Cerebellar ataxias (CAs) encompass a wide spectrum of genetic and sporadic origins, of which a portion is driven by immune-mediated pathomechanisms. While some patients harbor known autoantibodies, assisting diagnosis and treatment, many remain seronegative. Here, we identify synaptophysin (SYP) as an autoantigen in CA by serum IgG staining on primate tissue, combined with human protein array and cell-based assay (CBA). SYP is abundant in presynaptic vesicles and is transiently exposed on the cell surface. Out of 43 patients with CA with synaptic serum reactivity on cerebellar sections, SYP antibodies were identified by CBA in 2 patients. Exposure of human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons to patient’s IgG with SYP antibodies causes selective SYP accumulation at the presynaptic membrane. Patient’s IgG and SYP monoclonal antibody reduce neuronal populational activity recorded by multi-electrode array. Altogether, we identify SYP as an autoantigen for further stratifying patients with CA. Our functional experiments with SYP antibodies uncover a previously unrecognized mechanism of antibody-mediated synaptic dysfunction.

ObjectivesThe aim of this study was to analyze changes in hospital incidence cases and disease severity of autoantibody-associated autoimmune encephalitis (AE) during the COVID-19 pandemic compared with the prepandemic period.MethodsA retrospective multicenter study analyzed data from 24 centers within the German Network for Research on Autoimmune Encephalitis (GENERATE). Patients with a new diagnosis of definite antibody-positive autoimmune encephalitis from 2017 to 2022 were included and divided into prepandemic (2017-2019) and pandemic (2020-2022) periods.ResultsAmong 392 patients, 227 were diagnosed before and 165 during the pandemic (mean 9.5 vs 6.9 per site, p = 0.04). A reduction was observed in cases with antibodies to neuronal surface antigens (174 vs 122 cases; mean 7.3 vs 5.1 per site, p = 0.02), while cases with antibodies against intracellular antigens remained stable (p = 0.40). No differences were observed in disease severity, age, or sex distribution between periods.DiscussionThis study provides clinical data on antibody-positive AE before and during the COVID-19 pandemic. The findings do not support the hypothesis that SARS-CoV-2 infection triggers autoantibody-associated AE or increases disease severity.

INTRODUCTION:Susac syndrome is a rare disease affecting arterioles in the brain, retina and inner ear. There is uncertainty about a clinical benefit of adding intravenous immunoglobulins or immunosuppressants to corticosteroid maintenance treatment. METHODS:This restrospective study identified adult patients from case records who met crite-ria for probable or definite Susac syndrome. Patients with a sole manifestation of arterial wall hyperintensity (AWH) on retinal fluorescein angiography (RFA) were also included. All clinically symptomatic disease activity and clinically asymptomatic AWH on RFA within a 3-month period from first signs were summarized as one event. Following an event, immunosuppressive treatments in consecutive 3-month observation periods were recorded until the next event has occurred or the treatment was discontinued. RESULTS:Sixteen patients (9 female) were identified (mean age 34 years, range 2065 years). Median follow-up was 79 months (range 16-274 months). In a total of 69 observation periods in all patients, corticosteroids, IVIG, or both in combination, were applied with or without other immunosuppressants. Fewer events occurred in patients treated with IVIG (n = 6) compared to those treated with corticosteroids (n = 10) without statistical significance. Based on our data, a total of 126 observation periods would be required to obtain a statistically significant difference between both treatments, IVIG and corticosteroids. This corresponds to a total of 31.5 patient years needed for a prospective clinical trial. DISCUSSION:This retrospective analysis in patients with Susac syndrome provides a basis for future structured prospective studies. From our data, a prospective evaluation of an additional clinical benefit of IVIG maintenance therapy in relapse prevention is supported.

BACKGROUND AND OBJECTIVES:Comorbidities greatly influence the course of many diseases. However, systematic data on comorbidities in patients with autoimmune encephalitis (AE) are scarce. We aimed to characterize comorbidities in patients with common AE variants and assess their influence on outcome and occurrence of infectious complications. METHODS:This multicenter, retrospective cohort study analyzed adult patients with definite anti-N-methyl-d-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated-1 (LGI1), anti-contactin-associated protein-like-2 (CASPR2), and anti-immunoglobulin-like cell adhesion molecule-5 (IgLON5) AE registered by the GErman NEtwork for REsearch on AuToimmune Encephalitis between June 2004 and July 2023. Preexisting conditions (PECs), secondary diagnoses, and infectious complications documented during hospitalization were analyzed. Outcome was evaluated using a modified Rankin Scale (mRS), with unfavorable outcome defined as mRS >2 after a minimum of 12 months of follow-up. RESULTS:Among 308 patients with AE (144 NMDAR-AE, 98 LGI1-AE, 47 CASPR2-AE, and 19 IgLON5-AE), nearly half had cardiovascular and metabolic/endocrine, one-third neurologic, and one-fifth psychiatric comorbidities. Accompanying autoimmunity was observed in 12.7%. Univariable analysis showed that the presence of ≥3 PECs (OR 2.80, 95% CI 1.57-4.92), especially cardiovascular (OR 1.93, 95% CI 1.09-3.30) and psychiatric PECs (OR 3.84, 95% CI 1.96-7.31), was associated with unfavorable outcome. Multivariable regression analysis confirmed psychiatric PECs as independent risk factors (OR 4.55, 95% CI 1.99-10.60). During hospitalization, 13.6% of patients developed severe infections, although these were not associated with unfavorable outcome (OR 1.94, 95% CI 0.97-3.89). AE disease severity (OR 5.41, 95% CI 1.38-27.67) and intensive care unit admission emerged as the only independent predictors of severe infections (OR 20.76, 95% CI 7.02-75.10). DISCUSSION:As premorbid psychiatric conditions are main factors associated with unfavorable outcomes, these patients would highly benefit from integrated interdisciplinary treatment centers, or at least heightened awareness of these factors. Concomitant autoimmunity affecting other organs is frequent and should be sought. The risk of severe infections during the acute phase of AE is moderate and, given their lack of effect on outcome, should not justify withholding appropriate immunotherapy, even in elderly patients with comorbidities. Future prognostic models should incorporate comorbidities, particularly psychiatric ones, to enhance risk assessment and guide personalized care strategies.

BackgroundAnti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance.MethodsIgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method.ResultsThe median age at onset was 66 years (range: 54–75), disease duration 10 years (range: 15–156 months), and follow-up 25 months (range: 0–83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab.ConclusionOur findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.

Background/objective The use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria. Methods Retrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records. The expanded disability status scale (EDSS) was used to measure neurological disability and outcome. Results As of December 2022, we identified 15 NAT-PML cases in Austria; only 20% occurred after 2016, when increased vigilance commenced. Two patients did not survive acute PML, and an additional patient died five years later, yielding a mortality rate of 20%. Seizures occurred exclusively in patients with pronounced EDSS increase. Gadolinium (Gd)-enhancement on brain magnetic resonance imaging (MRI) on PML suspicion was associated with minor changes of post-PML neurological disability. Long-term follow-up of up to 132 months (median 76 months) was available in 11/15. The overall median EDSS increased from 3.5 at pre-PML to 6.5 at the last assessment. Regarding inflammatory MS-related disease activity during the observation period, one single individual experienced an MS relapse and another patient had two Gd-enhancing brain lesions. Three patients converted to progressive MS within three years from PML and the EDSS further increased in 6/11. Conclusions The number of NAT-PML cases is decreasing over time. While many patients accumulated severe persistent neurological deficits compared to pre-PML, inflammatory MS-related disease activity after PML recovery was rare.

Autoantibodies against contactin-associated protein 2 (Caspr2) not only induce limbic autoimmune encephalitis but are also associated with pain conditions. Here, we analyzed clinical data on pain in a large cohort of patients included into the German Network for Research in Autoimmune Encephalitis. Out of 102 patients in our cohort, pain was a frequent symptom (36% of all patients), often severe (63.6% of the patients with pain) and/or even the major symptom (55.6% of the patients with pain). Pain phenotypes differed between patients. Cluster analysis revealed two major phenotypes including mostly distal-symmetric burning pain and widespread pain with myalgia and cramps. Almost all patients had IgG4 autoantibodies and some additional IgG1, 2, and/or 3 autoantibodies, but IgG subclasses, titers, and presence or absence of intrathecal synthesis were not associated with the occurrence of pain. However, certain pre-existing risk factors for chronic pain like diabetes mellitus, peripheral neuropathy, or preexisting chronic back pain tended to occur more frequently in patients with anti-Caspr2 autoantibodies and pain. Our data show that pain is a relevant symptom in patients with anti-Caspr2 autoantibodies and support the idea of decreased algesic thresholds leading to pain. Testing for anti-Caspr2 autoantibodies needs to be considered in patients with various pain phenotypes.

Wiederkehrende Episoden entzündlicher Schädigungen des Sehnervs und des Rückenmarks sind als eigenständige Erkrankung schon aus historischen Überlieferungen bekannt. Im Jahr 2004 gelang die Identifikation des pathognomonischen, gegen Aquaporin‑4 auf Astrozyten gerichteten Antikörpers. Zugehörige klinische Manifestationen werden als Neuromyelitis-optica-Spektrum-Erkrankungen („neuromyelitis optica spectrum disorders“, NMOSD) zusammengefasst. Diagnostische Kriterien basieren auf der klinischen Präsentation sowie der Bildgebung und berücksichtigen den Antikörperstatus. Histologisch sind NMOSD durch eine primäre Schädigung der Astrozyten mit sekundärer Demyelinisierung charakterisiert. Nach Gabe von Methylprednisolon und evtl. Anwendung von Plasmapherese in der Akutsituation schließt sich die langdauernde Immunsuppression zur Schubprophylaxe an. Diese basiert auf B‑Zell-Depletion, Interleukin-6-Antagonismus oder Komplementhemmung. Klinisch ähnlich können sich Erkrankungen präsentieren, die mit Antikörpern gegen Myelin-Oligodendrozyten-Glykoprotein assoziiert sind („anti-MOG-antibody-associated diseases“, MOGAD). Hier kommt es zur primären entzündlichen Demyelinisierung im zentralen Nervensystem. Im Gegensatz zu mit Aquaporin-4-Antikörpern assoziierten NMOSD gibt es für MOGAD bisher keine kontrollierten Therapiestudien.

Introduction A contribution of neutrophil granulocytes to the pathogenesis of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) is recognized. Anti-CD20 treatments applied in these diseases are associated with infectious complications and neutropenia. No data is available about functional characteristics of neutrophils obtained from patients with anti-CD20 treatments. Methods In neutrophils isolated from 13 patients with anti-CD20 treatment (9 MS, 4 NMOSD), 11 patients without anti-CD20 treatment (9 MS, 2 NMOSD) and 5 healthy controls, we analyzed chemotaxis, production of reactive oxygen species (ROS), phagocytosis, and formation of neutrophil extracellular traps (NET) in vitro. Results Chemotaxis and ROS production were found unchanged between patients with and without anti-CD20 treatment or between patients and healthy controls. We found a higher proportion of non-phagocytosing cells in patients without anti-CD20 treatment compared to patients with anti-CD20 treatment and healthy controls. As compared to healthy controls, a higher proportion of neutrophils from patients without anti-CD20 treatments underwent NET formation, either unstimulated or stimulated with phorbol 12-myristate 3-acetate for 3 h. In about half of patients with anti-CD20 treatment (n = 7), NET formation of unstimulated neutrophils occurred already within 20 min of incubation. This was not observed in patients without anti-CD20 treatment and healthy controls. Conclusion Anti-CD20 treatment in MS and NMOSD patients does not alter chemotaxis and ROS production of neutrophils in vitro but might restore their impaired phagocytosis in these diseases. Our study reveals a predisposition to early NET formation in vitro of neutrophils obtained from patients with anti-CD20 treatment. This may contribute to associated risks of neutropenia and infections.

B-cell depleting therapies result in diminished humoral immunity following vaccination against COVID-19, but our understanding on the impact on cellular immune responses is limited. Here, we performed a detailed analysis of cellular immunity following mRNA vaccination in patients receiving B-cell depleting therapy using ELISpot assay and flow cytometry. Anti-SARS-CoV-2 spike receptor-binding domain antibody assays were performed to elucidate B-cell responses. To complement our cellular analysis, we performed immunophenotyping for T- and B-cell subsets. We show that SARS-CoV-2 vaccination using mRNA vaccines elicits cellular T-cell responses in patients under B-cell depleting therapy. Some facets of this immune response including TNFα production of CD4+ T-cells and granzyme B production of CD8+ T-cells, however, are distinctly diminished in these patients. Consequently, it appears that the finely coordinated process of T-cell activation with a uniform involvement of CD4+ and CD8+ T-cells as seen in HCs is disturbed in autoimmune patients. In addition, we observed that immune cell composition does impact cellular immunity as well as sustainability of anti-spike antibody titers. Our data suggest disturbed cellular immunity following mRNA vaccination in patients treated with B-cell depleting therapy. Immune cell composition may be an important determinant for vaccination efficacy.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.

The gold standard for detecting intrathecal immunoglobulin synthesis is the determination of the oligoclonal band (OCB) in the cerebrospinal fluid (CSF) using isoelectric focusing (IEF). Controversy still exists regarding the significance of an isolated band in the CSF. A highly promising alternative method for the assessment of intrathecal inflammation is the quantification of kappa free light chains (k-FLC). Our aim was to evaluate the clinical significance of quantitative k-FLC in patients with an isolated band in the CSF. Using the Human Kappa Freelite Mx Kit on a turbidimetric Optilite®, we quantified the k-FLCs in paired CSF and serum samples in 47 patients with a single band in IEF. We classified patients into 27× inflammatory neurological disorders (IND), 2× peripheral inflammatory neurological disorders (PIND), 9× non-inflammatory neurological disorders (NIND) and 9× symptomatic controls (SC) based on their medical diagnosis. k-FLC were below the lower measurement limit of the analyser (LML) in all SC and PIND, as well as in 8 out of 9 NIND and 11 IND. Only 1 NIND and 16 IND were above the LML, and of these, only 14 IND were above the upper discrimination limit (Qlim). A neuroinflammatory nature of the diseases can be indicated in many cases by positive k-FLC in patients with an isolated band in IEF. The measurement of k-FLC can support the diagnosis of neurological diseases if they are included in the routine work-up.

Zusammenfassung Die primäre Angiitis des Zentralnervensystems ist eine sehr seltene Erkrankung, welche durch eine entzündliche Infiltration der Gefäßwände von mittleren und kleinen Gefäßen ausschließlich im Zentralnervensystem, vorwiegend im Gehirn, gekennzeichnet ist. Klinisch und radiologisch kann sich die Erkrankung äußerst vielgestaltig präsentieren und stellt daher eine besondere diagnostische Herausforderung dar. Die häufigsten klinischen Manifestationen sind subakut auftretende Kopfschmerzen, enzephalopathische Zustandsbilder oder schlaganfallähnliche Episoden bei Auftreten von akuten zerebralen Ischämien oder Blutungen. Eine umfassende differenzialdiagnostische Abklärung ist nötig. Neben einer sorgfältigen Anamnese und klinischen Untersuchung stellen die zerebrale MRT, Lumbalpunktion, digitale Subtraktionsangiographie sowie weiterführend die Hirnbiopsie wichtige diagnostische Modalitäten dar. Vor Einleitung der notwendigen immunsuppressiven Therapie, welche zumeist aus Kortikosteroiden und Cyclophosphamid besteht, sollte eine histopathologische Diagnosesicherung erfolgen. Aufgrund der Seltenheit und Komplexität der Erkrankung und des individuellen Therapie- und Nachsorgekonzeptes soll die Betreuung (inkl. regelmäßigen klinischen Kontrollen) von PatientInnen mit primärer Angiitis des Zentralnervensystems an einem Zentrum mit entsprechender Erfahrung und Expertise erfolgen.

Background: Spinal cord infarction (SCI) is a neurological emergency associated with high rates of persistent neurological deficits. Knowledge about this rare but potentially treatable condition needs to be expanded. Objective: To describe the characteristics of spontaneous SCI in a large retrospective series of patients treated at two tertiary care centers in Austria. Methods: We performed a descriptive and comparative analysis of spontaneous SCI treated at the University Hospitals of Salzburg and Graz between the years 2000 and 2020. The analysis included pre- and in-hospital procedures, clinical presentation, etiology, diagnostic certainty, reperfusion therapy, and functional outcome at discharge. Results: We identified 88 cases, 61% were ascertained in the second half of the study period. The median age was 65.5 years [interquartile range (IQR) = 56–74], 51.1% were women. Anterior spinal artery infarction was the predominant syndrome (82.9%). Demographics, vascular comorbidities, and clinical presentation did not differ between the centers. The most frequent etiology and level of diagnostic certainty were distinct, with atherosclerosis (50%) and definite SCI (42%), and unknown (52.5%) and probable SCI (60%) as front runners in Salzburg and Graz, respectively. Patients arrived after a median of 258.5 min (IQR = 110–528) at the emergency room. The first magnetic resonance imaging (MRI) of the spinal cord was performed after a median of 148 min (IQR = 90–312) from admission and was diagnostic for SCI in 45%. Two patients received intravenous thrombolysis (2.2%). The outcome was poor in 37/77 (48%). Conclusion: Demographics, clinical syndromes, and quality benchmarks for spontaneous SCI were consistent at two Austrian tertiary care centers. Our findings provide the foundation for establishing standards for pre- and in-hospital care to improve outcomes.

BACKGROUND AND OBJECTIVES:Anti-IgLON5 disease is a recently described neurologic disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are underreported. We describe the frequency and types of movement disorders in a series of consecutive patients with this disease.METHODS:In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by 3 experts in movement disorders.RESULTS:Seventy-two patients were included. In 41 (57%), the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least 1 movement disorder with a median of 3 per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients [72%]), chorea (24 [33%]), bradykinesia (20 [28%]), dystonia (19 [26%]), abnormal body postures or rigidity (18 [25%]), and tremor (15 [21%]). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients [32%]) including dystonia (13), myorhythmia (6), chorea (4), or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31 (43%) patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only 7 (13%) cases.DISCUSSION:Movement disorders are a frequent and leading cause of initial neurologic consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment.

Background:Prospective observations of functional recovery are lacking in patients with autoimmune encephalitis defined by antibodies against synaptic proteins and neuronal cell surface receptors.Methods:Adult patients with a diagnosis of autoimmune encephalitis were included into a prospective registry. At 3, 6 and 12 months of follow-up, the patients' modified Rankin Scale (mRS) was obtained.Results:Patients were stratified into three groups according to their antibody (Ab) status: anti-NMDAR-Ab (n=12; group I), anti-LGI1/CASPR2-Ab (n=35; group II), and other antibodies (n=24; group III). A comparably higher proportion of patients in group I received plasma exchange/immunoadsorption and second line immunosuppressive treatments at baseline. A higher proportion of patients in group II presented with seizures. Group III mainly included patients with anti-GABABR-, anti-GAD65- and anti-GlyR-Ab. At baseline, one third of them had cancer. Patients in groups I and III had much higher median mRS scores at 3 months compared to patients in group II. A median mRS of 1 was found at all follow-up time points in group II.Conclusions:The different dynamics in the recovery of patients with certain autoimmune encephalitides have important implications for clinical trials. The high proportion of patients with significant disability at 3 months after diagnosis in groups I and III points to the need for improving treatment options. More distinct scores rather than the mRS are necessary to differentiate potential neurological improvements in patients with anti-LGI1-/CASPR2-encephalitis.

Zusammenfassung Hochwirksame krankheitsmodifizierende Therapien der multiplen Sklerose sind mit einem allgemein höheren Risiko für Infektionserkrankungen verbunden. Darüber hinaus bestehen substanzspezifische Risiken. Unter Anti-CD20-Therapien ist die Reaktivierung einer Hepatitis-B-Infektion möglich. Die Reaktivierung einer Tuberkulose ist vor der Anwendung von Teriflunomid, Cladribin und Alemtuzumab zu berücksichtigen. Zur Risikostratifizierung des Auftretens einer progressiven multifokalen Leukenzephalopathie unter Therapie mit Natalizumab ist der Anti-JCV-Antikörperindex etabliert. Eine Vorbeugung von Varizella-zoster-Virus- (VZV-)Infektionen ist für eine Therapie mit Fingolimod, Cladribin und Alemtuzumab erforderlich. Vor Beginn einer hochwirksamen krankheitsmodifizierenden Therapie sollen ausständige Impfungen verabreicht werden, dabei müssen Lebendimpfungen, wie z. B. gegen VZV, mindestens 4 Wochen vor Therapiebeginn appliziert werden. Unter Therapie können nur Totimpfstoffe verwendet werden, deren Impferfolg reduziert ist. In der aktuellen COVID-19-Pandemie gehören Patient(inn)en mit hochwirksamen krankheitsmodifizierenden Therapien zur Risikogruppe. Die aktuell (Stand Januar 2021) gegen SARS-CoV‑2 zugelassenen Impfstoffe sind unter diesen Therapien anwendbar.

Bei der limbischen Enzephalitis handelt es sich um ein neuropsychiatrisches Syndrom, das hauptsächlich durch eine Inflammation der anatomischen Strukturen des limbischen Systems (Hippocampus, Amygdala, Hypothalamus, Gyrus cinguli, limbischer Kortex), aber auch von anderen Hirnregionen entsteht. Diese immunmediierten Enzephalitiden beinhalten die klassischen paraneoplastischen Enzephalitiden assoziiert mit onkoneuronalen Antikörpern und die autoimmunen Enzephalitiden mit Antikörpern gegen neuronale Oberflächen-/synaptische Proteine. Autoimmune Enzephalitiden (AE) galten bisher als seltene Erkrankungen. Neuere epidemiologische Studien zeigen aber einen Anstieg der Prävalenz und der Inzidenz durch bessere Diagnostik. Etwa 1/3 der Patienten mit einer AE werden primär auf einer psychiatrischen Station aufgenommen. 2/3 der Patienten zeigen psychotische Symptome am Anfang ihrer Erkrankung. Da eine frühe Diagnose einen bedeutsamen Einfluss auf die Prognose der Erkrankung hat, ist die multidisziplinäre Zusammenarbeit zwischen Neurologie und Psychiatrie entscheidend. In diesem Bericht soll ein Überblick über dieses Syndrom erzielt und im Anschluss daran zwei Fallbeschreibungen dargestellt werden.