Full Text Available A key component of multiple sclerosis is the occurrence of episodes of clinical worsening with either new symptoms or an increase in older symptoms over a few days or weeks. These are known as exacerbations of multiple sclerosis. In this review, we summarize the pathophysiology and treatment of exacerbations and describe how they are related to the overall management of this disease.
Multiple sclerosis (MS) is considered the most common demyelinating process involving the CNS. Although usually considered an adult disease multiple sclerosis can begin to manifest during childhood. The clinical presentation of the disease in early childhood can range from paraesthesias to dramatic presentations, suggesting diffuse encephalopathy with cerebral oedema, meningismus and impaired consciousness. Multiple sclerosis is usually characterized by a typical relapsing-remitting clinical course. But there are acute, clinically fulminant forms with atypical. neurologic symptoms and death in months. MRI has become increasingly relevant in the diagnosis of multiple sclerosis in the past years. Yet, the specificity is limited. Atypical forms of MS and other diseases of CNS may show similar patterns on MRI. We report a case of 7 years old boy with clinically fulminant Marburg type of multiple sclerosis that ended with death in two months. The patient was a diagnostic problem despite the certain degree of clinical and radiological suspicion. The postmortem diagnosis is based on pathomorphologic changes (gross pathologic and microscopic features) in CNS.The present case is of clinical, radiological and pathomorphologic interest because of its early onset in childhood, unusual clinical course and acute progression. Awareness of the MRI features of multiple sclerosis and MS-variants (subtypes) may help in such atypical presentations in childhood. (authors)
Despite the frequent involvement of the spinal cord by multiple sclerosis, reports concerning neuroradiological findings regarding these lesions have been limited; most of them have demonstrated a normal or small spinal cord. Two cases of acute paraparesis showed evidence of spinal-cord swelling on myelography and CT myelography, initially suggesting the diagnosis of an intramedullary tumor. Spinal-cord swelling was demonstrated more clearly on CT myelography than on conventional myelography. The diagnosis of multiple sclerosis was made with the aid of the CSF findings, the clinical course, and the contracting-cord sign. The ''contracting-cord sign'' means the diminution of the spinal-cord diameter in the chronic stage. Since acute multiple sclerosis may produce spinal-cord swelling simulating a tumor, careful investigations are necessary to avoid unwarranted surgical interventions. (author)
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 ...
Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.)
Bernheimer, James H.
Restless legs syndrome is common in patients with multiple sclerosis but has not been reported as occurring due to an acute, inflammatory, demyelinating attack. Restless legs syndrome is known to be related to low brain iron levels. Multiple sclerosis has been associated with the abnormal accumulation of iron in the chronic, progressive phase of axonal degeneration. Iron deficiency may play a role in demyelination. This suggests that restless legs syndrome may be caused by the inflammator...
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…
Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)
Stenager, Egon; Stenager, E N; Knudsen, Lone;
, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap....... Ninety-five percent lived in own house or flat and 70 percent received disablement pension. More than half of the patients (56.4 percent) were dependent on help from close relatives, most frequently spouse. The need for help, the risk of divorce, loss of contact with relatives, difficulty in going out...
Jaffe, Stephen L; Glabus, Michael F; Kelley, Roger E; Minagar, Alireza
Cortical speech disorders rarely occur in multiple sclerosis (MS). We report a patient with relapsing-remitting MS, who presented with acute verbal dyspraxia. Magnetic resonance imaging (MRI) demonstrated an acute T2/Flair hyperintense, primarily white matter lesion underlying the middle third of the inferior frontal gyrus. The verbal dyspraxia cleared beginning 48 hours after the initiation of iv dexamethasone. Follow-up MRI demonstrated qualitative and quantitative diminution of the hyperintensity. This is the first report of a clinically definite MS patient with acute verbal dyspraxia. Moreover, there was a suggestive localization of verbal praxis to Brodmann areas 44/45. PMID:14664479
Cobo Calvo, Álvaro; Mañé Martínez, M Alba; Alentorn-Palau, Agustí; Bruna Escuer, Jordi; Romero Pinel, Lucía; Martínez-Yélamos, Sergio
Background: in 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM) to delimit and unify this group of patients. This study aimed to describe the conversion rate to multiple sclerosis (MS) and variables associated with conversion, and to analyze functional outcome and prognostic factors associated with functional recovery in patients who fulfilled the current TMCWG criteria for definite and possible IAT...
Brenton, J Nicholas; Banwell, Brenda L
Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination. PMID:26496907
Kjølhede, T; Dalgas, U; Gade, A B;
Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying...... attention to the medical treatments of the patient. At present, PwMS are routinely enrolled in immunosuppressive medication, but exercise-induced immunomodulatory effects have not been investigated under these circumstances. The objective of this study was to investigate the acute and chronic cytokines...... responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-β, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1β, IL-4, IL-10, IL-17F, IL-23, tumor...
Nutr 2004 Aug; 58:1095-109. 22. Willer CJ, Dyment DA, Sadovnick AD, Rothwell PM, Murray TJ, Ebers GC, et al. Timing of birth and risk of multiple sclerosis: population based study. BMJ 2005 Jan;330(7:120.23. Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Bellman AL, et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 2010 May;67(5:618-24.24. Banwell B, Bar-Or A, Arnold DL, Sadovnick D, Narayanan S, Mc Gowan M, et al. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lnacet Neurol 2011 May;10(5:436-45.25. Disanto G, Morahan JM, Ramagopalan SV. Multiple sclerosis: risk factors and their interactions. CNS NeurolDisord Drug Targets. 2012 Aug;11(5:545-55. 26. Munger KL, Chitnis T, Ascherio A. Body size and risk of MS in two cohorts of US women. Neuroloty 2009 Nov 10;73(19:1543-50.27. Renoux C, Vukusic S, Mikaeloff Y, Edan G, Clanet M, Dubois B, et al. Natural history of multiple sclerosis withchildhood onset. N Engl J Med 2007 Jun; 356(25:2603-13.28. Gusev E, Boiko A, Bikova O, Maslova O, Guseva M, Boiko S, et al. The natural history of early onset multiple sclerosis: comparison of data from Moscow and Vancouver. Clin Neurol Neurosurg 2002 Jul;104(3:203-7.29. Simone IL, Carrara D, Tortorella C, Liquori M, Lepore V, Pellegrini F, et al. Course and prognosis in early-onsetMS: comparison with adult-onset forms. Neurology 2002 Dec;59(12:1922-8.30. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001 Jul; 50(1:121-7.31. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005 Dec;58:840-6.32. Swanton JK, Rovira A, Tintore M
Kjølhede, T; Dalgas, U; Gade, A B; Bjerre, M; Stenager, E; Petersen, T; Vissing, K
Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying attention to the medical treatments of the patient. At present, PwMS are routinely enrolled in immunosuppressive medication, but exercise-induced immunomodulatory effects have not been investigated under these circumstances. The objective of this study was to investigate the acute and chronic cytokines responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-β, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1β, IL-4, IL-10, IL-17F, IL-23, tumor necrosis factor-α and IFN-γ were measured before and after 24 weeks of PRT. The acute effect was evaluated following standardized single-bout resistance exercise in the untrained and the trained state. No changes were observed in resting cytokine levels after PRT. However, an indication of reduced IL-17F secretion following resistance exercise was observed in the trained compared with the untrained state. This study suggests little acute and chronic effect of PRT on cytokine levels in IFN-treated PwMS. PMID:26105554
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Your doctor has told you that you have multiple sclerosis. This disease affects the brain and spinal cord ( ... your doctor may prescribe medicine. Some people with multiple sclerosis need to use a urinary catheter . This is ...
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Ensari, Ipek; Brian M. Sandroff; Motl, Robert W.
Background: Little is known about the acute or immediate effects of walking exercise and yoga on mood in people with multiple sclerosis (MS). Such an examination is important for identifying an exercise modality for inclusion in exercise-training interventions that yields mood benefits in MS. We examined the effects of single bouts of treadmill walking and yoga compared with a quiet, seated-rest control condition on acute mood symptoms in MS.
Stenager, E N; Stenager, Egon; Koch-Henriksen, Nils;
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...
Full Text Available Abstract Background The ability to predict the spatial frequency of relapses in multiple sclerosis (MS would enable physicians to decide when to intervene more aggressively and to plan clinical trials more accurately. Methods In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS. The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray. Results We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p Conclusion We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature.
Yun Jin Lee
Full Text Available Acute disseminated encephalomyelitis (ADEM is a demyelinating disease of the central nervous system (CNS that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is considered an autoimmune disorder that is triggered by an environmental stimulus in genetically susceptible individuals. The diagnosis of ADEM is based on clinical and radiological features. Most children with ADEM initially present with fever, meningeal signs, and acute encephalopathy. The level of consciousness ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and gray-matter lesions such as thalami and basal ganglia on magnetic resonance imaging (MRI are associated with ADEM. In a child who presents with signs of encephalitis, bacterial and viral meningitis or encephalitis must be ruled out. Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple sclerosis (MS. Pediatric MS, defined as onset of MS before the age of 16, is being increasingly recognized. MS is characterized by recurrent episodes of demyelination in the CNS separated in space and time. The McDonald criteria for diagnosis of MS include evidence from MRI and allow the clinician to make a diagnosis of clinically definite MS on the basis of the interval preceding the development of new white matter lesions, even in the absence of new clinical findings. The most important alternative diagnosis to MS is ADEM. At the initial presentation, the 2 disorders cannot be distinguished with certainty. Therefore, prolonged follow-up is needed to establish a diagnosis.
Perry, V.H.; Anthony, D. C.
It is well known that within long-standing multiple sclerosis (MS) lesions there is axonal loss but whether it is an early or late event has been more difficult to establish. The use of immunocytochemical methods that reveal axonal end-bulbs is a valuable approach to investigating acute axonal injury in human pathological material. The application of these techniques to multiple sclerosis tissue reveals evidence of axonal injury in acute lesions; the distribution of the end-bulbs in acute and...
This volume proceedings contains four contributions which are in INIS scope, dealing with MRI and SPECT in the diagnosis of multiple sclerosis and assessment of disease activity. (H.W.). refs.; figs.; tabs
In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point...... of their lives, emphasising the importance of rehabilitation in order to maintain quality of life. An important aspect of multiple sclerosis rehabilitation is the preservation of physical functioning. Hot topics in the rehabilitation of physical function include (1) exercise therapy, (2) robot-assisted training...... and (3) pharmacological interventions. Exercise therapy has for many years been a controversial issue in multiple sclerosis rehabilitation and the advice generally given to patients was not to participate in physical exercise, since it was thought to lead to a worsening of symptoms or fatigue. However...
Larsson, H B; Frederiksen, J; Petersen, J;
This study intended to investigate the possibility of magnetic resonance (MR) to characterize the acute plaque due to multiple sclerosis (MS). To obtain information, in vivo measurements of relaxation processes were performed in 10 patients with known acute MS plaques, using a whole-body supercon...
Dendrou, Calliope A; Fugger, Lars; Friese, Manuel A
Two decades of clinical experience with immunomodulatory treatments for multiple sclerosis point to distinct immunological pathways that drive disease relapses and progression. In light of this, we discuss our current understanding of multiple sclerosis immunopathology, evaluate long-standing hypotheses regarding the role of the immune system in the disease and delineate key questions that are still unanswered. Recent and anticipated advances in the field of immunology, and the increasing recognition of inflammation as an important component of neurodegeneration, are shaping our conceptualization of disease pathophysiology, and we explore the potential implications for improved healthcare provision to patients in the future. PMID:26250739
Ludwin, Samuel K; Rao, Vijayaraghava Ts; Moore, Craig S; Antel, Jack P
Recent experimental and clinical studies on astrocytes are unraveling the capabilities of these multi-functional cells in normal homeostasis, and in central nervous system (CNS) disease. This review focuses on understanding their behavior in all aspects of the initiation, evolution, and resolution of the multiple sclerosis (MS) lesion. Astrocytes display remarkable flexibility and variability of their physical structure and biochemical output, each aspect finely tuned to the specific stage and location of the disease, participating in both pathogenic and beneficial changes seen in acute and progressive forms. As examples, chemo-attractive or repulsive molecules may facilitate the entry of destructive immune cells but may also aid in the recruitment of oligodendrocyte precursors, essential for repair. Pro-inflammatory cytokines may attack pathogenic cells and also destroy normal oligodendrocytes, myelin, and axons. Protective trophic factors may also open the blood-brain barrier and modulate the extracellular matrix to favor recruitment and persistence of CNS-specific immune cells. A chronic glial scar may confer structural support following tissue loss and inhibit ingress of further noxious insults and also inhibit migration of reparative cells and molecules into the damaged tissue. Continual study into these processes offers the therapeutic opportunities to enhance the beneficial capabilities of these cells while limiting their destructive effects. PMID:27207458
Full Text Available Multiple sclerosis (MS is a suspected autoimmune disease in which myelin-specific CD4+ and CD8+ T cells enter the central nervous system (CNS and initiate an inflammatory response directed against myelin and other components of the CNS. Acute MS exacerbations are believed be the result of active inflammation, and progression of disability is generally believed to reflect accumulation of damage to the CNS, particularly axonal damage. Over the last several years, the pathophysiology of MS is being appreciated to be much more complex, and it appears that the development of the MS plaque involves a large number of cell populations, including CD8+ T lymphocytes, B cells, and Th17 cells (a population of helper T cells that secrete the inflammatory cytokine IL-17. The axonal transection and degeneration that is thought to represent the basis for progressive MS is now recognized to begin early in the disease process and to continue in the progressive forms of the disease. Molecules important for limiting aberrant neural connections in the CNS have been identified, which suppress axonal sprouting and regeneration of transected axons within the CNS. Pathways have also been identified that prevent remyelination of the MS lesion by oligodendrocyte precursors. Novel neuroimaging methodologies and potential biomarkers are being developed to monitor various aspects of the disease process in MS. As we identify the pathways responsible for the clinical phenomena of MS, we will be able to develop new therapeutic strategies for this disabling illness of young adults.
Full Text Available There have been presented general information of neurogenic bladder and the data on pathophysiology of lower urinary tract dysfunction in patients with multiple sclerosis. The characteristics of clinical presentations of neurogenic bladder in multiple sclerosis have been stated. There have been considered diagnosis and treatment problems of urinary disorders in patients with multiple sclerosis.
A 34-year-old woman presented with urination difficulty and consciousness disturbance, followed by persistent neurologic findings, such as semicomatose mental status and bilateral optic neuritis, and monophasic clinical course. Cranial CT showed multifocal low density areas in cerebral white matter. The patient was clinically diagnosed as having acute disseminated encephalomyelitis. She died of sepsis four months later. Autopsy revealed multifocal large demyelinating lesions confined to the cerebral white matter, shown as low density areas on CT scans, and demyelinating plaques scattered in the optic nerves and chiasm, and cerebral peduncle. The final diagnosis was acute multiple sclerosis. The CT appearance of multifocal low density areas was most likely due to demyelinating lesions causing edema and tissue necrosis. (Namekawa, K.)
A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Istituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable
Claffey, Austin M
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. The concept of metamemory proposes that supplementary to typically measured memory abilities, memory monitoring and control processes are used to optimise learning. Accurate memory monitoring appears to be underpinned by a range of cognitive, and possibly affective, contributions. In populations with these deficits, metamemory has been shown to be impaired. In Multiple Sclerosis (MS), only...
LeVine, Steven M
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. Furth...
M. Sanei Taheri
Full Text Available Introduction: Tuberous sclerosis is an autosomal do-minant genetic disorder that involves multiple or-gans. The predominant lesions are the hamartomas. Classically tuberous sclerosis has been characterized by a classic clinical triad of facial angiofibromas in 90%,retardation in 50-80%,seizure 80-90% and all three in 30%."nThe disease occurs in 1:100,000 persons in all races with nearly equal distribution between the sexes. "nCase Presentation: We had six patients who admitted with different presentations of tuberous sclerosis with a past history of convulsion from childhood, skin le-sions and mental retardation, also with new onset headache and changed pattern of convulsion. In physical examination facial angiofibromas and sub-ungual fibromas apparently detected. Brain CT scan study with contrast showed multiple calcified nod-ules associated with tubers and ventriculomegaly, also an enhancing enlarged nodule at foramen of mo-nro, which was suggestive of subependymal giant cell astrocytoma (SGCA. In abdominal and pelvic CT scan and ultrasonography, massive bilateral angio-myolipomatosis diagnosed. Also Focal hypodense le-sions in liver which were hyperechoic in ultrasono-graphy were diagnosed. With MRI study tubers, white matter lesions and subependymal nodules asso-ciated with SGCA were detected better. After surgery SGCA was proved."nDiscussion: Our patients had different presentations and various findings of this spectrum discussed in this lecture.
Ángela María Gutiérrez-Álvarez
Introduction: Multiple sclerosis is a chronicrecurrent inflammatory disorder of the centralnervous system. The pharmacological treatmentof multiple sclerosis has been evaluated withmultiple controlled clinical trials that allow theclinician to count with evidence based informationto decide the more indicated treatmentfor each patient.Methodology: A review of the scientific literaturewas conducted to clarify controversialissues in a clinical relevant topic.Development: The diagnostic criteria ...
... Editors David C. Spencer, MD Steven Karceski, MD Multiple sclerosis and vitamin D Andrew J. Solomon, MD WHAT IS VITAMIN ... 133:1869 –1888. 8. Solomon AJ, Whitham RH. Multiple sclerosis and vitamin D: a review and recommendations. Curr Neurol Neurosci ...
Bhargava, Pavan; Calabresi, Peter A
Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system with inflammatory and degenerative components. The cause of MS remains unknown although genetic and environmental factors appear to play a role in its etiopathogenesis. Metabolomics is a new "omics" technology that aims at measuring small molecules in various biological matrices and can provide information that is not readily obtained from genomics, transcriptomics, or proteomics. Currently, several different analytical platforms exist for metabolomics, and both untargeted and targeted approaches are being employed. Methods of analysis of metabolomics data are also being developed and no consensus currently exists on the optimal approach to analysis and interpretation of these data. Metabolomics has the potential to provide putative biomarkers, insights into the pathophysiology of the disease, and to aid in precision medicine for patients with MS. PMID:26754801
Simsarian JP; Saunders C.; Smith DM
James P Simsarian, Carol Saunders, D Michelle SmithNeurology Center of Fairfax Ltd, Fairfax, VA, USABackground: Despite over 50 years of experience with adrenocorticotropic hormone (ACTH) as a treatment for acute exacerbations of multiple sclerosis, there have been no trials examining the options of the 2–3-week dosing regimen or intramuscular injection protocol used in the original trials. At our clinic, we performed a small, prospective, randomized pilot study to examine the effic...
Lee, Ji Y; Chitnis, Tanuja
Pediatric multiple sclerosis (MS) is a chronic inflammatory neurologic disease that is challenging to diagnose and treat. Although there are many clinical parallels between pediatric-onset MS and adult-onset MS, there is also accumulating evidence of distinguishing clinical features that may, in part, arise from development-specific, neuroimmune processes governing MS pathogenesis in children. Here the authors describe the clinical features, diagnosis, and treatment of pediatric MS, with a particular focus on describing clinical features and highlighting new developments that promise a better understanding of pediatric MS pathogenesis. An important task that lies ahead for pediatric neurologists is better understanding the early gene-environment interaction that precipitates the first demyelinating event in pediatric MS. This area is of particular importance for understanding the MS etiology and the natural history of pediatric MS. Such understanding should in turn inform new developments in diagnostic tools, long-term therapies, and much-needed biomarkers. Such biomarkers are not only valuable for defining the disease onset, but also for monitoring both the treatment response and a disease evolution that spans multiple decades in children with MS. PMID:27116721
LeVine, Steven M
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. PMID:27067000
Yadav, R; Zigmond, A S
Lesions in the temporal lobe are associated with psychiatric manifestations in multiple sclerosis. The authors describe this case of a young man with multiple sclerosis who presented with first-episode psychosis and had acute lesions in the temporal lobe. He was successfully treated with olanzapine and β-interferon.
Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk; Koch-Henriksen, Nils; Haahr, Sven; Sørensen, Per Soelberg; Hjalgrim, Henrik
BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis......, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the...... Danish Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul...
This volume contains 9 articles dealing with the use of nuclear magnetic resonance imaging and positron emitted tomography in the diagnosis and staging of multiple sclerosis. (H.W.). refs.; figs.; tabs
Mortensen, J T; Brønnum-Hansen, Henrik; Rasmussen, K
We investigated a possible causal relation between exposure to organic solvents in Danish workers (housepainters, typographers/printers, carpenters/cabinetmakers) and onset of multiple sclerosis. Data on men included in the Danish Multiple Sclerosis Register (3,241 men) were linked with data from...... butchers. Over a follow-up period of 20 years, we observed no increase in the incidence of multiple sclerosis among men presumed to be exposed to organic solvents. It was not possible to obtain data on potential confounders, and the study design has some potential for selection bias. Nevertheless, the...... study does not support existing hypotheses regarding an association between occupational exposure to organic solvents and multiple sclerosis....
Rocco Totaro; Caterina Di Carmine; Carmine Marini; Antonio Carolei
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 acti...
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 reso...
Objective To explore the effect of leptin on cytokine production by PBMCs obtained from MS patients either in acute (relapse) or in stable (nonrelapse) phase of disease. Methods PBMCs were collected from 25 untreated acute MS patients, 11 stable MS patients and 20 healthy controls. PBMCs were cultured either with RPMI-1640 alone or with leptin (1.25 nmol/ml), phytohemagglutinin (PHA) ( 100 μg/ml), and leptin + PHA. 72 h later the supernate of the culture medium were collected and stored at -70℃. The pro-inflammatory cytokine (IFN-γ) concentration were determined using an enzyme-linked immunosorbent assay ( ELISA), and the anti-inflammatory cytokine (IL-4) concentration were investigated by radioimmunity methods. Results Our data showed that leptin induced IFN-γproduction by PBMCs of patients in an acute phase of disease but not in a stable phase or in healthy controls. Moreover, we found that PHA induced IL-4 production by PBMCs of patients in an acute phase of disease, but leptin inhibited this ability of PHA. Conclusion Leptin can affect on pro- and anti-inflammatory cytokine production by PBMCs collected from MS patients, may be this connected with leptin increase the susceptiveness of MS.
Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)
Lund, H; Jønsson, A; Andresen, Jesper Graubæk;
Objectives - Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part of the...... Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Impairment Scale (MSIS). Voxel-wise T2 estimates and total T2 lesion volume were tested for correlations with eight cognitive domains, a general cognitive dysfunction factor (CDF), and the two clinical scales. Results - We found distinct...
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Leray, E; Moreau, T; Fromont, A; Edan, G
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
Frischer, J.M.; Bramow, S.; Dal-Bianco, A.;
Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation to...... disease or brain lesions. We found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease. T- and B-cell infiltrates correlated with the activity of demyelinating lesions, while plasma cell...... infiltrates were most pronounced in patients with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS) and even persisted, when T- and B-cell infiltrates declined to levels seen in age matched controls. A highly significant association between inflammation and...
complex genetic backgrounds. HLA controls immune response genes and HLA associations indicate the involvement of autoimmunity. Multiple sclerosis (MS) was one of the first conditions proven to be HLA associated involving primarily HLA class II factors. We review how HLA studies give fundamental...
Sorensen, P.S.; Sellebjerg, F.
In 1996 interferon (IFN)beta was the first biopharmaceutical product to be approved for the treatment of relapsing-remitting multiple sclerosis (MS). In 2006 the more potent monoclonal antibody natalizumab was approved. Presently, a number of monoclonal antibodies are being studied, including...
In 26 patients with multiple sclerosis 100% responded abnormally to magnetic resonance imaging of the brain. Lesions in the posterior fossa were observed in 18 patients. The auditory brain stem response was abnormal in 15 patients, and 22 had abnormal immunoglobulins in the cerebrospinal fluid. The correlation between abnormalities of the auditory brain stem response and the magnetic resonance images was greatest in a subgroup where the two investigations were performed within a ten day interval. Results from magnetic resonance imaging, evoked potentials and cerebrospinal fluid investigations were used to reclassify 13 of 15 patients with clinically ''possible'' or ''probable''multiple sclerosis to a higher level using Poser's criteria. Evoked potentials (the auditory brain stem response in particular) correlated best with clinical multiple sclerosis category. The authors recommend that the magnetic resonance imaging is established as a first-hand investigation in evaluation of multiple sclerosis. Evoked potentials and cerebrospinal fluid investigations may prove to be more specific, however, and these investigations should also be performed as a routine. 23 refs., 2 figs., 2 tabs
We present a patient with psychotic disorder as onset of relapsing-remitting multiple sclerosis (MS). In this patient, a 26-year-old female, neurological examination revealed only minor abnormalities. As cranial CT scan was normal, her psychosis was diagnosed as psychogenic. Literature on psychiatri
Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Cardol, M.; Nes, J.C.M. van de; Ende, C.H.M. van den
Background: Multiple sclerosis (MS) patients are referred to occupational therapy with complaints about fatigue, limb weakness, alteration of upper extremity fine motor coordination, loss of sensation and spasticity that causes limitations in performance of activities of daily living and social part
Tabira, T.; Tsuji, S; Nagashima, T; T. Nakajima; Kuroiwa, Y
Cortical deafness in a patient with multiple sclerosis is reported. Complete recovery from total deafness was seen following stages of auditory agnosia and pure word deafness. The otological and neurophysiological studies suggested lesions in subcortical white matter. This report stresses the rarity of the condition, its subcortical origin and good prognosis.
Koch, M; De Keyser, J
Peroxynitrite, a reactive oxidant formed by the reaction of nitric oxide with superoxide at sites of inflammation in multiple sclerosis (MS), is capable of damaging tissues and cells. Uric acid, a natural scavenger of peroxynitrite, reduces inflammatory demyelination in experimental allergic encepha
Bennett, J. L.; de Seze, J.; Lana-Peixoto, M.;
Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel...
... factors associated with an increased risk of developing multiple sclerosis include changes in the IL7R gene and environmental factors, such as exposure to the Epstein-Barr virus, low levels of vitamin D, and smoking. The HLA-DRB1 gene belongs ...
Full Text Available James P Simsarian, Carol Saunders, D Michelle SmithNeurology Center of Fairfax Ltd, Fairfax, VA, USABackground: Despite over 50 years of experience with adrenocorticotropic hormone (ACTH as a treatment for acute exacerbations of multiple sclerosis, there have been no trials examining the options of the 2–3-week dosing regimen or intramuscular injection protocol used in the original trials. At our clinic, we performed a small, prospective, randomized pilot study to examine the efficacy and safety of, and patient satisfaction with, a short (five-day self-administered ACTH dosing protocol for exacerbations of multiple sclerosis, and to compare the subcutaneous and intramuscular routes of administration.Methods: Patients for this study were recruited from an outpatient treatment clinic. Each patient self-administered natural ACTH gel 80 U/day by subcutaneous or intramuscular injection for five consecutive days and was evaluated at baseline and on days 7 and 14. Patient feedback was collected using the Patient Global Impression of Change (PGI-C, the primary efficacy measure, a patient global visual analog scale, the Expanded Disability Status Scale, a timed walk, the Nine-hole Peg Test, and the Clinical Global Impression of Change.Results: Of the 20 enrolled patients (mean age 39.5 years, 19 completed the study. On day 14, 61.1% of patients (11 of 18 with day 14 scores were treatment responders, and rated their condition as "very much improved" or "much improved" on the PGI-C. The intramuscular group had numerically more responders, but there was no significant difference in the proportion of responders between the intramuscular and subcutaneous groups at day 14 (P = 0.3. The intramuscular route of injection was associated with more injection site pain than the subcutaneous route.Conclusion: A shorter five-day course of intramuscular or subcutaneous ACTH gel may improve symptoms associated with acute exacerbations of multiple sclerosis. Larger
Full Text Available Background. Uveitis is 20 times more frequent in multiple sclerosis (MS patients than in the general population. Methods. A retrospective study of local multiple sclerosis (n=700 and uveitis cohorts (n=450 described the ophthalmological and neurological characteristics of patients with multiple sclerosis and uveitis. Results. Uveitis and multiple sclerosis were associated in seven patients. The time intervals between diagnoses of MS and uveitis ranged from 6 months to 15 years. Analysis of the patients’ characteristics revealed that multiple sclerosis was associated with an older age of onset than usually expected, that is, 39 years. Uveitis was bilateral in three cases and mainly posterior (5/10. Five patients presented with acute optic neuritis (two in one eye and three in both eyes. All eyes presenting with acute optic neuritis were also affected by uveitis (P=0.02, though not simultaneously. Conclusion. The ipsilateral association between optic neuritis and uveitis in this series of patients with multiple sclerosis may suggest a reciprocal potentiation between optic neuritis and uveitis in multiple sclerosis.
Guilherme Sciascia do Olival
Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.
... 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 ...
Michael Namaka; Michael R. Mulvey; Sabina Kapoor; Leann Simms; Christine Leong; Amy Grossberndt; Michael Prouta; Emma Frost; Farid Esfahani; Andrew Gomori
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Although the exact underlying mechanism leading to myelin destruction is unknown, the molecular mimicry theory is the most commonly acknowledged elucidation of MS pathology. Although various antigens have been associated with MS induction, this review presents studies focused on key bacterial and viral antigens that lead to the development of MS. The research specific to a molecular mimicry theory of MS via each implicated agent is weak; however, collectively the reports provide credible support for this theory. Given that homologous sequences are not required to lead to antigenic cross-reactivity, it is reasonable to conclude that certain viral and bacterial antigens with 5-10 similar amino acids in sequence can lead to self destruction of similar myelin sequences. Thus, this literature review has provided insight to further the understanding of the etiology of multiple sclerosis.
The authors analyzed MR examination of 277 patients with multiple sclerosis. White matter hyperintesities in brain were found in 270 of them, in spinal cord in 32. The most frequently they were found in periventricular white matter, in subcortical localization and in the corpus callosum. MR examination allows the estimate the activity of the disease on the basis of the presence of edema around the plaques and their contrast enhancement with Gd-DTPA. About one third of all cases were accompanied by cortical brain atrophy (the most often seen in the frontal lobes), subcortical brain atrophy was less frequent. In about two third of all cases the corpus callosum atrophy was found. MR examination is a highly sensitive method of multiple sclerosis diagnosis, of the assessment of its activity and progression. (author)
Full Text Available 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.
Riccio, Paolo; Rossano, Rocco
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 p...
Kelsey J. Weigel; Sharon G. Lynch; Steven M. LeVine
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 prote...
Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Cardol, M.; Nes, J.C.M. van de; Ende, C.H.M. van den
Background: Multiple sclerosis (MS) patients are referred to occupational therapy with complaints about fatigue, limb weakness, alteration of upper extremity fine motor coordination, loss of sensation and spasticity that causes limitations in performance of activities of daily living and social participation. The primary purpose of occupational therapy is to enable individuals to participate in self-care, work and leisure activities that they want or need to perform. Objectives: to determine ...
Mine Hayriye Sorgun; Bilge Koçer; Funda Kaplan; Nesrin Yılmaz; Nezih Yücemen; Canan Yücesan
OBJECTIVE: It has been reported that cranial neuropathy findings could be seen in the neurologic examination of multiple sclerosis (MS) patients, although brain magnetic resonance imaging (MRI) may not reveal any lesion responsible for the cranial nerve involvement. The aim of this study was to determine the frequency of brainstem and cranial nerve involvement, except for olfactory and optic nerves, during MS attacks, and to investigate the rate of an available explanation for the cranial neu...
James, W. H.
Studies on the birth order of patients with multiple sclerosis have yielded contradictory conclusions. Most of the sets of data, however, have been tested by biased tests. Data that have been submitted to unbiased tests seem to suggest that cases are more likely to occur in early birth ranks. This should be tested on further samples and some comments are offered on how this should be done.
The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic pl...
Raghuwanshi, Anita; Joshi, Sneha S.; Christakos, Sylvia
Vitamin D is a principal regulator of calcium homeostasis. However, recent evidence has indicated that vitamin D can have numerous other physiological functions including inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells and protection against certain immune mediated disorders including multiple sclerosis (MS). The geographic incidence of MS indicates an increase in MS with a decrease in sunlight exposure. Since vitamin D is produced in the ...
Joana eGuimarães; Maria José eSá
In Multiple Sclerosis (MS) prevalence studies of community and clinical samples, indicate that 45–60% of patients are cognitively impaired. These cognitive dysfunctions have been traditionally described as heterogeneous, but more recent studies suggest that there is a specific pattern of MS-related cognitive dysfunctions. With the advent of disease-modifying medications for MS and emphasis on early intervention and treatment, detection of cognitive impairment at its earliest stage becomes par...
Magnetic Resonance Imaging was performed in more than 200 patients with clinical suspicion or knowledge of Multiple Sclerosis. One hundred and forty-seven (60 males and 87 females) had MR evidence of multiple sclerosis lesions. The MR signal of demyelinating plaques characteristically has prolonged T1 and T2 relaxation times and the T2-weighted spin-echo sequences are generally superior to the T1-weighted images because the lesions are better visualized as areas of increased signal intensity. MR is also able to detect plaques in the brainstem, cerebellum and within the cervical spinal cord. MR appears to be an important, non-invasive method for the diagnosis of Multiple Sclerosis and has proven to be diagnostically superior to CT, evoked potentials (EP) and CSF examination. In a selected group of 30 patients, with the whole battery of the relevant MS studies, MR was positive in 100%, CT in 33,3%, EP in 56% and CSF examination in 60%. In patients clinically presenting only with signs of spinal cord involvement or optic neuritis or when the clinical presentation is uncertain MR has proven to be a very useful diagnostic tool for diagnosis of MS by demonstrating unsuspected lesions in the cerebral hemispheres. (orig.)
Full Text Available INTRODUCTION Multiple sclerosis is an immune-mediated disease that produces chronic inflammation and neural degeneration. The disease progresses with acute attacks that result in myelin inflammation. This in turn increases oxidative stress and favors the appearance of reactive oxygen species. Reactive oxygen species damage neural cells causing apoptosis. The etiology of multiple sclerosis remains unknown and current therapy is aggressive and expensive. Recently, complementary and alternative medicine therapies have been proposed to control pathogenesis and symptoms of this disease. It is believed that these therapies help slow the progression of multiple sclerosis and improve survival. METHODS We conducted a MEDLINE/PubMed search using the following MeSH terms: diet, multiple sclerosis, antioxidants. We selected the main articles containing multiple sclerosis and diet. RESULTS We analyzed three case control studies that evaluated different dietary approaches in multiple sclerosis. For this review, we also included five experimental studies that studied the efficacy of lipoic acid in humans and rodents in diseases like multiple sclerosis, experimental autoimmune encephalomyelitis, and breast cancer.
Full Text Available Multiple sclerosis (MS is a chronic, inflammatory disease of the central nervous system characterised by immune-mediated demyelination, and is a leading cause of neurological disability worldwide. It has a wide spectrum of clinical presentations which overlap with other neurological conditions many times. Further, the radiological array of findings in MS can also be confused for multiple other conditions, leading to the need to look for the more typical findings, and interpret these in close conjunction with the clinical picture including temporal evolution. This review aims to revisit the MRI findings in MS, including recent innovations in imaging, and to help distinguish MS from its mimics.
Orefice, Ns; Carotenuto, A; Mangone, G; Bues, B; Rehm, R; Cerillo, I; Saccà, F; Calignano, A; Orefice, G
Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR-MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium-enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological
Asghar Amini Harandi; Ali Amini Harandi; Hossein Pakdaman; Mohammad Ali Sahraian
Multiple sclerosis (MS) is a chronic demyelinating disease and also is one of the most common disabling neurological disorders in young and middle-aged adults. The main pathogenesis of MS has long been thought to be an immune mediated disorder of the central nervous system. The function of the immune system is under the influence of vitamin D which as a modulator of immune response could play a role in autoimmune diseases including MS. Deficiency of vitamin D or variations in DNA sequence (po...
Full Text Available Fingolimod, an oral sphingosine 1-phosphate (S1P receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS. The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7 expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls, and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition.
Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M; Jordan, J; Benkhedah, Nadia; Kleesiek, Jens
The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ(2)(1) = 27.89, p < 0.001) and fluid-attenuated (χ(2)(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776
Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M.; Jordan, J.; Benkhedah, Nadia; Kleesiek, Jens
The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ2(1) = 27.89, p < 0.001) and fluid-attenuated (χ2(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776
Noha t. Abokrysha
Full Text Available Multiple sclerosis (MS is widely believed to be an autoimmune disorder. Another exciting idea regarding the aetiology of MS may be that the immune response in MS could result from a chronic infection rather than autoimmunity in the usual sense. M. leprae-induced myelin damage in the early infectious process provides valuable insights into the pathologic mechanisms of multiple sclerosis. However, no research has hypothesized the possible involvement of mycobacterium leprae or its components in pathogenesis of MS. Most of the antigens of mycobacterium leprae and mycobacterium tuberculosis are members of stress protein families. Of the M. leprae and M. tuberculosis antigens identified by monoclonal antibodies, all except the 18-kDa M. leprae antigen and the 19-kDa M. tuberculosis antigen are strongly coded with very similar genes. I hypothesize that MS is a syndrome of diseases, induced by intradermal BCG vaccine which may contain the antigen component resembling that of leprae that can either produce central demyelination by itself, or by delayed hypersensitivity. The hypothesis should be assessed in several experimental and clinical trials. If my hypothesis can be verified experimentally and clinically, then measurements to prevent MS disease could be accomplished.
Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T
This thesis describes recently developed research methods for the diagnosis of multiple sclerosis. In Chapter X the use of the CT-scan in the detection of hemispheral or cerebellar lesions is discussed. In chapter XIII the results of the application of all methods to a group of 89 patients with definite, probable or possible multiple sclerosis and to a group of 25 purely optic neuritis patients are presented. With the aid of the CT-scan, hypo- or hyperdense areas in the white matter of the cerebral hemispheres were found in 52% of the 114 patients. Most reports ascribe these lesions to demyelinating cerebral plaques. The CT-scan showed no cerebellar or brainstem lesions. The CT-scan is independent of the duration of, and degree of incapacitation due to, the disease and can be helpful in giving a definite diagnosis in an early stage of the disease. The CT-scan will always play an important role for the differential diagnosis. (Auth.)
Magyari, Melinda; Koch-Henriksen, Nils Iørgen; Pfleger, Claudia Christina;
The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men.......The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men....
Sorensen, Per Soelberg
complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis...
Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.
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.
MR imaging is very useful in detecting the intracranial lesion of multiple sclerosis (MS). We present six patients of MS with atypical MR imaging findings. Six patients aged 27-56 years (mean 36 years), and sexuality of six patients were 2 men and 4 females. Three patient's clinical course had episodes of optic neuritis. The plaque's size of the predominant lesion of the patients ranged from 3.0 to 9.0 cm in diameter. The plaques were oval, elliptically and other shaped. At acute stage, MR imaging detected perfocal edema and focal mass effect in three cases of our study. Two out of six cases showed multiple irregularly enhancing lesion with Gadolinium-DTPA. Plaques of all cases did not disappear completely in final MR imaging study. (author)
Katagiri, Shinako; Kan, Shinichi; Ikeda, Toshiaki; Nishiyama, Syougo; Nishimaki, Hiroshi; Matsubayashi, Takashi; Hata, Takashi [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine
MR imaging is very useful in detecting the intracranial lesion of multiple sclerosis (MS). We present six patients of MS with atypical MR imaging findings. Six patients aged 27-56 years (mean 36 years), and sexuality of six patients were 2 men and 4 females. Three patient`s clinical course had episodes of optic neuritis. The plaque`s size of the predominant lesion of the patients ranged from 3.0 to 9.0 cm in diameter. The plaques were oval, elliptically and other shaped. At acute stage, MR imaging detected perfocal edema and focal mass effect in three cases of our study. Two out of six cases showed multiple irregularly enhancing lesion with Gadolinium-DTPA. Plaques of all cases did not disappear completely in final MR imaging study. (author).
Bramow, Stephan; Frischer, Josa M; Lassmann, Hans;
The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments for...
Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple
Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia [III Neurological Clinic, University Hospital Saint Naum, Sofia (Bulgaria); Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria [Laboratory of Radiation Genetics, NCRRP, Sofia (Bulgaria); Groudeva, Violeta [Department of Diagnostic Imaging, University Hospital St. Ekaterina, Sofia (Bulgaria); Hadjidekova, Savina [Department of Medical Genetics, Medical University, Sofia (Bulgaria); Domínguez, Inmaculada, E-mail: firstname.lastname@example.org [Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes 6, 41012 (Spain)
Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple
Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.
Full Text Available A number of neuropsychological studies have revealed that memory problems are relatively common in patients with multiple sclerosis (MS. It may be useful to compare MS with conditions such as Huntington's disease (HD, which have been referred to as subcortical dementia. A characteristic of these conditions may be an impairment in implicit (unconscious memory, but not in explicit (conscious memory. The present study examined the functioning of explicit and implicit memory in MS. Results showed that implicit memory was not significantly impaired in the MS subjects, and that they were impaired on recall but not recognition. A correlation was found between implicit memory performance and disability status in MS patients. Findings also suggest the possibility of long-term priming of implicit memory in the control subjects. The implications of these results are discussed.
Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E
Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620
Stenager, Elsebeth Nylev; Jensen, Børge; Stenager, Maria;
The purposes of the study were (1) to estimate the risk of suicide attempts in multiple sclerosis (MS) patients in Denmark and compare the risk to the background population in the County of Funen, Denmark; (2) to estimate the risk of suicide attempts in MS patients receiving immunomodulating...... therapy compared with untreated patients. The Danish MS Registry, the Danish MS Treatment Registry and the Suicide Attempt Registry are linked and merged together using a person identification number given to all persons residing in Denmark. Among 404 MS patients, 15 patients had attempted suicide......, although no increased risk for suicide attempts was found in MS patients. No difference in number of suicide attempts in treated and untreated patients was found....
Niino, Masaaki; Miyazaki, Yusei
While cognitive impairment is a major symptom of multiple sclerosis (MS), it is commonly overlooked. This may be explained by the fact that it is difficult to evaluate cognitive function in patients with MS using screening batteries for the detection of dementia such as the mini-mental state examination. Further more, cognitive impairment in MS typically involves domain-specific deficits such as imparement of sustained attention and information processing speed rather than global cognitive decline. Cognitive impairment may influence the daily living and social lines of affected patients. This review discusses the characteristics of cognitive impairment, appropreate tests to evaluate its symptoms, and the current status of clinical trials for the treatment of MS. PMID:27056855
Pintér, Alexandra; Cseh, Domonkos; Sárközi, Adrienn; Illigens, Ben M; Siepmann, Timo
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
de Lorenzo-Pinto, Ana; Rodríguez-González, Carmen Guadalupe; Ais-Larisgoitia, Arantza
Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system considered the second cause of disability in young adults. The prognosis of MS has improved significantly since the approval of the first interferon β in 1993 but, compared to other diseases, few new therapeutic products have been commercialized in the last years. However, currently, there are more than 600 ongoing clinical trials and new drugs that aim to improve efficacy and a more convenient schedule of administration, will appear shortly on the market. On the other hand, new safety issues will arise as well as a significant economic impact on the health system. The main efficacy and safety results of these drugs are reviewed in this paper. They can be classified into 2 groups: oral (fingolimod, laquinimod, teriflunomide, BG-12 [dimethyl fumarate], oral cladribine, dalfampridine) and monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab). PMID:22766059
Cree, Bruce A. C.
Rapid advances are occurring in multiple sclerosis disease modifying therapies. Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. interferon beta and glatiramer acetate), development of novel anti-neuroinflammatory medications (e.g. fingolimod, teriflunomide and dimethyl fumarate, daclizumab, alemtuzumab, ocrelizumab) and investigation of treatments in progressive MS (e.g. natalizumab, mastinib, natalizumab, siponimod). The impact of vitamin D supplementation on the disease course in relapsing MS patients is also being studied in several clinical trials. This article reviews the current state of the field with a forward look to the next phase of MS research that could focus on strategies to promote remyelination and provide neuronal protection. PMID:24707333
Diana, R; Grosz, A; Mancini, E
To test the claim that peculiar personality bias is detectable in multiple sclerosis (MS) we used the Szondi test to investigate the psychodynamic aspects of 110 MS patients in comparison with 200 healthy subjects. MS patients appeared to have a greater need for love in a passive form than normal people, rigid defense mechanisms, difficulty in resolving their inner conflicts either by sublimation or by internalization of satisfactory new emotional experiences, feelings of autoaggressiveness, and many symptoms of depression. Some of these aspects correlate with the severity of the disease, others seem to date back to early childhood as peculiar personality patterns. An investigation of childhood events in 110 controls confirmed that MS patients had had many more unhappy experiences in childhood than might commonly be expected. Further, the oft-reported psychiatric troubles preceding MS clinical onset suggest that at least in some MS patients there are specific gaps in personality structure dating back to early phases of their development. PMID:4086262
Niino, Masaaki; Miyazaki, Yusei
The geographic epidemiology of multiple sclerosis (MS) suggests that low vitamin D levels are a modifiable risk factor. Previous studies have shown that patients with MS have significantly lower vitamin D levels compared with healthy controls. Vitamin D is a potent immunomodulator important for immune function and development, and it offers potential benefits by reducing inflammation. Vitamin D has beneficial effects in experimental autoimmune encephalomyelitis, an animal model of MS. In summation, these studies suggest that vitamin D may have therapeutic potential for MS. This has not been established although preliminary clinical trials for vitamin D in MS look promising. Genetic studies suggest that genes associated with vitamin D are critical susceptible genes for MS. In this review, we discuss current research investigating the association between vitamin D and MS and the issues that need to be resolved. PMID:26560958
Asghar Amini Harandi
Full Text Available Multiple sclerosis (MS is a chronic demyelinating disease and also is one of the most common disabling neurological disorders in young and middle-aged adults. The main pathogenesis of MS has long been thought to be an immune mediated disorder of the central nervous system. The function of the immune system is under the influence of vitamin D which as a modulator of immune response could play a role in autoimmune diseases including MS. Deficiency of vitamin D or variations in DNA sequence (polymorphism of vitamin D receptor gene diminishes its optimal function on immune system that consequently could lead to increasing risk of MS. However, its role in development and modulating the course of MS is still under investigation. In this review we aimed to discuss the role of vitamin D in body, immune system and consequently altering the risk of MS.
Full Text Available In Multiple Sclerosis (MS prevalence studies of community and clinical samples, indicate that 45–60% of patients are cognitively impaired. These cognitive dysfunctions have been traditionally described as heterogeneous, but more recent studies suggest that there is a specific pattern of MS-related cognitive dysfunctions. With the advent of disease-modifying medications for MS and emphasis on early intervention and treatment, detection of cognitive impairment at its earliest stage becomes particularly important. In this review the authors address: the cognitive domains most commonly impaired in MS (memory, attention, executive functions, speed of information processing and visual spatial abilities; the physiopathological mechanism implied in MS cognitive dysfunction and correlated brain MRI features; the importance of neuropsychological assessment of MS patients in different stages of the disease and the influence of its course on cognitive performance; the most used tests and batteries for neuropsychological assessment; therapeutic strategies to improve cognitive abilities.
Balcer, Laura J; Miller, David H; Reingold, Stephen C;
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......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...... 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...
The diagnosis of multiple sclerosis (MS) by computerized tomography and nuclear magnetic resonance are shown, including the examination of cerebral spinal fluid. Lymphocytic, foamy histiocytic perivascular cuffing, degenerated oligodendrocytes, and microglia proliferation with relative axonal sparing are presented. In the latter stage of the chronic MS plaque there is sclerosis with microcystic formation with complete demyelination and organization. (author)
Miller, D H; Hornabrook, R W; Dagger, J; Fong, R
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
Alexander J Steven
Full Text Available Abstract 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 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.
Koch-Henriksen, N; Magyari, M; Laursen, B
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...... 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...
Zhen-Ni Guo; Si-Yuan He; Hong-Liang Zhang; Jiang Wu; Yi Yang
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.
Dong, Aisheng; Gao, Mingjun; Wang, Yang; Gao, Lei; Zuo, Changjing
Tumefactive multiple sclerosis refers to the presentation of large demyelinating lesions (≥2 cm in diameter) mimicking brain tumors clinically and radiologically. We present the MRI and FDG PET/CT findings in a case with tumefactive multiple sclerosis, who had chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Head MRI showed 7 cerebral lesions with incomplete ring enhancement. All but one lesion had size more than 2 cm. All these demyelinating lesions showed increased uptake at the rims of the lesions with central hypometabolism. Stereotactic brain biopsy of the right frontal lesion revealed extensive macrophage and lymphocyte infiltration. PMID:26909714
X-radiation of 27 patients with thyroid at acute therapeutically resistant, progradient form of multiple sclerosis has been applied. Indistinct therapeutic effect attributed to depression of auto-aggressive allergic processes in cerebrospinal formations is noted in 20 patients after one or two courses of radiotherapy. The method can be used in complex therapy of progradient forms of multiple sclerosis
Lublin, Fred D; Reingold, Stephen C; Cohen, Jeffrey A;
Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts...
Seven papers in this volume are in INIS scope, one dealing with autoradiographic detection of multiple sclerosis plaques with radiologands, and the others with magnetic resonance imaging of MS lesions. (H.W.). refs.; figs.; tabs
... of multiple sclerosis (MS). The American Academy of Neurology (AAN) is the world’s largest association of neurologists ... modifying and symptomatic treatments. ©2014 American Academy of Neurology AAN. com What is CAM therapy? How does ...
Balcer, Laura J; Miller, David H; Reingold, Stephen C; Cohen, Jeffrey A
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
Ascherio, Alberto; Munger, Kassandra L; Lünemann, Jan D.
Although there are strong genetic determinants of multiple sclerosis, the results of migration studies support a role for the environment, and through rigorous epidemiological investigation, Epstein-Barr virus infection, vitamin D nutrition, and cigarette smoking have been identified as likely causal factors for multiple sclerosis. In this review, we discuss the strength of this evidence, as well as the potential biological mechanisms underlying these associations. Both vitamin D nutrition an...
Vladimir V. Markelov; Maxim V. Trushin
ABSTRACTThe data presented in this manuscript suggest a pivotal role of the central nervous system (CNS) in the regulation of immune status. We describe here that some neurochemical disturbances may provoke development of various diseases including multiple sclerosis. Some theoretic and practical backgrounds, how to improve the multiple sclerosis sufferers and patients with other autoimmune disorders, are also given.RESUMENLos datos que presentamos en este manuscrito, sugieren un papel guia d...
Nielsen, Nete Munk; Jørgensen, Kristian Tore; Stenager, Egon; Jensen, Allan; Pedersen, Bo V; Hjalgrim, Henrik; Kjær, Susanne Krüger; Frisch, Morten
It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting.......It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting....
Motomu Shimaoka; Hiroshi Imai; Takayuki Okamoto; Susumu Nakahashi; Eiji Kawamoto
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 pr...
Vedavathy Nayak; Sreelatha S; Sahana Punneshetty
Multiple sclerosis is primarily a disease of women in their reproductive years. Relapse rate decreases during pregnancy and rises after delivery. Pregnancy and puerperium have opposite effects on the course of the disease. The case presented is that of a second gravida who was a known case of multiple sclerosis. She was managed conservatively during pregnancy and puerperium. [Int J Reprod Contracept Obstet Gynecol 2012; 1(1.000): 67-68
Full Text Available While current immunomodulating drugs aim to reduce multiple sclerosis (MS exacerbations and slow disease progression, rehabilitation aims to improve and maintain the functional abilities of patients in the face of disease progression. An increasing number of journal articles are describing the value of the many rehabilitation interventions that can be used throughout the course of the disease, from the initial symptoms to the advanced stages. An integrated team of healthcare professionals is necessary to address a myriad of problems to reduce impairments, disabilities, and handicaps. The problems may be related to fatigue, weakness, spasticity, mobility, balance, pain, cognition, mood, relationships, bowel, bladder, sexual function, swallowing, speech, transportation, employment, recreation, and activities of daily living (ADL such as dressing, eating, bathing, and household chores. The team can help prevent complications and secondary disabilities, while increasing patient safety. Improving neurologically related function, maintaining good relationships, and feeling productive and creative adds enormously to the quality of life of people with MS and their families. Rehabilitation is more than an ′extra′ service that is given after medical therapies; it is an integral part of the management of the diverse set of problems encountered throughout the course of the disease. An interdisciplinary team may have many members, including physicians, nurses, physical therapists, occupational therapists, speech and language pathologists, psychotherapists, social workers, recreational therapists, vocational rehabilitation therapists, patients, families, and other caregivers.
Multiple sclerosis (MS) is the commonest disabling neurological disease of young and middle-aged adults affecting 1 million persons world wide. The illness begins with a relapsing-remitting MS course in 85%–90% of patients; the other 10%–15% have a primary progressive onset MS. Our current understanding is that MS is an autoimmune disorder with an inflammatory T-cell attack on myelin or some component of the oligodendrocyte--myelin structure. Relapses of disease activity result in plaques of demyelination with destruction of myelin and, to a lesser, extent axons. Lymphocytes within the central nervous system tissue recruit more cells leading to an inflammatory cascade that causes myelin damage, axonal disruption, and neuronal death. If the plaque occurs in a vocal area of the central nervous system then symptoms relating to that area result. However, magnetic resonance imaging shows that approximately 10 times more lesions occur in asymptomatic areas of the brain. Recovery from an initial relapse may appear relatively complete but persistent inflammation results in axonal injury and residual disability results. With time and accumulated lesion load, secondary degeneration of denuded axons results in the phase of secondary progressive MS usually 15-20 years after onset. PMID:20874255
Full Text Available 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.
Joaquín A. Peña
Full Text Available OBJECTIVE: To describe the epidemiological and clinical characteristics of Venezuelan pediatric patients with multiple sclerosis (MS. METHODS: Database records from the National Program for MS were searched for patients with an established diagnosis of MS whose first symptoms appeared before age 18. RESULTS: The national database held records of 1.710 patients; 3.8% had onset of the first symptoms before age 18. 46.7% were boys, yielding an F:M ratio of 1.13:1. Many children had a disease onset characterized by motor impairment (30.7%, brainstem/cerebellum and spinal cord affectation (27.6%, headache (26%. Less frequent symptoms were sensory symptoms (8% and optic neuritis (7%. DISCUSSION: Pediatric MS patients in Venezuela represent a significant proportion of all MS cases. The clinical pattern is characterized by motor symptoms at onset, and predominantly monosymptomatic presentation with a relapsing-remitting pattern. This is the first systematic attempt to estimate the prevalence of pediatric MS in Venezuela.
Multiple sclerosis (MS) is the commonest disabling neurological disease of young and middle-aged adults affecting 1 million persons world wide. The illness begins with a relapsing-remitting MS course in 85%-90% of patients; the other 10%-15% have a primary progressive onset MS. Our current understanding is that MS is an autoimmune disorder with an inflammatory T-cell attack on myelin or some component of the oligodendrocyte--myelin structure. Relapses of disease activity result in plaques of demyelination with destruction of myelin and, to a lesser, extent axons. Lymphocytes within the central nervous system tissue recruit more cells leading to an inflammatory cascade that causes myelin damage, axonal disruption, and neuronal death. If the plaque occurs in a vocal area of the central nervous system then symptoms relating to that area result. However, magnetic resonance imaging shows that approximately 10 times more lesions occur in asymptomatic areas of the brain. Recovery from an initial relapse may appear relatively complete but persistent inflammation results in axonal injury and residual disability results. With time and accumulated lesion load, secondary degeneration of denuded axons results in the phase of secondary progressive MS usually 15-20 years after onset.
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
Hauser, Stephen L; Chan, Jonah R; Oksenberg, Jorge R
We have entered a golden era in multiple sclerosis (MS) research. Two decades ago, our understanding of the disease was largely descriptive and there were no approved therapies to modify the natural history of MS. Today, delineation of immune pathways relevant to MS have been clarified; a comprehensive map of genes that influence risk compiled; clues to environmental triggers identified; noninvasive in vivo monitoring of the MS disease process has been revolutionized by high-field MRI; and many effective therapies for the early, relapsing, component of MS now exist. However, major challenges remain. We still have no useful treatment for progressive MS (the holy grail of MS research), no means to repair injured axons or protect neurons, and extremely limited evidence to guide treatment decisions. Recent advances have set in place a foundation for development of increasingly selective immunotherapy for patients; application of genetic and genomic discoveries to improve therapeutic options; development of remyelination or neuroprotection therapies for progressive MS; and integrating clinical, imaging and genomic data for personalized medicine. MS has now advanced from the backwaters of autoimmune disease research to the front-line, and definitive answers, including cures, are now realistic goals for the next decade. Many of the breakthrough discoveries in MS have also resulted from meaningful interactions across disciplines, and especially from translational and basic scientists working closely with clinicians, highlighting that the clinical value of discoveries are most often revealed when ideas developed in the laboratory are tested at the bedside. PMID:23955638
Objective: It's a study of MRI diagnosis and differential diagnosis of multiple sclerosis (MS) in 49 cases. Methods: 49 patients were diagnosed as MS of brain or/and spinal cord in the year of 1995 to 2002. All cases had clinical informations, including evoked potential. MR brain scan was done in 49 patients, and spinal cord scan was performed in 10 cases out of 49. Enhanced scan were done in 29 cases. A follow-up examination was done in 17 patients within 30 days after the initial study. Results: Multiple brain lesions, located in peri-ventricular region, semi-elliptical center, cerebellum and brain stem, were revealed in 47 patients, MS plaques were speckle or patchy and the largest one was 2.2 x 5.0 cm. Simple spinal Cord lesions involving at least 2 sections were revealed in 2 patients. Two cases were initially misdiagnosed as encephalitis. Another case was defined as tumor because of the brainstem swelling and enhanced plaques. Optic nerve impairment was found in a case besides the brain lesions. Complicated brain and spinal Cord lesions were shown in 4 cases. Enhanced MRI scan was performed in 29 cases: non-enhanced lesions were revealed in 7 cases and lesions were enhanced in the rest 22. Mottling or plaque enhancement was presented in 20 cases, while ring enhancement was presented in 2. Follow-up study showed the improvement in 17 cases. Conclusion: Brain and spinal cord MS plaques can be demonstrated on MRI, while clinical manifestation is necessary for MRI diagnosis in atypical lesions. Serial study is helpful for differential diagnosis
Doty, Richard L; Tourbier, Isabelle A; Pham, Dzung L; Cuzzocreo, Jennifer L; Udupa, Jayaram K; Karacali, Bilge; Beals, Evan; Fabius, Laura; Leon-Sarmiento, Fidias E; Moonis, Gul; Kim, Taehoon; Mihama, Toru; Geckle, Rena J; Yousem, David M
Empirical studies of taste function in multiple sclerosis (MS) are rare. Moreover, a detailed assessment of whether quantitative measures of taste function correlate with the punctate and patchy myelin-related lesions found throughout the CNS of MS patients has not been made. We administered a 96-trial test of sweet (sucrose), sour (citric acid), bitter (caffeine) and salty (NaCl) taste perception to the left and right anterior (CN VII) and posterior (CN IX) tongue regions of 73 MS patients and 73 matched controls. The number and volume of lesions were assessed using quantitative MRI in 52 brain regions of 63 of the MS patients. Taste identification scores were significantly lower in the MS patients for sucrose (p = 0.0002), citric acid (p = 0.0001), caffeine (p = 0.0372) and NaCl (p = 0.0004) and were present in both anterior and posterior tongue regions. The percent of MS patients with identification scores falling below the 5th percentile of controls was 15.07 % for caffeine, 21.9 % for citric acid, 24.66 % for sucrose, and 31.50 % for NaCl. Such scores were inversely correlated with lesion volumes in the temporal, medial frontal, and superior frontal lobes, and with the number of lesions in the left and right superior frontal lobes, right anterior cingulate gyrus, and left parietal operculum. Regardless of the subject group, women outperformed men on the taste measures. These findings indicate that a sizable number of MS patients exhibit taste deficits that are associated with MS-related lesions throughout the brain. PMID:26810729
Riccio, Paolo; Rossano, Rocco
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
Kelsey J. Weigel
Full Text Available 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.
Furst, Miriam; Levine, Robert A
Multiple sclerosis (MS) is a disease that is both a focal inflammatory and a chronic neurodegenerative disease. The focal inflammatory component is characterized by destruction of central nervous system myelin, including the spinal cord; as such it can impair any central neural system, including the auditory system. While on the one hand auditory complaints in MS patients are rare compared to other senses, such as vision and proprioception, on the other hand auditory tests of precise neural timing are never "silent." Whenever focal MS lesions are detected involving the pontine auditory pathway, auditory tests requiring precise neural timing are always abnormal, while auditory functions not requiring such precise timing are often normal. Azimuth sound localization is accomplished by comparing the timing and loudness of the sound at the two ears. Hence tests of azimuth sound localization must obligatorily involve the central nervous system and particularly the brainstem. Whenever a focal lesion was localized to the pontine auditory pathway, timing tests were always abnormal, but loudness tests were not. Moreover, a timing test that included only high-frequency sounds was very often abnormal, even when there was no detectable focal MS lesion involving the pontine auditory pathway. This test may be a marker for the chronic neurodegenerative aspect of MS, and, as such could be used to complement the magnetic resonance imaging scan in monitoring the neurodegenerative aspect of MS. Studies of MS brainstem lesion location and auditory function have led to advances in understanding how the human brain processes sound. The brain processes binaural sounds independently for time and level in a two-stage process. The first stage is at the level of the superior olivary complex (SOC) and the second at a level rostral to the SOC. PMID:25726295
Pihl-Jensen, Gorm; Frederiksen, Jette Lautrup
Optic neuritis (ON) is a common first symptom of MS and only few studies have thus far investigated vitamin D at this early stage of MS. The objectives of the study were to examine total 25-hydroxyvitamin D levels (25HVITDL) in patients in acute (A) ON and to determine whether 25HVITD levels in AON (1) predict risk of RRMS and (2) are associated with visual tests of ON severity. A cross-sectional study was conducted of mean 25HVITDL differences between ON (n = 164) and MS (n = 948) patients and of prevalence of 25HVITDL deficiency (vitamin D in the early stages of MS, but does not support the use of 25HVITDL as a predictor of MS development in acute ON. PMID:25929657
Full Text Available 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.
Rebeca A. Fernández Carriera
Full Text Available Fundament: The proteolitic rupture of the extracellular matrix due to metalloproteinase 2 and 9 is one of the aspects that can influence in the alteration of the permeability of the blood-brain barrier (BBB in multiple sclerosis. Objective: To determine metalloproteinase activity with gelatinous activity in patients suffering from multiple sclerosis. Methods: the cerebrospinal fluid (CSF samples taken from 31 patients suffering from multiple sclerosis and a control group formed by 21 patients without neurological disease. The metalloproteinase 2 and 9 activities in the cerebrospinal fluid were determined by zimográfica technique through polyacrylamide gel electrophoresis. The bands were later analysed by their molecular weight and the relative metalloproteinase 9 activity was calculated. Total protein concentrations, albumin and immunoglobulin G (IgG, the IgG rate and the Q rate were assessed to evaluate the IgG intrathecal and the functional state of the blood-brain barrier. Results: metalloproteinase 2 activity was detected in the cerebrospinal fluid of all patients and control group. Metalloproteinase 9 activity was only found in the 61.3 % of the patients. The presence of relative metalloproteinase 9 activity was neither associated with the clinical variables nor the laboratory ones. An association was found between its presence and the oligoclonal bands in patients with multiple sclerosis. In those patients under immunomodular treatment it was presented with less frequency. Conclusions: There is a possible participation of Metalloproteinase 9 in the immunopathological mechanisms of the multiple sclerosis.
Full Text Available 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.
Koch-Henriksen, Nils; Brønnum-Hansen, Henrik; Stenager, Egon
To determine the underlying causes of death in a large population based register series of patients with multiple sclerosis.......To determine the underlying causes of death in a large population based register series of patients with multiple sclerosis....
Olsen, D.B.; Langkilde, Annika Reynberg; Schmalbruch, H;
The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed......The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed...
M.P. Stoop (Marcel)
textabstractMultiple sclerosis (MScl) is a highly heterogeneous disease of the central nervous system, and its pathology is characterized by a combination of factors such as inflammation, demyelination and axonal damage [1, 2]. Cerebrospinal fluid (CSF) is a relatively interesting body fluid in whic
Stenager, Egon; Brønnum-Hansen, Henrik; Koch-Henriksen, Nils
The incidence of multiple sclerosis (MS) in nurses during the period 1980-1996 was calculated in a nationwide study. The cohort consisted of 69,428 nurses, 2185 men and 67,243 women. Sixty (two men and 58 women) with definite MS were observed, whereas 69.3 were expected. We found no significant...
Full Text Available Multiple sclerosis is a demyelinating disease of the central nervous system, occurs most commonly in adults between 20 and 40 years of age. Etiology of this disease is still not known, and one of the analyzed environmental factors is food. In this study, based on literature, discusses the impact of dietary intake of food on the occurrence and development of the disease. This study demonstrated that patients with multiple sclerosis less than healthy people ate bread and cereal products, fish, some vegetables and fruits. While patients often consumed an animal products, whole milk and sweets. It also discusses Swank’s diet, which suggest that the severity of symptoms disease may be responsible food of animal origin, which is rich in saturated fatty acids. The author found that patients who comply a diet, after 34 years of application, the risk of death due to multiple sclerosis was three times lower than in those who have not complied with all the dietary recommendations. Moreover, research demonstrated a correlation between deficiency of omega-3, vitamin D, B12, antioxidant vitamins and folic acid in diet, and the development and exacerbation of symptoms of multiple sclerosis. Results of research concerning the relationship between dietary factors and the occurrence and development of this disease are inconclusive why the need is greater the amount thereof in this field. Patients may consider using a diet or supplements, if pharmacotherapy and other alternative and complementary methods do not bring expected effects.
Hansen, T; Skytthe, Axel; Stenager, Egon;
The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study...
Sørensen, Per Soelberg
Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis of...
Magyari, Melinda; Koch-Henriksen, Nils; Pfleger, Claudia C;
BACKGROUND: The female preponderance in incidence of multiple sclerosis (MS) calls for investigations into sex differences in comorbidity with other autoimmune diseases (ADs). OBJECTIVES: To determine whether male and female patients with MS have a higher frequency of autoimmune comorbidity than...
Sørensen, Torben Lykke; Ransohoff, R M
The cause of multiple sclerosis (MS) remains unknown despite decades of intense research. The major research disciplines that have been brought to bear on this question include genetics, epidemiology, neuropathology, immunology, and virology. Recent advances in the understanding of the inflammatory...
Boesen, Magnus Spangsberg; Sellebjerg, Finn; Blinkenberg, Morten
INTRODUCTION: Paediatric multiple sclerosis (MS) carries a relatively higher mortality and morbidity than adult MS. Paediatric MS symptoms and paraclinical findings at the first demyelinating event have never before been characterised in a Danish setting. The aim of this study was to compare...
Koch, Marcus; van Harten, Annemarie; Uyttenboogaart, Maarten; De Keyser, Jacques
OBJECTIVE: To investigate the influence of cigarette smoking on progression and disability accumulation in multiple sclerosis (MS). METHODS: Information on past and present smoking of 364 patients with MS was obtained through a structured questionnaire survey. We used Kaplan-Meier analyses and Cox r
Hoang, Huong; Laursen, Bjarne; Stenager, Elsebeth N; Stenager, Egon
BACKGROUND: Studies of depression and anxiety in multiple sclerosis (MS) patients have reported higher rates in MS patients than the general population. OBJECTIVE: To estimate the risk of depression and anxiety and the use of tricyclic antidepressant and selective serotonin reuptake inhibitors...
Simon A. Broadley
Full Text Available The treatment of multiple sclerosis has been radically transformed over the past 20 years and this special issue of IJMS, focusing on the molecular aspects of the disease, highlights the growing conformity of the various investigative approaches. It is a very exciting time to be involved in the research of this disease.
Larsson, H B; Barker, G J; MacKay, A
OBJECTIVES: The theory of relaxation processes and their measurements are described. An overview is presented of the literature on relaxation time measurements in the normal and the developing brain, in experimental diseases in animals, and in patients with multiple sclerosis. RESULTS AND CONCLUS...
Rogojan, C; Frederiksen, J L
Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...
Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis
The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007-2012. We describe the patients' history and treatment...
J Gordon Millichap
Researchers at University of California, San Francisco, and State University of New York at Stony Brook, NY consecutively recruited patients with pediatric-onset multiple sclerosis into a prospective cohort to determine if vitamin D status is associated with the rate of subsequent clinical relapses.
Full Text Available 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.
Full Text Available Abstract Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis.
Swathi Balantrapu; Sosnoff, Jacob J.; Pula, John H.; Brian M. Sandroff; Motl, Robert W.
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)...
Computer tomography was performed in 41 patients with multiple sclerosis, the average age of patients being 40.8 years. Native examinations were made of 17 patients, examinations with contrast medium of 19, both methods were used in the examination of 5 patients. In 26 patients, i.e. in almost two-thirds, cerebral atrophy was found, in 11 of a severe type. In 9 patients atrophy affected only the hemispheres, in 16 also the stem and cerebellum. The stem and cerebellum only were affected in 1 patient. Hypodense foci were found in 21 patients, i.e. more than half of those examined. In 9 there were multiple foci. In most of the 19 examined patients the hypodense changes were in the hemispheres and only in 2 in the cerebellum and brain stem. No hyperdense changes were detected. The value and possibilities are discussed of examinations by computer tomography multiple sclerosis. (author)
Biswas Sangita; Benedict Stephen H; Lynch Sharon G; LeVine Steven M
Abstract Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activ...
Vladimir V. Markelov
Full Text Available ABSTRACTThe data presented in this manuscript suggest a pivotal role of the central nervous system (CNS in the regulation of immune status. We describe here that some neurochemical disturbances may provoke development of various diseases including multiple sclerosis. Some theoretic and practical backgrounds, how to improve the multiple sclerosis sufferers and patients with other autoimmune disorders, are also given.RESUMENLos datos que presentamos en este manuscrito, sugieren un papel guia del sistema nervioso central (SNC en la regulación del estado inmune. Describimos aquí que varias alteraciones neuroquímicas pueden provocar el desarrollo de varias enfermedades, incluyendo esclerosis múltiple. También se comenta acerca del trasfondo teórico y práctico, y cómo mejorar a víctimas y pacientes con esclerosis múltiple y otras alteraciones autoinmunes.
Moreira, Shirlene Vianna; França, Cecília Cavalieri; Moreira, Marcos Aurélio; Lana-Peixoto, Marco Aurélio
Musical autobiographies consist of a powerful therapeutic tool by which individuals define themselves. The use of this technique may help (re)construction personal identities and improve quality of life of patients with multiple sclerosis (MS). Eight adult patients on treatment at CIEM Multiple Sclerosis Investigation Center after selecting 10 to 15 pieces of music most significant in their lives were interviewed. The data collected were classified according to Even Rudd categories, which reveal how a person expresses his personal, social, temporal and transpersonal identities. We observed that recall of musical history makes MS patients get better perception both of their feelings and body awareness, as well as provide them with an alternative way to express themselves, activate and contextualize affective memories, and achieving a sense of life continuity in spite of the disease. PMID:19330210
Nielsen, Nete M; Westergaard, Tine; Frisch, Morten; Rostgaard, Klaus; Wohlfahrt, Jan; Koch-Henriksen, Nils; Melbye, Mads; Hjalgrim, Henrik
BACKGROUND: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported...... Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil......, 1.63; 95% confidence interval, 1.26-2.12; n = 56) for development of T1D. However, adjusting for familial relationship to patients with T1D reduced the excess risk to 44% (relative risk, 1.44; 95% confidence interval, 1.11-1.88; n = 56). CONCLUSION: The present nationwide cohort study demonstrates...
Totaro, Rocco; Di Carmine, Caterina; Marini, Carmine; Carolei, Antonio
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
Pryce, Gareth; Baker, David
There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS). These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms. This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS. PMID:26408162
Mahdi Aloosh; Mansoureh Toghae; Mohammad Jamal Razeghi Jahromi; Soodeh Razeghi Jahromi
Background It has been suggested that nutrition might play a role in the etiology of multiple sclerosis (MS). However, dietary patterns associated with MS risk are unknown. This study was conducted to compare the dietary patterns of patients with MS and healthy controls to find the relationship between dietary patterns and MS. Methods Usual dietary intake of 75 women with relapsing/remitting MS (RRMS) and 75 healthy controls were assessed with a food frequency questionnaire consisting of 168 ...
To elucidate neuronal degeneration in spinal multiple sclerosis the spinal cord of 27 post mortem patients of the years 1997 to 2000 was investigated in comparison to 29 controls matched for sex, age and year of death. In addition to immunohistochemical examinations and demonstration of pathological cell changes, we also quantified the neurons of the cervical and thoracic spinal cord. In comparison to controls, MS-patients show a significant loss of 43% of the cervical neurons and a signif...
Calabresi, Peter A
Multiple sclerosis, an idiopathic inflammatory disease of the central nervous system, is characterized pathologically by demyelination and subsequent axonal degeneration. The disease commonly presents in young adults and affects twice as many women as men. Common presenting symptoms include numbness, weakness, visual impairment, loss of balance, dizziness, urinary bladder urgency, fatigue, and depression. The diagnosis of multiple sclerosis should be made by a physician with experience in identifying the disease. Diagnosis should be based on objective evidence of two or more neurologic signs that are localized to the brain or spinal cord and are disseminated in time and space (i.e., occur in different parts of the central nervous system at least three months apart). Magnetic resonance imaging with gadolinium contrast, especially during or following a first attack, can be helpful in providing evidence of lesions in other parts of the brain and spinal cord. A second magnetic resonance scan may be useful at least three months after the initial attack to identify new lesions and provide evidence of dissemination over time. It is critical to exclude other diseases that can mimic multiple sclerosis, including vascular disease, spinal cord compression, vitamin B12 deficiency, central nervous system infection (e.g., Lyme disease, syphilis), and other inflammatory conditions (e.g., sarcoidosis, systemic lupus erythematosus, Sjögren's syndrome). Symptom-specific drugs can relieve spasticity, bladder dysfunction, depression, and fatigue. Five disease-modifying treatments for multiple sclerosis have been approved by the U.S. Food and Drug Administration. These treatments are partially effective in reducing exacerbations and may slow progression of disability. PMID:15571060
Noorbakhsh, Farshid; Ellestad, Kristofor K.; Maingat, Ferdinand; Warren, Kenneth G; Han, May H.; Steinman, Lawrence; Baker, Glen B.; Power, Christopher
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...
Berardelli, A; Inghilleri, M; Cruccu, G.; Fornarelli, M; Accornero, N; Manfredi, M.
Percutaneous electrical stimulation of the motor cortex was used to evaluate corticospinal conduction to upper-limb motoneurons in 29 patients with multiple sclerosis. Central motor conduction abnormalities were correlated with clinical signs and somatosensory evoked potentials. Muscle responses to cortical stimulation were altered in 20 patients. The most common abnormality was increased central motor conduction time; in two cases the responses to cortical stimulation were absent. Abnormalit...
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-perf...
Zadro, Ivana; Barun, Barbara; Habek, Mario; Brinar, Vesna V.
During a 10 year period 24 patients with definite multiple sclerosis with isolated cranial nerve palsies were studied (third and fourth nerve: one patient each, sixth nerve: 12 patients, seventh nerve: three patients, eighth nerve: seven patients), in whom cranial nerve palsies were the presenting sign in 14 and the only clinical sign of an exacerbation in 10 patients. MRI was carried out in 20 patients and substantiated corresponding brainstem lesions in seven patients (...
Full Text Available 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. 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.
Alharbi, Fatimah M.
Multiple sclerosis (MS) is a common neurological disease, and its etiology remains unknown. In recent years, increasing attention has been paid to the possible association between MS and vitamin D deficiency. Here, we review the current literature between MS and vitamin D, showing clear evidence that vitamin D deficiency is a risk factor for MS despite the lack of direct evidence for the effects of vitamin D in MS progression.
Cantorna, Margherita T.
Observational studies document a positive relationship between vitamin D from the environment (sunlight or diet), circulating vitamin D status, and improved symptoms or prevention of multiple sclerosis (MS). Experimental animal models of MS reproduce the beneficial effects of vitamin D and 1,25(OH)2D3. The geographical distribution of MS can be explained by both the hygiene hypothesis and the vitamin D hypothesis. It therefore seems more likely that both hypotheses may be correct and that the...
Alharbi, Fatimah M
Multiple sclerosis (MS) is a common neurological disease, and its etiology remains unknown. In recent years, increasing attention has been paid to the possible association between MS and vitamin D deficiency. Here, we review the current literature between MS and vitamin D, showing clear evidence that vitamin D deficiency is a risk factor for MS despite the lack of direct evidence for the effects of vitamin D in MS progression. PMID:26492110
Gentile, Salvatore; Ferrero, Margherita; Vaula, Giovanna; Rainero, Innocenzo; Pinessi, Lorenzo
We report the case of a patient who developed typical cluster headache attacks and was diagnosed as having multiple sclerosis (MS) at the same time. The headache attacks resolved after i.v. treatment with methylprednisolone. MR imaging showed a pontine demyelinating lesion involving the trigeminal nerve root inlet area, on the same side as the pain. The association between cluster headache and MS has been rarely described before. This case suggests that in patients with cluster headache neuro...
Slaets, Leen; Hendriks, Jerome J. A.; STINISSEN, Piet; Kilpatrick, Trevor J.; Hellings, Niels
Therapies for multiple sclerosis (MS) reduce the relapse rate but are unable to stop neurological decline. Here, we evaluate the potential of leukemia inhibitory factor (LIF) as a novel therapeutic in diseases with a neurodegenerative and inflammatory component, such as MS. LIF, which can be a proinflammatory cytokine, can also modulate the immune response in a beneficial way. Recent evidence demonstrates a crucial role of LIF in neuroprotection and axonal regeneration as well as the preventi...
Szklarczyk, Arek; Conant, Katherine
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.
Full Text Available Óscar Fernandez Institute of Clinical Neuroscience, Neurology Department, Hospital Regional Universitario Carlos Haya, FIMABIS, Malaga, Spain Abstract: Alemtuzumab (formerly known as Campath-1H has recently been approved by the European Medicines Agency for highly-active, relapsing-remitting multiple sclerosis (MS. The molecule targets the CD52 surface glycoprotein on certain T cells and B cells and is thought to exert its effect in MS through a “resetting” of the lymphocyte population. Approval was granted on the strength of two pivotal studies, Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS-1 in the first-line setting and CARE-MS-2 in patients who had failed first-line therapy. In both studies, alemtuzumab significantly reduced the relapse rate compared to the comparator, interferon beta-1a (44 µg given subcutaneously three-times per week (Rebif®. In the first-line study, alemtuzumab was also found to significantly reduce the number of patients with sustained progression compared to interferon beta-1a therapy. Autoimmune disorders represent the major side effect of alemtuzumab therapy although they can be managed by careful monitoring and early treatment. Overall, alemtuzumab is likely to be a valuable addition to the neurologist´s armamentarium for the treatment of relapsing-remitting MS. Keywords: alemtuzumab, multiple sclerosis, new therapies, interferon beta-1a, monoclonal antibody, treatment
In 1983 the Multiple Sclerosis Society of Great Britain and Northern Ireland set up the Multiple Sclerosis NMR Research Group at the Institute of Neurology and the National Hospital, Queen Square. The first aim of the Group was to define the role of MRI in the diagnosis and differential diagnosis of multiple sclerosis, and this Atlas represents a summary of that work. Our strategy was to determine the pattern of MRI abnormalities in clinically definite MS and to compare it with those of isolated clinical syndromes of the kind seen in MS (e.g. optic neuritis) and of other disorders with which MS can be confused clinically or radiologically. We have also been involved in a major program of experimental work designed to elucidate the origin of the abnormal signals in MRI. To describe this in full detail would go beyond the scope of the Atlas, but we have incorporated such results as far as they illuminate our clinical problems. The imager used was a 0.5 Tesla Picker superconducting system. Technical advances have been rapid since we began. Nevertheless, the quality of the images obtained at our relatively low field has enabled us to establish the patterns of abnormality in the brain in MS and the diseases which must be distinguished from it. (orig./MG)
Full Text Available BACKGROUND:To study the dimensions of fatigue in multiple sclerosis, its pathophysiology, the efficacy, tolerability and safety of drug and non-drug treatments and measurement of fatigue. METHODS: Relevant articles from PubMed and Google scholar search engines from January 1987 until September 2006 were studied to compose a short clinical update (not a systematic review and make the required clinical information available for the clinicians. RESULTS: There is evidence that fatigue is very common in all types and stages of multiple sclerosis, but its pathophysiology is not well explained. Consequently, few drug options have been offered for its treatment. Amantadine is the bestknown drug, though its efficacy and duration of action are limited. Pemoline and modafinil are alternatives and have
some effects on fatigue. DAP (diaminopyridine, ASA (acetylsalicylic acid, methylphenidate and fluoxetine are other possible options but await further confirmation. Neurorehabilitation, regular exercise and cooling are confirmed to be of value in MS treatment. Measurement of fatigue is a complicated issue. At present fatigue does not have a laboratory marker. CONCLUSIONS: The results of this short clinical update provide guidelines for diagnosing MS-related fatigue and differentiating
it from other similar physical and psychological conditions. It also examines prescription drug options and other therapies for MS patients with fatigue.
KEYWORDS: Multiple sclerosis, fatigue, pathophysiology, treatment, measurement.
Pihl-Jensen, Gorm; Tsakiri, Anna; Frederiksen, Jette Lautrup
candidates for MS treatment due to reliable safety profiles and favorable costs. Studies of statins in a murine MS model and in open-label trials in MS have shown decreased disease severity. OBJECTIVE: Our objective was to assess current evidence to support statin treatment in MS and clinically isolated......)-β treatment in RRMS, one of statin monotherapy in CIS, one of statin monotherapy in optic neuritis (ON)/CIS, and one of statin monotherapy in secondary progressive MS (SPMS)]. Three trials with eligible characteristics had not been published in peer-reviewed journals and were therefore not included. Due to...... activity or risk of MS between statin monotherapy and placebo. In acute ON, statin monotherapy produced better visual outcome but no difference in relapse activity, MRI activity, or risk of MS. CONCLUSIONS: The pleiotropic effects and effects in the murine model of MS could not be converted to a proven...
It has been suggested that blood brain barrier (BBB) impairment is a necessary early event in the pathogenesis of the multiple sclerosis (MS) lesions. To evaluate such an hypothesis in vivo would require: (1) serial imaging studies using a modality with high sensitivity for detecting plaques; (2) a contrast enhancing agent which demonstrates BBB impairment. A serial magnetic resonance imaging (MRI) study was undertaken of a group of MS patients using the contrast agent gadolinium-DTPA. As it has been suggested that T1 and T2 relaxation times are longer in acute than chronic MS lesions, these were also measured. 3 refs.; 1 figure
POOROLAJAL, Jalal; Mazdeh, Mehrdokht; Saatchi, Mohammad; TALEBI GHANE, Elaheh; BIDERAFSH, Azam; LOTFI, Bahar; Mohammad FERYADRES; PAJOHI, Khabat
Background: Hamadan Province is one of the high-risk regions in Iran for Multiple sclerosis (MS). A majority of the epidemiological studies conducted in Iran addressing MS are descriptive. This study was conducted to assess MS and its associated risk factors in Hamadan Province, the west of Iran.Methods: This case-control study compared 100 patients with MS (case group) and 100 patients with acute infectious diseases (control group) from September 2013 to March 2014. A checklist was used to a...
Spalice, Alberto; Properzi, Enrico; Lo Faro, Valentina; Acampora, Barbara; Iannetti, Paola
Optic neuritis is a common clinical condition that causes loss of vision. It can be clinically isolated or can occur as one of the manifestations of multiple sclerosis. Multiple sclerosis is a severe disabling demyelinating disease of the central nervous system, which is rare among children. The treatment of optic neuritis has been investigated in several trials, the results of which have shown that corticosteroids speed up the recovery of vision without affecting the final visual outcome. Treatment of neurologic disorders with intravenous immunoglobulin is an increasing feature of our practice for an expanding range of indications, including multiple sclerosis. Owing to its anti-inflammatory properties, intravenous immunoglobulin can be beneficial in the treatment of acute relapses and in the prevention of new relapses of multiple sclerosis. To our knowledge, there is only one experience of treatment of optic neuritis with intravenous immunoglobulin in multiple sclerosis, even if therapeutic trials are used in the therapy of multiple sclerosis. We report on a girl with optic neuritis and multiple sclerosis in whom treatment with intravenous immunoglobulin at first alone and subsequently associated with interferon achieved great improvement in visual acuity. PMID:15605474
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
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......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...
Koch-Henriksen, N; Rasmussen, S; Stenager, E;
The Danish Multiple Sclerosis Registry was formally established in 1956 but started operating in 1949 with a nationwide prevalence survey. Since then, the Registry has continued collecting data on new and old cases of multiple sclerosis (MS) or suspected MS from multiple sources. The Registry...
Schmitz, Katja; Barthelmes, Julia; Stolz, Leonie; Beyer, Susanne; Diehl, Olaf; Tegeder, Irmgard
The association between vitamin D and multiple sclerosis has (re)-opened new interest in nutrition and natural compounds in the prevention and treatment of this neuroinflammatory disease. The dietary amount and type of fat, probiotics and biologicals, salmon proteoglycans, phytoestrogens and protease inhibitor of soy, sodium chloride and trace elements, and fat soluble vitamins including D, A and E were all considered as disease-modifying nutraceuticals. Studies in experimental autoimmune encephalomyelitis mice suggest that poly-unsaturated fatty acids and their 'inflammation-resolving' metabolites and the gut microflora may reduce auto-aggressive immune cells and reduce progression or risk of relapse, and infection with whipworm eggs may positively change the gut-brain communication. Encouraged by the recent interest in multiple sclerosis-nutrition nature's pharmacy has been searched for novel compounds with anti-inflammatory, immune-modifying and antioxidative properties, the most interesting being the scorpion toxins that inhibit specific potassium channels of T cells and antioxidative compounds including the green tea flavonoid epigallocatechin-3-gallate, curcumin and the mustard oil glycoside from e.g. broccoli and sulforaphane. They mostly also inhibit pro-inflammatory signaling through NF-κB or toll-like receptors and stabilize the blood brain barrier. Disease modifying functions may also complement analgesic and anti-spastic effects of cannabis, its constituents, and of 'endocannabinoid enhancing' drugs or nutricals like inhibitors of fatty acid amide hydrolase. Nutricals will not solve multiple sclerosis therapeutic challenges but possibly support pharmacological interventions or unearth novel structures. PMID:25435020
Full Text Available Objective: The presence of epileptic seizures in patients with multiple sclerosis (MS is a well-known phenomenon. The aims of our study, performed in our clinic are to point out the correlation of the mean age/gender and age of MS patients with the onset of seizures, to identify the types of epileptic seizures in MS patients by sex/age, to identify the correlation between relapses and seizures, and to identify the main electrophysiological / imaging changes. Material and Met-hod: The medical records of 300 MS patients observed between January 2000 and December 2009 in the Neurological Clinic of University Clinical Centre of Kosova were reviewed. All patients fulfilled the McDonald MS criteria Epilepsy diagnosis was based on the ILAE (International League against Epilepsy (1983 criteria while epileptic seizures were classified based on the ILAE classification (1981. Results: Out of 300 MS patients enrolled in this study, 49 (16.33% were identified with seizures or epilepsy. In 23 (47% patients out of 49, seizures or epilepsy appeared after the MS diagnosis. In 6 patients (12.2%, epileptic attacks preceded the MS diagnosis, while in 20 patients (40.8%, epilepsy was diagnosed before multiple sclerosis. These patients were treated with antiepileptics. Out of 23 patients (47% in whom the epileptic seizures appeared after the MS diagnosis, 17 (74% had simple partial seizures, and 6 (26% had complex partial seizures. Based to our study, the epileptic seizures in MS patients appeared about 2.2 years after the MS diagnosis. Discussion: Simple partial seizures were 2.8 times more frequent compared to complex partial seizures. In female patients the prevalence of complex partial seizures was higher than in male patients with multiple sclerosis. (Turkish Journal of Neurology 2013; 19: 40-3
Hashiguchi, S; Ogasawara, N; Mine, H; Kawachi, Y
A 31-year-old woman displayed sleepiness and impairment of recent memory. T2-weighted MRI revealed high signal intensity lesions in the bilateral basal ganglia, thalamus, and brainstem. Although remission was achieved with corticosteroid therapy, she again displayed memory dysfunction and emotional disturbance one year later, at which time MRI disclosed new lesions in the right caudate nucleus and left frontal white matter. Corticosteroid therapy lead to improvement, and she suffered no recurrence on maintenance steroid therapy. These findings suggest that caudate lesions do occur in multiple sclerosis, the manifestations of which can be abulia and memory dysfunction, as in the present case. PMID:11334400
Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by recurrent episodes of demyelination and axonal lesion mediated by CD4+ T cells with a proinflammatory T helper (Th1 and Th17 phenotypes, macrophages, and soluble inflammatory mediators. The overactive pro-inflammatory Th1 cells and clonal expansion of B cells initiate an inflammatory cascade with several cellular and molecular immune components participating in MS pathogenic mechanisms. In this scenario, autoantibodies and autoantigens have a significant role in immunopathogenesis, diagnosis and therapeutic targets of MS. In this review, we try to introduce the autoantigens and autoantibodies and explain their roles in pathogenesis of MS.
Quinn, Debbie; Adams, John
Reforms to the NHS following the passing of the Health and Social Care Act 2012 have created new purchaser organisations with responsibility for planning the configuration of healthcare services in their geographic areas. If a community multiple sclerosis (MS) nursing service is to survive in this environment, it must demonstrate its ability to contribute to achieving the purchaser organisations' objectives. Evaluation data, such as hospital admission avoidance and patient satisfaction, will be crucial in demonstrating the community MS nursing service's clinical and economic effectiveness. A strengths, weaknesses, opportunities and threats (SWOT) analysis of the issues facing a community MS service in this environment is provided. PMID:24823591
Jennum, Poul; Wanscher, Benedikte; Frederiksen, Jette;
Multiple sclerosis (MS) has serious negative effects on health-, social-, and work-related issues for the patients and their families, thus causing significant socioeconomic burden. The objective of the study was to determine healthcare costs and indirect illness costs in MS patient in a national...... rates of health-related contact and medication use and very low employment rate which incurred a higher socioeconomic cost. The income level of employed MS patients was significantly lower than that of control subjects. The annual total health sector costs and productivity costs were €14,575 for MS...
Full Text Available Multiple sclerosis (MS is an inflammatory, demyelinating condition affecting the central nervous system. MS exhibits characteristics of an auto-immune disease. Etiology of this condition remains unknown but environmental and genetic factors are often thought to be responsible. A possible relationship between dentistry and MS has often been mentioned in the literature. Special attention and interdisciplinary cooperation are required in the diagnosis of MS and the application of dental treatments in order to optimize general and dental health status of patients with MS. In this review, MS-dental related studies and recommendations for dental treatment approaches for individuals with MS are discussed.
Nielsen, N. M.; Jorgensen, K. T.; Stenager, E.; Jensen, A.; Pedersen, B. V.; Hjalgrim, H.; Kjaer, S. K.; Frisch, M.
Background: It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting. Methods: Using national databases, we established a cohort comprising 4.4 million......% confidence interval = 0.71-0.82]; in men, 0.89 [0.80-0.98]). RRs were inversely associated with number of children, age at first childbirth, and proximity in time since most recent birth. Among women, MS risk was unrelated to histories of pregnancy loss, pregnancy complications, or infertility. A...
Chen, J J; Carletti, F; Young, V; Mckean, D; Quaghebeur, G
Diagnosing multiple sclerosis (MS) can be very challenging owing to its variable clinical features and lack of a definitive test. Magnetic resonance imaging (MRI) is a core diagnostic tool in the detection of MS lesions and demonstration of spatial and temporal distribution of disease. Moreover, MRI plays a crucial role in the exclusion of alternative diagnoses of MS. The aim of this review is to describe the typical MRI features of MS and to present a series of common mimics of MS with emphasis on their distinguishing features from MS. PMID:27349475
Lucas, Robyn M; Byrne, Scott N; Correale, Jorge; Ilschner, Susanne; Hart, Prue H
There is compelling epidemiological evidence that the risk of developing multiple sclerosis is increased in association with low levels of sun exposure, possibly because this is associated with low vitamin D status. Recent work highlights both vitamin D and non-vitamin D effects on cellular immunity that suggests that higher levels of sun exposure and/or vitamin D status are beneficial for both MS risk and in ameliorating disease progression. Here we review this recent evidence, focusing on regulatory cells, dendritic cells, and chemokines and cytokines released from the skin following exposure to ultraviolet radiation. PMID:26477548
Kamber Zeqiraj; Nexhat Shatri; Jera Kruja; Afrim Blyta; Enver Isaku; Nazim Dakaj
Objective: The presence of epileptic seizures in patients with multiple sclerosis (MS) is a well-known phenomenon. The aims of our study, performed in our clinic are to point out the correlation of the mean age/gender and age of MS patients with the onset of seizures, to identify the types of epileptic seizures in MS patients by sex/age, to identify the correlation between relapses and seizures, and to identify the main electrophysiological / imaging changes. Material and Met-hod: The medi...
Schwarz, S; Knorr, C; Geiger, H; Flachenecker, P
We analyzed characteristics, motivation, and effectiveness of complementary and alternative medicine in a large sample of people with multiple sclerosis. A 53-item survey was mailed to the members of the German Multiple Sclerosis Society, chapter of Baden-Wuerttemberg. Surveys of 1573 patients (48.5 +/- 11.7 years, 74% women, duration of illness 18.1 +/- 10.5 years) were analyzed. In comparison with conventional medicine, more patients displayed a positive attitude toward complementary and alternative medicine (44% vs 38%, P job, and higher education (P < 0.05). Compared with conventional therapies, complementary and alternative medicine rarely showed unwanted side effects (9% vs 59%, P < 0.00001). A total of 52% stated that the initial consultation with their physician lasted less than 15 min. To conclude, main reasons for the use of complementary and alternative medicine include the high rate of side effects and low levels of satisfaction with conventional treatments and brief patients/physicians contacts. PMID:18632773
Full Text Available Mark D Willis, Neil P Robertson Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK Abstract: Alemtuzumab is an anti-CD52 monoclonal antibody, recently approved for the treatment of active, relapsing multiple sclerosis (MS. Administration of alemtuzumab causes a rapid and dramatic reduction in circulating lymphocytes, with a predictable subsequent pattern of immune reconstitution. Although the precise mode of action remains unclear, treatment results in a marked reduction in annualized relapse rates, slowing of disability progression compared with an active comparator, and may even cause disability reversal. Although conferring clear clinical benefits, alemtuzumab carries a significant long-term risk of autoimmune disease (AID, which has a particular predilection for the thyroid gland, although a wide range of other disorders have also been reported. However, risks of AID can usually be anticipated and treated successfully, provided rigorous monitoring and surveillance protocols are followed by clinicians and patients alike. Despite its immunosuppressive mechanism of action serious infections are rare and malignancies commonly associated with immunodeficiency have not been observed to date. Alemtuzumab’s unique mode of administration, as well as it’s durability of effect, provides an important addition to currently available therapeutic interventions for MS, and in particular is a valuable treatment option in recent onset and highly active relapsing disease. Keywords: multiple sclerosis, alemtuzumab, autoimmune disease
Brandon A Brown
Full Text Available Brandon A BrownDepartment of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USAAbstract: Natalizumab is a monoclonal antibody, representing a new class of medication for treating relapsing multiple sclerosis (MS. Conventional treatments include interferons, glatiramer acetate and chemotherapies such as mitoxantrone and cyclophosphamide. These therapies offer only modest clinical benefits and are commonly not tolerated due to side effects. Natalizumab has been proven in large-scale, blinded, randomized, controlled trials to have an exceptional effect on preventing relapses, decreasing the risk of sustained progression of disability, and increasing the rate of disease-free patients over a 24-month period compared to placebo. These trials led to the speedy approval of natalizumab for treating relapsing MS, but its use was halted a few months after its induction after several cases of progressive multifocal leukoencephalopathy (PML, a fatal demyelinating disease affecting the central nervous system. After a long deliberation by an FDA advisory panel and strong support from the MS community, natalizumab was reapproved with stringent restrictions including patient, provider and site registration. Natalizumab is now considered second-line therapy for patients who have failed first-line agents such as interferon or glatiramer acetate. As little is known about additional risk factors for PML and other potential infections, patients and providers must work together to carefully decide if potential benefits outweigh these rare but potentially devastating complications.Keywords: natalizumab, multiple sclerosis, progressive multifocal leukoencephalopathy
Doogan, Catherine; Playford, E Diane
People with multiple sclerosis experience some of the highest rates of unemployment among groups of individuals with severe and chronic disabilities. While unpredictable relapses, physical and cognitive symptoms all may play a role in job loss, it is more likely that job loss can be attributed to a complex interaction between disease-related factors and contextual factors, such as the working environment, and employer attitudes. This interaction leads to the concept of work instability, that is, the mismatch between work demands and the individual's capacity to meet these demands. Vocational rehabilitation services aim to provide people with multiple sclerosis vocational assessment, rehabilitation and support to enable them to find, regain or remain in work and access other occupational and educational opportunities. Such services consist of a multidisciplinary team with the ability to provide education around disclosure, and work-place accommodations, offer emotional support, maintain work performance, liaise with employers, and support to re-enter the workplace. Helpful interventions include early disclosure, proper workplace accommodation, education of employers, and government-funded initiatives to support disabled employees. Future research needs to agree on methods of recording outcomes and evaluate specific vocational rehabilitation interventions. PMID:24526662
Mohammad Ali Shafa
Full Text Available BACKGROUND: Multiple Sclerosis (MS is the most common demyelinating disease. An autoimmune basis has been confirmed for pathogenesis of MS. Prolactin (PRL has roles in these mechanisms. Its serum levels change in MS according to some reports. The purpose of this study was to survey these changes in MS patients. METHODS: Sixty MS patients were included in this cross-sectional study. The same number of controls matched for sex and age were studied. Pregnant, lactating women, consumers of specific medications and patients with underlying diseases were excluded from our study. RIA was used for determination of serum levels of PRL. RESULTS: In this study, PRL level in male patients was 14.23 ± 11.47 ng/ml compared to controls with mean level of 7.21 ± 4.12 ng/ml (P value <0.001. Mean PRL level in female patients was 20.18 ± 11.04 ng/ml whereas controls had a mean level of 14.45 ± 6.93 ng/ml (one-tailed P value <0.05. So there were significant differences in serum PRL level between case and control groups in both men and women CONCLUSIONS: PRL has a positive relation with MS in both sexes. Further studies for determination of causality relation and drug effect in endocrine system on MS pathogenesis are suggested. KEY WORDS: Multiple Sclerosis, prolactin, male, female
Gulick, Elsie E; Halper, June; Costello, Kathleen
Several studies document high levels of job satisfaction among certified nurses, but no study has examined job satisfaction and factors influencing job satisfaction of certified multiple sclerosis (MS) nurses. This study tested a theoretical model proposing that two organizational factors, colleague relationships and benefits, will predict job satisfaction. Job satisfaction was represented by four factors: autonomy, professional status, professional growth, and time efficiency. Participants included MS nurses certified for 6 months or more practicing mostly in three countries (Canada, Great Britain, and the United States) who anonymously completed the Misener Nurse Practitioner Job Satisfaction Scale, an overall job satisfaction rating, and demographic information. Findings indicate that colleague relationships and benefits significantly estimated organization structure and that autonomy, professional status, professional growth, and time efficiency significantly estimated job satisfaction; furthermore, organization factors such as colleague relationships and benefits significantly predict job satisfaction. Among the countries, several statistically significant differences were observed between job satisfaction factors as well as items in both organization and job satisfaction subscales. Average factor scores among the countries were mostly rated satisfactory. The International Organization of Multiple Sclerosis Nurses Executive Board plans to use the study findings to see how it needs to focus efforts as an organization toward enhancing and standardizing MS care and develop MS nurse professionalism worldwide. PMID:17847673
Michel, Laure; Larochelle, Catherine; Prat, Alexandre
While there is no cure for multiple sclerosis (MS), numerous disease-modifying drugs are now available to treat MS patients. In fact, the therapeutic strategies are now more and more complex, directly impacting the management of patients. Despite the good safety profile of the first-line immunomodulatory drugs, the clinical response is often suboptimal. Important questions remain about the right timing to switch for a second-line agent and whether escalation therapy is an appropriate therapeutic strategy. In this review, we conducted a systematic search by PubMed using the terms: treatment, multiple sclerosis, therapeutic, DMT and treatment response. Randomized trials and reviews addressing MS, DMTs and management strategies were selected and included in this review. Herein, we present the currently approved and emerging drugs used for the treatment of MS with their relative benefit/risk profiles, and their respective positions in the therapeutic arsenal. We then focused on the different therapeutic strategies and criteria available to evaluate the response to disease-modifying therapies (DMTs). PMID:25813102
Vighetto, A; Grochowicki, M; Cousin, J
Spatial contrast sensitivity was measured in 110 patients with multiple sclerosis (definite = 72, probable = 22, possible = 16) as part of a routine evaluation in a neuro-ophthalmological clinic. Results were compared with those of 37 normal controls matched for age. The test was abnormal in 71 p. 100 of patients. Contrast sensitivity was attenuated for 97 p. 100 of the eyes with optic neuritis and visual acuity drop, for 60 p. 100 of the eyes with recovered optic neuritis and for 36 p. 100 of the non affected eyes in the cases of unilateral optic neuritis. Among the 57 patients with normal visual acuity and no history of optic neuritis, 62 p. 100 had abnormal findings. Globally, contrast sensitivity was reduced on the whole spatial frequency range in cases of current optic neuritis, and mostly on the high or high and medium frequencies in the other cases. Our study confirms that spatial contrast sensitivity is the most sensitive of psychophysical methods to detect subclinical visual impairement in multiple sclerosis. Comparison with VEP's was performed in 66 patients. Both tests were roughly equally sensitive, but findings were concordant in only 63 p. 100 of the cases. The use of both VEP's and spatial contrast sensitivity increases the detection of latent optic neuritis. PMID:2359900
Sagar, HJ; Warlow, CP; Sheldon, PWE; Esiri, MM
Three cases of multiple sclerosis, all confirmed pathologically, are described in whom both the unusual clinical features and the CT scan appearances suggested cerebral tumours. The failure of mass effect reliably to differentiate plaques and tumours on a CT scan is stressed and the literature relating to CT scanning in multiple sclerosis is reviewed.
Sellebjerg, F; Kristiansen, T B; Wittenhagen, P;
To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....
Li, J; Johansen, C; Brønnum-Hansen, Henrik;
Previous studies have suggested that psychological stress may play a role in the risk of multiple sclerosis (MS), but the evidence is very limited.......Previous studies have suggested that psychological stress may play a role in the risk of multiple sclerosis (MS), but the evidence is very limited....
Koch-Henriksen, Nils; Brønnum-Hansen, Henrik; Hyllested, K
The incidence rates of multiple sclerosis (MS) in Denmark were estimated as a result of a continuous nationwide epidemiological survey since 1948 by the Danish Multiple Sclerosis Registry (DMSR). Among cases notified to the DMSR, 6,478 met the diagnostic criteria and had onset of MS from 1948...
Multiple sclerosis is an important and frequent neurological disease and the diagnosis might be difficult. The clinical criteria of multiple sclerosis and the role of laboratory examinations in the diagnosis of the disease are discussed. In particular the help offered by the magnetic resonance imaging method is the subject of this paper. Three patients are reported and discussed
Bagert, Bridget A; Bourdette, Dennis
Several promising, oral disease-modifying therapies for multiple sclerosis are currently being evaluated in clinical trials. The arrival of effective oral agents for multiple sclerosis will be a major advance in the global effort to alter the natural history of this chronic disease.
MINDERHOUD, JM; MOOYAART, EL; KAMMAN, RL; TEELKEN, AW; HOOGSTRATEN, MC; VENCKEN, LM; GRAVENMADE, EJ; VANDENBURG, W
Localized phosphorus magnetic resonance spectroscopy at 1.5 T was performed in 39 patients with multiple sclerosis and in 15 healthy controls. The multiple sclerosis spectra showed increased creatine phosphate levels. This increase was correlated with the severity of the handicap and was greater in
Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.
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…
Ingalls, T.H. (Boston Univ. School of Medicine, MA (USA))
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.
Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.
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…
Omar ede Faria Jr.
Full Text Available Multiple Sclerosis (MS is a chronic inflammatory disease characterized by central nervous system (CNS demyelination and axonal degeneration. Although the cause of MS is still unknown, it is widely accepted that novel drug targets need to focus on both decreasing inflammation and promoting CNS repair. In MS and experimental autoimmune encephalomyelitis (EAE non-coding small microRNAs (miRNAs are dysregulated in the immune and central nervous systems. Since individual miRNAs are able to downregulate multiple targeted mRNA transcripts, even minor changes in miRNA expression may lead to significant alterations in post-transcriptional gene expression. Herein, we review miRNA signatures reported in CNS tissue and immune cells of MS patients and consider how altered miRNA expression may influence MS pathology.
Jobin, Céline; Larochelle, Catherine; Parpal, Hélène; Coyle, Patricia K; Duquette, Pierre
Although multiple sclerosis (MS) affects both women and men, women are more susceptible to MS than men. Accumulating evidence indicates that the incidence and prevalence of MS is increasing, more so in women than in men. Owing to pregnancy, differing hormonal states and distinct social roles, the impact of MS differs between women and men. Since Patricia K Coyle published a review on gender issues in MS, multiple studies have added to the body of knowledge. This update will summarize the current thinking on gender-related issues in MS and we will address incidence and prevalence, hormonal factors, pregnancy and breastfeeding, genetics, course and prognosis, imaging, treatment and psychosocial aspects. Future progression within this field will help elucidate the cause of and define the treatment of MS. PMID:21118039
Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey;
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...
Full Text Available 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.
Balantrapu, Swathi; Sosnoff, Jacob J.; Pula, John H.; Sandroff, Brian M.; Motl, Robert W.
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
Fifty-one high-field MR imaging studies (1.5 T, General Electric Signa) of the spinal cord were performed in 42 patients (27 female, 15 male; mean age, 40 years) with clinically definitive (n = 34) or probable (n = 8) multiple sclerosis and suspected spinal cord lesions. MR imaging showed focal spinal cord abnormalities in 38 (75%) of 51 studies. T2-weighted images were abnormal (showing foci of high signal intensity) in 38 studies, T1-weighted images were abnormal (showing areas of low signal intensity or mass effect) in 16 (42%) of 38, and GRASS images were abnormal (showing foci of high signal intensity) in 9 (82%) of 11 cases. Brain MR imaging showed periventricular lesions typical of multiple sclerosis in 34 (81%) of 42 studies. Spinal cord studies were positive in eight cases with normal brain MR images, and brain studies were positive in 13 instances of normal spinal cord MR images. Four lesions were at the cervicomedullary junction, 44 in the cervical spinal cord, and three in the thoracic cord. Mass effect in cord lesions, simulating neoplasm, was seen in seven patients during the acute symptomatic phase. Serial studies in three patients with decreasing symptoms showed a reduction after 3-4 weeks and resolution of the mass effect after 2-6 months
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.
Habib, A.C.; Zheng, W.; Haacke, E.M.; Webb, S.; Nichol, H.; /SLAC
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.
Dalgas, Ulrik; Stenager, Egon
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. Di...
Full Text Available Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.
Stenager, E N; Koch-Henriksen, N; Stenager, E
BACKGROUND: The purpose of the present study was to identify risk factors for suicide in patients with multiple sclerosis (MS). METHODS: The study is based on available information about MS patients identified in the Danish MS Registry (DMSR) with onset in the period 1950-1985. We compared the MS...... suicides with the 1950-1985 onset cohort patients in the DSMR as to distribution of age at onset, presenting symptoms, and time from onset to diagnosis. We reviewed sociodemographic data, age of onset, the course of the disease, recent deterioration, type of deterioration, Kurtzke Disability Status Scale...... (DSS) score, previous mental disorder, type of mental disorder, previous suicide attempts, expression of suicidal intentions, circumstances at suicide, and suicide method for all MS patients who had committed suicide. In order to characterize MS suicides with respect to risk factors, comparisons were...
Husseini, L; Leussink, V I; Warnke, C; Hartung, H-P; Kieseier, B C
Spasticity represents a common troublesome symptom in patients with multiple sclerosis (MS). Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations. Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients. Sativex is a 1:1 mix of delta-9-tetrahydocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which recently received a label for treating MS-related spasticity in Germany. The present article reviews the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option in MS. PMID:22080198
Full Text Available 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.
Rodneys Mauricio Jiménez Morales
Full Text Available Multiple sclerosis is an inflammatory disease of the central nervous system that is characterized by demyelination and degeneration. The objective of this article is to offer a review of the latest scientific discoveries in the field of neuropsychology in ME. A description is presented of the most frequent neuropsychological manifestations and their probable association with other factors such as: school level, fatigue, disability, cerebral dysfunction, time and clinical form of evolution, as well as depression and other states of mind starting from recent evidences in the scientific community. Also addressed is the development of tests and valid sensitive neuropsychological sets to evaluate cognitive functions. The use of sensitive and specific test facilitates the evaluation of neuropsychological alterations associated to ME, besides other socio-demographic and clinical-evaluative factors to contemplate in the exploration.
Motl, Robert W; Sandroff, Brian M
Exercise training represents a behavioral approach for safely managing many of the functional, symptomatic, and quality of life consequences of multiple sclerosis (MS). This topical review paper summarizes evidence from literature reviews and meta-analyses, supplemented by recent individual studies, indicating that exercise training can yield small but important improvements in walking, balance, cognition, fatigue, depression, and quality of life in MS. The paper highlights limitations of research on exercise training and its consequences and future research directions and provides an overview for promotion of exercise training in MS based on recent prescriptive guidelines. Collectively, the evidence for the benefits of exercise training in MS suggests that the time is ripe for the promotion of exercise by healthcare providers, particularly neurologists as a central part of the clinical care and management of MS patients. PMID:26223831
Rommer, P S; Dudesek, A; Stüve, O; Zettl, UK
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
Bhim S Singhal
Full Text Available 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.
Miljković, Djordje; Timotijević, Gordana; Mostarica Stojković, Marija
Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well as numerous immunity-related actions that these cells are capable of, imply that astrocytes should have a prominent role in neuroinflammatory disorders, such as multiple sclerosis (MS). The role of astrocytes in MS is rather ambiguous, as they have the capacity to both stimulate and restrain neuroinflammation and tissue destruction. In this paper we present some of the proved and the proposed functions of astrocytes in neuroinflammation and discuss the effect of MS therapeutics on astrocytes. PMID:21443873
Yara Dadalti Fragoso
Full Text Available Potential environmental modifiable factors involved in multiple sclerosis (MS include low adherence to treatment, smoking, obesity, low levels of liposoluble vitamins A and D, high consumption of salt, and a sedentary lifestyle. Chronic tobacco use, obesity, sedentarism and insufficient levels of these vitamins all contribute to maintenance of a proinflammatory state. It is unlikely that there will be noticeable improvement in the inflammatory condition of MS if stopping smoking, reducing weight, exercising, increasing vitamin levels are done in an isolated and erratic manner. Modification of each and every one of these environmental risk factors is likely to be an important approach in the management of MS. The present review presents the arguments for an association between these hazardous modifiable factors and the chronic inflammatory state observed in MS.
De Ridder, D; Vermeulen, C; Ketelaer, P; Van Poppel, H; Baert, L
Although primarily used for treatment of stress incontinence, pelvic floor rehabilitation has been reported to have some value in the treatment of detrusor instability and urgency. In neurogenic bladder dysfunction due to Multiple Sclerosis, many authors have suggested the possible use of pelvic floor rehabilitation as a treatment modality. Therefore, we designed an open prospective trial to look at the possible role of pelvic floor rehabilitation in voiding dysfunction due to MS, concentrating upon the clinical and neurological parameters in relation to the outcome. A new scoring system for pelvic floor dysfunction is introduced. Thirty female patients were evaluated. In 25, the strength of the pelvic floor was significantly improved after one month (p rehabiltation has a place in the treatment of MS patients with a low Kurtzke score and without pelvic floor spasticity. PMID:10218095
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
Myelinoclastic diffuse sclerosis (MDS, Schilder's disease) is a rare CNS demyelinating disorder affecting mainly children and usually presenting as an intracranial mass lesion. We report the first case of recurrent intracranial MDS where the third episode of demyelination involved the cervical spinal cord. This may represent a subset of the disease, which should be considered as Schilder's variant (childhood form) of multiple sclerosis. (orig.)
David Otaegui; Baranzini, Sergio E; Ruben Armañanzas; Borja Calvo; Maider Muñoz-Culla; Puya Khankhanian; Iñaki Inza; Lozano, Jose A.; Tamara Castillo-Triviño; Ana Asensio; Javier Olaskoaga; Adolfo López de Munain
Differences in gene expression patterns have been documented not only in Multiple Sclerosis patients versus healthy controls but also in the relapse of the disease. Recently a new gene expression modulator has been identified: the microRNA or miRNA. The aim of this work is to analyze the possible role of miRNAs in multiple sclerosis, focusing on the relapse stage. We have analyzed the expression patterns of 364 miRNAs in PBMC obtained from multiple sclerosis patients in relapse status, in rem...
Black, Rebecca; Dorstyn, Diana
The concept of resilience remains under-researched in the multiple sclerosis literature. Consequently, current understanding of the unique and joint contribution of disability-specific variables, cognitive-behavioural skills and social resources to this dynamic process is limited. A holistic model of resilience was therefore developed and tested. Results of an online survey completed by 196 adults with multiple sclerosis revealed both direct and indirect pathways to resilience, with positive affect and self-efficacy being the strongest predictors. The findings lend support to psychological interventions which focus on promoting the personal resources and assets needed to cope effectively with multiple sclerosis. PMID:24323335
Full Text Available Rebecca C Selter,1 Bernhard Hemmer1–3 1Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; 2Munich Cluster for Systems Neurology (SyNergy, Munich, Germany; 3Competence Network on Multiple Sklerosis, Munich, Germany Abstract: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Both genetic and environmental factors are believed to contribute to the pathogenesis of the disease. Histopathological findings suggest that multiple sclerosis is an immune-mediated disease, involving both the cellular and humoral immune systems. Within the last 20 years, several disease-modifying therapies for the treatment of multiple sclerosis were established. Moreover, promising new substances are currently being tested in clinical trials and will likely broaden the therapeutic opportunities available within the upcoming years. Keywords: multiple sclerosis, immunopathogenesis, disease-modifying therapy
Çubuk R et al.
Full Text Available Objective: We aimed to determine if there are quantifiable diffusion differences among focal multiple sclerosis lesions that appear differently on T1-weighted Magnetic Resonance images in MS patients with acute attack. Methods: Average apparent diffusion coefficient was calculated for 153 lesions identified on T2-weighted images in 15 patients with acute multiple sclerosis attack. One hundred and thirty-tree nonenhancing lesions (78 isointense, 55 hypointense and 20 enhancing lesions (5 isointense, 15 hypointense were categorized on the basis of un-enhanced T1-weighted images. Results: In 18 of 20 active lesions, which were seen in 9 patients, the contrast enhancement was homogeneous. White matter of multiple sclerosis patients showed significantly higher ADC than normal white matter (p=0.01. Hypointense non-enhancing lesions showed higher ADC values than isointense non-enhancing lesions (p<0.05. Diffusion in enhancing portions of enhancing lesions was decreased when compared with non-enhanced hypointense lesions. Conclusion: The data of our patients showed that hipointense lesions of non-active ones had higher ADC than active lesions with homogeneous contrast enhancement. These quantitative differences may indicate another easy and useful measurement in documenting acute multiple sclerosis attack.
Full Text Available 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.
Marco Aurélio Lana-Peixoto
Full Text Available As Lyme neuroborreliosis (LNB may clinically mimick multiple sclerosis (MS the presence of antibodies to Borrelia burgdorferi in serum of patients with a MS-like disease in non-edemic areas for Lyme disease may be troublesome. We report the case of a 45-year-old white female with the diagnosis of relapsing/ remitting form of MS due to a 15-year history of optic neuritis and recurrent episodes of motor and sensation disturbance in the upper right limb and in both lower extremites associated with bladder dysfunction. A magnetic resonance imaging of the brain revealed multiple high intensity periventricular white matter lesions. The patient had been exposed to ticks but did not recall the presence of erythema migrans. ELISA for Lyme disease was positive in two different laboratories and the positive serology was confirmed by Western blotting. No convincing reponse followed treatment with ceftriaxone. Although it is clear that the patient had been infect by Borrelia burgdorferi the relationship of this spirochetal infection with the neurological disease could not be ascertained.
Multiple sclerosis is a chronic, persistent inflammatory-demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an