Management of Autoimmune Encephalitis: An Observational Monocentric Study of 38 Patients

Over the last years the clinical picture of autoimmune encephalitis has gained importance in neurology. The broad field of symptoms and syndromes poses a great challenge in diagnosis for clinicians. Early diagnosis and the initiation of the appropriate treatment is the most relevant step in the management of the patients. Over the last years advances in neuroimmunology have elucidated pathophysiological basis and improved treatment concepts. In this monocentric study we compare demographics, diagnostics, treatment options and outcomes with knowledge from literature. We present 38 patients suffering from autoimmune encephalitis. Antibodies were detected against NMDAR and LGI1 in seven patients, against GAD in 6 patients) one patient had coexisting antibodies against GABAA and GABAB), against CASPR2, IGLON5, YO, Glycine in 3 patients, against Ma-2 in 2 patients, against CV2 and AMPAR in 1 patient; two patients were diagnosed with hashimoto encephalitis with antibodies against TPO/TG. First, we compare baseline data of patients who were consecutively diagnosed with autoimmune encephalitis from a retrospective view. Further, we discuss when to stop immunosuppressive therapy since how long treatment should be performed after clinical stabilization or an acute relapse is still a matter of debate. Our experiences are comparable with data from literature. However, in contrary to other experts in the field we stop treatment and monitor patients very closely after tumor removal and after rehabilitation from first attack

Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance

In 70-80% of cases, neuromyelitis optica (NMO) is associated with highly specific serum auto-antibodies to aquaporin-4 (termed AQP4-Ab or NMO-IgG). Recent evidence strongly suggests that AQP4-Ab are directly involved in the immunopathogenesis of NMO

Detection Methods for Autoantibodies in Suspected Autoimmune Encephalitis

This review provides an overview on different antibody test methods that can be applied in cases of suspected paraneoplastic neurological syndromes (PNS) and anti-neuronal autoimmune encephalitis (AIE) in order to explain their diagnostic value, describe potential pitfalls and limitations, and discuss novel approaches aimed at discovering further autoantibodies. Onconeuronal antibodies are well-established biomarkers for PNS and may serve as specific tumor markers. The recommended procedure to detect onconeuronal antibodies is a combination of indirect immunohistochemistry on fixed rodent cerebellum and confirmation of the specificity by line assays. Simplification of this approach by only using line assays with recombinant proteins bears the risk to miss antibody-positive samples. Anti-neuronal surface antibodies are sensitive and specific biomarkers for AIE. Their identification requires the use of test methods that allow the recognition of conformation dependent epitopes. These commonly include cell-based assays and tissue based assays with unfixed rodent brain tissue. Tissue based assays can detect most of the currently known neuronal surface antibodies and thus enable broad screening of biological samples. A complementary testing on live neuronal cell cultures may confirm that the antibody recognizes a surface epitope. In patients with peripheral neuropathy, the screening may be expanded to teased nerve fibers to identify antibodies against the node of Ranvier. This method helps to identify a novel subgroup of peripheral autoimmune neuropathies, resulting in improved immunotherapy of these patients. Tissue based assays are useful to discover additional autoantibody targets that play a role in diverse autoimmune neurological syndromes. Antibody screening assays represent promising avenues of research to improve the diagnostic yield of current assays for antibody-associated autoimmune encephalitis

Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

BACKGROUND: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjogren's syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation. OBJECTIVES: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms. METHODS: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) (n = 54), possible CTD (n = 42), or vasculitis (n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4. RESULTS: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON (n = 69). CONCLUSION: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients

Management of secondary progressive multiple sclerosis: prophylactic treatment-past, present, and future aspects.

Whereas the number of treatment options in relapsing-remitting multiple sclerosis (RRMS) is growing constantly, alternatives are rare in the case of secondary-progressive multiple sclerosis (SPMS). Besides mitoxantrone in North America and Europe, interferon beta-1b and beta-1a are approved for treatment in Europe. Glucocorticosteroids, azathioprine, intravenous immunoglobulins (IVIG) and cyclophosphamide (CYC), although not approved, are commonly utilized in SPMS. Currently monoclonal antibodies (mab), and masitinib are under examination for treatment for SPMS. Hematopoietic stem cell transplantation and immunoablative stem cell transplantation are therapies with the aim of reconstitution of the immune system. This review gives information on the different therapeutics and the trials that tested them. Pathophysiological considerations are presented in view of efficacy of the therapeutics. In addition, therapeutics that showed no efficacy in trials or with unacceptable side effects are topics of this review

Immunosenescence in Neurological Diseases—Is There Enough Evidence?

The aging of the immune system has recently attracted a lot of attention. Immune senescence describes changes that the immune system undergoes over time. The importance of immune senescence in neurological diseases is increasingly discussed. For this review, we considered studies that investigated cellular changes in the aging immune system and in neurological disease. Twenty-six studies were included in our analysis (for the following diseases: multiple sclerosis, stroke, Parkinson’s disease, and dementia). The studies differed considerably in terms of the patient groups included and the cell types studied. Evidence for immunosenescence in neurological diseases is currently very limited. Prospective studies in well-defined patient groups with appropriate control groups, as well as comprehensive methodology and reporting, are essential prerequisites to generate clear insights into immunosenescence in neurological diseases

Patients characteristics influencing the longitudinal utilization of steroids in multiple sclerosis--an observational study.

Multiple Sclerosis is the most common disease in young adults affecting the central nervous system. Disease may progress with acute attacks (relapsing MS) or continuously (progressive MS). Glucocorticosteroids are used in the treatment of acute attacks. The aim of this study was to analyse characteristics of patients with MS, and their influence on current treatment patterns of relapses with glucocorticosteroids.In 2001, the German National MS Society initiated the German MS-Registry. Patients with relapsing MS were included (n = 5106) from this registry. Logistic regression models were used to detect trends over time. The likelihood of administration of steroids is modelled in dependence of calendar year and in dependence to confounders in treatment conditions. The sample size allows that odds ratios can be detected with a power of 90% (alpha = 0.05).Administration of glucocorticosteroids was influenced by EDSS (P < 0.0001), age (P < 0.0001) and disease duration (P < 0.0001). Therapy administration in an outpatient setting was more likely in patients with higher EDSS (P < 0.0001) and longer disease duration (P < 0.0001). The utilization of glucocorticosteroids increased with higher EDSS for all relapsing patients. Interestingly, all overutilization of glucocorticosteroids decreased over time and was accompanied by a steadily increased administration of emergent therapeutics. Although there are about 70% of registered patients with relapsing MS on immune-modulatory treatment, almost 60% of them received glucocorticosteroids for treatment of relapses.Treatment patterns with glucocorticosteroids in patients with MS are influenced mainly by EDSS and disease duration. The decline in the utilization of glucocorticosteroids is accompanied by an increase in natalizumab treatment

Multiple Sclerosis and SARS-CoV-2 Vaccination: Considerations for Immune-Depleting Therapies

Several concerns have been raised about the use of immunodepleting agents including alemtuzumab, cladribine and CD20-depleting antibodies in people with multiple sclerosis (pwMS) during the coronavirus disease (COVID) 2019 pandemic. As the end of the pandemic is not yet in sight, vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) may be an elegant strategy to overcome the potential hazards associated with initiating and continuing treatment with immune-depleting agents. In this review, we summarize the immunological effects of immune-depleting therapy and underlying considerations for the hitherto existing recommendations that suggest a restricted use of immune-deleting therapies during the pandemic. Moreover, we critically discuss open questions regarding vaccination in general and against SARS-CoV-2 in pwMS

Multiple Sclerosis and SARS-CoV-2 Vaccination: Considerations for Immune-Depleting Therapies

Several concerns have been raised about the use of immunodepleting agents including alemtuzumab, cladribine and CD20-depleting antibodies in people with multiple sclerosis (pwMS) during the coronavirus disease (COVID) 2019 pandemic. As the end of the pandemic is not yet in sight, vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) may be an elegant strategy to overcome the potential hazards associated with initiating and continuing treatment with immune-depleting agents. In this review, we summarize the immunological effects of immune-depleting therapy and underlying considerations for the hitherto existing recommendations that suggest a restricted use of immune-deleting therapies during the pandemic. Moreover, we critically discuss open questions regarding vaccination in general and against SARS-CoV-2 in pwMS