Multiple Sclerosis Exacerbations Research Articles

Risk of venous thromboembolism in neuromyelitis optica patients hospitalized for acute relapse

Background: Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. Objective: To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. Methods: Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. Results: A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 (p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. Conclusion: NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis.

Women's experiences of menopause in an online MS cohort: A case series

BackgroundMany women with multiple sclerosis (MS) are postmenopausal. Previously reported findings from an online MS cohort suggested that earlier, surgical menopause may be associated with higher patient-reported MS severity scores. ObjectiveTo explore experiences of menopause in a series of MS women responding to a reproductive survey from an online research platform, PatientsLikeMe (PLM). MethodsThe free-text responses from a detailed reproductive history survey deployed to PLM members were analyzed using grounded theory approach. ResultsOf the 208 free text responses, 127 responses related to menopause. Five themes emerged: (1) perimenopausal onset of MS symptoms, (2) overlap of MS and menopausal symptoms, (3) MS exacerbations and pseudo-exacerbations triggered by hot flashes, (4) escalation of disease course after menopause, including increasing fatigue, cognitive disturbance, and other symptoms; and (5) effect of HRT on MS symptoms. Some women reported no effects of menopause or HRT. ConclusionGiven an aging population and a median age of individuals currently living with MS very close to menopausal age in many cohorts, there is a pressing need to understand the impact of menopause on MS course. Qualitative responses in this study illustrated several specific themes that require quantitative testing in clinic-based cohorts.

H.P. Acthar Gel (repository corticotropin injection) treatment of patients with multiple sclerosis and diabetes.

Background:Treatment of multiple sclerosis (MS) relapses can be complex in patients with concomitant diabetes. Corticosteroids and adrenocorticotropic hormones are known to cause alterations in glucose tolerance. Many patients have poor tolerability to therapy, necessitating alternative treatment options. Adrenocorticotropic hormone (H.P. Acthar Gel, repository corticotropin injection, Mallinckrodt ARD Inc., Hazelwood, MO, USA) is currently indicated for the treatment of MS relapses.Objectives:The objective of this study was to review patients’ experiences of Acthar Gel for the treatment of MS exacerbations in patients with MS and diabetes.Methods:A retrospective review of 13 patients’ experiences with treatment. Qualified healthcare providers completed a questionnaire following Acthar Gel treatment for MS relapse.Results:Previous corticosteroid treatment with either intravenous methylprednisolone or prednisone was reported by 84.6% of patients; eight patients had complications following administration of prior steroid treatment, seven of whom experienced elevated blood glucose levels. Acthar Gel was administered daily for a mean of 5.3 days, with 61.5% of patients reporting relapse resolution. Two patients experienced elevated blood glucose.Conclusion:The majority of patients experienced a timely resolution of their MS relapse with few hyperglycemic adverse events. Although more studies are necessary, these data suggest that Acthar Gel may be a well-tolerated and effective treatment option for patients with diabetes experiencing an MS relapse.

Acute Multiple Sclerosis Relapse.

This article discusses acute exacerbations (relapses) of multiple sclerosis (MS). Relapses are a hallmark of MS and are often associated with significant functional impairment and decreased quality of life. This review discusses the proposed pathophysiology of MS relapses, triggering factors, associated markers, variants of clinical presentation, and diagnostic recommendations. Most MS exacerbations are followed by a period of repair leading to clinical remission; however, residual deficits may persist after MS relapse and contribute to the stepwise progression of disability. Treatment of MS relapses is important as it helps to shorten the duration of disability associated with their course. Successful treatment of relapse helps patients with MS obtain a vital sense of being able to gain control over the disease. Patients with relapsing MS who receive treatment report better outcomes than those who are simply observed. This article discusses treatment options for MS relapse, including systemic corticosteroids, adrenocorticotropic hormone, and plasma exchange. Recent findings related to the mechanisms of action of steroids and adrenocorticotropic hormone are also reviewed, and other potential therapies are assessed. A proposed algorithm for MS relapse management is presented, including strategies for steroid-resistant MS exacerbations. MS relapses need to be recognized in a timely manner and treated using recommended therapeutic methods.

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.

Occupational Therapy Interventions for Adults With Multiple Sclerosis

This Evidence Connection describes a case report of a woman with an exacerbation of multiple sclerosis (MS), applying the evidence for intervention from the systematic reviews on MS that were conducted in conjunction with the American Occupational Therapy Association's (AOTA's) Evidence-Based Practice Project. The occupational therapy assessment and treatment processes for an inpatient rehabilitation setting are described. Evidence Connection articles provide a clinical application of systematic reviews developed in conjunction with the AOTA's Evidence-Based Practice Project.

Severe exacerbation of relapsing-remitting multiple sclerosis after G-CSF therapy.

A 31-year-old woman (figure) with relapsing-remitting multiple sclerosis (MS) (first symptoms February 1994, first diagnosis August 1994, Expanded Disability Status Scale [EDSS] 3.0) was diagnosed with breast cancer in January 2014. The last relapse had occurred in August 2007. Under treatment with natalizumab from August 2007 to June 2013, the patient was clinically stable and the brain MRI showed no signs of disease activity. Because of a positive JC virus antibody test, the immunomodulatory therapy was changed to fingolimod in July 2013. The patient remained clinically stable during the switching period and thereafter. In January 2014, a brain MRI showed 2 new lesions without contrast enhancement. After diagnosis of breast cancer in January 2014 and subsequent surgery in February 2014, adjuvant chemotherapy with cyclophosphamide, doxorubicin, and docetaxel was started (March–July 2014). Fingolimod was stopped in March 2014 considering the strong immunosuppressive effect of cyclophosphamide. The patient received granulocyte colony-stimulating factor (G-CSF; pegfilgrastim) 6 mg subcutaneously at each of the 6 cycles of chemotherapy to reduce the risk of infection during the phase of chemotherapy-induced neutropenia. In July 2014, the patient experienced a numbness and tingling in her right leg, which progressed to a severe hemiparesis (EDSS 7.0) leading to hospitalization. The MRI scan of the brain revealed several new lesions including a lesion with contrast enhancement. An IV steroid pulse therapy was administered. She recovered partially (EDSS 6.5). Fingolimod was started again in August 2014. Subsequently the patient developed another relapse with a worsening of the atactic hemiparesis on the left side, resulting in an inability to walk (EDSS 7.5). Again an IV steroid pulse therapy was administered. The patient recovered partially until the end of August 2014, when she was discharged from rehabilitation. At that time, she was able to walk for 50 meters without aid (EDSS 6.0). Another brain MRI in September 2014 revealed confluent progressive lesions in the white matter with partial contrast enhancement. The patient was referred to our inpatient clinic, where again a steroid pulse therapy was administered. In the following months, the patient recovered to a clinical condition similar to that before the start of the chemotherapy (as of August 2015, EDSS 3.0). An MRI scan of the brain in September 2015 did not show new lesions or contrast enhancement compared to the preceding MRI examination in September 2014.

Multiple sclerosis-related fatigue and possibilities of its correction

Multiple sclerosis (MS)-related fatigue is encountered in 75–92% of patients and it is one of the key symptoms that affect quality of life. Physicians and patients' relatives frequently underestimate MS-related fatigue; the latter may occur at any disease stage, its degree is inadequate to physical exercise and reduces after a short-term daytime rest. Fatigue due to MS is not directly related to the degree of paresis; however, it is more common in patients with pyramidal insufficiency. Overfatigue may be the first symptom of an MS exacerbation. The genesis of fatigue in MS is not known with certainty. The development of this symptom is associated with impairments in neuroimmune responses and biochemical processes and with the administration of some drugs. Special tests and scales are used to objectify the degree of fatigue. The most commonly used questionnaires are the Fatigue Severity Scores to rate physical and mental fatigue, as well as the Modified Fatigue Impact Scale in patients having MS. When a patient with MS complains about fatigue, it is necessary to rule out its other possible causes and to specify its relation to MS and the necessity of fatigue correction. Аmantadine is one of the drugs used for the symptomatic therapy of MS. This paper presents the data of randomized clinical trials evaluating the efficacy and safety of this drug for the symptomatic treatment of MS. Correction of MS-related fatigue requires a multidisciplinary approach that involves a combination of drug therapy, therapeutic exercises, active lifestyle, and relatives' understanding.

GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs) has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective) action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis. The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs). To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

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.

The Ins and Outs of B Cells in Multiple Sclerosis.

B cells play a central role in multiple sclerosis (MS) pathology. B and plasma cells may contribute to disease activity through multiple mechanisms: antigen presentation, cytokine secretion, or antibody production. Molecular analyses of B cell populations in MS patients have revealed significant overlaps between peripheral lymphoid and clonally expanded central nervous system (CNS) B cell populations, indicating that B cell trafficking may play a critical role in driving MS exacerbations. In this review, we will assess our current knowledge of the mechanisms and pathways governing B cell migration into the CNS and examine evidence for and against a compartmentalized B cell response driving progressive MS pathology.

Pharmacodynamics and tolerability of repository corticotropin injection in healthy human subjects: A comparison with intravenous methylprednisolone.

Repository corticotropin injection (porcine adrenocorticotropic hormone [ACTH] analog) and intravenous methylprednisolone (IVMP) are used to treat inflammatory conditions such as multiple sclerosis (MS) exacerbations and rheumatoid arthritis. This multiple‐dose, randomized, crossover, open‐label study evaluated and compared pharmacodynamic outcomes in subjects who received ACTH analog (80 U subcutaneously) or IVMP (1 g) daily for 5 days. Specific outcome measures included IVMP and cortisol concentrations, total cortisol‐equivalent exposure, immune cell population changes, and tolerability. IVMP and ACTH analog increased granulocyte numbers and decreased lymphocyte counts; effects on both were significantly less pronounced with ACTH analog. Based on total cortisol‐equivalent exposure (assuming linearity), administration of 80 U of ACTH analog equates to 30 mg IVMP. Because IVMP doses significantly higher than 30 mg are usually required to treat MS exacerbations, the lower cortisol‐equivalent exposure of 80 U ACTH analog supports the hypothesis that efficacy of ACTH analog results from both steroid‐dependent and ‐independent properties. Adverse events were mild in severity; subject incidence for adverse‐event reporting was similar following both regimens. The clinical relevance of these findings in autoimmune disease populations is unknown and requires further evaluation.

Resistant Strains of Enterotoxigenic Staphylococcus aureus; Unknown Risk for Multiple Sclerosis Exacerbation.

Background:Despite all advances in neurological sciences, there are unknown aspects in the epidemiology of multiple sclerosis (MS). Based on this hypothesis, the enterotoxigenic strains of Staphylococcus aureus (S. aureus) are possible risk factors for exacerbations of MS.Objectives:The present study was carried out to investigate the role of resistant strains of enterotoxigenic S. aureus in MS exacerbation.Materials and Methods:Two-hundred nasal swab samples were collected from non-MS (n = 80), MS stable (n = 60) and MS exacerbation (n = 60) groups. Samples were cultured and those that were S. aureus-positive were analyzed for the presence of enterotoxins, using polymerase chain reaction (PCR). Antimicrobial susceptibility was performed using disk diffusion method.Results:Ninety out of 200 nasal samples (45%) were positive for S. aureus. The highest levels of nasal colonization were seen in MS exacerbation group (68.33%). The most commonly detected enterotoxins were sea (30%), sec (15.55%) and seb (11.11%). There were significant differences between S. aureus colonization and type of samples (P = 0.026) and, also, between type of samples and prevalence of enterotoxins (P = 0.022). The highest levels of enterotoxigenic genes were seen in MS exacerbation group. The S. aureus strains had the highest levels of resistance against tetracycline (80%), ampicillin (72.22%), methicillin (66.66%), erythromycin (66.66%), oxacillin (63.33%), trimethoprim-sulfamethoxazole (61.11%) and cotrimoxazole (55.55%).Conclusions:Our findings should raise awareness about the role of sea and sec enterotoxins, in resistant strains of S. aureus, as a risk factor for MS exacerbation. It is better to keep MS patients away from polluted environments of hospitals and health centers.

Clinical and experimental studies of multiple sclerosis in Russia: experience of the leading national research centers.

Mechanisms of axonal damage and adaptive capacity in multiple sclerosis (MS), including cortical reorganization, have been actively studied in recent years. The lack of regenerative capabilities and the irreversibility of neurodegeneration in MS are critical factors for the optimization of MS treatment. In this study, we present the results of clinical and basic studies in the field of MS by two leading Russian centers. Clinical and neuroimaging correlations show that spinal damage in MS is accompanied by functional reorganization of the cerebral cortex, which is determined not only by the efferent component but also by the afferent component. Comparative analysis of MS treatment with both interferon β1b (IFN-β1b) and IFN-β1a at a dosage of 22 µg for 3 years through subcutaneous administration and glatiramer acetate showed equally high efficiency in reducing the number of exacerbations in relapsing-remitting MS and secondary-progressive MS. We demonstrate a reduced risk of disability in relapsing-remitting MS and secondary-progressive MS patients in all groups treated with IFN-β1 and glatiramer acetate. MS appears to be a disease that would greatly benefit from the development of personalized therapy; thus, adequate molecular predictors of myelin degradation are greatly needed. Therefore, novel ideas related to the viral hypothesis of the etiology of MS and new targets for therapeutic intervention are currently being developed. In this manuscript, we discuss findings of both clinical practice and fundamental research reflecting challenges and future directions of MS treatment in the Russian Federation.

Gender influence in EBV antibody response in multiple sclerosis patients from Kuwait

BackgroundEpstein–Barr virus (EBV) infection is implicated with multiple sclerosis (MS) risk, exacerbation, and progression. The HLA-DRB1*1501 haplotype is a strong MS risk factor consistently documented in MS populations. There are no studies of EBV infections and HLA-DRB1*1501 haplotype associating with MS from Kuwait where MS prevalence has increased significantly. ObjectivesTo determine the association of EBV infection with MS incidence, and to investigate HLA-DRB1*1501 as a potential genetic risk factor for MS in Kuwait. MethodsThis is a case–control study involving 141 MS patients and 40 healthy controls. Antibody titers against EBV antigens' viral capsid antigen (VCA) and Epstein–Barr nuclear antigen 1 (EBNA1) were measured using enzyme-linked immunosorbent assays. HLA-DRB1*1501 haplotype assessment was done using rs3135005 TaqMan genotyping assay. ResultsAntibody titers against EBV were significantly elevated in MS patients compared to healthy controls (anti-EBNA1, p=0.008; anti-VCA, p=0.028). MS males had higher antibody titers to EBNA1 than healthy male controls (p=0.005) and female MS patients (p=0.03). HLA-DRB1*1501 haplotype genotypes failed to generate a risk association with MS or EBV antibody titers (p=0.6). ConclusionAn increased immune response to EBV infection is associated with MS incidence influenced by the type of antigen and sex. HLA-DRB1*1501 haplotype is not associated with MS risk in our Kuwaiti MS cohort.

Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis.

Objectives:To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity.Methods:In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety.Results:Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time.Conclusions:MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found.Classification of evidence:This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS.

Epilepsy in patients with multiple sclerosis: specific features of diagnosis and therapy

Once the symptoms of multiple sclerosis (MS) occur, the risk of developing epilepsy within 5 years is 1.1%; this indicator doubles and triples 10 and 15 years after MS. Objective : to specify the epidemiology of MS in the Moscow Region and management tactics for patients with MS and epileptic seizures (ES). Patients and methods . Out of 906 patients diagnosed with MS, 9 (0.99%) (4 men and 5 women; mean age 28.62 ± 4.59 years) were observed to have ES. The annual MS exacerbation rate was 1.2 ± 1.19. Two MS patients were untreated for MS; 7 took MS-modifying drugs: interferon β 1a (n=2) or glatiramer acetate (n=5). The course of epilepsy and MS was retrospectively assessed. Two patient groups were identified: the first diagnosis was epilepsy (Group 1) and MS (Group 2). The patients were followed up jointly by a MS center physician and an epileptologist. If they had any indications, the patients underwent brain contrast-enhanced magnetic resonance imaging (MRI) (at least 1.5 T) and electroencephalography (EEG), EDSS health assessment, antiepileptic therapy (AET) analysis and correction. Results . The incidence rate of ES in MS patients is about 1%, which is 2.5 times greater than that for the adult population in the Moscow Region. ESs are accompanied by secondary generalization in more than 60% of the cases; serial and status convulsive seizures are recorded in one third of the patients. More than half of ES cases are associated with MS exacerbations. Conclusion . The use of AET after the first ESs is justified due to a high risk of recurrent seizures. Complete ES control can be achieved by AET as monotherapy in more than 70% of cases. If EP occurs, the patients with MS should undergo contrast-enhanced MRI of the brain to rule out an exacerbation.

Infection risk in patients on multiple sclerosis therapeutics.

The interface of multiple sclerosis (MS) and infection occurs on several levels. First, infectious disease has been postulated as a potential trigger, if not cause, of MS. Second, exacerbation of MS has been well-documented as a consequence of infection, and, lastly, infectious diseases have been recognized as a complication of the therapies currently employed in the treatment of MS. MS is a disease in which immune dysregulation is a key component. Examination of central nervous system (CNS) tissue of people affected by MS demonstrates immune cell infiltration, activation and inflammation. Therapies that alter the immune response have demonstrated efficacy in reducing relapse rates and evidence of brain inflammation on magnetic resonance imaging (MRI). Despite the altered immune response in MS, there is a lack of evidence that these patients are at increased risk of infectious disease in the absence of treatment or debility. Links between infections and disease-modifying therapies (DMTs) used in MS will be discussed in this review, as well as estimates of occurrence and ways to potentially minimize these risks. We address infection in MS in a comprehensive fashion, including (1) the impact of infections on relapse rates in patients with MS; (2) a review of available infection data from pivotal trials and postmarketing studies for the approved and experimental DMTs, including frequency, types and severity of infections; and (3) relevant risk minimization strategies, particularly as they pertain to progressive multifocal leukoencephalopathy (PML).

Should plasma exchange be offered to patients with multiple sclerosis-associated optic neuritis?

Should plasma exchange be offered to patients with multiple sclerosis-associated optic neuritis?