self-efficacy with a sense of perceived control over symptoms and activities. Self-efficacy—the belief in one's own ability to achieve an outcome—has also been linked to engagement in healthy behaviors such as exercise. We sampled men with MS to better understand how MS-related fatigue influences exercise participation. Guided by the interpretive description method, we interviewed 18 men about their fatigue and exercise experiences. One overarching theme and three subthemes were developed through multiple readings, author comparisons, and participant reflections. The men described a process of goal readjustment with regard to exercise that helped them stay engaged in meaningful physical activity despite fatigue. Health care professionals might consider introducing goal readjustment strategies to help men with MS-related fatigue retain perceived control over exercise engagement and achieve greater self-efficacy.

  19. Immunomodulation in the treatment of multiple sclerosis and amyotrophic lateral sclerosis: a model for autoimmune disorders.

    PubMed Central

    Alonso, K.; Medenica, R.

    1995-01-01

    Seventeen multiple sclerosis (MS) patients progressing under conventional therapy (average treatment duration: 3 years) with performance status 3-4 (mean Disability Status Scale [DSS]: 82) who demonstrated circulating lymphokine inhibitor factors were selected for a monthly immunomodulatory protocol using plasmapheresis, followed by 3 days of human intravenous immunoglobulin, and low-dose methylprednisolone, cyclophosphamide, interferon-a, and interferon-g, as well as octreide. Twelve of the 17 patients presented with visual problems, 12 had lower extremity weakness or paraperesis/paralysis, and 6 had bladder/bowel dysfunction. Following 4 months of therapy, 4 recovered completely, 7 showed loss of paralysis/paraparesis, and 5 had improvement in lower extremity weakness. One patient progressed (mean DSS: 51). Lymphokine inhibitor factors declined in 14 patients with concomitant normalization of circulating immune complexes. Eight patients experienced rises in CD4 levels with stabilization of CD8 levels. Hypotension and hypocalcemia were observed during plasmapheresis. Twelve patients with amyotrophic lateral sclerosis with poor performance status also were studied. Four of the 12 improved with the regimen, whereas six stabilized disease. Similar alterations in laboratory parameters were described. The rationale for this approach is discussed. PMID:7674346

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

    PubMed

    Weisfeld-Adams, James D; Katz Sand, Ilana B; Honce, Justin M; Lublin, Fred D

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric Analysis Software: From Idea to Application.

    PubMed

    Bambo, Maria Pilar; Garcia-Martin, Elena; Perez-Olivan, Susana; Larrosa-Povés, José Manuel; Polo-Llorens, Vicente; Gonzalez-De la Rosa, Manuel

    2016-01-01

    Neuro-ophthalmologists typically observe a temporal pallor of the optic disc in patients with multiple sclerosis. Here, we describe the emergence of an idea to quantify these optic disc color changes in multiple sclerosis patients. We recruited 12 multiple sclerosis patients with previous optic neuritis attack and obtained photographs of their optic discs. The Laguna ONhE, a new colorimetric software using hemoglobin as the reference pigment in the papilla, was used for the analysis. The papilla of these multiple sclerosis patients showed greater pallor, especially in the temporal sector. The software detected the pallor and assigned hemoglobin percentages below normal reference values. Measurements of optic disc hemoglobin levels obtained with the Laguna ONhE software program had good ability to detect optic atrophy and, consequently, axonal loss in multiple sclerosis patients. This new technology is easy to implement in routine clinical practice.

  3. The Latest Innovations in the Drug Pipeline for Multiple Sclerosis

    PubMed Central

    Radick, Lea; Mehr, Stanton R.

    2015-01-01

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

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

    DTIC Science & Technology

    2014-09-01

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

  5. Long-term management of patients with multiple sclerosis.

    PubMed

    Weightman, Cherie

    2006-07-01

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

  6. Mind-Body Medicine for Multiple Sclerosis: A Systematic Review

    PubMed Central

    Senders, Angela; Wahbeh, Helané; Spain, Rebecca; Shinto, Lynne

    2012-01-01

    Background. Mind-body therapies are used to manage physical and psychological symptoms in many chronic health conditions. Objective. To assess the published evidence for using mind-body techniques for symptom management of multiple sclerosis. Methods. MEDLINE, PsycINFO, and Cochrane Clinical Trials Register were searched from inception to March 24, 2012. Eleven mind-body studies were reviewed (meditation, yoga, biofeedback, hypnosis, relaxation, and imagery). Results. Four high quality trials (yoga, mindfulness, relaxation, and biofeedback) were found helpful for a variety of MS symptoms. Conclusions. The evidence for mind-body medicine in MS is limited, yet mind-body therapies are relatively safe and may provide a nonpharmacological benefit for MS symptoms. PMID:23227313

  7. Pediatric Multiple Sclerosis: Current Concepts and Consensus Definitions

    PubMed Central

    Pena, Joaquin A.; Lotze, Timothy E.

    2013-01-01

    Multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central nervous system (CNS) commonly diagnosed in adults, is being recognized increasingly in children. An estimated 1.7%–5.6% of all patients with MS have clinical symptoms before reaching the age of 18 years. In comparison with adults, the diagnosis of MS in children can be more difficult, being dismissed or misdiagnosed as other clinical disorders. Although adults and children share basic aspects of the disorder, children have distinctive clinical features, neuroimaging, laboratory, and courses of the disease. The 2010 McDonald criteria have simplified the requirements for establishing the diagnosis of MS and have been proposed to be applicable for the diagnosis of pediatric MS, mainly in children 12 years and older. This paper describes the distinctive features of common pediatric demyelinating disorders, including MS, and summarizes the most recent advances based on the available literature. PMID:24294520

  8. Association between pathological and MRI findings in multiple sclerosis.

    PubMed

    Filippi, Massimo; Rocca, Maria A; Barkhof, Frederik; Brück, Wolfgang; Chen, Jacqueline T; Comi, Giancarlo; DeLuca, Gabriele; De Stefano, Nicola; Erickson, Bradley J; Evangelou, Nikos; Fazekas, Franz; Geurts, Jeroen J G; Lucchinetti, Claudia; Miller, David H; Pelletier, Daniel; Popescu, Bogdan F Gh; Lassmann, Hans

    2012-04-01

    The identification of pathological processes that could be targeted by therapeutic interventions is a major goal of research into multiple sclerosis (MS). Pathological assessment is the gold standard for such identification, but has intrinsic limitations owing to the limited availability of autopsy and biopsy tissue. MRI has gained a leading role in the assessment of MS because it allows doctors to obtain an ante mortem picture of the degree of CNS involvement. A number of correlative pathological and MRI studies have helped to define in vivo the pathological substrates of MS in focal lesions and normal-appearing white matter, not only in the brain, but also in the spinal cord. These studies have resulted in the identification of aspects of pathophysiology that were previously neglected, including grey matter involvement and vascular pathology. Despite these important achievements, numerous open questions still need to be addressed to resolve controversies about how the pathology of MS results in fixed neurological disability.

  9. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration.

    PubMed

    Hauser, Stephen L; Oksenberg, Jorge R

    2006-10-05

    The autoimmune model of multiple sclerosis (MS) pathogenesis provided for many years a useful but incomplete conceptual framework for understanding the complex array of factors that lead to the loss of immune homeostasis, myelin and axonal injury, and progressive neurological symptoms. The availability of novel tools in molecular neurogenetics and increasingly sophisticated neuroimaging technologies, together with the revitalization of MS neuropathology, has created a new paradigm for the multidisciplinary study of this disease. This is reflected by the growing resolution of the MS genomic map, discovery of delicate inflammatory networks that are perturbed in MS, identification of mediators of demyelination, and recognition that cumulative axonal loss and neuronal injury are the histological correlates of neurological disability. Together, these advances have set the stage for the development of therapeutic approaches designed to target the demyelinating and neurodegenerative components of the disease and promote repair.

  10. Defective autologous mixed lymphocyte reactivity in multiple sclerosis.

    PubMed Central

    Hirsch, R L

    1986-01-01

    T cells from patients with multiple sclerosis (MS) and normal controls were assessed for their ability to respond in the autologous mixed lymphocyte reaction (AMLR). Cells from stable MS patients demonstrated a significant defect in their proliferative response to non-T cells in comparison to normal controls. Despite the defective AMLR response, T cells from MS patients reacted as well as T cells from normal controls to allogeneic stimuli. Furthermore, MS non-T-cells were fully capable of stimulating allogeneic MLR responses by normal and MS T cells. Since the T4+ cell is the major subpopulation which proliferates in the AMLR, these studies suggest a functional defect in a subpopulation of T4+ cells in MS patients. Since the AMLR may represent an important mechanism by which immune responses are regulated, a defect in the ability of MS T cells to respond to autologous cells could account for several of the autoimmune features of the disease. PMID:2942317

  11. Gender distributions in parents and children concordant for multiple sclerosis.

    PubMed

    Roth, M P; Clayton, J; Patois, E; Alperovitch, A

    1994-01-01

    The family histories of 7,802 multiple sclerosis (MS) patients were reviewed with respect to the familial pattern of the disease and the gender of the affected individuals. These patients joined an epidemiological study following a call for patients on French television and answered a questionnaire with the help of their physician. 170 had an affected parent, providing 72 mother-daughter pairs, 48 mother-son pairs, 37 father-daughter pairs, and 13 father-son pairs. From these data, the maximum likelihood estimate of the female to male ratio is 2.06, which is not different from what could be expected given the ratio of 2:1 usually found among patients. The apparent deficit of father-son concordant pairs probably simply reflects the well-known preponderance of the disease among females.

  12. Current and emerging therapies in multiple sclerosis: a systematic review

    PubMed Central

    Graves, Donna; Frohman, Teresa C.; Flores, Angela Bates; Hardeman, Paula; Logan, Diana; Orchard, Megan; Greenberg, Benjamin; Frohman, Elliot M.

    2012-01-01

    Multiple sclerosis (MS) is a potentially disabling chronic autoimmune neurological disease that mainly affects young adults. Our understanding of the pathophysiology of MS has significantly advanced in the past quarter of a century. This has led to the development of many disease-modifying therapies (DMTs) that prevent exacerbations and new lesions in patients with relapsing remitting MS (RRMS). So far there is no drug available that can completely halt the neurodegenerative changes associated with the disease. It is the purpose of this review to provide concise information regarding mechanism of action, indications, side effects and safety of Food and Drug Administration and European Medicines Agency approved agents for MS, emerging therapies, and drugs that can be considered for off-label use in MS. PMID:22783370

  13. Heat Shock Protein 70: Roles in Multiple Sclerosis

    PubMed Central

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

    2012-01-01

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

  14. An additional monogenic disorder that masquerades as multiple sclerosis

    SciTech Connect

    Vahedi, K.; Tournier-Lasserve, E.; Vahedi, K.

    1996-11-11

    In their comprehensive differential diagnosis of monogenic diseases that can mimic multiple sclerosis, Natowicz and Bejjani did not include a newly recognized monogenic disorder known under the acronym of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy); this disorder can mimic MS clinically and radiologically to a remarkable extent. The underlying histopathological lesion of CADASIL is a non-atherosclerotic, non-amyloid arteriopathy affecting mainly the penetrating medullary arteries to the subcortical white matter and basal ganglia. Electron microscopy shows an abnormal deposit of granular osmiophilic material in the arterial wall. These arterial changes are observed in various tissues even though clinical manifestations seem to be restricted to the central nervous system. The CADASIL gene was mapped recently to chromosome 19 and gene identification is ongoing. 6 refs., 1 fig.

  15. Gray Matter Is Targeted in First-Attack Multiple Sclerosis

    SciTech Connect

    Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao; Schepmoes, Athena A.; Xie, Fang; Bergquist, Jonas P.; Vecsei, Lazlo'; Zadori, Denes; Camp, David G.; Holland, Bart K.; Smith, Richard D.; Coyle, Patricia K.

    2013-09-10

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

  16. Alterations of the human gut microbiome in multiple sclerosis

    PubMed Central

    Jangi, Sushrut; Gandhi, Roopali; Cox, Laura M.; Li, Ning; von Glehn, Felipe; Yan, Raymond; Patel, Bonny; Mazzola, Maria Antonietta; Liu, Shirong; Glanz, Bonnie L.; Cook, Sandra; Tankou, Stephanie; Stuart, Fiona; Melo, Kirsy; Nejad, Parham; Smith, Kathleen; Topçuolu, Begüm D.; Holden, James; Kivisäkk, Pia; Chitnis, Tanuja; De Jager, Philip L.; Quintana, Francisco J.; Gerber, Georg K.; Bry, Lynn; Weiner, Howard L.

    2016-01-01

    The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis. PMID:27352007

  17. Clinical Overlap of Multiple Sclerosis and Autoimmune Hepatitis: Three Cases.

    PubMed

    Sayin, Refah; Gokgul, Alper; Ebinc, Senar; Dulger, Ahmet Cumhur; Tombul, Temel

    2016-06-01

    Multiple sclerosis (MS) is an autoimmune, inflammatory disease characterized by demyelination and axonal degeneration in the central nervous system. MS is the second major cause of disability following trauma, and is mostly seen between the ages of 20 - 40 years and in women. Autoimmune hepatitis (AH) is a chronic disease characterized by hypergammaglobulinemia, high levels of transaminases, presence of antibodies, and histologically by the necroinflammatory process with interface hepatitis. In AH, the etiological agent of the disease and the cause of liver injury remain unknown. MS may be associated with AH, autoimmune thyroiditis, and type 1 diabetes mellitus (DM). In literature, 8 cases with overlap of MS and AH have been reported. In this report, we present 3 cases which were detected with overlap of MS and AH, and are very rare condition in literature.

  18. Cortical excitability changes over time in progressive multiple sclerosis

    PubMed Central

    Ayache, Samar S.; Créange, Alain; Farhat, Wassim H.; Zouari, Hela G.; Lesage, Catherine; Palm, Ulrich; Abdellaoui, Mohammed; Lefaucheur, Jean-Pascal

    2015-01-01

    Summary In 25 patients with progressive forms of multiple sclerosis (MS), motor cortex excitability was longitudinally studied over one year by means of transcranial magnetic stimulation (TMS). The following TMS parameters were considered: resting and active motor thresholds (MTs), input-output curve, short-interval intracortical inhibition (SICI), and intracortical facilitation. Clinical evaluation was based on the Expanded Disability Status Scale (EDSS). In the 16 patients not receiving disease-modifying drugs, the EDSS score worsened, resting MT increased, and SICI decreased. By contrast, no clinical or neurophysiological changes were found over time in the nine patients receiving immunomodulatory therapy. The natural course of progressive MS appears to be associated with a decline in cortical excitability of both pyramidal neurons and inhibitory circuits. This pilot study based on a small sample suggests that disease-modifying drugs may allow cortical excitability to remain stable, even in patients with progressive MS. PMID:26727704

  19. Yoga as a method of symptom management in multiple sclerosis.

    PubMed

    Frank, Rachael; Larimore, Jennifer

    2015-01-01

    Multiple Sclerosis (MS) is an immune-mediated process in which the body's immune system damages myelin in the central nervous system (CNS). The onset of this disorder typically occurs in young adults, and it is more common among women. Currently, there is no cure and the long-term disease progression makes symptomatic management critical for maintaining quality of life. Several pharmacotherapeutic agents are approved for treatment, but many patients seek complementary and alternative interventions. Reviews have been conducted regarding broad topics such as mindfulness-based interventions for people diagnosed with MS and the impact of yoga on a range of neurological disorders. The objective of the present review is to examine the potential benefits of yoga for individuals with MS and address its use in managing symptoms including pain, mental health, fatigue, spasticity, balance, bladder control, and sexual function.

  20. Multiple sclerosis: getting personal with induced pluripotent stem cells

    PubMed Central

    Di Ruscio, A; Patti, F; Welner, R S; Tenen, D G; Amabile, G

    2015-01-01

    Human induced pluripotent stem (iPS) cells can be derived from lineage-restricted cells and represent an important tool to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. Recently, patient-derived iPS cells, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. By offering an unlimited source of patient-specific disease-relevant cells, iPS cells hold great promise for understanding disease mechanisms, identifying molecular targets and developing phenotypic screens for drug discovery. This review will discuss the potential impact of using iPS cell-derived models in multiple sclerosis (MS) research and highlight some of the current challenges and prospective for generating novel therapeutic treatments for MS patients. PMID:26158512

  1. Uses of Complementary and Alternative Medicine in Multiple Sclerosis

    PubMed Central

    Namjooyan, Foroogh; Ghanavati, Rahil; Majdinasab, Nastaran; Jokari, Shiva; Janbozorgi, Mohammad

    2014-01-01

    Multiple sclerosis (MS) is a chronic, disabling, recurrent demyelination of the central nervous system (CNS). It could affect different regions in the brain and spinal cord, and according to the domain which is affected, it could cause different symptoms such as motor, sensory, or visual impairment; fatigue; bowel, bladder, and sexual dysfunction; cognitive impairment; and depression. MS patients also face reduced quality of life. Drugs that are used in MS are not fully efficient and patients suffer from many symptoms and adverse effects. Today there is an increasing trend of using complementary and alternative medicine (CAM). People are more likely to use this type of treatment. Using appropriate lifestyle and CAM therapy can subside some of the symptoms and could improve the quality of life in these patients. Many people with MS explore CAM therapies for their symptoms. This review is aimed to introduce CAM therapies that could be used in MS patients. PMID:25161918

  2. The Gas6/TAM System and Multiple Sclerosis

    PubMed Central

    Bellan, Mattia; Pirisi, Mario; Sainaghi, Pier Paolo

    2016-01-01

    Growth arrest specific 6 (Gas6) is a multimodular circulating protein, the biological actions of which are mediated by the interaction with three transmembrane tyrosine kinase receptors: Tyro3, Axl, and MerTK, collectively named TAM. Over the last few decades, many progresses have been done in the understanding of the biological activities of this highly pleiotropic system, which plays a role in the regulation of immune response, inflammation, coagulation, cell growth, and clearance of apoptotic bodies. Recent findings have further related Gas6 and TAM receptors to neuroinflammation in general and, specifically, to multiple sclerosis (MS). In this paper, we review the biology of the Gas6/TAM system and the current evidence supporting its potential role in the pathogenesis of MS. PMID:27801848

  3. Gray Matter Is Targeted in First-Attack Multiple Sclerosis

    PubMed Central

    Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao; Schepmoes, Athena A.; Xie, Fang; Bergquist, Jonas; Vécsei, László; Zadori, Denes; Camp, David G.; Holland, Bart K.; Smith, Richard D.; Coyle, Patricia K.

    2013-01-01

    The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation. PMID:24039694

  4. Regulatory Functions of Natural Killer Cells in Multiple Sclerosis

    PubMed Central

    Gross, Catharina C.; Schulte-Mecklenbeck, Andreas; Wiendl, Heinz; Marcenaro, Emanuela; Kerlero de Rosbo, Nicole; Uccelli, Antonio; Laroni, Alice

    2016-01-01

    There is increasing evidence that natural killer (NK) cells exhibit regulatory features. Among them, CD56bright NK cells have been suggested to play a major role in controlling T cell responses and maintaining homeostasis. Dysfunction in NK cell-mediated regulatory features has been recently described in untreated multiple sclerosis (MS), suggesting a contribution to MS pathogenesis. Moreover, biological disease-modifying treatments effective in MS apparently enhance the frequencies and/or regulatory function of NK cells, further pointing toward an immunoprotective role of NK cells in MS. Here, we summarize the current knowledge on the regulatory functions of NK cells, based on their interactions with other cells belonging to the innate compartment, as well as with adaptive effector cells. We review the more recent data reporting disruption of NK cell/T cell interactions in MS and discuss how disease-modifying treatments for MS affect NK cells. PMID:28066417

  5. Sudden sensorineural hearing loss in a multiple sclerosis case.

    PubMed

    Tekin, Muhammet; Acar, Gul Ozbilen; Cam, Osman Halit; Hanege, Fatih Mehmet

    2014-01-01

    Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. MS involves different regions of the central nervous system in different periods, and causes demyelination. MS is a neuromotor disorder which progresses with remissions and relapses. Symptoms of MS may regress completely or heal after the relapses leaving sequelae. Sudden sensorinerural hearing loss (SSHL) is hearing loss of 30 dB or more over at least three contiguous audiometric frequencies that develops over a period of a few hours to 3 days. In 4-10 % of the MS patients, sensorineural hearing loss occurs between relapses or remissions. In this case, audiotory brainstem response (ABR) test is the most appropriate test for the diagnosis of sensorineural hearing loss in MS patients. In this article, we will discuss a patient diagnosed as MS who presented with sudden sensorineural hearing loss during the remission of the disease.

  6. A mighty mouse: building a better model of multiple sclerosis

    PubMed Central

    Ransohoff, Richard M.

    2006-01-01

    The 2 cardinal cell populations mediating adaptive immunity are T and B lymphocytes. These cells play important but poorly understood roles in the immunopathological demyelinating disease multiple sclerosis (MS) and in a widely used animal model of human MS known as EAE. In the current issue of the JCI, 2 research teams report their parallel studies of double-transgenic mice expressing T and B cell receptors that recognize the same myelin protein (see the related articles beginning on pages 2385 and 2393). More than half of the double-transgenic mice spontaneously developed autoimmune demyelination in their spinal cords and optic nerves, exhibiting pathologies reminiscent of human MS. The studies describe an important new model for MS research. PMID:16955130

  7. No quiet surrender: molecular guardians in multiple sclerosis brain

    PubMed Central

    Steinman, Lawrence

    2015-01-01

    The brain under immunological attack does not surrender quietly. Investigation of brain lesions in multiple sclerosis (MS) reveals a coordinated molecular response involving various proteins and small molecules ranging from heat shock proteins to small lipids, neurotransmitters, and even gases, which provide protection and foster repair. Reduction of inflammation serves as a necessary prerequisite for effective recovery and regeneration. Remarkably, many lesion-resident molecules activate pathways leading to both suppression of inflammation and promotion of repair mechanisms. These guardian molecules and their corresponding physiologic pathways could potentially be exploited to silence inflammation and repair the injured and degenerating brain and spinal cord in both relapsing-remitting and progressive forms of MS and may be beneficial in other neurologic and psychiatric conditions. PMID:25831441

  8. Multiple sclerosis in Gijon health district, Asturias, northern Spain.

    PubMed

    Uria, D F; Abad, P; Calatayud, M T; Virgala, P; Diaz, A; Chamizo, C; Dean, G

    1997-12-01

    The objective of this study was to ascertain the prevalence and incidence of Multiple Sclerosis (MS) in a population of 33,775 in two primary health care centres in the sanitary district of Gijon, Asturias, northern Spain. Many information sources were used but the unique advantage of Gijon was that the city has a centralized computerized register of all diagnoses made for all consultations in the clinics and hospitals in the area. The HLA distribution in the population was already known and the Poser classification of MS was used. The crude MS prevalence was 65/100,000, a similar prevalence to that found in southern and eastern Spain, Sicily and Greek-speaking Cyprus. The mean incidence was 3.7/100,000 per year. The study demonstrated the advantage of a centralized and computerized medical recording system and demonstrates that northern Spain is a moderately high or medium MS risk zone.

  9. [Early retirement and occupational rehabilitation of patients with multiple sclerosis].

    PubMed

    Hassink, G; Manegold, U; Poser, S

    1993-05-01

    Statistical data are set out describing the situation of persons with multiple sclerosis (MS) relative to early pensioning and vocational rehabilitation. Findings show that MS gives rise to extraordinarily early pensioning, also when compared to other conditions. From 1980-1990, a total of 14,811 persons with MS were pensioned prematurely; average age at the time, in 1990, was 44.2 years for men and 41.1 years for women with MS. The number of temporary disability pensions has been decreasing since 1985. Vocational rehabilitation (VR) services are relatively rarely provided in MS; in 1990, a total of 626 rehabilitees with MS were registered at the Federal Employment Institute. The majority of VR benefits provided to persons with MS concentrated on mobility allowances to facilitate placement or continued employment. Concluding, the findings are discussed, also touching on the possibilities for persons with MS being paid greater attention concerning VR service provision.

  10. An update on immunopathogenesis, diagnosis, and treatment of multiple sclerosis

    PubMed Central

    Garg, Neeta; Smith, Thomas W

    2015-01-01

    Background Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after head trauma. Discussion The etiology of MS is probably multifactorial, related to genetic, environmental, and several other factors. The pathogenesis is not fully understood but is believed to involve T-cell-mediated inflammation directed against myelin and other related proteins with a possible role for B cells. The McDonald criteria have been proposed and revised over the years to guide the diagnosis of MS and are based on clinical presentation and magnetic resonance imaging (MRI) of the brain and spinal cord to establish dissemination in time and space. The treatment of MS includes disease modification with immunomodulator drugs and symptom management to address the specific symptoms such as fatigue, spasticity, and pain. Conclusion An update on etiology, pathogenesis, diagnosis, and immunomodulatory treatment of MS is presented. PMID:26445701

  11. [Autotransplantation of hematopoietic progenitor cells in multiple sclerosis].

    PubMed

    Fernández, J; Correale, J; Campestri, R; Koziner, B

    1999-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disease exhibiting great clinical variability. For control of its primary and secondary progressive variants, treatment has met with limited success. In recent years, increasing experience has been gained with the administration of high dose chemotherapy supported by the autologous infusion of hematopoietic progenitor cells (HPC), in some instances depleted of T cells. The European and International Registry of Hematopoietic Cell Transplantation for Autoimmune Diseases include 43 MS patients. BEAM was the most frequently used conditioning therapy. Treatment related mortality was 7%. The actuarial disease free survival and the overall projected survival at 38 months were 85% and 90% respectively. The inclusion of an increasing number of MS patients into these treatment programs and the growing submission of cases to the Registries will provide useful information to determine if the initial enthusiasm generated by this approach for the control of primary and secondary progressive forms of MS is justified.

  12. [Monoclonal antibodies for the treatment of multiple sclerosis].

    PubMed

    Sánchez-Seco, Victoria Galán; Casanova Peño, Ignacio; Arroyo González, Rafael

    2014-12-01

    Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs.

  13. Sativex for the management of multiple sclerosis symptoms.

    PubMed

    Perras C

    2005-09-01

    Sativex (R) is a cannabis-based pharmaceutical product containing delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio, delivered in an oromucosal (mouth) spray. It has been approved as adjunctive treatment for neuropathic pain in patients with multiple sclerosis (MS). It is being investigated for the management of other MS symptoms, such as spasticity. THC:CBD spray is regulated as a narcotic. Five randomized controlled trials (RCTs) compared the benefits and harms of THC:CBD spray with placebo. A total of 368 patients with various neurological conditions (including MS) were recruited. In some trials, THC:CBD spray significantly reduced neuropathic pain, spasticity, muscle spasms and sleep disturbances. The most common adverse events (AEs) reported in trials were dizziness, sleepiness, fatigue, feeling of intoxication and a bad taste. Long-term safety and the potential for dependence, abuse, misuse and diversion are unknown.

  14. [Clinical features of pediatric multiple sclerosis: epidemiology and treatment].

    PubMed

    Torisu, Hiroyuki; Hara, Toshiro

    2014-11-01

    Multiple sclerosis (MS) in children is essentially not different from MS in adults; however, in children, it is sometimes difficult to distinguish MS from other demyelinating diseases. The main reason for this is that acute encephalitis/encephalopathy associated with infectious diseases, especially acute disseminated encephalomyelitis (ADEM), often causes demyelinating events in the central nervous system in childhood, and that the demyelinating episodes of MS in younger children clinically resemble ADEM events. Therefore, a number of studies on pediatric demyelinating diseases have been conducted to elucidate the clinical features of pediatric MS. In this article, the clinical features of pediatric MS in Japan were reviewed on the basis of the results of a nationwide survey as well as those in other countries.

  15. Monitoring technology for wheelchair users with advanced multiple sclerosis.

    PubMed

    Pino, Esteban J; Arias, Diego E; Aqueveque, Pablo; Vilugrón, Luis; Hermosilla, Daniela; Curtis, Dorothy W

    2013-01-01

    This paper presents a non-invasive assistive device for people with advanced Multiple Sclerosis (MS) who use electric power wheelchairs (EPW). The proposed system can acquire respiration and heart activity from ballistocardiogram (BCG), seat and back pressure distribution, wheelchair tilt angle and ambient temperature and relative humidity. The sensors collect information related to the main issues of MS patients: fatigue, heat sensitivity and low mobility. Preliminary results show the signals as the wheelchair is moving, stopped and tilting. The system is able to capture sufficient relevant information to provide suggestions and alarms in a future stage. The system will be tested at The Boston Home, a specialized residence for adults with advanced MS.

  16. Exercise in multiple sclerosis -- an integral component of disease management

    PubMed Central

    2012-01-01

    Multiple sclerosis (MS) is the most common chronic inflammatory disorder of the central nervous system (CNS) in young adults. The disease causes a wide range of symptoms depending on the localization and characteristics of the CNS pathology. In addition to drug-based immunomodulatory treatment, both drug-based and non-drug approaches are established as complementary strategies to alleviate existing symptoms and to prevent secondary diseases. In particular, physical therapy like exercise and physiotherapy can be customized to the individual patient's needs and has the potential to improve the individual outcome. However, high quality systematic data on physical therapy in MS are rare. This article summarizes the current knowledge on the influence of physical activity and exercise on disease-related symptoms and physical restrictions in MS patients. Other treatment strategies such as drug treatments or cognitive training were deliberately excluded for the purposes of this article. PMID:22738091

  17. Symptoms and physical activity behavior in individuals with multiple sclerosis.

    PubMed

    Motl, Robert W; Snook, Erin M; Schapiro, Randall T

    2008-10-01

    We examined overall and specific symptoms as correlates of physical activity in individuals with multiple sclerosis (MS). Participants (N = 133) completed questionnaires that measured overall symptoms; and specific symptoms of depression, pain, and fatigue; difficulty walking; and physical activity. Initial analyses indicated that higher levels of overall symptoms (r = -.50), fatigue (r = -.26), and difficulty walking (r = -.46) were associated with lower levels of physical activity. Path analysis demonstrated that higher levels of overall symptoms were directly and indirectly associated with lower levels of physical activity; the indirect pathway involved difficulty walking (gamma beta = -.17). Such findings indicate that walking difficulty may partially explain the negative relationship between overall symptoms and physical activity behavior in MS.

  18. Biological monitoring of IFN-β therapy in Multiple Sclerosis.

    PubMed

    Bertolotto, A; Granieri, L; Marnetto, F; Valentino, P; Sala, A; Capobianco, M; Malucchi, S; Di Sapio, A; Malentacchi, M; Matta, M; Caldano, M

    2015-04-01

    Multiple Sclerosis (MS) is a heterogeneous disease and a variable percentage of patients are non-responders to common treatment. Early diagnosis of non-responders allows change to a more useful therapy for the patient and better allocates a large amount of financial resources. Quantification of Neutralizing antibodies (Nabs) and of biological activity of IFN-β are recognized approaches to identify immuno-pharmacological non-responders. A consistent number of studies have demonstrated that quantification of Myxovirus-induced protein A (MxA) is a valid biomarker to detect immune-pharmacological non responders after one year of treatment. Persistent high titre of Nabs and absence of biological activity predict abolition of IFN-β effects in disease activity measured through MRI, number of relapses and disability. Guidelines and flow-charts including both Nabs and MxA quantification are presented.

  19. Multiple sclerosis: overview of disease-modifying agents.

    PubMed

    Finkelsztejn, Alessandro

    2014-01-01

    Multiple sclerosis (MS) is a chronic autoimmune disease that usually affects young adults, causing progressive physical and cognitive disability. Since the 1990s, its treatment has been based on parenteral medications known collectively as immunomodulators. This drug class is considered safe and usually prevents 30% of MS relapses. Drugs in this class exert almost the same efficacy and require an inconvenient administration route. New medications have recently been launched worldwide. Thus, new oral drugs are increasingly being administered to MS patients and contributing to a better quality of life, since these have better efficacy than the old immunomodulators. Today, 10 different drugs for MS are marketed worldwide, which requires deep knowledge among neurologists and other healthcare professionals. This paper summarizes all the drugs approved for MS in the US and Europe, emphasizing their mechanism of action, the results from phase II and III studies, and the product safety.

  20. Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis.

    PubMed

    Ghezzi, A; Comi, G; Federico, A

    2011-02-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.

  1. Current recommendations for multiple sclerosis treatment in pregnancy and puerperium.

    PubMed

    Ghezzi, Angelo; Annovazzi, Pietro; Portaccio, Emilio; Cesari, Elana; Amato, Maria P

    2013-07-01

    As multiple sclerosis (MS) typically starts at about 30 years of age, and is twice more frequent in females than in males, women with MS frequently face issues related to pregnancy and to the effects of medications commonly used in MS treatment. In this review, the authors provide and summarize literature data addressing the effect of MS and its treatments on pregnancy, delivery, postpartum and conception. There is a strong evidence that relapses are fewer during pregnancy but more frequent during postpartum, and that IFN-β and glatiramer acetate do not expose patients and their babies to relevant adverse events; nevertheless, these drugs should be discontinued during pregnancy and before conception. However, if their preventive withdrawal exposes patients to a high risk of disease activity, these medications could be continued until proven conception. Little information is available on the effect of natalizumab and fingolimod.

  2. Disease-modifying therapies and infectious risks in multiple sclerosis.

    PubMed

    Winkelmann, Alexander; Loebermann, Micha; Reisinger, Emil C; Hartung, Hans-Peter; Zettl, Uwe K

    2016-04-01

    Immunomodulatory and immunosuppressive treatments for multiple sclerosis (MS) are associated with an increased risk of infection, which makes treatment of this condition challenging in daily clinical practice. Use of the expanding range of available drugs to treat MS requires extensive knowledge of treatment-associated infections, risk-minimizing strategies and approaches to monitoring and treatment of such adverse events. An interdisciplinary approach to evaluate the infectious events associated with available MS treatments has become increasingly relevant. In addition, individual stratification of treatment-related infectious risks is necessary when choosing therapies for patients with MS, as well as during and after therapy. Determination of the individual risk of infection following serial administration of different immunotherapies is also crucial. Here, we review the modes of action of the available MS drugs, and relate this information to the current knowledge of drug-specific infectious risks and risk-minimizing strategies.

  3. The impact of drugs for multiple sclerosis on sleep.

    PubMed

    Lanza, Giuseppe; Ferri, Raffaele; Bella, Rita; Ferini-Strambi, Luigi

    2017-01-01

    Although there is a growing literature on the presence of sleep disorders in multiple sclerosis (MS), few studies have specifically addressed the impact of drugs on sleep of these patients. Moreover, even when sleep is considered, quantitative assessment by standardized questionnaires or polysomnography is lacking. The studies that have been done highlight that interferon-beta and some symptomatic medications may affect sleep, thus contributing to fatigue, depression, and poor quality of life; conversely, natalizumab and cannabinoids may improve sleep. Common limitations of the literature reviewed here are small sample size, selection bias, and often a lack of objective outcome measures. Clinicians need to remember to ask about sleep in all MS patients and intervene when appropriate. A systematic approach that takes sleep into account is recommended to enhance recognition and appropriate management of sleep disruption, including disorders related to medication. Consideration of the impact on sleep should also be part of the design of trials of new therapies.

  4. Multiple sclerosis: an example of pathogenic viral interaction?

    PubMed

    Fierz, Walter

    2017-02-28

    A hypothesis is formulated on viral interaction between HHV-6A and EBV as a pathogenic mechanism in Multiple Sclerosis (MS). Evidence of molecular and genetic mechanisms suggests a link between HHV-6A infection and EBV activation in the brain of MS patients leading to intrathecal B-cell transformation. Consequent T-cell immune response against the EBV-infected cells is postulated as a pathogenic basis for inflammatory lesion formation in the brain of susceptible individuals. A further link between HHV-6A and EBV involves their induction of expression of the human endogenous retrovirus HERV-K18-encoded superantigen. Such virally induced T-cell responses might secondarily also lead to local autoimmune phenomena. Finally, research recommendations are formulated for substantiating the hypothesis on several levels: epidemiologically, genetically, and viral expression in the brain.

  5. Clinical correlates of generalized worry in multiple sclerosis.

    PubMed

    Bruce, Jared M; Arnett, Peter

    2009-08-01

    Anxiety disorders are common in multiple sclerosis (MS). Chronic worry is the defining feature of generalized anxiety. Despite this, only one study has examined the impact of chronic worry in MS. The present investigation explored the relationship between excessive worry and common physical, emotional, and neuropsychological symptoms in a community-based sample of 50 patients with relapsing-remitting and secondary progressive MS. As expected, MS patients reported significantly more worry than a group of 45 healthy controls. Correlational analyses revealed that MS patients' elevated worry was associated with fatigue, sleep disturbance, problem-solving deficits, pain, and disability status. Follow-up analyses indicated that worry and anxiety may represent related but distinct constructs. Clinicians are urged to regularly monitor and treat pathological worry in MS.

  6. Social conflict exacerbates an animal model of multiple sclerosis.

    PubMed

    Meagher, Mary W; Johnson, Robin R; Vichaya, Elisabeth Good; Young, Erin E; Lunt, Shannon; Welsh, C Jane

    2007-07-01

    A growing body of evidence suggests that social conflict is associated with inflammatory disease onset and exacerbations in multiple sclerosis (MS) patients and in animal models of MS. This review illustrates how animal research can be used to elucidate the biobehavioral mechanisms underlying the adverse health effects of social conflict. The authors review studies indicating that social conflict exacerbates a virally initiated animal model of MS. This research suggests that the deleterious effects of social conflict may be partially mediated by stress-induced increases in pro-inflammatory cytokine levels in the central nervous system. In addition, they provide evidence that the adverse health effects of social conflict can be prevented by blocking the stress-induced increases in cytokine activity. This suggests that interventions designed to prevent or reverse the stress-induced increases in cytokine activity may be able to prevent or reverse some of the negative health effects of social conflict in humans.

  7. Computational modeling of brain pathologies: the case of multiple sclerosis.

    PubMed

    Pappalardo, Francesco; Rajput, Abdul-Mateen; Motta, Santo

    2016-12-22

    The central nervous system is the most complex network of the human body. The existence and functionality of a large number of molecular species in human brain are still ambiguous and mostly unknown, thus posing a challenge to Science and Medicine. Neurological diseases inherit the same level of complexity, making effective treatments difficult to be found. Multiple sclerosis (MS) is a major neurological disease that causes severe inabilities and also a significant social burden on health care system: between 2 and 2.5 million people are affected by it, and the cost associated with it is significantly higher as compared with other neurological diseases because of the chronic nature of the disease and to the partial efficacy of current therapies. Despite difficulties in understanding and treating MS, many computational models have been developed to help neurologists. In the present work, we briefly review the main characteristics of MS and present a selection criteria of modeling approaches.

  8. Yoga as a method of symptom management in multiple sclerosis

    PubMed Central

    Frank, Rachael; Larimore, Jennifer

    2015-01-01

    Multiple Sclerosis (MS) is an immune-mediated process in which the body's immune system damages myelin in the central nervous system (CNS). The onset of this disorder typically occurs in young adults, and it is more common among women. Currently, there is no cure and the long-term disease progression makes symptomatic management critical for maintaining quality of life. Several pharmacotherapeutic agents are approved for treatment, but many patients seek complementary and alternative interventions. Reviews have been conducted regarding broad topics such as mindfulness-based interventions for people diagnosed with MS and the impact of yoga on a range of neurological disorders. The objective of the present review is to examine the potential benefits of yoga for individuals with MS and address its use in managing symptoms including pain, mental health, fatigue, spasticity, balance, bladder control, and sexual function. PMID:25983675

  9. Social Cognition in Multiple Sclerosis: a Meta-Analysis.

    PubMed

    Bora, Emre; Özakbaş, Serkan; Velakoulis, Dennis; Walterfang, Mark

    2016-06-01

    Multiple sclerosis (MS) is associated with cognitive decline and impairment in social functioning. Accumulating evidence suggests that patients with MS are impaired in social cognition, including theory of mind (ToM) and emotion recognition. In this meta-analysis of 24 studies, facial emotion recognition and ToM performances of 989 patients with MS and 836 healthy controls were compared. MS was associated with significant impairments with medium effect sizes in ToM (d = 0.57) and facial emotion recognition (d = 0.61). Among individual emotions recognition of fear and anger were particularly impaired. The severity of social cognitive deficits was significantly associated with non-social cognitive impairment. These deficits in social cognition may underpin difficulties in social functioning in MS. However, there is a need for further studies investigating the longitudinal evolution of social cognitive deficits and their neural correlates in MS.

  10. Cannabinoids in the management of spasticity associated with multiple sclerosis

    PubMed Central

    Malfitano, Anna Maria; Proto, Maria Chiara; Bifulco, Maurizio

    2008-01-01

    The endocannabinoid system and cannabinoid-based treatments have been involved in a wide number of diseases. In particular, several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis (MS). In this study we highlight the main findings reported in literature about the relevance of cannabinoid drugs in the management and treatment of MS. An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of MS, including spasticity and pain. In this report we focus on the effects of cannabinoids in the relief of spasticity describing the main findings in vivo, in the mouse experimental allergic encephalomyelitis model of MS. We report on the current treatments used to control MS symptoms and the most recent clinical studies based on cannabinoid treatments, although long-term studies are required to establish whether cannabinoids may have a role beyond symptom amelioration in MS. PMID:19183777

  11. New candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis.

    PubMed

    Hoppmann, Nicola; Graetz, Christiane; Paterka, Magdalena; Poisa-Beiro, Laura; Larochelle, Catherine; Hasan, Maruf; Lill, Christina M; Zipp, Frauke; Siffrin, Volker

    2015-04-01

    Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system, which is thought to be triggered by environmental factors in genetically susceptible individuals leading to activation of autoreactive T lymphocytes. Large multi-centre genome-wide association studies have identified multiple genetic risk loci in multiple sclerosis. In this study, we investigated T cell transcriptomic changes in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. We correlated these findings with the multiple sclerosis risk genes postulated by the most recent Immunochip analysis and found that multiple sclerosis susceptibility genes were significantly regulated in experimental autoimmune encephalomyelitis. Our data indicate that nine distinct genes associated with multiple sclerosis risk, Bach2, Il2ra, Irf8, Mertk, Odf3b, Plek, Rgs1, Slc30a7 and Thada, can be confirmed to be differentially regulated in pathogenic CD4(+) T cells. During the effector phase within the inflamed CNS, CD4(+) T cells undergo comprehensive transformation and we identified key transcription factors and signalling networks involved in this process. The transformation was linked to metabolic changes with the involvement of liver X receptor/retinoid X receptor signalling and cholesterol biosynthesis, which might control the T cell effector function in the central nervous system. Thus, our study confirms the involvement of multiple sclerosis risk genes in the pathophysiology of the animal model and sheds light on additional disease-relevant inflammatory networks.

  12. MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis.

    PubMed

    Severin, Mary E; Lee, Priscilla W; Liu, Yue; Selhorst, Amanda J; Gormley, Matthew G; Pei, Wei; Yang, Yuhong; Guerau-de-Arellano, Mireia; Racke, Michael K; Lovett-Racke, Amy E

    2016-06-01

    Transforming growth factor beta (TGFβ) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naïve CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFβ signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFβ signalling components in their naïve CD4 T cells. The differentially expressed miRNAs negatively regulated the TGFβ pathway, resulting in a reduced capacity of naïve CD4 T cells to differentiate into regulatory T cells. Interestingly, the limited number of regulatory T cells, that did develop when these TGFβ-targeting miRNAs were overexpressed, were capable of suppressing effector T cells. As it has previously been demonstrated that compromising TGFβ signalling results in a reduced regulatory T cell repertoire insufficient to control autoimmunity, and patients with multiple sclerosis have a reduced regulatory T cell repertoire, these data indicate that the elevated expression of multiple TGFβ-targeting miRNAs in naïve CD4 T cells of patients with multiple sclerosis impairs TGFβ signalling, and dampens regulatory T cell development, thereby enhancing susceptibility to developing multiple sclerosis.

  13. Obstructive Sleep Apnea and Fatigue in Patients with Multiple Sclerosis

    PubMed Central

    Braley, Tiffany J.; Segal, Benjamin M.; Chervin, Ronald D.

    2014-01-01

    Study Objectives: The prevalence of obstructive sleep apnea (OSA) in persons with multiple sclerosis (MS) remains unknown, and little information exists regarding the relative contributions of OSA to symptoms of MS-related fatigue in the presence of other clinical and sleep-related confounders. The objectives of this study were to investigate the prevalence of diagnosed OSA and OSA risk among MS patients, and to assess relationships between fatigue severity, OSA, OSA risk, and sleep quality among persons with MS. Methods: N = 195 MS patients completed a questionnaire comprised of items regarding OSA diagnosis, sleep quality and quantity, daytime symptoms, and 4 validated scales: the Epworth Sleepiness Scale, Fatigue Severity Scale, Insomnia Severity Index, and STOP-Bang questionnaire. Medical records were also accessed to examine clinical characteristics that may predict fatigue or OSA risk. Results: N = 41 patients (21%) carried a formal diagnosis of OSA. N = 110 (56%) of all patients, and 38 (93%) of those with diagnosed OSA had STOP-Bang scores ≥ 3, indicating an elevated OSA risk. In regression models, the most significant predictors of higher FSS scores were higher STOP-Bang scores (p = 0.01), higher number of nocturnal symptoms (p < 0.0001), and higher disability level (p < 0.0001). Conclusions: Sleep disturbances, and OSA in particular, may be highly prevalent yet underrecognized contributors to fatigue in persons with MS. Citation: Braley TJ; Segal BM; Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med 2014;10(2):155-162. PMID:24532998

  14. A Bayesian hierarchical surrogate outcome model for multiple sclerosis.

    PubMed

    Pozzi, Luca; Schmidli, Heinz; Ohlssen, David I

    2016-07-01

    The development of novel therapies in multiple sclerosis (MS) is one area where a range of surrogate outcomes are used in various stages of clinical research. While the aim of treatments in MS is to prevent disability, a clinical trial for evaluating a drugs effect on disability progression would require a large sample of patients with many years of follow-up. The early stage of MS is characterized by relapses. To reduce study size and duration, clinical relapses are accepted as primary endpoints in phase III trials. For phase II studies, the primary outcomes are typically lesion counts based on magnetic resonance imaging (MRI), as these are considerably more sensitive than clinical measures for detecting MS activity. Recently, Sormani and colleagues in 'Surrogate endpoints for EDSS worsening in multiple sclerosis' provided a systematic review and used weighted regression analyses to examine the role of either MRI lesions or relapses as trial level surrogate outcomes for disability. We build on this work by developing a Bayesian three-level model, accommodating the two surrogates and the disability endpoint, and properly taking into account that treatment effects are estimated with errors. Specifically, a combination of treatment effects based on MRI lesion count outcomes and clinical relapse was used to develop a study-level surrogate outcome model for the corresponding treatment effects based on disability progression. While the primary aim for developing this model was to support decision-making in drug development, the proposed model may also be considered for future validation. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Impact of multiple sclerosis relapse: The NARCOMS participant perspective.

    PubMed

    Nickerson, Molly; Cofield, Stacey S; Tyry, Tuula; Salter, Amber R; Cutter, Gary R; Marrie, Ruth Ann

    2015-05-01

    Acute relapses continue to be a significant aspect of multiple sclerosis (MS) on both the epidemiologic level and the individual patient level. Past work demonstrates residual disability from relapses as well as high patient-reported rates of ineffective relapse treatment. To better characterize the impact of MS relapses on the patient, a relapse-specific survey was administered through the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry to 1000 registry participants who had reported at least one relapse in the past 12 months. Thirty percent of respondents confirmed lack of relapse treatment efficacy at one month and at three months. Relapses also impacted socioeconomic measures; for individuals still going to school or working, more than half missed days and their average loss of school or work was 12.7 days. An impact on household tasks was reported by 68% of respondents. A healthcare facility such as a hospital, emergency room or urgent care center was utilized by 20.4% of respondents. The most common relapse symptoms were fatigue, weakness of the lower extremity, sensory symptoms, problems walking, and weakness of the upper extremity. Of the respondents who reported receiving corticosteroid treatment (53.3%), over half reported an adverse event. However, this was not a significant factor in dictating whether or not respondents would seek a different treatment on their next relapse, although 31% would choose a different treatment for their next relapse. Relapses continue to be an impactful experience that requires continued clinical attention. Improved follow-up from relapses and relapse treatment might be beneficial.

  16. Antinuclear and antiphospholipid antibodies in patients with multiple sclerosis.

    PubMed

    Szmyrka-Kaczmarek, M; Pokryszko-Dragan, A; Pawlik, B; Gruszka, E; Korman, L; Podemski, R; Wiland, P; Szechinski, J

    2012-04-01

    The prevalence of autoantibodies in multiple sclerosis (MS) patients and their clinical associations differ between various studies. This study investigated antiphospholipid and antinuclear antibodies in 85 patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) with regard to their association with demographic features, MS specific clinical features and symptoms of connective tissue diseases. Autoantibodies tested included antinuclear antibodies (ANA) with their specificities and anticardiolipin (aCL) and anti-beta-2-glycoprotein I (anti-β2GPI) antibodies. Antinuclear antibodies were more prevalent in MS patients than in controls (63.5% vs. 3.3%; p < 0.01) and in 19% of patients specific antinuclear antibodies were detected. Anti-β2GPI IgM antibodies were more frequent in MS patients than in the control group (20% vs. 3.3%; p < 0.05). The frequency of anticardiolipin antibodies did not differ between MS patients and controls. MS patients seropositive for ANA and extractable nuclear antigens (ENA) had significantly shorter disease duration than seronegative patients (p < 0.05) and a lower disability score (Expanded Disability Status Score; EDSS) (p < 0.05). Anti-β2GPI antibodies were more frequent in patients with secondary progressive MS (SP-MS) and specific ANA antibodies were more frequent in patients with clinically isolated syndrome (CIS) (p < 0.05). The presence of autoantibodies was not associated with the predominant site of neurological involvement or the clinical features of connective tissue diseases.

  17. Mouse models of multiple sclerosis: lost in translation?

    PubMed

    Baker, David; Amor, Sandra

    2015-01-01

    Multiple sclerosis (MS) is a chronic neurological disorder of the central nervous system (CNS) leading to progressive accumulation of neurological deficits arising from recurrent episodes of inflammation, demyelination and neuronal degeneration. While the aetiology of the disease is unknown MS is widely considered to be the result of aberrant T cell and antibody responses to CNS antigens giving rise to the common concept that MS is an autoimmune disease or that there is an autoimmune component in the pathogenesis. This idea has lead to the development of experimental autoimmune encephalomyelitis (EAE) mouse models of MS in which immunisation with CNS antigens induces neurological and pathological signs of disease in mice. In addition to EAE models, injection with neurotropic viruses has been used to examine how infections are implicated in the disease process and how they may generate autoimmune responses in the CNS. Viral models are also crucial to investigate the impact of blocking trafficking of immune responses into the CNS since an emerging side-effect of current immunotherapeutic approaches in MS is the reactivation of viruses within the CNS. To investigate myelin damage and repair in the absence of the adaptive immune response, toxin-induced demyelination using cuprizone, ethidium bromide and lysolecithin, which rapidly leads to remyelination when the toxins are withdrawn, is also reviewed. Mice also lend themselves to the vast array of transgenic technologies to probe specific pathways as well as the use of humanised transgenic mice to examine the impact of human molecules. Despite the vast array of mouse models EAE is the most frequently exploited paradigm used to develop therapeutic approaches. However, despite over one thousand compounds used in the treatment of EAE few have become licenced for treatment of MS so far. Thus, this review also debates the reasons for these failures in mouse models as well as discusses how mouse models can be better utilised

  18. Hypothalamic Dysfunction and Multiple Sclerosis: Implications for Fatigue and Weight Dysregulation.

    PubMed

    Burfeind, Kevin G; Yadav, Vijayshree; Marks, Daniel L

    2016-11-01

    Signs and symptoms of multiple sclerosis are usually attributed to demyelinating lesions in the spinal cord or cerebral cortex. The hypothalamus is a region that is often overlooked yet controls many important homeostatic functions, including those that are perturbed in multiple sclerosis. In this review we discuss how hypothalamic dysfunction may contribute to signs and symptoms in people with multiple sclerosis. While dysfunction of the hypothalamic-pituitary-adrenal axis is common in multiple sclerosis, the effects and mechanisms of this dysfunction are not well understood. We discuss three hypothalamic mechanisms of fatigue in multiple sclerosis: (1) general hypothalamic-pituitary-adrenal axis hyperactivity, (2) disordered orexin neurotransmission, (3) abnormal cortisol secretion. We then review potential mechanisms of weight dysregulation caused by hypothalamic dysfunction. Lastly, we propose future studies and therapeutics to better understand and treat hypothalamic dysfunction in multiple sclerosis. Hypothalamic dysfunction appears to be common in multiple sclerosis, yet current studies are underpowered and contradictory. Future studies should contain larger sample sizes and standardize hormone and neuropeptide measurements.

  19. Regulatory T cell number in multiple sclerosis patients: A meta-analysis.

    PubMed

    Noori-Zadeh, Ali; Mesbah-Namin, Seyed Alireza; Bistoon-Beigloo, Sara; Bakhtiyari, Salar; Abbaszadeh, Hojjat-Allah; Darabi, Shahram; Rajabibazl, Masoumeh; Abdanipour, Alireza

    2016-01-01

    Regulatory T cells (Treg cells), defined as CD4(+) CD25(+) FoxP3(+) T cells by expression of CD4, high-affinity IL-2 receptor and the transcription factor, forkhead box P3 (FoxP3). They play a pivotal role in protecting individuals from autoimmunity and a growing body of evidence suggests their role in the prevention of multiple sclerosis development. However, there are discrepancies about the type of defect in the Treg cells of multiple sclerosis patients and especially whether the Treg number alteration could be contributed to multiple sclerosis pathogenesis. Indeed, whether low number of Treg cells can be a risk factor contributing to multiple sclerosis pathogenesis is the matter of debate and there is not any comprehensive agreement on it. Thus, the objective of this systematic review and meta-analysis was to precisely quantify the nature and magnitude of the association between Treg cell number and the risk ratio/odds ratio (OR) of multiple sclerosis in the case-control studies. Hence, medical databases of Embase, PubMed/Medline, PubMed, PubMed Central and SCOPUS were searched for empirical papers using "Regulatory T cell frequency", "Treg frequency" in combination with "multiple sclerosis". In the case-control studies, papers were reviewed for inclusion/exclusion criteria and 8 publications were included. Under random-effect model meta-analysis the data showed that the frequency of Treg cells was not a risk factor in multiple sclerosis using current laboratory methods.

  20. Geographical Heterogeneity of Multiple Sclerosis Prevalence in France

    PubMed Central

    2016-01-01

    Introduction Geographical variation in the prevalence of multiple sclerosis (MS) is controversial. Heterogeneity is important to acknowledge to adapt the provision of care within the healthcare system. We aimed to investigate differences in prevalence of MS in departments in the French territory. Methods We estimated MS prevalence on October 31, 2004 in 21 administrative departments in France (22% of the metropolitan departments) by using multiple data sources: the main French health insurance systems, neurologist networks devoted to MS and the Technical Information Agency of Hospitalization. We used a spatial Bayesian approach based on estimating the number of MS cases from 2005 and 2008 capture–recapture studies to analyze differences in prevalence. Results The age- and sex-standardized prevalence of MS per 100,000 inhabitants ranged from 68.1 (95% credible interval 54.6, 84.4) in Hautes-Pyrénées (southwest France) to 296.5 (258.8, 338.9) in Moselle (northeast France). The greatest prevalence was in the northeast departments, and the other departments showed great variability. Discussion By combining multiple data sources into a spatial Bayesian model, we found heterogeneity in MS prevalence among the 21 departments of France, some with higher prevalence than anticipated from previous publications. No clear explanation related to health insurance coverage and hospital facilities can be advanced. Population migration, socioeconomic status of the population studied and environmental effects are suspected. PMID:27936086

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

    PubMed

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

    2014-03-01

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

  2. Lesion heterogeneity on high-field susceptibility MRI is associated with multiple sclerosis severity

    PubMed Central

    Harrison, Daniel M.; Li, Xu; Liu, Hongjun; Jones, Craig K.; Caffo, Brian; Calabresi, Peter A.; van Zijl, Peter

    2016-01-01

    Background and Purpose Susceptibility MRI contrast variations reflect alterations in brain iron and myelin content- making this imaging tool relevant to studies of multiple sclerosis lesion heterogeneity. In this study we aimed to characterize the relationship of high-field, susceptibility contrasts in multiple sclerosis lesions to clinical outcomes. Materials and Methods Twenty-four subjects with multiple sclerosis underwent 7-tesla MRI of the brain, disability exams, and a fatigue inventory. R2*, frequency, and relative susceptibility (from quantitative susceptibility mapping) were analyzed in 306 white matter lesions. Results Most lesions were hypointense on R2* (88% without a rim, 5% with). Lesions that were hyperintense on quantitative susceptibility mapping were more frequent in relapsing-remitting than progressive multiple sclerosis (54% vs. 35%, p = 0.018). Hyperintense lesion rims on quantitative susceptibility maps were more common in progressive multiple sclerosis and higher levels of disability and fatigue. Mean lesion R2* was inversely related to disability and fatigue and significantly reduced in progressive multiple sclerosis. Relative susceptibility was lower lesions in progressive multiple sclerosis (median -0.018 ppm, range -0.070 – 0.022) than relapsing-remitting (median -0.010 ppm, range -0.062 – 0.052, p = 0.003). Conclusion A progressive clinical phenotype, greater disability, and fatigue were associated with lower R2* and relative susceptibility values (suggestive of low iron due to oligodendrocyte loss) and rimmed lesions (suggestive of chronic inflammation) in this multiple sclerosis cohort. Lesion heterogeneity on susceptibility MRI may help explain disability in multiple sclerosis and provide a window into the processes of demyelination, oligodendrocyte loss, and chronic lesion inflammation. PMID:26939635

  3. Designing an Electronic Patient Management System for Multiple Sclerosis: Building a Next Generation Multiple Sclerosis Documentation System

    PubMed Central

    Kern, Raimar; Haase, Rocco; Eisele, Judith Christina; Thomas, Katja

    2016-01-01

    Background Technologies like electronic health records or telemedicine devices support the rapid mediation of health information and clinical data independent of time and location between patients and their physicians as well as among health care professionals. Today, every part of the treatment process from diagnosis, treatment selection, and application to patient education and long-term care may be enhanced by a quality-assured implementation of health information technology (HIT) that also takes data security standards and concerns into account. In order to increase the level of effectively realized benefits of eHealth services, a user-driven needs assessment should ensure the inclusion of health care professional perspectives into the process of technology development as we did in the development process of the Multiple Sclerosis Documentation System 3D. After analyzing the use of information technology by patients suffering from multiple sclerosis, we focused on the needs of neurological health care professionals and their handling of health information technology. Objective Therefore, we researched the status quo of eHealth adoption in neurological practices and clinics as well as health care professional opinions about potential benefits and requirements of eHealth services in the field of multiple sclerosis. Methods We conducted a paper-and-pencil–based mail survey in 2013 by sending our questionnaire to 600 randomly chosen neurological practices in Germany. The questionnaire consisted of 24 items covering characteristics of participating neurological practices (4 items), the current use of network technology and the Internet in such neurological practices (5 items), physicians’ attitudes toward the general and MS-related usefulness of eHealth systems (8 items) and toward the clinical documentation via electronic health records (4 items), and physicians’ knowledge about the Multiple Sclerosis Documentation System (3 items). Results From 600 mailed

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

    PubMed

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

    2017-01-13

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

  5. Quality Assessment in Multiple Sclerosis Therapy (QUASIMS): a comparison of interferon beta therapies for relapsing-remitting multiple sclerosis.

    PubMed

    Limmroth, Volker; Malessa, Rolf; Zettl, Uwe Klaus; Koehler, Jürgen; Japp, Gudrun; Haller, Peter; Elias, Wolfgang; Obhof, Winfried; Viehöver, Andrea; Meier, Uwe; Brosig, Arne; Hasford, Joerg; Putzki, Norman; Kalski, Gabriele; Wernsdörfer, Colin

    2007-01-01

    Interferon beta (IFN beta) preparations are the most frequently prescribed therapies for patients with relapsing multiple sclerosis (MS). Several open-label observational studies report similar efficacy among IFN beta preparations. The Quality Assessment in Multiple Sclerosis Therapy (QUASIMS) study is a large, open-label observational study designed to compare the effectiveness and tolerability of available IFN beta preparations as disease-modifying therapies for relapsing MS across a wide range of clinical practice settings. This retrospective, controlled cohort study was conducted by chart review at 510 sites in Germany, Austria, and Switzerland. Enrolled patients had received one of the four available IFN beta preparations/dosing regimens (intramuscular IFN beta-1a 30 microg 1x/week [Avonex], subcutaneous (SC) IFN beta-1a 22 or 44 microg 3 x/week [Rebif], or SC IFN beta-1b 250 microg 3.5x/week [Betaferon/Betaseron]) for >or= 2 years. Pre-planned outcomes at 1 and 2 years included change from baseline Expanded Disability Status Scale (EDSS) score, percentage of progression-free patients (< 1.0 EDSS point), annualised relapse rate (RR), percentage of relapse-free patients, and reasons for therapy change. Of 4754 evaluable patients, 3991 (84%) received IFN beta as initial therapy. There were no significant differences among IFN betas when used as initial or follow-up therapy on almost all outcome variables. Relapse rate was consistently higher and percentage of relapse-free patients consistently lower for all products used as follow-up versus initial therapy. Results of QUASIMS showed similar effectiveness among IFN beta products. Benefits were consistently superior when IFN beta was used as initial rather than follow-up therapy. Our results suggest that patients do not benefit in terms of disease outcome from switching between IFN beta preparations/dosing regimens.

  6. Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis

    SciTech Connect

    Vecsei, L.; Csala, B.; Widerloev, E.E.; Ekman, R.; Czopf, J.; Palffy, G. )

    1990-09-01

    The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

  7. Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

    SciTech Connect

    Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

    1987-11-01

    We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases.

  8. [Multiple sclerosis: etiology, epidemiology, some questions of pathogenicity].

    PubMed

    Chuprina, H M

    2012-01-01

    In the article the questions of ways of development of the dissipated sclerosis, as nosologies, are affected from the group of autoimmune diseases. Examined etiology, epidedemiologiya, separate links of pathogeny of the dissipated sclerosis. The analysis of multifaktors of his origin is conducted, with the detailed study of internal and external factors, marked on the important role of inherited predisposition, infectious and klimato-geograficheskogo factors in genesis of the dissipated sclerosis.

  9. Oligoclonal bands predict multiple sclerosis in children with optic neuritis.

    PubMed

    Heussinger, Nicole; Kontopantelis, Evangelos; Gburek-Augustat, Janina; Jenke, Andreas; Vollrath, Gesa; Korinthenberg, Rudolf; Hofstetter, Peter; Meyer, Sascha; Brecht, Isabel; Kornek, Barbara; Herkenrath, Peter; Schimmel, Mareike; Wenner, Kirsten; Häusler, Martin; Lutz, Soeren; Karenfort, Michael; Blaschek, Astrid; Smitka, Martin; Karch, Stephanie; Piepkorn, Martin; Rostasy, Kevin; Lücke, Thomas; Weber, Peter; Trollmann, Regina; Klepper, Jörg; Häussler, Martin; Hofmann, Regina; Weissert, Robert; Merkenschlager, Andreas; Buttmann, Mathias

    2015-06-01

    We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow-up of 4.0 years. Multiple Cox proportional-hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39-10.39, p < 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32-5.86, p < 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02-1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84-fold higher HR for developing MS compared to double negativity (95% CI = 12.26-58.74, p < 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON.

  10. Fatigue in Multiple Sclerosis: Misconceptions and Future Research Directions

    PubMed Central

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

    2016-01-01

    Fatigue is one of the most disabling side effects in people with multiple sclerosis. While this fact is well known, there has been a remarkable lack of progress in determining the pathophysiological mechanisms behind fatigue and the establishment of effective treatments. The main barrier has been the lack of a unified definition of fatigue that can be objectively tested with validated experimental models. In this “perspective article” we propose the use of the following model and definition of fatigue: the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors. These changes depend on the task being performed, the environmental conditions it is performed in, and the physical and mental capacity of the individual. Our definition and model of fatigue outlines specific causes of fatigue and how it affects task performance. We also outline the strengths and weaknesses of commonly used measures of fatigue and suggest, based on our model and definition, new research strategies, which should include multiple measures. These studies should be mechanistic with validated experimental models to determine changes in central, psychological, and/or peripheral factors that explain fatigue. The proposed new research strategies may lead to the identification of the origins of MS related fatigue and the development of new, more effective treatments. PMID:27531990

  11. Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

    PubMed Central

    Hernández-Pedro, Norma Y.; de la Cruz, Verónica Pérez; Pineda, Benjamín; Sotelo, Julio

    2013-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. Activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurological deficit. The immunological phenomena that lead to the activation of autoreactive T cells to myelin sheath components are the result of multiple and complex interactions between environment and genetic background conferring individual susceptibility. Within the CNS, an increase of TLR expression during MS is observed, even in the absence of any apparent microbial involvement. In the present review, we focus on the role of the innate immune system, the first line of defense of the organism, as promoter and mediator of cross reactions that generate molecular mimicry triggering the inflammatory response through an adaptive cytotoxic response in MS. PMID:24174969

  12. Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination

    PubMed Central

    Podbielska, Maria; Banik, Naren L.; Kurowska, Ewa; Hogan, Edward L.

    2013-01-01

    Multiple sclerosis (MS) is the most common demyelinating and an autoimmune disease of the central nervous system characterized by immune-mediated myelin and axonal damage, and chronic axonal loss attributable to the absence of myelin sheaths. T cell subsets (Th1, Th2, Th17, CD8+, NKT, CD4+CD25+ T regulatory cells) and B cells are involved in this disorder, thus new MS therapies seek damage prevention by resetting multiple components of the immune system. The currently approved therapies are immunoregulatory and reduce the number and rate of lesion formation but are only partially effective. This review summarizes current understanding of the processes at issue: myelination, demyelination and remyelination—with emphasis upon myelin composition/architecture and oligodendrocyte maturation and differentiation. The translational options target oligodendrocyte protection and myelin repair in animal models and assess their relevance in human. Remyelination may be enhanced by signals that promote myelin formation and repair. The crucial question of why remyelination fails is approached is several ways by examining the role in remyelination of available MS medications and avenues being actively pursued to promote remyelination including: (i) cytokine-based immune-intervention (targeting calpain inhibition), (ii) antigen-based immunomodulation (targeting glycolipid-reactive iNKT cells and sphingoid mediated inflammation) and (iii) recombinant monoclonal antibodies-induced remyelination. PMID:24961530

  13. Longitudinal multiple sclerosis lesion segmentation: Resource and challenge.

    PubMed

    Carass, Aaron; Roy, Snehashis; Jog, Amod; Cuzzocreo, Jennifer L; Magrath, Elizabeth; Gherman, Adrian; Button, Julia; Nguyen, James; Prados, Ferran; Sudre, Carole H; Jorge Cardoso, Manuel; Cawley, Niamh; Ciccarelli, Olga; Wheeler-Kingshott, Claudia A M; Ourselin, Sébastien; Catanese, Laurence; Deshpande, Hrishikesh; Maurel, Pierre; Commowick, Olivier; Barillot, Christian; Tomas-Fernandez, Xavier; Warfield, Simon K; Vaidya, Suthirth; Chunduru, Abhijith; Muthuganapathy, Ramanathan; Krishnamurthi, Ganapathy; Jesson, Andrew; Arbel, Tal; Maier, Oskar; Handels, Heinz; Iheme, Leonardo O; Unay, Devrim; Jain, Saurabh; Sima, Diana M; Smeets, Dirk; Ghafoorian, Mohsen; Platel, Bram; Birenbaum, Ariel; Greenspan, Hayit; Bazin, Pierre-Louis; Calabresi, Peter A; Crainiceanu, Ciprian M; Ellingsen, Lotta M; Reich, Daniel S; Prince, Jerry L; Pham, Dzung L

    2017-03-01

    In conjunction with the ISBI 2015 conference, we organized a longitudinal lesion segmentation challenge providing training and test data to registered participants. The training data consisted of five subjects with a mean of 4.4 time-points, and test data of fourteen subjects with a mean of 4.4 time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. Eleven teams submitted results using state-of-the-art lesion segmentation algorithms to the challenge, with ten teams presenting their results at the conference. We present a quantitative evaluation comparing the consistency of the two raters as well as exploring the performance of the eleven submitted results in addition to three other lesion segmentation algorithms. The challenge presented three unique opportunities: (1) the sharing of a rich data set; (2) collaboration and comparison of the various avenues of research being pursued in the community; and (3) a review and refinement of the evaluation metrics currently in use. We report on the performance of the challenge participants, as well as the construction and evaluation of a consensus delineation. The image data and manual delineations will continue to be available for download, through an evaluation website(2) as a resource for future researchers in the area. This data resource provides a platform to compare existing methods in a fair and consistent manner to each other and multiple manual raters.

  14. Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis

    PubMed Central

    2017-01-01

    Background: Current disease-modifying therapies (DMTs) are of benefit only in people with relapsing forms of multiple sclerosis (RMS). Thus, safely stopping DMTs in people with secondary progressive MS may be possible. Methods: Two groups of patients with MS were studied. Group A consisted of 77 patients with secondary progressive MS and no evidence of acute central nervous system inflammation for 2 to 20 years. These patients were advised to stop DMTs. Group B consisted of 17 individuals with RMS who stopped DMTs on their own. Both groups were evaluated at treatment cessation and for a minimum of 1 year thereafter. Multiple variables were assessed to determine those that predicted recurrent acute disease. Results: Nine patients in group A (11.7%) and ten patients in group B (58.8%) had recurrent acute disease, almost always within 1 to 2 years of stopping treatment. The only variable of significance in group A distinguishing stable and relapsing patients was age (P = .0003), with relapsing patients being younger. Group B patients were younger and had significantly lower Expanded Disability Status Scale scores than group A, with no significant differences in age between relapsed and stable patients. Conclusions: The DMTs can be stopped safely in older patients with MS (≥7 decades) with no evidence of acute disease for 2 years or longer, with an almost 90% probability of remaining free of acute recurrence. The high proportion of untreated patients with RMS experiencing recurrent acute disease is consistent with published data. PMID:28243181

  15. Neurological manifestations of connective tissue diseases mimicking multiple sclerosis.

    PubMed

    Pelidou, Sigliti-Henrietta; Giannopoulos, Sotiris; Tzavidi, Sotiria; Tsifetaki, Niki; Kitsos, Georgios; Stefanou, Dimitrios; Kostadima, Vassiliki; Drosos, Alexandros A; Kyritsis, Athanassios P

    2007-11-01

    The objective of the study was to analyze retrospectively the clinical, laboratory and imaging findings of multiple sclerosis (MS), such as the manifestations in a cohort of 132 patients referred to the neurology in and outpatient clinic. The proposed clinical and laboratory diagnostic criteria for MS and connective tissue disorders were systematically assessed in 132 consecutive patients. Cerebrospinal fluid serology and brain or spinal cord MRI were studied in all cases. In patients suspected for connective tissue disorder, schirmer test, rose bengal staining and biopsy of minor salivary glands were performed. A total of 115 (87%) patients were diagnosed to have definite MS, while 17 (13%) were diagnosed to have connective tissue disorder. Positive neurological and MRI findings were observed in both groups. The majority of patients with connective tissue disorder demonstrated extra-neurological manifestations like Raynaud's phenomenon, arthritis, livedo reticularis, purpura and presence of multiple autoantibodies in their sera. All patients with MS should be screened systematically for connective tissue disorder. In the absence of pathognomonic clinical and laboratory findings, the diagnosis of MS is a diagnosis of exclusion.

  16. Cognitive Rehabilitation in Multiple Sclerosis: The Role of Plasticity

    PubMed Central

    Chiaravalloti, Nancy D.; Genova, Helen M.; DeLuca, John

    2015-01-01

    Cognitive deficits are common in multiple sclerosis (MS), documented at many stages of the disease. Both structural and functional neuroimaging have demonstrated a relationship with cognitive abilities in MS. Significant neuroplasticity of cognitive functions in individuals with MS is evident. Homologous region adaptation, local activation expansion, and extra-region recruitment all occur in an effort to maintain cognitive functioning. While much of this neuroplasticity is adaptive, it may also be maladaptive, particularly in individuals that are demonstrating significant cognitive impairment and/or with disease progression. This maladaptive neuroplasticity may come at the cost of other cognitive functions. Studies of cognitive rehabilitation efficacy have also recently applied neuroimaging techniques to establish outcome. Researchers have successfully applied various neuroimaging techniques to study the effects of cognitive rehabilitation in MS including task-based fMRI and resting state functional connectivity across multiple realms of cognition including episodic memory, executive functioning, attention, and processing speed. These studies have demonstrated neuroplasticity in the brains of persons with MS through the documentation of changes at the level of the cerebral substrate from before to after non-invasive, non-pharmacological, behavioral treatment for deficits in cognition. Future research should seek to identify adaptive versus maladaptive neuroplasticity associated with specific cognitive rehabilitation programs within all MS phenotypes to foster the validation of the most effective cognitive rehabilitation interventions for persons with MS. PMID:25883585

  17. Emotional Intelligence (EI) of Patients with Multiple Sclerosis (MS)

    PubMed Central

    GHAJARZADEH, Mahsa; OWJI, Mahsa; SAURAIAN, Mohammad Ali; NASER MOGHADASI, Abdorreza; AZIMI, Amirreza

    2014-01-01

    Abstract Background Multiple sclerosis (MS) is an autoimmune disease that affects physical and emotional aspects of patient’s lives. The aim of this study was to evaluate Emotional Intelligence (EI) in cases with MS. Methods One hundred sixty six clinically definite MS and 110 healthy subjects were enrolled in this study. All participants filled valid and reliable Persian version Emotional Quotient inventory (EQ-i) questionnaire, which had been developed due to Bar-On model. Results Mean EI total score and 12 out of 15 subscales were significantly different between patients and controls. Total EI score and most of its subscales were significantly higher in patients with RR (Relapsing Remitting) than Secondary Progressive (SP) ones. There was significant negative correlation between EDSS and total EI score (rho=-0.4, P<0.001). Multiple linear regression analysis between the EI as a dependent variable and sex, type of disease, level of education, age and marital status as independent variables in patients showed that type of disease and level of education were independent predictors of EI. Conclusion Emotional intelligence as the ability to behave better and communicate with others should be considered in MS cases as their physical and psychological health are affected by their illness. PMID:26060723

  18. Multiple Sclerosis Lesion Detection Using Constrained GMM and Curve Evolution

    PubMed Central

    Freifeld, Oren; Greenspan, Hayit; Goldberger, Jacob

    2009-01-01

    This paper focuses on the detection and segmentation of Multiple Sclerosis (MS) lesions in magnetic resonance (MRI) brain images. To capture the complex tissue spatial layout, a probabilistic model termed Constrained Gaussian Mixture Model (CGMM) is proposed based on a mixture of multiple spatially oriented Gaussians per tissue. The intensity of a tissue is considered a global parameter and is constrained, by a parameter-tying scheme, to be the same value for the entire set of Gaussians that are related to the same tissue. MS lesions are identified as outlier Gaussian components and are grouped to form a new class in addition to the healthy tissue classes. A probability-based curve evolution technique is used to refine the delineation of lesion boundaries. The proposed CGMM-CE algorithm is used to segment 3D MRI brain images with an arbitrary number of channels. The CGMM-CE algorithm is automated and does not require an atlas for initialization or parameter learning. Experimental results on both standard brain MRI simulation data and real data indicate that the proposed method outperforms previously suggested approaches, especially for highly noisy data. PMID:19756161

  19. Activities-Specific Balance Confidence in People with Multiple Sclerosis

    PubMed Central

    Nilsagård, Ylva; Carling, Anna; Forsberg, Anette

    2012-01-01

    Objective. To evaluate the validity of the Activities-specific Balance Confidence scale (ABC) in people with multiple sclerosis (PwMS). Design. A multicentre, cross-sectional study. Setting. Six rural and urban Swedish sites, including specialized units at hospitals and primary care centers. Participants. A sample of 84 PwMS with subjective gait and balance impairment but still able to walk 100 m (comparable with EDSS 1–6). Outcome Measures. Timed Up and Go, Timed Up and Gocog, 25-foot Timed Walk Test, Four Square Step Test, Dynamic Gait Index, Chair Stand Test, 12-item MS Walking Scale, self-reported falls, and use of assistive walking device were used for validation. Results. The concurrent convergent validity was moderate to good (0.50 to −0.75) with the highest correlation found for the 12-item MS Walking Scale. The ABC discriminated between multiple fallers and nonfallers but not between men and women. Ecological validity is suggested since ABC discriminated between users of assistive walking device and nonusers. The internal consistency was high at α = 0.95, and interitem correlations were between 0.30 and 0.83. Conclusion. This study supports the validity of the ABC for persons with mild-to-moderate MS. The participants lacked balance confidence in many everyday activities, likely restricting their participation in society. PMID:22919491

  20. Pathologic Heterogeneity Persists in Early Active Multiple Sclerosis Lesions

    PubMed Central

    Metz, Imke; Weigand, Stephen D; Popescu, Bogdan F G; Frischer, Josa M; Parisi, Joseph E; Guo, Yong; Lassmann, Hans; Brück, Wolfgang; Lucchinetti, Claudia F.

    2014-01-01

    Objective Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods Archival tissue samples derived from patients with pathologically confirmed CNS inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy, were analyzed immunohistochemically. Inclusion criteria was the presence of early active demyelinating lesions - required for immunopattern classification - obtained from the same patient at two or more time points. Results Among 1321 surgical biopsies consistent with MS, 22 cases met study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches. PMID:24771535

  1. Activities-specific balance confidence in people with multiple sclerosis.

    PubMed

    Nilsagård, Ylva; Carling, Anna; Forsberg, Anette

    2012-01-01

    Objective. To evaluate the validity of the Activities-specific Balance Confidence scale (ABC) in people with multiple sclerosis (PwMS). Design. A multicentre, cross-sectional study. Setting. Six rural and urban Swedish sites, including specialized units at hospitals and primary care centers. Participants. A sample of 84 PwMS with subjective gait and balance impairment but still able to walk 100 m (comparable with EDSS 1-6). Outcome Measures. Timed Up and Go, Timed Up and Go(cog), 25-foot Timed Walk Test, Four Square Step Test, Dynamic Gait Index, Chair Stand Test, 12-item MS Walking Scale, self-reported falls, and use of assistive walking device were used for validation. Results. The concurrent convergent validity was moderate to good (0.50 to -0.75) with the highest correlation found for the 12-item MS Walking Scale. The ABC discriminated between multiple fallers and nonfallers but not between men and women. Ecological validity is suggested since ABC discriminated between users of assistive walking device and nonusers. The internal consistency was high at α = 0.95, and interitem correlations were between 0.30 and 0.83. Conclusion. This study supports the validity of the ABC for persons with mild-to-moderate MS. The participants lacked balance confidence in many everyday activities, likely restricting their participation in society.

  2. Predicting habitual walking performance in multiple sclerosis: relevance of capacity and self-report measures.

    PubMed

    Gijbels, Domien; Alders, Geert; Van Hoof, Elke; Charlier, Caroline; Roelants, Machteld; Broekmans, Tom; Eijnde, Bert Op 't; Feys, Peter

    2010-05-01

    The objective was to establish the extent to which physical functioning capacity and self-report measures are able to predict the habitual walking performance in ambulatory persons with multiple sclerosis. Fifty persons with multiple sclerosis (Expanded Disability Status Scale, EDSS, 1.5-6.5) were tested on leg muscle strength as well as walking and balance capacity, and completed self-report indices on perceived physical functioning. Habitual walking performance, that is, the real amount of steps that is performed in the customary living environment, was registered by means of an ambulant accelerometer-based monitor during seven consecutive days. Mild (EDSS 1.5-4.0, n = 29) and moderate (EDSS 4.5-6.5, n = 21) multiple sclerosis subgroups were additionally distinguished as predictor variables and values were hypothesized to differ depending on multiple sclerosis severity and concomitant ambulatory function. Multiple regression analyses yielded a single most significant predictor for each (sub)group with other variables making no independent contribution to the variation in habitual walking performance. For the total study sample, this was the 6-Minute Walking Test (R(2) = 0.458, p < 0.01). In the mild multiple sclerosis subgroup, the 6-Minute Walking Test was again most predictive, yet to a modest degree (R(2) = 0. 187, p = 0.02). In the moderate multiple sclerosis subgroup, the 2-Minute Walking Test explained over half of the variance (R(2) = 0.532, p < 0.01). Habitual walking performance is best reflected by longer walking capacity tests. The extent to which it can be predicted based on clinical testing is larger in a multiple sclerosis patient sample with more severe walking disability. Ambulatory monitoring, however, includes aspects of community ambulation not captured in the clinic, and must be considered as an additional outcome for evaluating interventions in multiple sclerosis.

  3. Telerehabilitation for persons with multiple sclerosis. A Cochrane review.

    PubMed

    Khan, F; Amatya, B; Kesselring, J; Galea, M P

    2015-06-01

    A wide range of telerehabilitation interventions are trialled in persons with multiple sclerosis (pwMS). However, the evidence for their effectiveness is unclear. Aim of the review was to systematically assess the effectiveness and safety of telerehabilitation intervention in pwMS, the types of approaches that are effective (setting, type, intensity) and the outcomes (impairment, activity limitation and participation) that are affected. The search strategy comprised: Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Review Group Specialised Register (up to 9 July, 2014). Relevant journals and reference lists of identified studies were screened for additional data. Selected studies included randomized and controlled clinical trials that compared telerehabilitation intervention/s in pwMS with a control intervention (such as lower level or different types of intervention, minimal intervention; waiting-list controls, no treatment or usual care; interventions given in different settings). Best evidence synthesis was based on methodological quality using the GRADEpro software. Nine RCTs (N.=531 participants, 469 included in analyses) investigated a variety of telerehabilitation interventions in adults with MS. The interventions evaluated were complex, with more than one rehabilitation component and included physical activity, educational, behavioural and symptom management programmes. All studies scored "low" on the methodological quality assessment. Evidence from included studies provides 'low-level' evidence for reduction in short-term disability (and symptoms) such as fatigue. There was also "low-level" evidence supporting telerehabilitation in the longer term for improved functional activities, impairments (such as fatigue, pain, insomnia); and participation. There were limited data on process evaluation (participants'/therapists' satisfaction) and no data available for cost effectiveness. There were no adverse events reported as a result of

  4. Multiple sclerosis: a review of existing therapy and future prospects.

    PubMed

    Khan, O A

    1996-01-01

    Multiple sclerosis (MS) is an incurable neurological illness that frequently causes chronic disability. Neurologists broach the diagnosis with dread. "I'll end up in a wheel chair" is the anguished cry of the newly diagnosed and mostly young patients. The past decade has improved our understanding of the immunopathogenesis of MS enormously. This has led to a plethora of clinical trials and the resultant emergence of several new drugs in various stages of development. In 1993, Food and Drug Administration (FDA) approved Betaseron for the treatment of MS. Todate, this is the only drug approved by the FDA, specifically for the treatment of MS. However, it would not be too long before several other drugs are approved, leaving the neurologist bewildered having gone from a state of practically little to offer to a state of several options to choose from. This review discusses the status of current and future therapy in the treatment of MS. Multiple sclerosis (MS) is the most common demyelinating disease of the human central nervous system (CNS). Medline includes over 13000 articles on MS since 1966 that exclude book chapters and other references. MS typically affects the youth and women more than men, between the ages of twenty and forty. Clinically, the illness is characterized into a relapsing-remitting (RR) or chronic progressive (CP) stage although more precisely defined stages exist for research purposes. It tends to follow a highly unpredictable course leading to chronic and sometimes devastating disability. More recently, follow up data suggested that the disease may fall into a pattern after several years. Despite decades of hectic research and better understanding of immunological mechanisms involving human CNS disease, the cause of MS remains unknown. However, it is widely believed that MS is the result of an autoimmune disorder in a genetically susceptible individual, mediated by autoreactive T cells that migrate into the CNS and initiate the inflammatory

  5. Hydroxycitric acid ameliorates inflammation and oxidative stress in mouse models of multiple sclerosis

    PubMed Central

    Goudarzvand, Mahdi; Afraei, Sanaz; Yaslianifard, Somaye; Ghiasy, Saleh; Sadri, Ghazal; Kalvandi, Mustafa; Alinia, Tina; Mohebbi, Ali; Yazdani, Reza; Azarian, Shahin Khadem; Mirshafiey, Abbas; Azizi, Gholamreza

    2016-01-01

    Hydroxycitric acid (HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis, using Complete Freund's Adjuvant (CFA) emulsion containing myelin oligodendrocyte glycoprotein (35–55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reductase activities. These findings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inflammation and oxidative stress. PMID:27904492

  6. Biopsy Proven Tumefactive Multiple Sclerosis with Concomitant Glioma: Case Report and Review of the Literature

    PubMed Central

    Golombievski, Esteban E.; McCoyd, Matthew A.; Lee, John M.; Schneck, Michael J.

    2015-01-01

    We report a case of pathologically confirmed tumefactive multiple sclerosis (MS) followed shortly thereafter by the diagnosis of an oligoastrocytoma. The complexity of diagnosis and management of concomitant presence of tumefactive MS and glial cell tumors is discussed. PMID:26236276

  7. The Impact of Disability on the Career Development of People with Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Salomone, Paul R.; O'Connell, Kathryn R.

    1998-01-01

    Interviews with 12 people with multiple sclerosis explored the meaning of career and work in their lives and the implications of living with a disability, as well as barriers they faced, particularly environmental barriers and societal attitudes. (SK)

  8. CT of multiple sclerosis: reassessment of delayed scanning with high doses of contrast material

    SciTech Connect

    Spiegel, S.M.; Vinuela, F.; Fox, A.J.; Pelz, D.M.

    1985-09-01

    A prospective study involving 87 patients was carried out to evaluate the necessity for a high dose of contrast material in addition to delayed computed tomographic (CT) scanning for optimal detection of the lesions of multiple sclerosis in the brain. In patients with either clinically definite multiple sclerosis or laboratory-supported definite multiple sclerosis, CT scans were obtained with a uniform protocol. Lesions consistent with multiple sclerosis were demonstrated on the second scan in 54 patients. In 36 of these 54 patients, the high-dose delayed scan added information. These results are quite similar to those of a previous study from this institution using different patients, in whom the second scan was obtained immediately after the bolus injection of contrast material containing 40 g of organically bound iodine. The lack of real difference in the results of the two studies indicate that the increased dose, not just the delay in scanning, is necessary for a proper study.

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

    ERIC Educational Resources Information Center

    Dyck, Isabel; Jongbloed, Lyn

    2000-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. T lymphocyte-derived demyelinating activity in multiple sclerosis patients in relapse.

    PubMed Central

    Selmaj, K; Alam, R; Perkin, G D; Rose, F C

    1987-01-01

    Supernatants of cultured T lymphocytes of multiple sclerosis patients were tested for a demyelinating activity in rat cerebellum explant cultures. Supernatants of unstimulated T lymphocytes in seven out of 10 multiple sclerosis patients in relapse produced demyelination when checked by phase contrast microscopy. Supernatants of unstimulated T lymphocytes from healthy subjects did not produce demyelination, but when T cells were stimulated by phytohaemagglutinin (PHA), 50% of tested supernatants produced demyelination, which was, however, never as advanced as in multiple sclerosis supernatant treated cerebellum cultures. The demyelinating activity proved to be heat labile. Gel filtration study revealed two fractions of the demyelinating activity 12.5-29.0 kD and 43.0-66.0 kD. The results suggest that lymphokines can be directly involved in the pathogenesis of demyelination in multiple sclerosis. Images PMID:3495638

  12. Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

    PubMed

    Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

    2017-03-01

    Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple

  13. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis

    PubMed Central

    Zamboni, P; Galeotti, R; Menegatti, E; Malagoni, A M; Tacconi, G; Dall’Ara, S; Bartolomei, I; Salvi, F

    2009-01-01

    Background: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated. Methods: Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent a combined transcranial and extracranial colour-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement. Results: CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated with CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher. Conclusion: CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease. PMID:19060024

  14. Children with multiple sclerosis should not become therapeutic hostages

    PubMed Central

    Rose, Klaus; Müller, Thomas

    2016-01-01

    Background: Both the United States (US) Food and Drug Administration (FDA) and the European Union (EU) European Medicines Agency (EMA) order pediatric clinical trials as a condition for approval of new compounds. We evaluate clinical value and likelihood of sufficient recruitment for pediatric multiple sclerosis (pMS) studies and discuss US and EU pediatric legislation with pMS as a paradigm. Methods: We analyzed pMS clinical trials requested by the FDA and the EMA and industry-sponsored pMS studies registered on www.clinicaltrials.gov and www.clinicaltrialsregister.eu. Results: The FDA demands four and the EMA 15 pMS trials Conclusions: pMS is rare. Neither FDA nor EMA prioritize compounds for potential benefit in pMS. The EMA in particular orders multiple pMS studies, which will probably not recruit enough patients. Therefore, it is likely that the pMS trial outcomes will not be relevant for evidence-based medicine analyses, clinical practice and a pMS label for the respective drug. EMA requests for multiple pediatric studies have been described in metastasized adolescent melanoma, another very rare pediatric disease. The terms ‘ghost studies’ and ‘therapeutic hostages’ have been proposed for such trials and children whose parents are lured into permitting study participation. Clinical studies are not ethical if the probability is high that they will not provide reasonable outcomes. For now, pMS clinicians will have to continue to use new MS drugs in children off-label. They might consider a more proactive international coordinating role in prioritizing and testing new MS compounds in children. PMID:27582894

  15. High frequency of psoriasis in relatives in a Turkish multiple sclerosis cohort.

    PubMed

    Dogan, Sibel; Atakan, Nilgün; Kurne, Asli; Karabudak, Rana

    2011-01-01

    Psoriasis was recently accepted as an autoimmune T cell-mediated disease. Various autoimmune disease associations for psoriasis have been defined, including multiple sclerosis, a model autoimmune demyelinating neurologic disorder. In this study, the familial frequency of psoriasis in a Turkish multiple sclerosis cohort was investigated, and a higher frequency of psoriasis was found, supporting the presence of a complex background of autoimmunity underlying psoriasis.

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

    PubMed

    Rubin, Keith; Glazer, Steven

    2016-04-01

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

  17. Inhibition of Th17 Cell Differentiation as a Treatment for Multiple Sclerosis

    DTIC Science & Technology

    2013-10-01

    0736 TITLE: Inhibition of Th17 Cell Differentiation as a Treatment for Multiple Sclerosis PRINCIPAL INVESTIGATOR: Annalisa D’Andrea, PhD...29September2013 4. TITLE AND SUBTITLE Inhibition of Th17 Cell Differentiation as a Treatment for Multiple Sclerosis 5a. CONTRACT NUMBER 5b...were not able to screen compounds. Additionally, experiments aimed to reproduce data showing an association of miR-326 with Th17 cells failed to

  18. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.

    PubMed

    Kalincik, Tomas; Vivek, Vino; Jokubaitis, Vilija; Lechner-Scott, Jeannette; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Grand'maison, Francois; Hupperts, Raymond; Oreja-Guevara, Celia; Bergamaschi, Roberto; Iuliano, Gerardo; Alroughani, Raed; Van Pesch, Vincent; Amato, Maria Pia; Slee, Mark; Verheul, Freek; Fernandez-Bolanos, Ricardo; Fiol, Marcela; Spitaleri, Daniele La; Cristiano, Edgardo; Gray, Orla; Cabrera-Gomez, Jose Antonio; Shaygannejad, Vahid; Herbert, Joseph; Vucic, Steve; Needham, Merilee; Petkovska-Boskova, Tatjana; Sirbu, Carmen-Adella; Duquette, Pierre; Girard, Marc; Grammond, Pierre; Boz, Cavit; Giuliani, Giorgio; Rio, Maria Edite; Barnett, Michael; Flechter, Shlomo; Moore, Fraser; Singhal, Bhim; Bacile, Elizabeth Alejandra; Saladino, Maria Laura; Shaw, Cameron; Skromne, Eli; Poehlau, Dieter; Vella, Norbert; Spelman, Timothy; Liew, Danny; Kilpatrick, Trevor J; Butzkueven, Helmut

    2013-12-01

    The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.

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

    PubMed Central

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

    2017-01-01

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

  20. Protein-Based Classifier to Predict Conversion from Clinically Isolated Syndrome to Multiple Sclerosis.

    PubMed

    Borràs, Eva; Cantó, Ester; Choi, Meena; Maria Villar, Luisa; Álvarez-Cermeño, José Carlos; Chiva, Cristina; Montalban, Xavier; Vitek, Olga; Comabella, Manuel; Sabidó, Eduard

    2016-01-01

    Multiple sclerosis is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. In most patients, the disease initiates with an episode of neurological disturbance referred to as clinically isolated syndrome, but not all patients with this syndrome develop multiple sclerosis over time, and currently, there is no clinical test that can conclusively establish whether a patient with a clinically isolated syndrome will eventually develop clinically defined multiple sclerosis. Here, we took advantage of the capabilities of targeted mass spectrometry to establish a diagnostic molecular classifier with high sensitivity and specificity able to differentiate between clinically isolated syndrome patients with a high and a low risk of developing multiple sclerosis. Based on the combination of abundances of proteins chitinase 3-like 1 and ala-β-his-dipeptidase in cerebrospinal fluid, we built a statistical model able to assign to each patient a precise probability of conversion to clinically defined multiple sclerosis. Our results are of special relevance for patients affected by multiple sclerosis as early treatment can prevent brain damage and slow down the disease progression.

  1. Detection of Protein Aggregates in Brain and Cerebrospinal Fluid Derived from Multiple Sclerosis Patients

    PubMed Central

    David, Monique Antoinette; Tayebi, Mourad

    2014-01-01

    Studies of the properties of soluble oligomer species of amyloidogenic proteins, derived from different proteins with little sequence homology, have indicated that they share a common structure and may share similar pathogenic mechanisms. Amyloid β, tau protein, as well as amyloid precursor protein normally associated with Alzheimer’s disease and Parkinson’s disease were found in lesions and plaques of multiple sclerosis patients. The objective of the study is to investigate whether brain and cerebrospinal fluid (CSF) samples derived from multiple sclerosis patients demonstrate the presence of soluble oligomers normally associated with protein-misfolding diseases such as Alzheimer’s disease. We have used anti-oligomer monoclonal antibodies to immunodetect soluble oligomers in CSF and brain tissues derived from multiple sclerosis patients. In this report, we describe the presence of soluble oligomers in the brain tissue and cerebral spinal fluid of multiple sclerosis patients detected with our monoclonal anti-oligomer antibodies with Western blot and Sandwich enzyme-linked immunosorbent assay (sELISA). These results might suggest that protein aggregation plays a role in multiple sclerosis pathogenesis although further and more refined studies are needed to confirm the role of soluble aggregates in multiple sclerosis. PMID:25520699

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

    PubMed

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

    2016-10-05

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

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

    PubMed

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

    2013-01-01

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

  4. Targeting Epstein-Barr virus infection as an intervention against multiple sclerosis.

    PubMed

    Jons, D; Sundström, P; Andersen, O

    2015-02-01

    We here review contemporary data on genetic and environmental risk factors, particularly Epstein-Barr virus infection, for multiple sclerosis. There is an important immunogenetic etiological factor for multiple sclerosis. However, a general assumption is that immune defense genes are activated by the environment, basically by infections. We contend that the relationship between infectious mononucleosis and multiple sclerosis cannot be completely explained by genetics and inverse causality. Epstein-Barr infection as indicated by positive serology is an obligatory precondition for multiple sclerosis, which is a stronger attribute than a risk factor only. Data on events in the early pathogenesis of multiple sclerosis are cumulating from bio-banks with presymptomatic specimens, but there is only little information from the critical age when Epstein-Barr infection including infectious mononucleosis is acquired, nor on the detailed immunological consequences of this infection in individuals with and without multiple sclerosis. We discuss how focused bio-banking may elaborate a rationale for the development of treatment or vaccination against Epstein-Barr virus infection. A cohort in which intervention against Epstein-Barr infections was performed should be the object of neurological follow-up.

  5. Protein-Based Classifier to Predict Conversion from Clinically Isolated Syndrome to Multiple Sclerosis*

    PubMed Central

    Borràs, Eva; Cantó, Ester; Choi, Meena; Maria Villar, Luisa; Álvarez-Cermeño, José Carlos; Chiva, Cristina; Montalban, Xavier; Vitek, Olga; Comabella, Manuel; Sabidó, Eduard

    2016-01-01

    Multiple sclerosis is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. In most patients, the disease initiates with an episode of neurological disturbance referred to as clinically isolated syndrome, but not all patients with this syndrome develop multiple sclerosis over time, and currently, there is no clinical test that can conclusively establish whether a patient with a clinically isolated syndrome will eventually develop clinically defined multiple sclerosis. Here, we took advantage of the capabilities of targeted mass spectrometry to establish a diagnostic molecular classifier with high sensitivity and specificity able to differentiate between clinically isolated syndrome patients with a high and a low risk of developing multiple sclerosis. Based on the combination of abundances of proteins chitinase 3-like 1 and ala-β-his-dipeptidase in cerebrospinal fluid, we built a statistical model able to assign to each patient a precise probability of conversion to clinically defined multiple sclerosis. Our results are of special relevance for patients affected by multiple sclerosis as early treatment can prevent brain damage and slow down the disease progression. PMID:26552840

  6. Longitudinal Changes in Self-Reported Walking Ability in Multiple Sclerosis

    PubMed Central

    Motl, Robert W.; Putzki, Norman; Pilutti, Lara A.; Cadavid, Diego

    2015-01-01

    Background Patient-reported outcomes are increasingly used to understand the clinical meaningfulness of multiple sclerosis disability and its treatments. For example, the 12-item Multiple Sclerosis Walking Scale (MSWS-12) measures the patient-reported impact of the disease on walking ability. Objective We studied longitudinal changes in walking ability using the MSWS-12 in a cohort of 108 patients with relapsing-remitting multiple sclerosis and moderate-to-severe disability from a single US center cohort study investigating multiple sclerosis symptoms and physical activity. Methods The MSWS-12 was completed every 6 months over 2 years together with self-reported measures of disease impact on daily life (Multiple Sclerosis Impact Scale) and walking disability (Patient Determined Disease Steps scale). Results The results revealed a high frequency of self-reported changes in walking ability at the individual level, affecting approximately 80% of patients for all four time periods. MSWS-12 scores remained stable at the group level for all four time periods. The magnitude of observed changes at the individual level was higher than the proposed minimal clinically important differences of 4 or 6 points and correlated better with Multiple Sclerosis Impact Scale physical scores than psychological scores, but little with self-reported Patient Determined Disease Steps Scale scores. Conclusions This novel finding of frequent fluctuations in self-reported walking ability is new and requires further investigation. PMID:25932911

  7. Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity.

    PubMed

    Guerau-de-Arellano, Mireia; Smith, Kristen M; Godlewski, Jakub; Liu, Yue; Winger, Ryan; Lawler, Sean E; Whitacre, Caroline C; Racke, Michael K; Lovett-Racke, Amy E

    2011-12-01

    Pro-inflammatory T cells mediate autoimmune demyelination in multiple sclerosis. However, the factors driving their development and multiple sclerosis susceptibility are incompletely understood. We investigated how micro-RNAs, newly described as post-transcriptional regulators of gene expression, contribute to pathogenic T-cell differentiation in multiple sclerosis. miR-128 and miR-27b were increased in naïve and miR-340 in memory CD4(+) T cells from patients with multiple sclerosis, inhibiting Th2 cell development and favouring pro-inflammatory Th1 responses. These effects were mediated by direct suppression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and interleukin-4 (IL4) expression, resulting in decreased GATA3 levels, and a Th2 to Th1 cytokine shift. Gain-of-function experiments with these micro-RNAs enhanced the encephalitogenic potential of myelin-specific T cells in experimental autoimmune encephalomyelitis. In addition, treatment of multiple sclerosis patient T cells with oligonucleotide micro-RNA inhibitors led to the restoration of Th2 responses. These data illustrate the biological significance and therapeutic potential of these micro-RNAs in regulating T-cell phenotypes in multiple sclerosis.

  8. Metabolomic signatures associated with disease severity in multiple sclerosis

    PubMed Central

    Alonso, Cristina; Agirrezabal, Ion; Kotelnikova, Ekaterina; Zubizarreta, Irati; Pulido-Valdeolivas, Irene; Saiz, Albert; Comabella, Manuel; Montalban, Xavier; Villar, Luisa; Alvarez-Cermeño, Jose Carlos; Fernández, Oscar; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Castro, Azucena

    2017-01-01

    Objective: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. Methods: We studied 2 cohorts of patients with MS: a retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS). Metabolomic profiling (lipids and amino acids) was performed by ultra-high-performance liquid chromatography coupled to mass spectrometry in serum samples. Data analysis was performed using parametric methods, principal component analysis, and partial least square discriminant analysis for assessing the differences between cases and controls and for subgroups based on disease severity. Results: We identified metabolomics signatures with high accuracy for classifying patients vs controls as well as for classifying patients with medium to high disability (EDSS >3.0). Among them, sphingomyelin and lysophosphatidylethanolamine were the metabolites that showed a more robust pattern in the time series analysis for discriminating between patients and controls. Moreover, levels of hydrocortisone, glutamic acid, tryptophan, eicosapentaenoic acid, 13S-hydroxyoctadecadienoic acid, lysophosphatidylcholines, and lysophosphatidylethanolamines were associated with more severe disease (non-relapse-free or increase in EDSS). Conclusions: We identified metabolomic signatures composed of hormones, lipids, and amino acids associated with MS and with a more severe course. PMID:28180139

  9. Excitotoxins, Mitochondrial and Redox Disturbances in Multiple Sclerosis

    PubMed Central

    Rajda, Cecilia; Pukoli, Dániel; Bende, Zsuzsanna; Majláth, Zsófia; Vécsei, László

    2017-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances. Mitochondrial dysfunction (energy disposal failure, apoptosis, etc.), redox disturbances (oxidative stress and enhanced reactive oxygen and nitrogen species production), and excitotoxicity (Glu mediated toxicity) may play an important role in the progression of the disease, causing axonal and neuronal damage. This review focuses on the mechanisms of mitochondrial dysfunction (including mitochondrial DNA (mtDNA) defects and mitochondrial structural/functional changes), oxidative stress (including reactive oxygen and nitric species), and excitotoxicity that are involved in MS and also discusses the potential targets and tools for therapeutic approaches in the future. PMID:28208701

  10. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

    PubMed Central

    Ksiazek-Winiarek, Dominika Justyna; Szpakowski, Piotr; Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

  11. Methylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis

    PubMed Central

    Wetzels, Suzan; Wouters, Kristiaan; Schalkwijk, Casper G.; Vanmierlo, Tim; Hendriks, Jerome J. A.

    2017-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The activation of inflammatory cells is crucial for the development of MS and is shown to induce intracellular glycolytic metabolism in pro-inflammatory microglia and macrophages, as well as CNS-resident astrocytes. Advanced glycation endproducts (AGEs) are stable endproducts formed by a reaction of the dicarbonyl compounds methylglyoxal (MGO) and glyoxal (GO) with amino acids in proteins, during glycolysis. This suggests that, in MS, MGO-derived AGEs are formed in glycolysis-driven cells. MGO and MGO-derived AGEs can further activate inflammatory cells by binding to the receptor for advanced glycation endproducts (RAGE). Recent studies have revealed that AGEs are increased in the plasma and brain of MS patients. Therefore, AGEs might contribute to the inflammatory status in MS. Moreover, the main detoxification system of dicarbonyl compounds, the glyoxalase system, seems to be affected in MS patients, which may contribute to high MGO-derived AGE levels. Altogether, evidence is emerging for a contributing role of AGEs in the pathology of MS. In this review, we provide an overview of the current knowledge on the involvement of AGEs in MS. PMID:28212304

  12. Black holes in multiple sclerosis: definition, evolution, and clinical correlations.

    PubMed

    Sahraian, M A; Radue, E-W; Haller, S; Kappos, L

    2010-07-01

    Magnetic resonance imaging (MRI) is a sensitive paraclinical test for diagnosis and assessment of disease progression in multiple sclerosis (MS) and is often used to evaluate therapeutic efficacy. The formation of new T2-hyperintense MRI lesions is commonly used to measure disease activity, but lacks specificity because edema, inflammation, gliosis, and axonal loss all contribute to T2 lesion formation. As the role of neurodegeneration in the pathophysiology of MS has become more prominent, the formation and evolution of chronic or persistent Tl-hypointense lesions (black holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. Despite the use of various detection methods, including advanced imaging techniques such as magnetization transfer imaging and magnetic resonance spectroscopy, correlation of persistent black holes with clinical outcomes in patients with MS remains uncertain. Furthermore, although axonal loss and neuronal tissue destruction are known to contribute to irreversible disability in patients with MS, there are limited data on the effect of therapy on longitudinal change in Tl-hypointense lesion volume. Measurement of black holes in clinical studies may elucidate the underlying pathophysiology of MS and may be an additional method of evaluating therapeutic efficacy.

  13. A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica.

    PubMed

    Gebregiworgis, Teklab; Nielsen, Helle H; Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Reddy, Jay; Illes, Zsolt; Powers, Robert

    2016-02-05

    Urine is a metabolite-rich biofluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum disorder (NMO-SD) patients and analyzed with NMR, multivariate statistics, one-way ANOVA, and univariate statistics. Urine from MS patients exhibited a statistically distinct metabolic signature from healthy and NMO-SD controls. A total of 27 metabolites were differentially altered in the urine from MS and NMO-SD patients and were associated with synthesis and degradation of ketone bodies, amino acids, propionate and pyruvate metabolism, tricarboxylic acid cycle, and glycolysis. Metabolites altered in urine from MS patients were shown to be related to known pathogenic processes relevant to MS, including alterations in energy and fatty acid metabolism, mitochondrial activity, and the gut microbiota.

  14. Multiple sclerosis: the role of melatonin and N-acetylserotonin.

    PubMed

    Anderson, George; Rodriguez, Moses

    2015-03-01

    Multiple sclerosis (MS) is an immune mediated disorder that is under intensive investigation in an attempt to improve on available treatments. Many of the changes occurring in MS, including increased mitochondrial dysfunction, pain reporting and depression may be partly mediated by increased indoleamine 2,3-dioxygenase, which drives tryptophan to the production of neuroregulatory tryptophan catabolites and away from serotonin, N-acetylserotonin and melatonin production. The consequences of decreased melatonin have classically been attributed to circadian changes following its release from the pineal gland. However, recent data shows that melatonin may be produced by all mitochondria containing cells to some degree, including astrocytes and immune cells, thereby providing another important MS treatment target. As well as being a powerful antioxidant, anti-inflammatory and antinociceptive, melatonin improves mitochondrial functioning, partly via increased oxidative phosphorylation. Melatonin also inhibits demyelination and increases remyelination, suggesting that its local regulation in white matter astrocytes by serotonin availability and apolipoprotein E4, among other potential factors, will be important in the etiology, course and treatment of MS. Here we review the role of local melatonin and its precursors, N-acetylserotonin and serotonin, in MS.

  15. Multiple sclerosis after infectious mononucleosis: record linkage study

    PubMed Central

    Goldacre, M.; Wotton, C.; Seagroatt, V.; Yeates, D.

    2004-01-01

    Objective: To ascertain if infectious mononucleosis is a risk factor for the development of multiple sclerosis (MS); and, if it is, whether its effect is close to or remote in time from the onset of MS. Design: Analysis of database of linked abstracts of records of hospital admission and death. Setting: Health region in central southern England. Main outcome measure: Ratio of rate of MS in a cohort of people admitted to hospital with infectious mononucleosis to the rate in a comparison cohort. Results: Considering all time intervals from admission with infection to admission with MS, there was a non-significant increase of risk of MS in the infectious mononucleosis cohort (rate ratio 2.17, 95% confidence intervals 0.79 to 4.77). At the interval of 10 years or more, there was a significant increase in risk of MS (rate ratio 4.01, 1.48 to 8.93). The mean time from infectious mononucleosis to first admission with MS was 14 years. Conclusion: This study adds support to the evidence that Epstein-Barr virus, the cause of infectious mononucleosis, is associated with MS. Its role is probably as an initiator of the disease process of MS, or as a contributor to its early development, rather than as an activator of latent, existing disease. PMID:15547068

  16. Risk evaluation and monitoring in multiple sclerosis therapeutics

    PubMed Central

    Wolinsky, Jerry S; Ashton, Raymond J; Hartung, Hans-Peter; Reingold, Stephen C

    2014-01-01

    Background: 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. Objectives: 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. Results: 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. Conclusions: 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. PMID:24293456

  17. Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis.

    PubMed

    Girolamo, Francesco; Coppola, Cristiana; Ribatti, Domenico; Trojano, Maria

    2014-07-22

    Angiogenesis, the formation of new vessels, is found in Multiple Sclerosis (MS) demyelinating lesions following Vascular Endothelial Growth Factor (VEGF) release and the production of several other angiogenic molecules. The increased energy demand of inflammatory cuffs and damaged neural cells explains the strong angiogenic response in plaques and surrounding white matter. An angiogenic response has also been documented in an experimental model of MS, experimental allergic encephalomyelitis (EAE), where blood-brain barrier disruption and vascular remodelling appeared in a pre-symptomatic disease phase. In both MS and EAE, VEGF acts as a pro-inflammatory factor in the early phase but its reduced responsivity in the late phase can disrupt neuroregenerative attempts, since VEGF naturally enhances neuron resistance to injury and regulates neural progenitor proliferation, migration, differentiation and oligodendrocyte precursor cell (OPC) survival and migration to demyelinated lesions. Angiogenesis, neurogenesis and oligodendroglia maturation are closely intertwined in the neurovascular niches of the subventricular zone, one of the preferential locations of inflammatory lesions in MS, and in all the other temporary vascular niches where the mutual fostering of angiogenesis and OPC maturation occurs. Angiogenesis, induced either by CNS inflammation or by hypoxic stimuli related to neurovascular uncoupling, appears to be ineffective in chronic MS due to a counterbalancing effect of vasoconstrictive mechanisms determined by the reduced axonal activity, astrocyte dysfunction, microglia secretion of free radical species and mitochondrial abnormalities. Thus, angiogenesis, that supplies several trophic factors, should be promoted in therapeutic neuroregeneration efforts to combat the progressive, degenerative phase of MS.

  18. The challenge of comorbidity in clinical trials for multiple sclerosis

    PubMed Central

    Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A.

    2016-01-01

    Objective: We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). Methods: We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. Results: We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Conclusion: Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to “real world” settings where the MS population commonly has comorbid conditions. PMID:26888986

  19. Recommendations for observational studies of comorbidity in multiple sclerosis

    PubMed Central

    Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Fiest, Kirsten; Reider, Nadia; Reingold, Stephen; Cohen, Jeffrey A.

    2016-01-01

    Objective: To reach consensus about the most relevant comorbidities to study in multiple sclerosis (MS) with respect to incidence, prevalence, and effect on outcomes; review datasets that may support studies of comorbidity in MS; and identify MS outcomes that should be prioritized in such studies. Methods: We held an international workshop to meet these objectives, informed by a systematic review of the incidence and prevalence of comorbidity in MS, and an international survey regarding research priorities for comorbidity. Results: We recommend establishing age- and sex-specific incidence and prevalence estimates for 5 comorbidities (depression, anxiety, hypertension, hyperlipidemia, and diabetes); evaluating the effect of 7 comorbidities (depression, anxiety, hypertension, diabetes, hyperlipidemia, chronic lung disease, and autoimmune diseases) on disability, quality of life, brain atrophy and other imaging parameters, health care utilization, employment, and mortality, including age, sex, race/ethnicity, socioeconomic status, and disease duration as potential confounders; harmonizing study designs across jurisdictions; and conducting such studies worldwide. Ultimately, clinical trials of treating comorbidity in MS are needed. Conclusion: Our recommendations will help address knowledge gaps regarding the incidence, prevalence, and effect of comorbidity on outcomes in MS. PMID:26865523

  20. The Meninges: New Therapeutic Targets For Multiple Sclerosis

    PubMed Central

    Russi, Abigail E.; Brown, Melissa A.

    2014-01-01

    The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. PMID:25241937

  1. CD4+ T cell activation in multiple sclerosis.

    PubMed

    Verselis, S J; Goust, J M

    1987-02-01

    Interleukin-2 (IL-2) production by CD4-enriched T cells from multiple sclerosis (MS) patients and normal individuals stimulated with concanavalin A (conA) and/or autologous and allogeneic B lymphoid cell lines (B-LCL) was evaluated 24, 48 and 96 h after stimulation. ConA-stimulated CD4+ cells from MS patients did not produce significantly more IL-2 than normal CD4+ cells. In contrast, autologous B-LCL-induced IL-2 production by MS CD4+ cells significantly (P = 0.026) exceeded that produced by normal CD4+ cells identically stimulated after 24 h in culture. Differences in IL-2 production by CD4+ cells from MS patients reached highest significance using allogeneic B-LCL, whose stimulatory capacity was similar, whether established from normal individuals or MS patients. This increased IL-2 production in response to B-LCL may represent a supranormal response of CD4+ cells from MS patients to class II major histocompatibility (MHC)-associated stimuli. It suggests that the deficiency of suppressor T cell functions postulated to play a role in MS does not arise from a lack of IL-2 induction and might indicate that bursts of IL-2 production could play a role in MS.

  2. Abnormal regulation of IgG production in multiple sclerosis.

    PubMed

    Goust, J M; Hogan, E L; Arnaud, P

    1982-03-01

    After stimulation with pokeweed mitogen (PWM), peripheral blood mononuclear cells (MNC) from patients with active multiple sclerosis (MS) produced significantly more IgG (8595 ng per milliliter, p less than 0.01) then MNC from normal age-matched controls (5477 ng per milliliter), whereas those tested during stable periods produced less IgG (4076 ng per milliliter, p less than 0.01). Treatment of MNC with sodium periodate (SP) generated suppressor cells for PWM-driven IgG production in normal controls and in most of the stable MS patients but in only 26% of those during active disease, in whom an increase in IgG production was often seen. This suggests a deficiency of inducible suppressor T cells associated with a supranormal B-cell response to polyclonal activation; T lymphocytes obtained from MS patients during active episodes strongly suppressed IgG production by normal B lymphocytes, whereas their B cells often produced more IgG in the presence of normal T cells. In active MS, a relative B-cell unresponsiveness to activated suppressor T cells would leave helper signals unbalanced, thus leading to increased B-cell activation, which might deplete the pool of inducible suppressor cells for IgG production.

  3. Multiple Sclerosis and Obesity: Possible Roles of Adipokines

    PubMed Central

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

    2016-01-01

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

  4. Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

    PubMed Central

    Katsavos, Serafeim; Anagnostouli, Maria

    2013-01-01

    During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the most important characteristics that a biomarker must possess in order to be considered as reliable. Additionally, up-to-date biomarkers are further divided into three subgroups, genetic-immunogenetic, laboratorial, and imaging. The most important representatives of each category are presented in the text and for the first time in a summarizing workable table, in a critical way, estimating their diagnostic potential and their efficacy to correlate with phenotypical expression, neuroinflammation, neurodegeneration, disability, and therapeutical response. Special attention is given to the “gold standards” of each category, like HLA-DRB1∗ polymorphisms, oligoclonal bands, vitamin D, and conventional and nonconventional imaging techniques. Moreover, not adequately established but quite promising, recently characterized biomarkers, like TOB-1 polymorphisms, are further discussed. PMID:23401777

  5. Oxidative modification of serum proteins in multiple sclerosis.

    PubMed

    Sadowska-Bartosz, Izabela; Adamczyk-Sowa, Monika; Galiniak, Sabina; Mucha, Sebastian; Pierzchala, Krystyna; Bartosz, Grzegorz

    2013-11-01

    Multiple sclerosis (MS) has been demonstrated to involve oxidative stress and augmented glycoxidation. In this study, several markers of protein oxidative damage and glycoxidation have been compared in 14 relapsing remittent in MS (RRMS) patients without immunomodifying treatment, 10 patients in clinical relapse, and clinically stable patient groups treated with interferon β 1a (18) , β 1b (19) and glatiramer acetate (GA; 6) in relation to healthy subjects (12). The glycophore content was increased in RRSM patients without treatment and in patients treated with GA. The level of advanced protein oxidation products (AOPP) was increased in RRSM patients without treatment and in patients with clinical relapse. The level of protein carbonyls was elevated in RRSM patients without treatment and in patients treated with interferon β 1b. The levels of dityrosine level and N'-formylkynureine were elevated in RRSM patients without treatment while serum protein thiol groups were decreased in RRSM patients in clinical relapse as well as RRMS patients treated with interferon β 1a. Several markers of protein modification showed correlation with the C-reactive protein level and white blood cell count, suggesting that oxidative protein modifications are linked to the inflammatory processes in MS. Results of this study confirm the occurrence of protein oxidative and glycoxidative damage in MS and show that spectrophotometric and fluorimetric markers of this damage, especially the AOPP level, may be useful in monitoring oxidative stress in the course of therapy of MS.

  6. FLT-3 Expression and Function on Microglia in Multiple Sclerosis

    PubMed Central

    DeBoy, Cynthia A.; Rus, Horea; Tegla, Cosmin; Cudrici, Cornelia; Jones, Melina V.; Pardo, Carlos A.; Small, Donald; Whartenby, Katharine A.; Calabresi, Peter A.

    2010-01-01

    Inflammatory cell infiltration and resident microglial activation within the central nervous system (CNS) are pathological events in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). While MS therapies target the peripheral immune system, no treatment is currently known to also modulate microglia. FMS-like tyrosine-3 (FLT-3) is expressed on hematopoietic and dendritic cells. We reported that FLT-3 inhibition ameliorates early actively induced EAE by predominantly modulating dendritic cell function as compared to microglia. We demonstrate in this report that FLT-3 is expressed in perivascular cuffs, brain parenchyma and in non-lesioned gray and white matter within MS brain but not in these regions within control brain. Furthermore, we demonstrate that FLT-3 is expressed on two populations of cells within MS brain; one which expresses the dendritic cell marker CD209, and the other which does not, suggesting that FLT-3 within MS brain is expressed on infiltrating dendritic cells and a non-dendritic cell such as microglia. Additionally, we report that FLT-3 inhibition in murine microglia blocks, in a dose dependent manner, IFN-γ-induced expression of MHC class II and CD86, and LPS-induced secretion of IL-6. These data suggest that FLT-3 is involved in microglial cell’s capacity to respond to environmental cues to function as antigen presenting cells and mediate CNS inflammation. Furthermore these data suggest that FLT-3 may be a therapeutic target on microglia to mitigate CNS inflammation. PMID:20566414

  7. An overview of assistive technology for persons with multiple sclerosis.

    PubMed

    Blake, Donna Jo; Bodine, Cathy

    2002-01-01

    Multiple sclerosis (MS) is a progressive neurologic disease clinically characterized by episodes of focal disorder of the cranial nerves, spinal cord, and the brain. MS affects a significant number of young adults, and they most often face a future of progressive functional losses as more of their central nervous system and cranial nerves are affected. As the disease progresses, they have new impairments with accompanying limitations in activities, restrictions to their participation in life, and compromised quality of life. Assistive technology includes any item that is used to maintain or improve functional capabilities. The rehabilitation healthcare provider has many opportunities to intervene with assistive technologies to decrease activity limitations and participation restrictions. The purpose of this article is to (1) review the impairments and associated activity limitations and participations restrictions experienced by persons with MS, (2) provide an overview of high- and low-tech assistive technologies appropriate for persons with MS, (3) discuss funding opportunities for assistive technologies, (4) review current studies of assistive technology used for persons with MS and discuss future research directions, and (5) consider assistive technology as an intervention for disability prevention.

  8. Two-locus linkage analysis in multiple sclerosis (MS)

    SciTech Connect

    Tienari, P.J. Univ. of Helsinki ); Terwilliger, J.D.; Ott, J. ); Palo, J. ); Peltonen, L. )

    1994-01-15

    One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

  9. Novel therapeutics in multiple sclerosis management: clinical applications.

    PubMed

    Leist, Thomas; Hunter, Samuel F; Kantor, Daniel; Markowitz, Clyde

    2014-01-01

    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.

  10. Anticipatory postural adjustments in individuals with multiple sclerosis.

    PubMed

    Krishnan, Vennila; Kanekar, Neeta; Aruin, Alexander S

    2012-01-11

    Individuals with multiple sclerosis (MS) frequently exhibit difficulties in balance maintenance. It is known that anticipatory postural adjustments (APAs) play an important role in postural control. However, no information exists on how people living with MS utilize APAs for control of posture. A group of individuals with MS and a group of healthy control subjects performed rapid arm flexion and extension movements while standing on a force platform. Electromyographic (EMG) activity of six trunk and leg muscles and displacement of center of pressure (COP) were recorded and quantified within the time intervals typical of APAs. Individuals with MS demonstrated diminished ability to produce directional specific patterns of anticipatory EMGs as compared to control subjects. In addition, individuals with MS demonstrated smaller magnitudes of anticipatory muscle activation. This was associated with larger displacements of the COP during the balance restoration phase. These results suggest the importance of anticipatory postural control in maintenance of vertical posture in individuals with MS. The outcome of the study could be used while developing rehabilitation strategies focused on balance restoration in individuals with MS.

  11. Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis

    PubMed Central

    Ahmetspahic, Diana; Ruck, Tobias; Schulte-Mecklenbeck, Andreas; Schwarte, Kathrin; Jörgens, Silke; Scheu, Stefanie; Windhagen, Susanne; Graefe, Bettina; Melzer, Nico; Klotz, Luisa; Arolt, Volker; Wiendl, Heinz; Meuth, Sven G.

    2016-01-01

    Objective: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. Methods: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)–23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined. Results: In comparison to CD4+ T lymphocytes, myeloid and lymphoid innate cell subsets of patients with MS expressed significantly lower amounts of CD52 on their cell surface. Six months after CD52 depletion, numbers of circulating plasmacytoid dendritic cells (DCs) and conventional DCs were reduced compared to baseline. GM-CSF and IL-23 production in DCs remained unchanged. Within the ILC compartment, the subset of CD56bright NK cells specifically expanded under alemtuzumab treatment, but their cytolytic activity did not change. Conclusions: Our findings demonstrate that 6 months after alemtuzumab treatment, specific DC subsets are reduced, while CD56bright NK cells expanded in patients with MS. Thus, alemtuzumab specifically restricts the DC compartment and expands the CD56bright NK cell subset with potential immunoregulatory properties in MS. We suggest that remodeling of the innate immune compartment may promote long-term efficacy of alemtuzumab and preserve immunocompetence in patients with MS. PMID:27766281

  12. Pain in multiple sclerosis: A systematic review of neuroimaging studies

    PubMed Central

    Seixas, D.; Foley, P.; Palace, J.; Lima, D.; Ramos, I.; Tracey, I.

    2014-01-01

    Introduction While pain in multiple sclerosis (MS) is common, in many cases the precise mechanisms are unclear. Neuroimaging studies could have a valuable role in investigating the aetiology of pain syndromes. The aim of this review was to synthesise and appraise the current literature on neuroimaging studies of pain syndromes in MS. Methods We systematically searched PubMed and Scopus from their inception dates to the 2nd of April 2013. Studies were selected by predefined inclusion and exclusion criteria. Methodological quality was appraised. Descriptive statistical analysis was conducted. Results We identified 38 studies of variable methodology and quality. All studies but one used conventional structural magnetic resonance imaging, and the majority reported a positive association between location of demyelinating lesions and specific neuropathic pain syndromes. Most investigated headache and facial pain, with more common pain syndromes such as limb pain being relatively understudied. We identified a number of methodological concerns, which along with variable study design and reporting limit our ability to synthesise data. Higher quality studies were however less likely to report positive associations of lesion distribution to pain syndromes. Conclusions Further high quality hypothesis-driven neuroimaging studies of pain syndromes in MS are required to clarify pain mechanisms, particularly for the commonest pain syndromes. PMID:25161898

  13. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background.

    PubMed

    Ksiazek-Winiarek, Dominika Justyna; Szpakowski, Piotr; Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets.

  14. Menarche Increases Relapse Risk in Pediatric Multiple Sclerosis

    PubMed Central

    Lulu, Sabeen; Graves, Jennifer; Waubant, Emmanuelle

    2015-01-01

    Background Multiple sclerosis (MS) predominantly affects women with a sex ratio of 3:1 in contrast with a 1:1 sex ratio seen in pre-pubertal onset. Thus, puberty may influence MS risk differentially in males and females. How puberty may be associated with MS clinical features and disease course remains unknown. Objective To determine the association of menarche with disease course in girls with MS. Methods This is a longitudinal retrospective study from the UCSF Regional Pediatric MS Center database. We categorized patients by time of disease onset: pre-menarche, peri-menarche and post-menarche. Poisson regression models were used for within subject relapse analyses offset by follow-up time. Results Seventy six girls were included (pre-menarche onset=17; peri-menarche onset=9; post-menarche onset=50). Age of menarche was similar in all groups (Kruskal-Wallis p=0.19). Relapse rate was the same in all three groups during first 2 years of follow-up. In girls with follow-up overlapping at least two time periods, within-subject analyses showed increased relapses during peri-menarche compared to post-menarche period (adjusted IRR=8.5, 95%CI 2.5–28.7, p=0.001). Conclusion Pubertal status may influence MS course at least in female patients. Understanding how puberty influences MS clinical features may offer new insights in important factors regulating disease processes. PMID:25948626

  15. Putaminal alteration in multiple sclerosis patients with spinal cord lesions.

    PubMed

    Zimmermann, Hilga; Rolfsnes, Hans O; Montag, Swantje; Wilting, Janine; Droby, Amgad; Reuter, Eva; Gawehn, Joachim; Zipp, Frauke; Gröger, Adriane

    2015-10-01

    Typical multiple sclerosis (MS) lesions occur in the brain as well as in the spinal cord. However, two extreme magnetic resonance imaging phenotypes appear occasionally: those with predominantly spinal cord lesions (MS + SL) and those with cerebral lesions and no detectable spinal lesions (MS + CL). We assessed whether morphological differences can be found between these two extreme phenotypes. We examined 19 patients with MS + SL, 18 with MS + CL and 20 controls. All subjects were examined using magnetic resonance imaging, including anatomical and diffusion tensor imaging sequences. Voxel-based morphologic and regions of interest-based analyses and tract-based spatial statistics were performed. Patients also underwent neuropsychological testing. Demographic, clinical and neuropsychological characteristics did not differ between MS + SL and MS + CL patients. Patients with MS + SL showed significantly larger putamen volumes than those with MS + CL which correlated negatively with disability. Compared to controls, only MS + CL revealed clear cortical and deep gray matter atrophy, which correlated with cerebral lesion volume. Additionally, extensive white matter microstructural damage was found only in MS + CL compared to MS + SL and controls in the tract-based spatial statistics. Higher putamen volumes in MS + SL could suggest compensatory mechanisms in this area responsible for motor control. Widely reduced fractional anisotropy values in MS + CL were caused by higher cerebral lesion volume and thus presumably stronger demyelination, which subsequently leads to higher global gray matter atrophy.

  16. Early and Degressive Putamen Atrophy in Multiple Sclerosis.

    PubMed

    Krämer, Julia; Meuth, Sven G; Tenberge, Jan-Gerd; Schiffler, Patrick; Wiendl, Heinz; Deppe, Michael

    2015-09-25

    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV). Patient's relative putamen volume (RPV), expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV) from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  17. Therapeutic strategies in multiple sclerosis. II. Long-term repair.

    PubMed Central

    Scolding, N

    1999-01-01

    Spontaneous myelin repair in multiple sclerosis (MS) provides a striking example of the brain's inherent capacity for sustained and stable regenerative tissue repair--but also clearly emphasizes the limitations of this capacity; remyelination ultimately fails widely in many patients, and disability and handicap accumulate. The observation of endogenous partial myelin repair has raised the possibility that therapeutic interventions designed to supplement or promote remyelination might have a useful and significant impact both in the short term, in restoring conduction, and in the long term, in safeguarding axons. Therapeutic remyelination interventions must involve manipulations to either the molecular or the cellular environment within lesions; both depend crucially on a detailed understanding of the biology of the repair process and of those glia implicated in spontaneous repair, or capable of contributing to exogenous repair. Here we explore the biology of myelin repair in MS, examining the glia responsible for successful remyelination, oligodendrocytes and Schwann cells, their 'target' cells, neurons and the roles of astrocytes. Options for therapeutic remyelinating strategies are reviewed, including glial cell transplantation and treatment with growth factors or other soluble molecules. Clinical aspects of remyelination therapies are considered--which patients, which lesions, which stage of the disease, and how to monitor an intervention--and the remaining obstacles and hazards to these approaches are discussed. PMID:10603622

  18. Multiple Sclerosis and Obesity: Possible Roles of Adipokines.

    PubMed

    Guerrero-García, José de Jesús; Carrera-Quintanar, Lucrecia; López-Roa, Rocío Ivette; Márquez-Aguirre, Ana Laura; Rojas-Mayorquín, Argelia Esperanza; Ortuño-Sahagún, Daniel

    2016-01-01

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

  19. Pain is Associated with Prospective Memory Dysfunction in Multiple Sclerosis

    PubMed Central

    Miller, Ashley K.; Basso, Michael R.; Candilis, Philip J.; Combs, Dennis R.; Woods, Steven Paul

    2014-01-01

    Prospective memory (PM) pertains to the execution of a future goal or behavior. Initial research implies that people with multiple sclerosis (MS) are apt to show impaired prospective memory for activities of daily living (Rendell, Jensen, & Henry, 2007; Rendell et al., 2012). Yet, PM impairment does not occur in all people with MS. Thus, some other variable besides disease status alone may contribute to PM dysfunction in people with MS. Chronic pain may be such a variable. Approximately 50-70% of people with MS experience significant pain, and such pain has been thought to diminish memory function (Moore, Keogh, and Eccleston, 2009). To investigate this possibility, 96 patients with MS and 29 healthy subjects were administered the Memory for Intentions Screening Test (MIST) (Raskin, Buckheit, & Sherrod, 2010), a well-validated measure of prospective memory, and the Medical Outcomes Study Pain Effects Scale (PES) (Fischer, Rudick, Cutter, & Reingold, 1999) to assess chronic pain. After controlling for demographic variables and disability severity, subjective pain accounted for significant variance in PM, particularly for time-based intentions over sustained delay periods. These data accord well with assertions that pain may degrade ability to remember new intentions, and suggests that pain is associated with PM dysfunction in people with MS. PMID:25338929

  20. An observational study of alemtuzumab following fingolimod for multiple sclerosis

    PubMed Central

    Willis, Mark; Pearson, Owen; Illes, Zsolt; Sejbaek, Tobias; Nielsen, Christian; Duddy, Martin; Petheram, Kate; van Munster, Caspar; Killestein, Joep; Malmeström, Clas; Tallantyre, Emma

    2017-01-01

    Objective: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. Methods: Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers. Results: Nine patients were identified. Median disease duration to alemtuzumab treatment was 94 (39–215) months and follow-up from time of first alemtuzumab cycle 20 (14–21) months. Following first alemtuzumab infusion cycle, 8 patients were identified by at least 1 clinical relapse and radiologic disease activity and 1 by significant radiologic disease activity alone. Conclusions: We acknowledge the potential for ascertainment bias; however, these cases may illustrate an important cause of reduced efficacy of alemtuzumab in a vulnerable group of patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive lymphocytes following fingolimod withdrawal, allowing these cells to be concealed from the usual biological effect of alemtuzumab. Subsequent lymphocyte egress then provokes disease reactivation. Further animal studies and clinical trials are required to confirm these phenomena and in the meantime careful consideration should be given to mode of action of individual therapies and sequential treatment effects in MS when designing personalized treatment regimens. PMID:28101520

  1. Methylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis.

    PubMed

    Wetzels, Suzan; Wouters, Kristiaan; Schalkwijk, Casper G; Vanmierlo, Tim; Hendriks, Jerome J A

    2017-02-15

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The activation of inflammatory cells is crucial for the development of MS and is shown to induce intracellular glycolytic metabolism in pro-inflammatory microglia and macrophages, as well as CNS-resident astrocytes. Advanced glycation endproducts (AGEs) are stable endproducts formed by a reaction of the dicarbonyl compounds methylglyoxal (MGO) and glyoxal (GO) with amino acids in proteins, during glycolysis. This suggests that, in MS, MGO-derived AGEs are formed in glycolysis-driven cells. MGO and MGO-derived AGEs can further activate inflammatory cells by binding to the receptor for advanced glycation endproducts (RAGE). Recent studies have revealed that AGEs are increased in the plasma and brain of MS patients. Therefore, AGEs might contribute to the inflammatory status in MS. Moreover, the main detoxification system of dicarbonyl compounds, the glyoxalase system, seems to be affected in MS patients, which may contribute to high MGO-derived AGE levels. Altogether, evidence is emerging for a contributing role of AGEs in the pathology of MS. In this review, we provide an overview of the current knowledge on the involvement of AGEs in MS.

  2. Brain-immune communication psychoneuroimmunology of multiple sclerosis.

    PubMed

    Kern, S; Ziemssen, T

    2008-01-01

    The central nervous system (CNS) and the immune system are two extremely complex and highly adaptive systems. In the face of a real or anticipated threat, be it physical (eg, infection) or psychological (eg, psychosocial stress) in nature, the two systems act in concert to provide optimal adaptation to the demanding internal or environmental conditions. During instances of well being, the communication between these two systems is well tuned and balanced. However, a disturbed crosstalk between the CNS and the immune system is thought to play a major role in a wide series of disorders characterized by a hyporesponsive or hyperresponsive immune system. In multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease, an excess of inflammatory processes seems to be a hallmark and there is growing evidence for a disturbed communication between the CNS and the immune system as a crucial pathogenic factor. While the exact mechanisms for these phenomena are still poorly understood, the young discipline of psychoneuroimmunology (PNI), which focuses on the mechanism underlying the brain to immune crosstalk, might offer some insights into the existing pathogenic mechanisms. Findings from the field of PNI might also help to gain a better understanding regarding the origin and course of MS clinical symptoms such as fatigue and depression.

  3. Metabolic Reprograming of Mononuclear Phagocytes in Progressive Multiple Sclerosis

    PubMed Central

    Tannahill, Gillian Margaret; Iraci, Nunzio; Gaude, Edoardo; Frezza, Christian; Pluchino, Stefano

    2015-01-01

    Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Accumulation of brain damage in progressive MS is partly the result of mononuclear phagocytes (MPs) attacking myelin sheaths in the CNS. Although there is no cure yet for MS, significant advances have been made in the development of disease modifying agents. Unfortunately, most of these drugs fail to reverse established neurological deficits and can have adverse effects. Recent evidence suggests that MPs polarization is accompanied by profound metabolic changes, whereby pro-inflammatory MPs (M1) switch toward glycolysis, whereas anti-inflammatory MPs (M2) become more oxidative. It is therefore possible that reprograming MPs metabolism could affect their function and repress immune cell activation. This mini review describes the metabolic changes underpinning macrophages polarization and anticipates how metabolic re-education of MPs could be used for the treatment of MS. Key points: Inflammation in progressive MS is mediated primarily by MPs.Cell metabolism regulates the function of MPs.DMAs can re-educate the metabolism of MPs to promote healing. PMID:25814990

  4. Induced stem cells as a novel multiple sclerosis therapy

    PubMed Central

    Xie, Chong; Liu, Yan-qun; Guan, Yang-tai; Zhang, Guang-Xian

    2016-01-01

    Stem cell replacement is providing hope for many degenerative diseases that lack effective therapeutic methods including multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Transplantation of neural stem cells or mesenchymal stem cells is a potential therapy for MS thanks to their capacity for cell repopulation as well as for their immunomodulatory and neurotrophic properties. Induced pluripotent stem cell (iPSC), an emerging cell source in regenerative medicine, is also being tested for the treatment of MS. Remarkable improvement in mobility and robust remyelination have been observed after transplantation of iPSC-derived neural cells into demyelinated models. Direct reprogramming of somatic cells into induced neural cells, such as induced neural stem cells (iNSCs) and induced oligodendrocyte progenitor cells (iOPCs), without passing through the pluripotency stage, is an alternative for transplantation that has been proved effective in the congenital hypomyelination model. iPSC technology is rapidly progressing as efforts are being made to increase the efficiency of iPSC therapy and reduce its potential side effects. In this review, we discuss the recent advances in application of stem cells, with particular focus on induced stem/progenitor cells (iPSCs, iNSC, iOPCs), which are promising in the treatment of MS. PMID:25732737

  5. Capturing the worlds of multiple sclerosis: Hannah Laycock's photography.

    PubMed

    Bolaki, Stella

    2017-03-01

    This essay explores UK photographer Hannah Laycock's Awakenings and, to a lesser extent, Perceiving Identity that were created in 2015, following her diagnosis with multiple sclerosis (MS) in 2013. It draws on scholarship by people with chronic illness while situating these two MS projects in the context of Laycock's earlier art and portrait photography dealing with fragility, image and desire, and power relations between subject and observer. The analysis illustrates how her evocative photography captures the lived or subjective experience of an invisible and often misunderstood condition by initially focusing on the tension between transparency and opacity in her work. It further shows how her images counter dominant didactic metaphors such as, 'the body as machine', that perpetuate the dehumanising and objectifying aspects of medical care. Subsequent sections trace the influence that Oliver Sacks has had on Laycock's practice, and reflect on other metaphors and tropes in Awakenings that illuminate the relationship between body and self in MS. The essay concludes by acknowledging the therapeutic power of art and calling upon health professionals to make more use of such artistic work in clinical practice.

  6. Physical activity and pediatric multiple sclerosis: Developing a research agenda.

    PubMed

    Yeh, E Ann; Kinnett-Hopkins, Dominique; Grover, Stephanie A; Motl, Robert W

    2015-11-01

    Three-quarters of children with multiple sclerosis (MS) experience fatigue or depression, and progressive neurocognitive decline may be seen as early as two years after MS diagnosis. Furthermore, a higher magnetic resonance imaging disease burden is seen in pediatric-onset MS compared with adult-onset MS. To date, limited knowledge exists regarding behavioral methods for managing symptoms and disease progression in pediatric MS. To that end, this paper builds an evidence-based argument for the possible symptomatic and disease-modifying effects of exercise and physical activity in pediatric MS. This will be accomplished through: (a) a review of pediatric MS and its consequences; (b) a brief overview of physical activity and its consequences in children and adults with MS; and (c) a selective review of research on the neurological benefits of physical activity in pediatric populations. This topical review concludes with a list of 10 questions to guide future research on physical activity and pediatric MS. The objective of this paper is the provision of a research interest, focus and agenda involving pediatric MS and its lifelong management though exercise and physical activity behavior. Such an agenda is critical as the effects and maintenance of physical activity and exercise track across the lifespan, particularly when developed in the early stages of life.

  7. Predictors of static balance in ambulatory persons with multiple sclerosis.

    PubMed

    Fry, Donna K; Huang, Min H; Rodda, Becky J

    2016-03-01

    People with multiple sclerosis (MS) experience a high rate of falls and have decreased static and dynamic balance. The purpose of this study was to determine best predictors of static standing balance, as measured by a single limb stance (SLS) timed test, in ambulatory persons with MS (PwMS) from among commonly used medical and rehabilitation clinical tests. Ambulatory PwMS participated in a single test session. Medical exam data gathered included the Function System (FS) neurologic exam and Expanded Disability Status Score (EDSS). A variety of commonly administered rehabilitation clinical tests addressing static balance, dynamic balance, gait endurance, functional lower extremity strength, abdominal and respiratory muscle strength were completed. Descriptive statistics, Pearson product moment correlations, and forward step-wise linear regressions were calculated. Twenty-eight ambulatory PwMS completed this study. Mean age was 54.74 years. Mean SLS score was 14.6 s. Pyramidal, sensory, bowel/bladder, and visual FS scores and the EDSS were significantly correlated with SLS. Maximal step length scores were significantly correlated with SLS at P less than 0.05 and the Functional Stair Test (FST) and 6-min walk test were correlated with SLS at P less than 0.10. Medical exam data EDSS and FS sensory explain 72.1% of the variance in SLS scores. Rehabilitation exam data FS sensory and FST explain 68.8% of the variance. The FS sensory, EDSS, and FST together explain 73.3% of the variance.

  8. Estimated prevalence of multiple sclerosis in Italy in 2015.

    PubMed

    Battaglia, Mario Alberto; Bezzini, Daiana

    2017-03-01

    Italy is a high risk area for multiple sclerosis (MS) as confirmed by the numerous prevalence and incidence studies conducted in several regions/districts of the country. Nevertheless, there are no recent published epidemiological data, nor studies about the total prevalence of MS in Italy. Our aim was to update as of 2015 the prevalence rates of MS in different geographical areas using already published epidemiological studies, and to estimate the overall prevalence of the disease in Italy. We made a search in MEDLINE database of all published studies on epidemiology of MS in Italy. Then, we applied, to the already published prevalence data, the last published incidence and mortality rates to recalculate, as of 2015, the prevalence of MS. So, we calculated the mean prevalence rate from our extrapolations, and we applied it to the population in 2015 to estimate the number of MS patients in Italy. Our prevalence extrapolations ranged from 122 to 232 cases/100,000 in the mainland and Sicily, with an average of 176/100,000, and from 280 to 317 cases/100,000 in Sardinia with an average of 299/100,000. Applying these media to the Italian population in 2015, we obtained an estimate of more than 109,000 MS patients in Italy. Our estimates were higher than the latest published rates but consistent with the annual increase of prevalence due to incidence that exceeds mortality, with the increase of survival and, maybe, with the probable increase of incidence.

  9. Complex approaches to study complex trait genetics in multiple sclerosis.

    PubMed

    Kálmán, Bernadette

    2014-09-30

    Multiple sclerosis (MS) is a complex trait disorder defined by several genes and their interactions with environmental factors. A comprehensive exploration of the susceptibility variants had not been feasible until recently when new developments in biotechnology and bioinformatics made possible sequencing of the whole human genome, cataloguing of nucleotide variants and alignments of these variants in haplotypes. Earlier observations from epidemiological, candidate gene and linkage studies provided ample evidence to support a complex genetic determination of MS. New biotechnology and bioinformatics resources have been recently applied to further successful explorations of the disease. These efforts were paralleled by more careful and reliable ascertainments of disease phenotypes, collaborations among specialized centers to generate sufficient sample size and involvement of clinician-scientists capable of working both on the clinical and scientific study sides. Data obtained from the whole genome association studies (GWAS) elevated our understanding of MS genetics to a new level by identifying an extensive list of genetic determinants. Pathway analyses of MS-associated variants provided evidence to support the immune etiology of the disease. Future research will likely explore how environmental factors interact with the genome, and contribute to the abnormal immune activation and inflammation. This review summarizes the outcomes of MS genetic explorations including those of recent GWAS, and highlights practical consequences of genetic and genomic studies by pointing out as to how the derived data facilitate further elucidation of MS pathogenesis. A better understanding of disease processes is necessary for future advancements in therapeutics and the development of disease prevention strategies.

  10. Multiple sclerosis in Colombia and other Latin American Countries.

    PubMed

    Toro, Jaime; Cárdenas, Simón; Fernando Martínez, Carlos; Urrutia, Julián; Díaz, Camilo

    2013-04-01

    The spectrum of multiple sclerosis (MS) in Latin America is characterized by geographic and racial/genetic particularities. In this review we describe major studies of MS epidemiology, genetics, and clinical presentation in Latin America, with a focus on Colombia. We also consider the influence of national health care systems on the treatment of MS in Latin American patients. Epidemiologic studies indicate that the regional incidence of MS in Latin America is more complex than once thought, and broadly consistent with the geographical (latitudinal) distribution of MS in other parts of the world. Low prevalence of MS is considered to be <5/100.000 inhabitants and high prevalence >30/100,000. Colombia is considered a low-risk region for MS, as are other countries located near the equator, such as Panama and Ecuador. By contrast, Latin American countries located farther from the equator are medium or high-risk regions. National health care systems generally cover MS treatment, although bureaucratic problems sometimes interfere with delivery of high-cost medications and access to diagnostic tests, particularly in rural areas. The population of Colombia is racially diverse and genetically heterogeneous, making it difficult to study genetic associations within a complex disease such as MS. The clinical spectrum of MS in Latin America is similar to that of Europe or North America.

  11. Complementary and alternative medicine for the treatment of multiple sclerosis

    PubMed Central

    Yadav, Vijayshree; Shinto, Lynne; Bourdette, Dennis

    2010-01-01

    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

  12. Therapeutic Decisions In Multiple Sclerosis: Moving Beyond Efficacy

    PubMed Central

    Brück, Wolfgang; Ralf, Gold; Lund, Brett T.; Celia, Oreja-Guevara; Prat, Alexandre; Spencer, Collin M.; Steinman, Lawrence; Mar, Tintoré; Vollmer, Timothy; Weber, Martin S.; Weiner, Leslie P.; Ziemssen, Tjalf; Zamvil, Scott S.

    2014-01-01

    Importance Several innovative disease-modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS) have been licensed recently, or are in late-stage development. The molecular targets of several of these DMTs are well defined. All affect at least one of four properties: (1) immune cell trafficking, (2) cell depletion, (3) immune cell function, or (4) cell replication. In contrast to β-interferons and glatiramer acetate, the first generation DMTs, several newer therapies are imbued with safety issues. In addition to efficacy, understanding the relationship between the mechanism of action (MOA) of the DMTs and their safety profile is essential for decision-making in patient care. Objective In this article, we relate safety issues of newer DMTs to their pharmacological characteristics, including molecular targets, MOA, chemical structure, and metabolism. Some newer DMTs also represent repurposing or modifications of previous treatments used in other diseases. Here, we describe how identification and understanding of adverse events (AEs) observed with these established drugs within the same class, provide clues regarding safety and toxicities of newer MS therapeutics. Conclusions and relevance While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients, and to ensure future therapies have the most advantageous risk-benefit profiles. Recognizing the individual classes of DMTs described here may be beneficial when considering use of such agents sequentially and possibly in combination. PMID:23921521

  13. Multiple sclerosis is not a disease of the immune system.

    PubMed

    Corthals, Angelique P

    2011-12-01

    Multiple sclerosis is a complex neurodegenerative disease, thought to arise through autoimmunity against antigens of the central nervous system. The autoimmunity hypothesis fails to explain why genetic and environmental risk factors linked to the disease in one population tend to be unimportant in other populations. Despite great advances in documenting the cell and molecular mechanisms underlying MS pathophysiology, the autoimmunity framework has also been unable to develop a comprehensive explanation of the etiology of the disease. I propose a new framework for understanding MS as a dysfunction of the metabolism of lipids. Specifically, the homeostasis of lipid metabolism collapses during acute-phase inflammatory response triggered by a pathogen, trauma, or stress, starting a feedback loop of increased oxidative stress, inflammatory response, and proliferation of cytoxic foam cells that cross the blood brain barrier and both catabolize myelin and prevent remyelination. Understanding MS as a chronic metabolic disorder illuminates four aspects of disease onset and progression: 1) its pathophysiology; 2) genetic susceptibility; 3) environmental and pathogen triggers; and 4) the skewed sex ratio of patients. It also suggests new avenues for treatment.

  14. Multiple sclerosis animal models: a clinical and histopathological perspective.

    PubMed

    Kipp, Markus; Nyamoya, Stella; Hochstrasser, Tanja; Amor, Sandra

    2017-03-01

    There is a broad consensus that multiple sclerosis (MS) represents more than an inflammatory disease: it harbors several characteristic aspects of a classical neurodegenerative disorder, that is, damage to axons, synapses and nerve cell bodies. While we are equipped with appropriate therapeutic options to prevent immune-cell driven relapses, effective therapeutic options to prevent the progressing neurodegeneration are still missing. In this review article, we will discuss to what extent pathology of the progressive disease stage can be modeled in MS animal models. While acute and relapsing-remitting forms of experimental autoimmune encephalomyelitis (EAE), which are T cell dependent, are aptly suited to model relapsing-remitting phases of MS, other EAE models, especially the secondary progressive EAE stage in Biozzi ABH mice is better representing the secondary progressive phase of MS, which is refractory to many immune therapies. Besides EAE, the cuprizone model is rapidly gaining popularity to study the formation and progression of demyelinating CNS lesions without T cell involvement. Here, we discuss these two non-popular MS models. It is our aim to point out the pathological hallmarks of MS, and discuss which pathological aspects of the disease can be best studied in the various animal models available.

  15. Increased incidence of rheumatoid arthritis in multiple sclerosis

    PubMed Central

    Tseng, Chia-Chun; Chang, Shun-Jen; Tsai, Wen-Chan; Ou, Tsan-Teng; Wu, Cheng-Chin; Sung, Wan-Yu; Hsieh, Ming-Chia; Yen, Jeng-Hsien

    2016-01-01

    Abstract Past studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness. A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01–2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24–2.56, P = 0.002). In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history. PMID:27368008

  16. Improving service delivery for relapse management in multiple sclerosis.

    PubMed

    Warner, Richard; Thomas, Del; Martin, Roswell

    This action research study was conducted over an 18 month period within a district general hospital. The study has improved the quality of the service provided to people experiencing a relapse of multiple sclerosis. The authors now identify and treat a three-fold increase in relapse patients. At least 85% of these patients are treated within 10 days of reporting symptoms to a specialist nurse. Before the study, only 12% of patients received treatment within this time. The authors' data identify what patients valued about this service and also inform debate around distress associated with relapse and how services should develop to respond to this. The study is of particular importance to the UK because the National Institute for Clinical Excellence (NICE) has published guidance to the NHS about the management of this specific patient group (NICE, 2003). This study also clearly demonstrates how specialist nursing services can combine a substantial clinical role with instigating and managing change in service delivery that results in improvements in patient care.

  17. Epidemiologic evidence for multiple sclerosis as an infection.

    PubMed Central

    Kurtzke, J F

    1993-01-01

    The worldwide distribution of multiple sclerosis (MS) can be described within three zones of frequency: high, medium, and low. The disease has a predilection for white races and for women. Migration studies show that changing residence changes MS risk. Studies of persons moving from high- to low-risk areas indicate that in the high-risk areas, MS is acquired by about age 15. Moves from low- to high-risk areas suggest that susceptibility is limited to persons between about ages 11 and 45. MS on the Faroe Islands has occurred as four successive epidemics beginning in 1943. The disease appears to have been introduced by British troops who occupied the islands for 5 years from 1940, and it has remained geographically localized within the Faroes for half a century. What was introduced must have been an infection, called the primary MS affection (PMSA), that was spread to and from successive cohorts of Faroese. In this concept, PMSA is a single widespread systemic infectious disease (perhaps asymptomatic) that only seldom leads to clinical neurologic MS. PMSA is also characterized by a need for prolonged exposure, limited age of susceptibility, and prolonged incubation. I believe that clinical MS is the rare late outcome of a specific, but unknown, infectious disease of adolescence and young adulthood and that this infection could well be caused by a thus-far-unidentified (retro)virus. Images PMID:8269393

  18. Care ethics for guiding the process of multiple sclerosis diagnosis.

    PubMed

    Krahn, Timothy Mark

    2014-12-01

    Multiple sclerosis (MS) is a chronic neurological disorder for which there is no definitive diagnostic test. Uncertainty characterises most of its features with diagnosis reached through a process of elimination. Coping with uncertainty has been recognised as a significant problem for MS patients. Discussions in the literature concerning the ethics of MS diagnosis have focused on an ethics of duty emphasising the rules for disclosure and healthcare professionals' obligations to provide information to patients. This narrow construal of the ethics at stake with MS diagnosis may be driven by a common misperception that diagnosis is an event, or series of events, rather than a process. Scant attention has been given to the dynamic, situated relational space between patient and physician as they journey potentially together (or apart) through the process of diagnosis. The healthcare provider cannot properly judge 'the how, what and when' of MS disclosure merely by applying rules pertaining to general professional duties to tell the truth and patients' rights to know their medical status. Proper disclosure and effective communication require the practice of flexible, caring responsibility and sustained, ongoing attention to the particular relational needs of 'this' patient in her own situational context. Accordingly, this article argues that care ethics is especially useful (but not without certain limitations) for attending to a broader swath of responsibilities (different from minimal duties) and affective components implicated in meeting patients' overall needs for care as the patient and physician cope with uncertainty through the process of establishing an MS diagnosis.

  19. Harmonization: a methodology for advancing research in multiple sclerosis.

    PubMed

    Magalhaes, S; Wolfson, C

    2012-01-01

    Decreasing research funding is in conflict with the increasing need to conduct large studies to examine rare risk factors and interactions between risk factors. As a result, investigators are searching for strategies to stretch research funds and to design studies that will maximize investments already made. Multiple sclerosis (MS) is generally accepted as a multifactorial disease, and the assessment of interactions between risk factors and the desire to assess risk factors within particular sub-groups requires a large number of participants. Harmonization is a methodology that may help address this problem. Harmonization is a methodological approach that aims to systematize the process of combining individual data that are collected in several observational studies. Combining data will increase sample size, but the quality of the harmonized result is only as high as the quality of the individual studies and the comparability of the constructs measured. In this short report, we introduce the concept of harmonization and provide examples where harmonization may be advantageous in MS research.

  20. The Role of Antigen Presenting Cells in Multiple Sclerosis

    PubMed Central

    Chastain, Emily M. L.; Duncan, D'Anne S.; Rodgers, Jane M.; Miller, Stephen D.

    2010-01-01

    Multiple Sclerosis (MS) is a debilitating T cell-mediated autoimmune disease of the central nervous system (CNS). Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus-Induced demyelinating disease (TMEV-IDD) have given light to cellular mechanisms involved in the initiation and progression of this organ-specific autoimmune disease. Within the CNS, antigen presenting cells (APC) such as microglia and astrocytes participate as first line defenders against infections or inflammation. However, during chronic inflammation they can participate in perpetuating the self-destructive environment by secretion of inflammatory factors and/or presentation of myelin epitopes to autoreactive T cells. Dendritic cells (DC) are also participants in the presentation of antigen to T cells, even within the CNS. While the APCs alone are not solely responsible for mediating the destruction to the myelin sheath, they are critical players in perpetuating the inflammatory milieu. This review will highlight relevant studies which have provided insight to the roles played by microglia, DCs and astrocytes in the context of CNS autoimmunity. PMID:20637861