Acute Exacerbations Of Multiple Sclerosis Research Articles

6489 Type 1 Diabetes Mellitus And Multiple Sclerosis: A Case Report Showing The Concurrent Association Of Two Autoimmune Diseases

Abstract Disclosure: P.B. Singh: None. B. Sabates: None. A. Sharifzadeh: None. R.F. Rodriguez: None. Introduction: Both Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS) represent persistent autoimmune conditions. T1DM is characterized by the presence of specific autoantibodies targeting pancreatic β-cells. In MS, autoreactive cells mediate a demyelinating inflammatory response directed against the central nervous system. Despite differences in demographics and clinical characteristics, their common root in autoimmunity has led researchers to discover commonalities in genetic, environmental and immunological features. Case Presentation We present a case of a 40-year-old female with medical history of T1DM diagnosed at 7 years of age and MS diagnosed at 32 years of age. She presented to the hospital with clinical features of optic neuritis and symptoms of squeezing ribcage pressure consistent with acute MS exacerbation. After confirmatory neuroimaging, high-dose intravenous corticosteroids were initiated, and Endocrinology services were consulted for inpatient glycemic management. As the patient’s diabetes was treated via continuous subcutaneous insulin infusion (CSII), her pump settings were adjusted to maintain euglycemia during hospitalization. This case is reported to highlight and discuss the association between T1DM and MS. Discussion About 4-5% of the general population is affected by autoimmune disorders, among which T1DM and MS comprise a substantial portion. Multiple studies demonstrate the association and shared etiopathogenesis between T1DM and MS. One study revealed that the prevalence of T1DM is five times higher in patients with MS in comparison to the general population. In another prospective cohort study, individuals with T1DM had a three times higher chance of subsequently developing MS. Additionally, first-degree relatives of MS patients had a roughly 40% higher risk of developing T1DM. Women with T1DM had a 20-fold higher risk of having MS than women without the condition, per another study. As T-cell mediated autoimmune disorders, both T1DM and MS are characterized by autoantigen specific T1-helper cell responses, decreased T-cell suppressor activity, and the presence of various autoantibodies, some of which are seen in both diseases. One study showed that autoreactive T cells could target both pancreatic islet and central nervous system autoantigens in patients with MS, patients with T1DM, and relatives of patients with T1DM. Since MS- and T1DM-associated HLA haplotypes differ between populations, HLA class II alleles per se may not alone be responsible for disease susceptibility. It is suggested that variation at other non-HLA class II loci and/or unknown environmental factors might contribute significantly to the co-occurrence of these 2 diseases. In conclusion, individuals who already have one autoimmune condition are more likely to have other autoimmune conditions, with T1DM and MS being associated more often than expected. Presentation: 6/2/2024

Cost-Effectiveness of Repository Corticotropin Injection for the Treatment of Acute Exacerbations in Multiple Sclerosis

BackgroundRelapses are common among patients with multiple sclerosis (MS) despite treatment with disease-modifying therapies. Repository corticotropin injection (RCI, Acthar® Gel), plasmapheresis (PMP), and intravenous immunoglobulin (IVIg) are alternative therapies for MS relapse. There is a dearth of economic assessments of these therapies for the acute exacerbations of MS. This study estimated the cost-effectiveness of RCI compared to PMP or IVIg.MethodsA Markov state-transition model compared outcomes (costs, relapses, remission, and utilities) with RCI versus PMP or IVIg for the acute exacerbations in MS. The model was developed from the United States (US) payer and societal perspectives over one to three years. Patients initiated on alternative therapies were evaluated in one-day increments for the first 30 days during treatment. The model assumes the natural history of MS after treatment in the first month, adjusting for the effect of treatment. Incremental cost-effectiveness ratios (ICERs) were estimated as cost per quality-adjusted life-year (QALY) gained. The uncertainty in model parameters was evaluated in probabilistic sensitivity analyses.ResultsIn the base case, RCI has an ICER of USD 42,078 per QALY compared to PMP over one year from the payer perspective and is dominant over two and three years; RCI is dominant compared to PMP from the societal perspective over all three years. Compared to IVIg, RCI is a dominant strategy from both payer and societal perspectives over all three years. Probabilistic sensitivity analysis supports the base case findings, suggesting that RCI may be cost-effective versus PMP and IVIg for acute exacerbations in MS.ConclusionRCI is a cost-effective alternative treatment for MS relapses compared to PMP and IVIg from the US payer and societal perspectives.

Cost per response analysis of repository corticotropin injection versus other alternative treatments for acute exacerbations of multiple sclerosis.

BackgroundRelapses are common in patients with multiple sclerosis (MS) even after the use of disease-modifying therapies. Repository corticotropin injection (RCI), plasmapheresis (PMP), and intravenous immunoglobulin (IVIg) may be utilized as alternative therapies in the management of MS relapse. There is a lack of health economic studies on these alternative therapies for the acute exacerbations of MS. The objective of this study was to estimate the cost per response of RCI compared with PMP or IVIg from the United States (US) commercial payer perspective.MethodsCosts and response rates were sourced from published peer-reviewed observational studies. The cost of care included MS-related inpatient, outpatient, and medication costs. Treatment response was defined as no evidence of additional relapse treatment or procedure claims within 30 days after treatment. The cost per response for each treatment was calculated by dividing the total annual cost of care by the proportion of patients with resolved relapse for each treatment. The incremental cost per response ratio was calculated by dividing the difference in costs and the proportion of responses for RCI versus PMP or IVIg. One-way sensitivity analysis (OWSA) was conducted for both costs and response rates. All included costs were inflated to the 2019 US dollars.ResultsWith a lower total annual cost of care and a higher response rate, RCI had a lower cost per response (US$141,970) compared with PMP or IVIg (US$253,331). RCI had a lower cost per response even when more stringent estimates for RCI were applied in the OWSA. The annual cost of care had a greater influence on the cost per response in the OWSA.ConclusionsBased on the estimates from the real-world evidence, our economic evaluation suggests that RCI may have real-world clinical and economic benefits for patients with MS relapse who fail on corticosteroid therapy.

Consequences of Insurance Denials Among U.S. Patients Prescribed Repository Corticotropin Injection for Acute Exacerbations of Multiple Sclerosis.

IntroductionRepository corticotropin injection (RCI; Acthar® Gel) is indicated for the treatment of acute exacerbations of multiple sclerosis (MS) in adults. Despite the well-documented clinical and economic benefits of RCI, many patients are denied use of the therapy by third-party payers. This study aims to understand the demographic and clinical characteristics of MS relapse patients who received a prescription for RCI from their physicians and then were either approved or denied treatment by their insurers. The study compares measurable clinical outcomes and healthcare resource utilization (HCRU) between approved and denied cohorts.MethodsA retrospective analysis of adults experiencing MS relapse from January 2015 to December 2018 was conducted using a de-identified open-source claims database [Symphony Health Integrated Dataverse® (IDV)]. Patients were identified using ICD codes for MS and considered to have relapsing/remitting type according to established claims-based methodology. Clinical characteristics and HCRU were analyzed during the year preceding (“baseline”) and the year following (“follow-up”) each patient’s index date, defined as the date of a patient’s first approved RCI claim (for patients with ≥ 1 approved claim) or first denied RCI claim (for patients with only denied claims). Baseline characteristics were reported with unadjusted differences and p values indicating the significance of characteristics between the two cohorts. For outcomes, match-adjusted results were reported using propensity matching to account for underlying differences between cohorts.ResultsThe study sample included 1902 MS relapse patients with at least one claim for RCI. At baseline, approved patients were slightly older compared to denied patients (mean age 48.0 vs. 47.2), had higher rates of hemiplegia/paraplegia (6.7% vs. 3.3%), greater mobility impairment (17% vs. 11.5%), more exacerbation episodes (66.2% vs. 59.9%), and a higher number of physical therapy/rehab claims (23.5 vs. 14.0), respectively. Outcomes among the matched sample show an increased use of corticosteroids for patients denied access to RCI compared to approved patients (51.1% vs. 42.4%), more exacerbation episodes (36.6% vs. 28.2%), and an increased number of physical therapy/rehab claims (11.5% vs. 9.9%), respectively.ConclusionThe results of this study may aid providers and payers in evaluating scenarios where RCI may be beneficial and improve quality of care for patients experiencing MS relapse.

Association between diurnal temperature range and emergency department visits for multiple sclerosis: A time-stratified case-crossover study

Although multiple sclerosis (MS) has been the leading cause of neurologically-induced disability in young adults, risk factors for the relapse and acute aggravation of MS remain unclear. A few studies have suggested a possible role of temperature changes on the relapse and acute aggravation of MS. We investigated the association between short-term exposure to wide diurnal temperature ranges (DTRs) and acute exacerbation of MS requiring an emergency department (ED) visit. A total of 1265 patients visited EDs for acute aggravation of MS as the primary disease in Seoul between 2008 and 2014 from the national emergency database. We conducted a conditional logistic regression analysis of the time-stratified case-crossover design to compare DTRs on the ED visit days for MS and those on control days matched according to the day of the week, month, and year. We examined possible associations with other temperature-related variables (ambient temperature, between-day temperature change, and sunlight hours). Short-term exposure to wide DTRs immediately increased the risk of ED visits for MS. Especially, 2-day average (lag0–1) DTR levels on the day of and one day prior to ED visits exhibited the strongest association (an 8.81% [95% CI: 3.46%–14.44%] change in the odds ratio per 1 °C increase in the DTR). Other temperature-related variables were not associated with MS aggravation. Our results suggest that exposure to wider DTR may increase the risk of acute exacerbation of MS. Given the increasing societal burden of MS and the increasing temperature variability due to climate change, further studies are required.

Multipl sklerozda femur başı avasküler nekrozu

Objective: Corticosteroid (CS) therapy is widely used as the standard treatment for acute exacerbations of multiple sclerosis (MS). Avascular necrosis (AVN) of the femoral head is one of the long–term complications related to CS therapy. Our study aims to investigate the association between annual and cumulative doses of CS treatment and radiographic assessment of AVN of the femoral head in MS. Material and Methods: One patient group and two control groups were formed. The study group consisted 60 MS cases treated with intravenous methylprednisolone (IVMP) and the 2 control groups consisted 22 MS patients (Control I) without CS treatment and 25 healthy controls (Control II). Sixty patients who underwent CS treatment were divided into 3 subgroups of 20 cases each, treated with either IVMP only, IVMP and interferon, and IVMP and glatiramer acetate (GA). Neurological examinations and demographic data of all cases were recorded. The presence of AVN of femoral head in patient and control groups was evaluated using magnetic resonance imaging and Ficat staging system. Results: Avascular necrosis (AVN) of femoral head was observed in 4 (6.7%) MS patients who were treated with CS. The mean annual CS dose was 8.07 g and mean cumulative dose was 31 gr. There was a significant but no statistical difference, in annual and cumulative IVMP doses between patients who have and don’t have AVN of femoral head (p=0.085 and p=0.246, respectively). Conclusion: Our all data support the idea that annual dose of CS may increase AVN of femoral head development in MS patients. It is important to evaluate the CS-treated MS patients with MRI in this respect, due to the possible treatment of early-stage AVN of femoral head.

Sleep Disorder as a Triggering Factor for Relapse in Multiple Sclerosis

Background/Aims: To determine the effect of sleep disturbances on predisposing multiple sclerosis (MS) patients for acute relapse. Methods: This case-control study was conducted on 80 MS patients including 40 patients in the remission phase and 40 in the relapse phase. Patients were asked to fill in the Pittsburgh Sleep Quality Index to determine their sleep quality during the previous month. Individuals with scores of 5 or less were considered having normal sleep quality. Results: Mean ± SD ages were 32.5 ± 7.7 and 30.2 ± 7.2 years among patients with and without acute relapses, respectively (p > 0.05). The mean disease duration and disease severity (according to Expanded Disability Status Scale [EDSS]) were comparable across the groups (p > 0.05). Among those with and without acute exacerbations, 87.5 and 50% had poor sleep quality, respectively (p = 0.0001), with OR of 1.75 (95% CI 1.25-2.43). The age, gender, EDSS, and disease duration did not associate with sleep quality in either groups (p > 0.05). Conclusions: This study showed that sleep disturbance might be a trigger for an acute MS exacerbation. Increasing the awareness of specialists and routine screening of sleep disorders in MS patients are warranted, as treatment of these disorders might decrease the likelihood of acute relapses.

Induction of regulatory T-cells from memory T-cells is perturbed during acute exacerbation of multiple sclerosis

Regulatory T-cells (Tregs) are vital for maintaining immunological self-tolerance, and the transcription factor FOXP3 is considered critical for their development and function. Peripheral Treg induction may significantly contribute to the total Treg pool in healthy adults, and this pathway may be enhanced in thymic-deficient conditions like multiple sclerosis (MS). Here, we evaluated iTreg formation from memory versus naïve CD4+CD25− T-cell precursors. We report the novel finding that memory T-cells readily expressed CD25 and FOXP3, and demonstrated significantly greater suppressive function. Additionally, the CD25−FOXP3− fraction of stimulated memory T-cells also displayed robust suppression not observed in naïve counterparts or ex vivo resting (CD25−) T-cells. This regulatory population was present in both healthy subjects and clinically-quiescent MS patients, but was specifically deficient during disease exacerbation. These studies indicate that iTreg development and function are precursor dependent. Furthermore, MS quiescence appears to correlate with restoration of suppressive function in memory-derived CD4+CD25−FOXP3− iTregs.

Clinical experience with repository corticotropin injection in patients with multiple sclerosis experiencing mood changes with intravenous methylprednisolone: a case series.

The elevated prevalence of neuropsychiatric symptoms and disorders among patients with multiple sclerosis (MS) is well recognized, as are potential neuropsychiatric side effects of treatment with corticosteroids. Both methylprednisolone (MP) and repository corticotropin injection (HP Acthar(®) gel) have demonstrated efficacy in reducing short-term disability after exacerbations of MS. Although historical data are limited, repository corticotropin injection has not generally been associated with detrimental neuropsychiatric effects. We describe six cases of patients with relapsing-remitting MS who had previously experienced detrimental mood changes with MP treatment. Some of these patients had previous histories of mood disorders or other neuropsychiatric symptoms prior to MS diagnosis. All six patients were subsequently treated with repository corticotropin injection for MS exacerbations and each demonstrated improvements in MS symptoms. This clinical experience suggests that repository corticotropin injection should be considered as an alternative for patients who do not tolerate corticosteroids or have difficulties associated with intravenous medication. Furthermore, the rate of neuropsychiatric side effects observed in these patients was low. These observations support repository corticotropin injection as a viable alternative for the treatment of acute exacerbations of MS, particularly in patients who have a history of neuropsychiatric disorders or symptoms either independently or in response to MP treatment. In reviewing both the published data and our own clinical experience regarding potential neuropsychiatric adverse events with treatment for MS exacerbations, we hope to stimulate further research into the potential efficacy and safety of repository corticotropin injection among patients with some form of neuropsychiatric complications that must be considered when establishing a treatment plan for MS.

The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasmamembrane.

Genetic defects in myelin formation and maintenance cause leukodystrophies, a group of white matter diseases whose mechanistic underpinnings are poorly understood. Hypomyelination and congenital cataract (HCC), one of these disorders, is caused by mutations in FAM126A, a gene of unknown function. We show that FAM126A, also known as hyccin, regulates the synthesis of phosphatidylinositol 4-phosphate (PtdIns(4)P), a determinant of plasma membrane identity. HCC patient fibroblasts exhibit reduced PtdIns(4)P levels. FAM126A is an intrinsic component of the plasma membrane phosphatidylinositol 4-kinase complex that comprises PI4KIIIα and its adaptors TTC7 and EFR3 (refs 5,7). A FAM126A-TTC7 co-crystal structure reveals an all-α-helical heterodimer with a large protein-protein interface and a conserved surface that may mediate binding to PI4KIIIα. Absence of FAM126A, the predominant FAM126 isoform in oligodendrocytes, destabilizes the PI4KIIIα complex in mouse brain and patient fibroblasts. We propose that HCC pathogenesis involves defects in PtdIns(4)P production in oligodendrocytes, whose specialized function requires massive plasma membrane expansion and thus generation of PtdIns(4)P and downstream phosphoinositides. Our results point to a role for FAM126A in supporting myelination, an important process in development and also following acute exacerbations in multiple sclerosis.

Acthar gel treatment suppresses acute exacerbations in a murine model of relapsing-remitting multiple sclerosis

Acthar gel is indicated for the treatment of acute exacerbations of multiple sclerosis (MS) in adults. Its effects on immune cells during a relapse are unknown. This study investigated the effects of Acthar in an animal model of relapsing-remitting MS, using SJL/J mice sensitized with myelin peptide. All animal studies were reviewed and approved by the University of Utah Institutional Animal Care and Use Committee and conducted in accordance with the guidelines prepared by the Committee on Care and Use of Laboratory Animals, Institute of Laboratory Animals Resources, National Research Council. Mice injected with Acthar to treat the second attack had a significantly lower mean clinical score during relapse and a significantly reduced cumulative disease burden compared to Placebo gel-treated mice. Furthermore, Acthar treatment ameliorated inflammation/demyelination in the spinal cord and markedly suppressed ex vivo myelin peptide-induced CD4+ T cell proliferation.

Conditional ablation of astroglial CCL2 suppresses CNS accumulation of M1 macrophages and preserves axons in mice with MOG peptide EAE.

Current multiple sclerosis (MS) therapies only partially prevent chronically worsening neurological deficits, which are largely attributable to progressive loss of CNS axons. Prior studies of experimental autoimmune encephalomyelitis (EAE) induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide), a model of MS, documented continued axon loss for months after acute CNS inflammatory infiltrates had subsided, and massive astroglial induction of CCL2 (MCP-1), a chemokine for CCR2(+) monocytes. We now report that conditional deletion of astroglial CCL2 significantly decreases CNS accumulation of classically activated (M1) monocyte-derived macrophages and microglial expression of M1 markers during the initial CNS inflammatory phase of MOG peptide EAE, reduces the acute and long-term severity of clinical deficits and slows the progression of spinal cord axon loss. In addition, lack of astroglial-derived CCL2 results in increased accumulation of Th17 cells within the CNS in these mice, but also in greater confinement of CD4(+) lymphocytes to CNS perivascular spaces. These findings suggest that therapies designed to inhibit astroglial CCL2-driven trafficking of monocyte-derived macrophages to the CNS during acute MS exacerbations have the potential to significantly reduce CNS axon loss and slow progression of neurological deficits.

Time matters - acute stress response and glucocorticoid sensitivity in early multiple sclerosis.

Psychosocial stress has frequently been associated with disease activity and acute exacerbations in multiple sclerosis (MS). Despite this well established finding, strikingly little is known about the acute hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) stress response in MS. Twenty-six early relapsing-remitting MS (RRMS) patients and seventeen age- and sex-matched healthy control subjects (CS) took part in the Trier Social Stress Test (TSST), a well validated psycho-social laboratory stress protocol. Repeated blood samples were analyzed for stress-related cortisol and catecholamine levels as well as for glucocorticoid sensitivity (GCS) of target immune cells. Chronic and acute stress appraisals were assessed by self-report measures. RRMS patients and CS did not differ in stress-related cortisol/catecholamine levels, GCS or stress appraisal in response to the TSST. However, cortisol release as well as GCS was strongly correlated with time since diagnosis but not with neurological disability. Patients with shorter disease duration (2-12 months) expressed a significantly higher cortisol stress response while MS patients with longer disease duration (14-36 months) showed a significantly diminished HPA response as well as lower post-stress GCS. There is evidence for a time-dependent variability in the HPA stress system with an increased cortisol stress response in the first year after diagnosis along with a more blunted HPA stress response and a diminished GCS in subsequent disease stages. Data underscore the highly dynamic nature of HPA axis regulation in the MS disease process, which could possibly relate to compensatory mechanisms within a cytokine-HPA axis feedback circuit model.

EPA-0967 – Corticosteroid-induced mania treated with risperidone - a case report

Corticosteroids have either somatic and psychiatric side effects. Somatic adverse effects are well described while neuropsychiatric have received less attention. Psychiatric symptoms such as depression, psychosis and especially mania are common side effects of corticotherapy. Describe a case of a 53-year-old female patient, with no psychiatric history, who developed psychiatric symptoms during the treatment of an acute exacerbation of multiple sclerosis with large parenteral doses of corticosteroids. Three days after the onset of corticotherapy she developed increased energy, elevated mood, increased motor activity, racing thoughts, and diminished need for sleep. She subsequently developed grandiose and persecutory ideation and then feared her grandson was going to die. This lead to her admission to psychiatric unit of our hospital to address these behavioral problems. Her husband noticed that she had become’hyper’ in the past when she received pulse corticosteroid therapy, but the most recent episode was by far the worst. Revision of the scientific literature through Pubmed, Embase and Psychinfo using search terms including corticosteroids, mania, depression, psychosis and mood. Prednisone was suspended and Risperidone 2mg was begun for presumed steroid-induced mood disorder, and the patient became calmer and much less guarded over the next 2-3 days. After a week she recovered complete euthymic mood and reverted to normal functioning. These data suggest that Risperidone is well tolerated and appears to be useful for mood disturbances associated with corticosteroid therapy. Controlled trials seem warranted to confirm these observations.

Biventricular Tako‐Tsubo cardiomyopathy: Usefulness of 2D speckle tracking strain echocardiography

Tako-Tsubo cardiomyopathy is a transient left ventricular apical ballooning syndrome also known as stress-induced cardiomyopathy. This reversible cardiomyopathy without epicardial coronary artery disease mimics acute myocardial infarction. Right ventricular involvement, which has been infrequently reported, is present in about a quarter of cases of Tako-Tsubo cardiomyopathy and is associated with a more severe clinical outcome. We report the case of a 55-year-old postmenopausal woman with transient biventricular apical ballooning. She recently had acute exacerbation of multiple sclerosis. Regional and global function of both ventricles was estimated using two-dimensional speckle tracking strain echocardiography.

1965 – Corticosteroid-induced mania treated with risperidone - a case report

Introduction Corticosteroids have either somatic and psychiatric side effects. Somatic adverse effects are well described while neuropsychiatric have received less attention. Psychiatric symptoms such as depression, psychosis and especially mania are common side effects of corticotherapy. Aims and Objectives Describe a case of a 53-year-old female patient, with no psychiatric history, who developed psychiatric symptoms during the treatment of an acute exacerbation of multiple sclerosis with large parenteral doses of corticosteroids. Three days after the onset of corticotherapy she developed increased energy, elevated mood, increased motor activity, racing thoughts, and diminished need for sleep. She subsequently developed grandiose and persecutory ideation and then feared her grandson was going to die. This lead to her admission to psychiatric unit of our hospital to address these behavioral problems. Her husband noticed that she had become’hyper’ in the past when she received pulse corticosteroid therapy, but the most recent episode was by far the worst. Methods Revision of the scientific literature through Pubmed, Embase and Psychinfo using search terms including corticosteroids, mania, depression, psychosis and mood. Results Prednisone was suspended and Risperidone 2mg was begun for presumed steroid-induced mood disorder, and the patient became calmer and much less guarded over the next 2-3 days. After a week she recovered complete euthymic mood and reverted to normal functioning. Conclusions These data suggest that Risperidone is well tolerated and appears to be useful for mood disturbances associated with corticosteroid therapy. Controlled trials seem warranted to confirm these observations.

Oral versus intravenous steroids for treatment of relapses in multiple sclerosis

This is an updated Cochrane review of the previous version published (Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD006921. DOI: 10.1002/14651858.CD006921.pub2).Multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS), is characterized by recurrent relapses of CNS inflammation ranging from mild to severely disabling. Relapses have long been treated with steroids to reduce inflammation and hasten recovery. However, the commonly used intravenous methylprednisolone (IVMP) requires repeated infusions with the added costs of homecare or hospitalization, and may interfere with daily responsibilities. Oral steroids have been used in place of intravenous steroids, with lower direct and indirect costs. The primary objective was to compare efficacy of oral versus intravenous steroids in promoting disability recovery in MS relapses <= six weeks. Secondary objectives included subsequent relapse rate, disability, ambulation, hospitalization, immunological markers, radiological markers, and quality of life. A literature search was performed using Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's Trials Register (January 2012), abstracts from meetings of the American Academy of Neurology (2008-2012), the European Federation of Neurological Sciences (2008-2012), the European Committee for Treatment and Research in Multiple Sclerosis and American Committee for Treatment and Research in Multiple Sclerosis (2008-2012) handsearching. No language restrictions were applied. Randomized or quasi-randomized trials comparing oral versus intravenous steroids for acute relapses (<= six weeks) in patients with clinically definite MSover age 16 were eligible. Three review authors (JB, PO and MH) participated in the independent assessment of all published articles as potentially relevant to the review. Any disagreement was resolved by discussion among review authors.We contacted study authors for additional information.Methodological quality was assessed by the same three review authors.Relevant data were extracted, and effect size was reported as mean difference (MD), mean difference (MD), odds ratio (OR) and absolute risk difference (ARD). With this current update, a total of five eligible studies (215 patients) were identified. Only one outcome, the proportion of patients with Expanded Disability Status Scale (EDSS) improvement at four weeks, was common to three trials, while two trials examined magnetic resonance imaging (MRI) outcomes. The results of this review shows there is no significant difference in relapse recovery at week four (MD -0.22, 95% confidence interval (95% CI), 0.71 to 0.26, P = 0.20) nor differences in magnetic resonance imaging (MRI) gadolinium enhancement activity based on oral versus intravenous steroid treatment. However, only two of the five studies employed more current and rigorous methodological techniques, so these results must be taken with some caution. The Oral Megadose Corticosteroid Therapy of Acute Exacerbations of Multiple Sclerosis (OMEGA) trial and the "Efficacy and Safety of Methylprednisolone Per os Versus IV for the Treatment of Multiple Sclerosis (MS) Relapses" (COPOUSEP) trial, designed to address such limitations, are currently underway. The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.

Acute exacerbation of multiple sclerosis presenting with facial metamorphopsia and palinopsia

We discuss the case of a patient with a known history of relapsing–remitting multiple sclerosis (MS) who presented with the isolated complaint of altered visual perception in the absence of abnormalities on ophthalmological examination. To the best of the authors’ knowledge, this is the first documented case of both facial metamorphopsia and palinopsia occurring as the symptoms of demyelinating brain lesions consistent with an acute MS exacerbation. These symptoms appear to be related to active demyelination that either involved the optic radiations in the visual pathway or the visual association area in the temporo-occipital region of the left hemisphere.

Incidence of various cardiac arrhythmias and conduction disturbances due to high dose intravenous methylprednisolone in patients with multiple sclerosis

Background High-dose intravenous methylprednisolone is the most common therapeutic modality to treat acute exacerbations in multiple sclerosis (MS). Various cardiac arrhythmias have been reported during corticosteroid pulse therapy. This study was conducted to detect cardiac rhythm changes in patients with MS while receiving high dose methylprednisolone. Methods We enrolled 52 consecutive MS patients with acute relapse to perform cardiac monitoring 4 h before, during and 18 h after infusion of 1000 mg intravenous (IV) methylprednisolone. Results Sinus tachycardia was the most common change in cardiac rhythms before, during, and after corticosteroid pulse therapy. Up to 41.9% of the patients, developed sinus bradycardia after pulse infusion. Sinus arrest and sinus exit block were observed in 12 patients. Atrial fibrillation and ventricular tachycardia were observed in three patients and one patient, respectively. The most important cardiac arrhythmias including ventricular tachycardia, sinus arrest, and sinus exit block, were correlated with smoking and more commonly observed during 12 h post infusion. Sinus bradycardia and atrial fibrillation were detected more commonly in patients with history of urinary dysfunction. Conclusion High dose intravenous prednisolone might cause different types of arrhythmias in MS patients. Cigarette smokers and patients with autonomic disturbances like sphincter and bowel problems have more chance to develop arrhythmias while receiving high dose steroids.

Neuroantigen-specific CD8+ regulatory T-cell function is deficient during acute exacerbation of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). MS is thought to be T-cell-mediated, with prior research predominantly focusing on CD4+ T-cells. There is a high prevalence of CNS-specific CD8+ T-cell responses in MS patients and healthy subjects. However, the role of neuroantigen-specific CD8+ T-cells in MS is poorly understood, with the prevalent notion that these may represent pathogenic T-cells. We show here that healthy subjects and MS patients demonstrate similar magnitudes of CD8+ and CD4+ T-cell responses to various antigenic stimuli. Interestingly, CD8+ T-cells specific for CNS autoantigens, but not those specific for control foreign antigens, exhibit immune regulatory ability, suppressing proliferation of CD4+CD25− T-cells when stimulated by their cognate antigen. While CD8+ T-cell-mediated immune suppression is similar between healthy subjects and clinically quiescent treatment-naïve MS patients, it is significantly deficient during acute exacerbation of MS. Of note, the recovery of neuroantigen-specific CD8+ T-cell suppression correlates with disease recovery post-relapse. These studies reveal a novel immune suppressor function for neuroantigen-specific CD8+ T-cells that is clinically relevant in the maintenance of peripheral tolerance and the intrinsic regulation of MS immune pathology.