Patient-reported outcomes with subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: the PATH study.

BACKGROUND AND PURPOSE: Chronic inflammatory demyelinating polyneuropathy (CIDP) causes weakness which adversely impacts function and quality of life (QOL). CIDP often requires long-term management with intravenous or subcutaneous immunoglobulin. The Polyneuropathy and Treatment with Hizentra® (PATH) study showed that subcutaneous immunoglobulin (SCIG) was efficacious in CIDP maintenance. Here, patient-reported outcomes in patients on SCIG are assessed. METHODS: Subjects stabilized on intravenous immunoglobulin were randomly allocated to receive weekly 0.2 or 0.4 g/kg bodyweight of 20% SCIG (IgPro20) or placebo. Overall QOL/health status was assessed using the EuroQoL 5-Dimension (EQ-5D) health profile and visual analog scale, treatment satisfaction was assessed with the Treatment Satisfaction Questionnaire for Medicine (TSQM) and work-related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI-GH). The EQ-5D health profile was assessed in terms of the percentage of subjects maintained or improved at week 25 of SCIG therapy on each of the EQ-5D domains versus baseline after intravenous immunoglobulin stabilization. TSQM and WPAI-GH were assessed by median score changes from baseline to week 25. RESULTS: In total, 172 subjects were randomized to placebo (n = 57), 0.2 g/kg IgPro20 (n = 57) and 0.4 g/kg IgPro20 (n = 58). Significantly higher proportions of IgPro20-treated subjects improved/maintained their health status on the EQ-5D usual activities dimension, and in additional dimensions (mobility and pain/discomfort) in sensitivity analyses. TSQM and WPAI-GH scores were more stable with IgPro20 treatment compared with placebo. CONCLUSIONS: IgPro20 maintained or improved QOL in most subjects with CIDP, consistent with the PATH study findings that both IgPro20 doses were efficacious in maintaining CIDP.

Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by an acute onset of severe headache and multi-focal segmental vasoconstriction of cerebral arteries resolving within 12 weeks. Diagnostic criteria include normal or near-normal findings in cerebrospinal fluid (CSF) analysis, especially leucocyte levels < 10/mm³. Distinguishing RCVS from primary angiitis of the central nervous system (PACNS) is essential to avoid unnecessary and sometimes unfavourable immunosuppressive treatment. We reviewed retrospectively the clinical and diagnostic data of 10 RCVS patients who presented in our neurological department from 1 January 2013 to February 2017. The main purpose was to verify whether CSF leucocyte counts < 10/mm³ serve to discriminate RCVS from PACNS. Five of six patients who underwent lumbar puncture presented with CSF leucocyte levels ≥ 10/mm³. Two patients had a history of misinterpretation of CSF pleocytosis as cerebral vasculitis and of immunosuppressive treatment. A complete restitution of cerebral vasoconstriction was evident in all. No patient had further cerebral strokes or bleedings without immunosuppressive treatment over more than 12 weeks. Despite the established diagnostic criteria, RCVS can manifest with CSF leucocyte levels > 10/mm³. Careful anamnesis and the response of 'vasculitis-like angiography' to nimodipine given as a test during angiography and as oral medication are key to differentiate RCVS from cerebral vasculitis.

Survey of diagnostic and treatment practices for multiple sclerosis (MS) in Europe. Part 2: Progressive MS, paediatric MS, pregnancy and general management.

BACKGROUND AND PURPOSE: The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. METHODS: A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. RESULTS: Respondents generally favoured changing rather than stopping disease-modifying treatment (DMT) in patients transitioning from relapsing-remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium-enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice-based questions and management are summarized. CONCLUSIONS: Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines.

ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. METHODS: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.

Late age onset of amyotrophic lateral sclerosis is often not considered in elderly people.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing an upper and lower motor neuron loss. It is neurology textbook knowledge that the mean age of onset is about 60 years. However, recent investigations show an increasing incidence in older persons. We therefore evaluated whether ALS is potentially not considered in elderly people with ALS symptoms, respectively, not recognized. MATERIALS AND METHODS: We included retrospectively all patients with ALS diagnoses after work-up that were admitted to our neurological and geriatric departments from 2007 to 2010 and collected their clinical data. The diagnosis of ALS was based on the El Escorial criteria. Patients were grouped into three categories according to age (<50, between 50 and 70, >70), and differences in clinical and/ or biographical factors were investigated. RESULTS: We identified 35 patients (18 men and 17 women) with a median age at onset of 71.5 years (range: 36-87 years). When establishing the diagnosis, 51% were older than 70 years, 40% (14/35) between 50 and 70, and only 9% younger than 50. Only in 46 per cent of patients who were sent to our departments with ALS symptoms ALS was considered by the referring physician. CONCLUSION: Late age onset of ALS seems to be more common than formerly assumed and is presumably under-recognized in elderly patients. ALS needs to be considered as a differential diagnosis in older patients. Potential factors accounting for older people being underdiagnosed with ALS relate to frequent presentation with symptoms like dysphagia, frailty or general weakness for other reasons.

[Cladribine tablets : Oral immunotherapy of relapsing-remitting multiple sclerosis with short yearly treatment periods]. / Cladribin-Tabletten : Orale Immuntherapie der schubförmigen Multiplen Sklerose mit kurzen, jährlichen Behandlungsphasen.

BACKGROUND: The selective modulation of lymphocyte numbers and function is an attractive concept in the treatment of relapsing-remitting multiple sclerosis (RMS). OBJECTIVE: Cladribine tablets (Mavenclad®), an oral RMS medication with an innovative treatment concept, have been available since August 2017. This review article summarizes the currently available clinical study data on cladribine tablets and aspects of their use in clinical practice. RESULTS: Cladribine tablets are administered during two treatment phases of 8-10 (two times 4-5) days with a 1-year interval. The drug selectively reduces the number of T and B lymphocytes, which are subsequently gradually reconstituted with divergent kinetics. A pronounced and sustained effect on the clinical and paraclinical MS disease activity is achieved with good tolerability and a favorable overall safety profile. After completing the two short treatment phases, a relevant proportion of the treated patients experience a prolonged treatment-free period with absence of relevant disease activity. Regular monitoring of lymphocyte counts and reliable contraception during the required time frames are the most important safety measures. There is no evidence of an increased risk of malignancies. CONCLUSION: Cladribine tablets are an important addition to the therapeutic landscape in RMS. With patient-friendly short dosing periods and a favorable adverse event profile, cladribine tablets provide a sustained and strong reduction of MS disease activity. The primary target population for cladribine tablets is patients with relevant MS disease activity (highly active RMS) while on first-line treatment, e. g. with injectable disease-modifying drugs.

[Diagnosis of multiple sclerosis: revision of the McDonald criteria 2017]. / Diagnose der Multiplen Sklerose: Revision der McDonald-Kriterien 2017.

Multiple sclerosis (MS) is the most common chronic autoimmune disorder of the central nervous system (CNS) largely affecting young adults. The diagnosis of MS is based on two pillars: 1) detection of the spatial and temporal dissemination of focal neurological deficits and 2) exclusion of important differential diagnoses. The current revision of the diagnostic criteria (McDonald 2017) also follows these principles, takes new data on magnetic resonance imaging (MRI) into account and reintroduces the role of cerebrospinal fluid (CSF) diagnostics for relapsing-remitting forms. The main priority is a reliable diagnosis as early as possible with the aim of a timely initiation of course-adapted treatment. Some of the concrete innovations are the consideration of cortical MRI lesions (equivalent to juxtacortical foci), the elimination of a distinction between asymptomatic and symptomatic MRI lesions and consideration of characteristic CSF findings for the criterion of temporal dissemination. Relapsing MS can be diagnosed at the time of the first attack by the detection of CSF-specific oligoclonal bands and the MRI detection of a typical local lesion distribution (even without simultaneous detection of a contrast-enhancing lesion). For the primary progressive course, for which a first treatment option has recently been approved, the known definition remains unaltered. With respect to the differential diagnosis there is a clear demarcation from Devic's syndrome, now known as neuromyelitis optica spectrum disorders (NMOSD), as recent insights indicate a separate disease entity caused by an autoimmune response against the astrocytic aquaporin 4 (AQP4) water channel. Finally, future studies will have to provide a definition for secondary progressive MS courses and clarify how to handle diseases characterized by antibodies against myelin oligodendrocyte glycoprotein (MOG) or patients with radiologically isolated syndrome (RIS), i. e. incidental MRI-based detection of CNS lesions in the absence of any clinical event. In summary, McDonald 2017 is within the conceptual structure of its predecessor and simplifies an early diagnosis, thus paving the way to early treatment of MS.

[Multiple sclerosis and hepatitis B vaccination : What does the verdict of the European Court of Justice on liability after vaccination mean?] / Multiple Sklerose und Hepatitis-B-Impfung : Was bedeutet das Urteil des EuGH zur Haftung nach Impfung?

In June 2017 the European Court of Justice (ECJ) issued a verdict on the legal assessment of the association between hepatitis B immunization and the subsequent manifestation of multiple sclerosis (MS). This led to a high level of insecurity in the medical field as well as the normal population, especially in MS patients. The aim of this article is to briefly present the evidence-based medical facts and in particular to clearly highlight the legal aspects of the abovenamed ECJ verdict.

Survey of diagnostic and treatment practices for multiple sclerosis in Europe.

BACKGROUND AND PURPOSE: Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. METHODS: A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. RESULTS: Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. CONCLUSIONS: Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.

Dual roles of the adenosine A2a receptor in autoimmune neuroinflammation.

BACKGROUND: Conditions of inflammatory tissue distress are associated with high extracellular levels of adenosine, due to increased adenosine triphosphate (ATP) degradation upon cellular stress or the release of extracellular ATP upon cell death, which can be degraded to adenosine by membrane-bound ecto-enzymes like CD39 and CD73. Adenosine is recognised to mediate anti-inflammatory effects via the adenosine A2a receptor (A2aR), as shown in experimental models of arthritis. Here, using pharmacological interventions and genetic inactivation, we investigated the roles of A2aR in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). METHODS: We used two independent mouse EAE variants, i.e. active immunization in C57BL/6 with myelin oligodendrocyte glycoprotein (MOG)35-55 or transfer-EAE by proteolipid protein (PLP)139-155-stimulated T lymphocytes and EAE in mice treated with A2aR-agonist CGS21680 at different stages of disease course and in mice lacking A2aR (A2aR(-/-)) compared to direct wild-type littermates. In EAE, we analysed myelin-specific proliferation and cytokine synthesis ex vivo, as well as inflammation and demyelination by immunohistochemistry. In vitro, we investigated the effect of A2aR on migration of CD4(+) T cells, macrophages and microglia, as well as the impact of A2aR on phagocytosis of macrophages and microglia. Statistical tests were Mann-Whitney U and Student's t test. RESULTS: We found an upregulation of A2aR in the central nervous system (CNS) in EAE, predominantly detected on T cells and macrophages/microglia within the inflamed tissue. Preventive EAE treatment with A2aR-specific agonist inhibited myelin-specific T cell proliferation ex vivo and ameliorated disease, while application of the same agonist after disease onset exacerbated non-remitting EAE progression and resulted in more severe tissue destruction. Accordingly, A2aR-deficient mice showed accelerated and exacerbated disease manifestation with increased frequencies of IFN-γ-, IL-17- and GM-CSF-producing CD4(+) T helper cells and higher numbers of inflammatory lesions in the early stage. However, EAE quickly ameliorated and myelin debris accumulation was lower in A2aR(-/-) mice. In vitro, activation of A2aR inhibited phagocytosis of myelin by macrophages and primary microglia as well as migration of CD4(+) T cells, macrophages and primary microglia. CONCLUSIONS: A2aR activation exerts a complex pattern in chronic autoimmune neurodegeneration: while providing anti-inflammatory effects on T cells and thus protection at early stages, A2aR seems to play a detrimental role during later stages of disease and may thus contribute to sustained tissue damage within the inflamed CNS.

[Hermann Oppenheim. Comments on his life and works]. / Hermann Oppenheim. Anmerkungen zu seinem Leben und Wirken.

The outstanding neurologist Hermann Oppenheim was renowned worldwide during his lifetime and was highly esteemed; however, he was also a contradictory, complex personality and his life was marked by several tragic events. Even for his contemporaries, his life and work was the subject of lively discussions and debates and also some 100 years later, it is an interesting challenge to obtain an insight into the extensive work of this famous man and to understand the reasons for his great successes and failures.

[Progressive multifocal leukoencephalopathy]. / Progressive multifokale Leukenzephalopathie.

Progressive multifocal leukoencephalopathy (PML) is a disease of immunosuppressed patients caused by the JC polyomavirus (JCPyV). Due to the elevated risk in patients treated with natalizumab for multiple sclerosis (MS) and also treatment with other biologicals for different indications, the relevance of PML has increased in recent years. This article summarizes the published knowledge on the biology and pathogenesis of PML with a focus on the role of cerebrospinal fluid diagnostics in the work-up for PML and the current PML case definition. Current recommendations regarding risk management are discussed, as are possible therapies and prevention.

[New therapeutic strategies for remyelination in multiple sclerosis]. / Neue Therapiestrategien zur Myelinreparatur bei der Multiplen Sklerose.

Multiple sclerosis (MS) is characterized by oligodendrocyte death and myelin sheath destruction of the central nervous system (CNS) in response to autoinflammatory processes. Besides demyelination axonal degeneration constitutes the second histopathological hallmark of this disease. A large number of immunomodulatory and targeted immunosuppression treatments have been approved for relapsing remitting (RR) MS where they effectively reduce relapse rates; however, currently no treatment options exist to repair injured axonal tracts or myelin damage that accumulates over time particularly in progressive MS. In light of the growing available therapeutic repertoire of highly potent immunomodulatory medications there is an increasing interest in the development of therapies aimed at neutralizing neurodegenerative damage. Endogenous remyelination processes occur mainly as a result of oligodendrocyte precursor cell (OPC) activation, recruitment and maturation; however, this repair activity appears to be limited and increasingly fails during disease progression. Based on these observations OPCs are considered as promising targets for the regenerative treatment of all stages of MS. This article presents an overview of approved medications with a suggested role in regeneration, regenerative treatments that are currently being tested in clinical trials, as well as promising future therapeutic approaches derived from basic glial cell research aiming at the promotion of the endogenous repair activity of the brain.

[Infection risks in multiple sclerosis therapy by infusion of disease modifying drugs]. / Infektiologische Risiken in der Multiple-Sklerose-Therapie durch infundierbare Immuntherapeutika.

The increased risk of developing infections when using disease-modifying drugs for treatment of multiple sclerosis (MS) is a major challenge in the daily clinical routine. In the growing field of treatment options specific knowledge of treatment-related risks of infections and appropriate preventive and countermeasures is mandatory. Current clinical experience shows that an individual risk stratification is necessary when choosing treatment options and while monitoring during and after treatment administration. The determination of the individual risk of infection in the context of serial use of disease-modifying drugs remains a challenging issue. In addition to the mechanisms of action, the warning notices and current recommendations on infection prophylaxis when using intravenous disease-modifying drugs, such as alemtuzumab, natalizumab and mitoxantron, are presented in detail.

[Immunotherapy and infectious issues in multiple sclerosis. Self-injectable and oral drugs for immunotherapy]. / Immuntherapien und infektiologische Probleme bei Multipler Sklerose. Selbst injizierbare und orale Immuntherapeutika.

Immunotherapy is generally associated with an increased risk for the development of infections. Due to the continuously expanding spectrum of new and potent immunotherapy treatment options for multiple sclerosis (MS), this article describes the currently known risks for treatment-related infections and the current recommendations for prevention of corresponding problems with drugs used in treatment strategies for MS and their mechanisms of action. The new treatment options in particular are linked to specific and severe infections; therefore, intensive and long-lasting monitoring is required before, during and after treatment and multidisciplinary surveillance of patients is needed. This article gives a detailed review of drug-specific red flags and current recommendations for the prophylaxis of infections associated with treatment of relapsing-remitting MS and when using self-injectable and oral disease-modifying immunotherapeutic drugs.

[Current aspects of therapy conversion for multiple sclerosis]. / Aktuelles zur Therapieumstellung bei Multipler Sklerose.

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

Bacteria and their cell wall components uniformly co-activate interleukin-17-producing thymocytes.

Interleukin (IL)-17-producing T cells play a critical role in the immune response against microbial pathogens. Traditionally, experimental studies have focused upon understanding the activity of IL-17-producing T cells which differentiate from naive T cells in the peripheral immune system. However, we have demonstrated previously that IL-17-producing T cells are also present in the thymus of naive wild-type mice and can be co-activated there by microbial stimuli. Other studies have supported the concept that IL-17-producing thymocytes have a specific role in the immediate defence against microbial pathogens, which is independent from the development of an adaptive immune response. Given an important role of the thymus in systemic bacterial infection and sepsis, in this study we investigate the effect of a broad spectrum of bacteria and cell wall components on thymocyte cytokine production. Surprisingly, we find that all types of bacteria investigated (including non-pathogenic species) uniformly activate IL-17-producing thymocytes upon α-CD3 stimulation. In contrast, there is a heterogeneous effect on IL-6 and interferon (IFN)-γ-production with Gram-negative bacteria inducing far higher frequencies of IL-6- and IFN-γ-producing thymocytes than Gram-positive bacteria. We conclude that IL-17-producing thymocytes constitute a 'first line of recognition', but not a 'first line of defence' against bacteria in general. Their activity might lead to immune activation, but not necessarily to a pathological inflammatory disease condition. The difference between these two states might be determined by other immunological effector molecules, such as IL-6 and IFN-γ.

Requirement for safety monitoring for approved multiple sclerosis therapies: an overview.

During the last two decades, treatment options for patients with multiple sclerosis (MS) have broadened tremendously. All agents that are currently approved for clinical use have potential side effects, and a careful risk-benefit evaluation is part of a decision algorithm to identify the optimal treatment choice for an individual patient. Whereas glatiramer acetate and interferon beta preparations have been used in MS for decades and have a proven safety record, more recently approved drugs appear to be more effective, but potential risks might be more severe. The potential complications of some novel therapies might not even have been identified to their full extent. This review is aimed at the clinical neurologist in that it offers insights into potential adverse events of each of the approved MS therapeutics: interferon beta, glatiramer acetate, mitoxantrone, natalizumab, fingolimod and teriflunomide, as well as recently approved therapeutics such as dimethyl fumarate and alemtuzumab. It also provides recommendations for monitoring the different drugs during therapy in order to avoid common side effects.

Long-term impact of interferon beta-1b in patients with CIS: 8-year follow-up of BENEFIT.

OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 µg or placebo subcutaneously every other day. After 2 years or diagnosis of clinically definite MS (CDMS), all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years. Thereafter, patients were enrolled in an observational extension study for up to 8.7 years. RESULTS: Of the initial 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation period (HR 0.678; 95% CI 0.525 to 0.875; p=0.0030), a longer median time to CDMS by 1345 days (95% CI 389 to 2301), and a lower annualised relapse rate (0.196 (95% CI 0.176 to 0.218) versus 0.255 (95% CI 0.226 to 0.287), p=0.0012), with differences mainly emerging in the first year of the study. Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms. CONCLUSIONS: These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS.

Contribution of spinal cord biopsy to diagnosis of aquaporin-4 antibody positive neuromyelitis optica spectrum disorder.

Longitudinally extensive transverse myelitis is characteristic but not pathognomonic for neuromyelitis optica spectrum disorders (NMOSDs) and may mimic local tumors. In this retrospective study based on a cohort of 175 NMOSD patients we identified seven patients who initially presented with a longitudinally extensive spinal cord lesion and underwent spinal cord biopsy due to magnetic resonance imaging (MRI)-suspected malignancies. Remarkably, routine neuropathology was inconclusive and did not guide the diagnostic process to anti-aquaporin-4 (AQP4)-seropositive NMOSD. Serious postoperative complications occurred in 5/7 patients and persisted during follow-up in 2/7 patients (29%). Considering these sequelae, AQP4-antibody testing should be mandatory in patients with inconclusive longitudinally extensive spinal cord lesions prior to biopsy.