Moyamoya disease in Southeast Asians: genetic and autopsy data, new cases, systematic review, and meta-analysis of all patients from the literature.

BACKGROUND: Moyamoya disease (MMD) is a rare disorder causing ischemic and hemorrhagic juvenile stroke. It is associated with the founder susceptibility variant p.R4810K in the RNF213 gene in East Asia. Our aim was to enhance understanding of MMD in so far poorly characterized Southeast Asians and exploring differences with Caucasian Europeans. METHODS: By retrospective analysis of medical records and systematic database search on PubMed for all published cases, we identified Southeast Asian patients with MMD. We extracted and pooled proportions using fixed-effects models. Our own cohort was tested for the East Asian RNF213 founder variant p.R4810K. One of our Southeast Asian patients underwent post-mortem histopathological examination. RESULTS: The study cohort comprised 32 Southeast Asians. Mean age at onset in the entire cohort was 32.5 ± 20.3 years (n = 24), 43.4 ± 8.7 years in patients admitted to our center (n = 11), and 23.4 ± 22.4 years in patients from the international literature (n = 13). Female-to-male ratio was 1.6:1. MMD predominantly affected bilateral anterior intracranial vessels. Cerebral ischemia outnumbered transient ischemic attacks (TIAs) and intracranial hemorrhage. TIAs, arterial hypertension and obesity were significantly less frequent in Southeast Asian patients compared to Caucasian Europeans. p.R4810K was absent in all examined Southeast Asians despite of typical histopathological signs of MMD in one autopsy case. CONCLUSION: Clinical and histopathological manifestations of MMD in Southeast Asians are similar to those in Caucasian Europeans. The genotype of MMD in Southeast Asians differs from that of most East Asian patients.

Recommendations for optimal interdisciplinary management and healthcare settings for patients with rare neurological diseases.

BACKGROUND: In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts. METHODS: An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented. RESULTS: 38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy. CONCLUSIONS: This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.

Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome - an exploratory study.

BACKGROUND: Susac syndrome (SuS) is a rare autoimmune disease that leads to hearing impairment, visual field deficits, and encephalopathy due to an occlusion of precapillary arterioles in the brain, retina, and inner ear. Given the potentially disastrous outcome and difficulties in distinguishing SuS from its differential diagnoses, such as multiple sclerosis (MS), our exploratory study aimed at identifying potential new SuS-specific neuroimaging markers. METHODS: Seven patients with a definite diagnosis of SuS underwent magnetic resonance imaging (MRI) at 7 Tesla (7T), including T2* weighted and quantitative susceptibility mapping (QSM) sequences. T2 weighted hyperintense lesions were analyzed with regard to number, volume, localization, central vein sign, T1 hypointensity, and focal iron deposits in the center of SuS lesions ("iron dots"). Seven T MRI datasets from the same institute, comprising 75 patients with, among others, MS, served as controls. RESULTS: The "iron dot" sign was present in 71.4% (5/7) of the SuS patients, compared to 0% in our control cohort. Thus, sensitivity was 71.4% and specificity 100%. A central vein sign was only incidentally detected. CONCLUSION: We are the first to demonstrate this type of "iron dot" lesions on highly resolving 7T T2*w and QSM images in vivo as a promising neuroimaging marker of SuS, corroborating previous histopathological ex vivo findings.

Time to Disability Milestones and Annualized Relapse Rates in NMOSD and MOGAD.

OBJECTIVE: To investigate accumulation of disability in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) in a changing treatment landscape. We aimed to identify risk factors for the development of disability milestones in relation to disease duration, number of attacks, and age. METHODS: We analyzed data from individuals with NMOSD and MOGAD from the German Neuromyelitis Optica Study Group registry. Applying survival analyses, we estimated risk factors and computed time to disability milestones as defined by the Expanded Disability Status Score (EDSS). RESULTS: We included 483 patients: 298 AQP4-IgG+ NMOSD, 52 AQP4-IgG- /MOG-IgG- NMOSD patients, and 133 patients with MOGAD. Despite comparable annualized attack rates, disability milestones occurred earlier and after less attacks in NMOSD patients than MOGAD patients (median time to EDSS 3: AQP4-IgG+ NMOSD 7.7 (95% CI 6.6-9.6) years, AQP4-IgG- /MOG-IgG- NMOSD 8.7) years, MOGAD 14.1 (95% CI 10.4-27.6) years; EDSS 4: 11.9 (95% CI 9.7-14.7), 11.6 (95% lower CI 7.6) and 20.4 (95% lower CI 14.1) years; EDSS 6: 20.1 (95% CI 16.5-32.1), 20.7 (95% lower CI 11.6), and 37.3 (95% lower CI 29.4) years; and EDSS 7: 34.2 (95% lower CI 31.1) for AQP4-IgG+ NMOSD). Higher age at onset increased the risk for all disability milestones, while risk of disability decreased over time. INTERPRETATION: AQP4-IgG+ NMOSD, AQP4-IgG- /MOG-IgG- NMOSD, and MOGAD patients show distinctive relapse-associated disability progression, with MOGAD having a less severe disease course. Investigator-initiated research has led to increasing awareness and improved treatment strategies appearing to ameliorate disease outcomes for NMOSD and MOGAD. ANN NEUROL 2024.

A familial missense ACTA2 variant p.Arg198Cys leading to Moyamoya-like arteriopathy with straight course of the intracranial arteries, aortic aneurysm and lethal aortic dissection.

BACKGROUND: Cerebral vasculopathies frequently lead to severe medical conditions such as stroke or intracranial hemorrhage and have a broad range of possible etiologies that require different therapeutic regimens. However, vasculopathies sometimes present with characteristic angiographic findings, that - if recognized - can guide a more specific diagnostic work-up. Certain ACTA2 variants are associated with a distinctive cerebrovascular phenotype characterized by an anomalously straight course of intracranial arteries, dilatation of proximal ICA and stenosis of distal ICA, in the absence of a compensatory basal collateral network found in Moyamoya disease. Until recently, this ACTA2 cerebral arteriopathy has been reported only in ACTA2 variants impairing Arg179. METHODS AND MATERIALS: We report a familial case of a missense ACTA2 variant p.Arg198Cys with angiographic features of an ACTA2 cerebral arteriopathy. We analyzed the neuroimaging features of all four variant carrying family members and discussed the cerebrovascular abnormalities we found on the background of the current literature on ACTA2 arteriopathies. RESULTS: Neuroimaging of the variant carriers revealed angiographic abnormalities characteristic for ACTA2 cerebral arteriopathy such as stenoses of the terminal internal carotid artery, occlusion of the proximal middle cerebral artery and an anomalously straight course of the intracranial arteries. In our index patient catheter angiography showed a Moyamoya-like basal collateral network alongside with the above-mentioned features of an ACTA2 cerebral arteriopathy. The detected missense ACTA2 variant p.Arg198Cys was not known to be associated a cerebral arteriopathy, so far. One of the patients later died from aortic dissection - a common vascular complication of ACTA2 variants. CONCLUSION: The familial case expands the phenotype of the detected ACTA2 variant p.Arg198Cys and hereby broadens the range of ACTA2 variants associated with a cerebral arteriopathy. Further, it emphasizes the importance of an interdisciplinary approach of vasculopathies.

Progression of initially unilateral Moyamoya angiopathy in Caucasian Europeans.

BACKGROUND: Moyamoya angiopathy (MMA) is a rare cause of stroke in Caucasians, but it is much more frequent in East Asia. Since 2021, diagnostic criteria not only comprise bilateral, but also unilateral MMA. Hitherto, progression of unilateral MMA has predominantly been described in East Asians. Our study aimed to analyze the occurrence and characteristics of progression of initially unilateral MMA in Caucasian Europeans. METHODS: By retrospective analysis of medical records of 200 European Caucasians with MMA, admitted to our German center between 2010 and 2022, cases of unilateral MMA and its progression, i.e. progressive ipsi- or novel contralateral arterial stenosis, during follow-up were identified. Kruskal Wallis Test and Fisher's Exact Test were used to identify statistically significant differences between progressive and stable patients concerning demographic, clinical, laboratory, and radiographic features. RESULTS: Our cohort comprised 63 patients with initially unilateral MMA. Fourteen (22.2%) had an ipsi- (n = 3, 21.4%) or contralateral (n = 11, 78.6%) progression. Mean age of patients with progressive MMA at symptom onset was 32 ± 14.1 years. The ratio of women to men in this subgroup was 2.5:1. Mean follow-up period was 5.4 ± 3.7 years, mean age at progression was 39.9 ± 12.7 years. Mean time interval between penultimate follow-up and progression was 4.8 ± 4.5 years. Patients with progression showed affection of the posterior cerebral artery (p = 0.009) and suffered from vertigo (p = 0.009) significantly more often. CONCLUSION: Unilateral MMA progresses in a substantial proportion in European Caucasians. Long-term follow-up is required due to potential late progression with consecutive symptoms and the need for bypass surgery.

Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease.

Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses found the families were related, and ANO1 p.Met658Val segregated with moyamoya disease in the family with an LOD score of 3.3. Six additional ANO1 rare variants were identified in moyamoya disease families. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harbouring these gain-of-function ANO1 variants had classic features of moyamoya disease, but also had aneurysm, stenosis and/or occlusion in the posterior circulation. Our studies support that ANO1 gain-of-function pathogenic variants predispose to moyamoya disease and are associated with unique involvement of the posterior circulation.

European Stroke Organisation (ESO) Guidelines on Moyamoya angiopathy Endorsed by Vascular European Reference Network (VASCERN).

The European Stroke Organisation (ESO) guidelines on Moyamoya Angiopathy (MMA), developed according to ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, were compiled to assist clinicians in managing patients with MMA in their decision making. A working group involving neurologists, neurosurgeons, a geneticist and methodologists identified nine relevant clinical questions, performed systematic literature reviews and, whenever possible, meta-analyses. Quality assessment of the available evidence was made with specific recommendations. In the absence of sufficient evidence to provide recommendations, Expert Consensus Statements were formulated. Based on low quality evidence from one RCT, we recommend direct bypass surgery in adult patients with haemorrhagic presentation. For ischaemic adult patients and children, we suggest revascularization surgery using direct or combined technique rather than indirect, in the presence of haemodynamic impairment and with an interval of 6-12 weeks between the last cerebrovascular event and surgery. In the absence of robust trial, an Expert Consensus was reached recommending long-term antiplatelet therapy in non-haemorrhagic MMA, as it may reduce risk of embolic stroke. We also agreed on the utility of performing pre- and post- operative haemodynamic and posterior cerebral artery assessment. There were insufficient data to recommend systematic variant screening of RNF213 p.R4810K. Additionally, we suggest that long-term MMA neuroimaging follow up may guide therapeutic decision making by assessing the disease progression. We believe that this guideline, which is the first comprehensive European guideline on MMA management using GRADE methods will assist clinicians to choose the most effective management strategy for MMA.

Aptamers as Novel Binding Molecules on an Antimicrobial Peptide-Armored Composite Hydrogel Wound Dressing for Specific Removal and Efficient Eradication of Pseudomonas aeruginosa.

Here we present for the first time a potential wound dressing material implementing aptamers as binding entities to remove pathogenic cells from newly contaminated surfaces of wound matrix-mimicking collagen gels. The model pathogen in this study was the Gram-negative opportunistic bacterium Pseudomonas aeruginosa, which represents a considerable health threat in hospital environments as a cause of severe infections of burn or post-surgery wounds. A two-layered hydrogel composite material was constructed based on an established eight-membered focused anti-P. aeruginosa polyclonal aptamer library, which was chemically crosslinked to the material surface to form a trapping zone for efficient binding of the pathogen. A drug-loaded zone of the composite released the C14R antimicrobial peptide to deliver it directly to the bound pathogenic cells. We demonstrate that this material combining aptamer-mediated affinity and peptide-dependent pathogen eradication can quantitatively remove bacterial cells from the "wound" surface, and we show that the surface-trapped bacteria are completely killed. The drug delivery function of the composite thus represents an extra safeguarding property and thus probably one of the most important additional advances of a next-generation or smart wound dressing ensuring the complete removal and/or eradication of the pathogen of a freshly infected wound.

Effects of the COVID-19 Pandemic on Patients With NMO Spectrum Disorders and MOG-Antibody-Associated Diseases: COPANMO(G)-Study.

BACKGROUND AND OBJECTIVES: To evaluate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the life of patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). METHODS: This multicenter, cross-sectional study included data of 187 patients recruited from 19 different German and Austrian Neuromyelitis Optica Study Group (NEMOS) centers between July 2021 and March 2022. The effects of the pandemic on immunotherapeutic treatment and access to care, the possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of vaccination against SARS-CoV-2 on disease incidence and relapse risk were assessed using a patient questionnaire. Health-related quality of life (HRQoL) was measured with the EuroQoL Group 5-Dimension 5-Level Scale (EQ-5D-5L). Demographic and clinical characteristics were retrieved from the NEMOS database. RESULTS: One hundred eighty-seven patients (75% women; median age 47 [range 21-86] years; median disease duration 5.5 [range 0-67] years; median Expanded Disability Status Scale 2.0 [range 0-8.0]; 51% aquaporin-4 immunoglobulin G (AQP4-IgG)-positive, 36% myelin oligodendrocyte glycoprotein (MOG)-IgG-positive 13% double-seronegative) were analyzed. Most patients maintained excellent access to healthcare services throughout the pandemic. Immunotherapy was not changed in 88% of patients. Ninety-one percent of all patients were satisfied with medical care during the pandemic. Nearly two-thirds (64%) of patients rated their risk of infection with SARS-CoV-2 as low or moderate. Among this study sample, 23 patients (12%) knowingly acquired an infection with SARS-CoV-2 and predominantly had a nonsevere course of illness (n = 22/23, 96%). The SARS-CoV-2 vaccination rate was 89%, with 4 cases of confirmed attack or first manifestation of NMOSD/MOGAD occurring in temporal association with the vaccination (range 2-9 days). The reported HRQoL did not decline compared with a prepandemic assessment (mean EQ-5D-5L index value 0.76, 95% bootstrap confidence interval [CI] 0.72-0.80; mean EQ-VAS 66.5, 95% bootstrap CI 63.5-69.3). DISCUSSION: This study demonstrates that, overall, patients with NMOSD/MOGAD affiliated with specialized centers received ongoing medical care during the pandemic. Patients' satisfaction with medical care and HRQoL did not decrease.

How relevant are cerebral white matter lesions in the D313Y variant of the α-galactosidase A gene? Neurological, cardiological, laboratory, and MRI data of 21 patients within a follow-up of 3 years.

BACKGROUND: Fabry disease is an inherited metabolic disorder with various symptoms. Neurological manifestations are small fiber neuropathy, cerebral white matter lesions (WML), megadolicho basilar artery, and stroke. The relevance of the D313Y variant in the galactosidase alpha gene is controversially discussed. OBJECTIVES: We aimed at elucidating the implications of this differential diagnosis of multiple sclerosis (MS), focussing on the analysis of WML over time and correlations with other markers. METHODS: We reviewed retrospectively the clinical, laboratory, and magnetic resonance imaging data of 21 carriers of the D313Y variant at a single German outpatient clinic for MS between 2004 and 2021. RESULTS: In our cohort (15 females, 6 males), mean age at diagnosis was 44.1 ± 16.3 years, and mean follow-up duration was 3.1 ± 3.9 years. WML were rated on both, the Fazekas scale and the age-related white matter changes rating scale, and were of variable interindividual extent. Follow-up imaging showed virtually no progress. WML did not correlate with the severity of clinical findings or lysoGb3 levels. Symptomatic carriers of the variant are characterized by an almost complete lack of internal organ manifestations and laboratory findings, usually associated with Fabry disease. CONCLUSION: WML in carriers of the D313Y variant do not seem to be suitable for assessing or predicting the (para-) clinical status. Concerning MS patients, the variant and its clinical signs can be a differential diagnosis, but also a co-factor. Imaging and cerebrospinal fluid findings facilitate the distinction between both entities.

Profile of precipitating factors and its implication in 160 Indian patients with Moyamoya angiopathy.

INTRODUCTION: Moyamoya angiopathy (MMA) has been known to manifest with myriad of neurological manifestations, often in association with various precipitating factors. This is the first study to systematically analyze the precipitating triggers to neurological symptoms done on the largest cohort of MMA in India. METHODS: A single-centered, cross-sectional observational study, recruiting 160 patients with consecutive angiographically proven MMA over a period of 5 years (2016-2021), was undertaken to evaluate the profile of immediate precipitating factors in temporal association to the neurological symptoms, along with their clinical and radiological characteristics. SPSS 25 was used for statistical analysis. RESULTS: Among the 160 patients (Adult-85, children-75), precipitating factors were seen in 41.3%, significantly higher in children (52%) than adults (31.8%) (p value: 0.011). The commonest triggers included fever (18.8%), emotional stress (8.1%), heavy exercise and diarrhea (6.3% each). Cold bath triggered MMA symptoms in 1.3%. Fever (p value: 0.008) and persistent crying (p value: 0.010) triggered neurological symptoms more commonly in children than in adults. Amongst MMA patients with precipitating factors, the commonest MMA presentation included cerebral infarction type (37.9%) and TIA (31.8%). The majority of precipitating factors that preceded an ischemic event were BP-lowing ones (54.7%). CONCLUSION: Neurological symptoms of MMA are commonly associated with several precipitating factors, including the lesser known triggers like cold bath. The frequency and profile precipitating factors varies with the age of presentation and type of MMA. It can serve as an early clue to the diagnosis of MMA and its careful avoidance can be largely beneficial in limiting the distressing transient neurological symptoms.

Microembolic signals and antiplatelet therapy in Moyamoya angiopathy.

BACKGROUND: Embolism as a cause of stroke is widely neglected in Moyamoya angiopathy (MMA), and recommendations for use of antiplatelet therapy (APT) vary. We examined the presence of microembolic signals (MES) during transcranial Doppler (TCD) monitoring and assessed the effects of APT on the occurrence of MES in MMA. PATIENTS AND METHODS: We retrospectively analysed patients with MMA treated at our centre between 2011 and 2021. TCD was performed at first presentation and at most visits, while number of visits varied between individual patients. TCD was performed for 30 min bilaterally. Patient demographics, vascular risk factors, and antiplatelet treatment were collected from each clinic visit and ischemic and haemorrhagic episodes were captured as recorded during follow-up visits. RESULTS: 209 patients were included in the analysis (mean age 38.7 ± 15.3, 28% male). 21 patients with 27 MES-positive TCD examinations were identified (10%). Patient characteristics were similar in MES-positive and MES-negative groups. However, recent ischemic events were detected at a significantly higher rate in MES-positive patients (42.9% vs 4.8%, p < 0.001). After MES detection, change of antiplatelet drug regime was performed, leading to loss of MES in all cases. Dual APT was preferably used in the MES-positive group (p < 0.001) but no significant difference of haemorrhage during follow-up-visits was observed. Reduction of APT before bypass-surgery triggered MES in four patients. CONCLUSION: APT is required in patients with MMA. MES monitoring may help to identify risk patients in need of intensified APT.

Recovery of intracranial stenoses in varicella zoster virus vasculitis after long-term treatment with valacyclovir and prednisolone.

BACKGROUND AND PURPOSE: Optimal treatment of intracranial stenoses in varicella zoster virus (VZV)-associated vasculitis is unknown. This study aims to evaluate the merits and potential pitfalls of a specific therapeutic strategy, initially proposed by Don Gilden in 2015. METHODS: We describe three patients with intracranial stenoses caused by VZV vasculitis successfully treated by a long-term combination of valacyclovir and prednisolone. RESULTS: All three patients were young men suffering from stroke. Only one reported a first contact to VZV in adulthood. All three presented stenoses in the intracranial part of the internal carotid artery or the proximal segments of the middle cerebral artery as well as an elevated cell count and positive VZV antibody index in cerebrospinal fluid. They received a combination therapy regimen with prednisone and valacyclovir about a minimum of one year. Intracranial stenoses improved markedly in one and almost resolved completely in the other two patients. Side effects of corticosteroid treatment occurred in two patients. CONCLUSIONS: Long-term combination treatment with prednisone and valacyclovir proved to be effective in three young men suffering from intracranial stenosis due to VZV vasculitis.

Intra-arterial application of nimodipine in reversible cerebral vasoconstriction syndrome: a neuroradiological method to help differentiate from primary central nervous system vasculitis.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by a prolonged, but self-limiting segmental cerebral vasoconstriction. Neurological outcomes vary, but can be severe. The clinical hallmark of RCVS is thunderclap headache, which might come along with further neurological symptoms. Distinguishing RCVS from other entities, such as primary angiitis of the central nervous system (PACNS), is of utmost importance for appropriate therapy. The angiographic response to intra-arterial nimodipine application has been suggested as an additional diagnostic criterion for RCVS but confirmatory studies are limited. We aimed to evaluate the angiographic nimodipine test. METHODS: We reviewed retrospectively the clinical and imaging data of 13 RCVS patients, who were admitted to a single German neurological department between January 2013 and December 2020. RESULTS: Out of 13 patients diagnosed with RCVS, 4 patients underwent an angiographic nimodipine test. In all 4 patients cerebral vasoconstriction completely resolved during nimodipine application. Among the four patients with a positive test, there was one individual, in whom a response was detected after a delay of 60 min. In all patients, we found a complete resolution of cerebral vasoconstriction within 12 weeks. CONCLUSION: Our findings support the usefulness of the application of nimodipine in diagnosing RCVS. Prolonged angiographic observation of the vascular response after nimodipine injection is important.

MOG-antibody-associated longitudinal extensive myelitis after ChAdOx1 nCoV-19 vaccination.

This case report describes a 59-year-old man with myelin oligodendrocyte glycoprotein (MOG)-positive longitudinal extensive transverse myelitis (LETM) after being vaccinated with the COVID-19 vaccine ChAdOx1 nCoV-19. He presented with urinary retention, gait disturbance, hypoesthesia and brisk reflexes in his lower extremities without paresis. Due to the ineffectiveness of high-dose intravenous methylprednisolone, therapeutic plasma exchange was performed, gradually improving the patient's condition. Vaccination as a trigger for an excessive immunological response seems plausible, though unspecific for the ChAdOx1 nCoV-19 vaccine.

Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND OBJECTIVES: To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). METHODS: Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. RESULTS: Patients received TCZ for 23.8 months (median; interquartile range 13.0-51.1 months), with an IV dose of 8.0 mg/kg (median; range 6-12 mg/kg) every 31.6 days (mean; range 26-44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5-5) to 0 (range 0-0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0-5] to 0 [range 0-4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. DISCUSSION: This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.

[Diagnostics and treatment of giant cell arteritis]. / Diagnostik und Therapie der Riesenzellarteriitis.

Giant cell arteritis (GCA) is the most common idiopathic systemic vasculitis in the age group over 50 years. It requires prompt diagnostics and treatment to avoid severe complications, such as visual loss or stroke. The tendency to relapse makes a glucocorticoid (GC) treatment necessary for several years and sometimes lifelong, which increases the risk of GC-induced long-term side effects. Therefore, additive GC-sparing treatment is recommended in the majority of patients. For this purpose, the anti-IL­6 receptor antibody tocilizumab is available as an approved substance for subcutaneous application; alternatively, methotrexate (MTX) can be used (off-label).