Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized MG requires increasingly differentiated therapeutic strategies that consider the enormous therapeutic developments of recent years. To include the newest therapy recommendations, a comprehensive update of the available German-language guideline ‘Diagnostics and therapy of myasthenic syndromes’ has been published by the German Neurological society with the aid of an interdisciplinary expert panel. This paper is an adapted translation of the updated and partly newly developed treatment guideline. It defines the rapid achievement of complete disease control in myasthenic patients as a central treatment goal. The use of standard therapies, as well as modern immunotherapeutics, is subject to a staged regimen that takes into account autoantibody status and disease activity. With the advent of modern, fast-acting immunomodulators, disease activity assessment has become pivotal and requires evaluation of the clinical course, including severity and required therapies. Applying MG-specific scores and classifications such as Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Foundation of America allows differentiation between mild/moderate and (highly) active (including refractory) disease. Therapy decisions must consider age, thymic pathology, antibody status, and disease activity. Glucocorticosteroids and the classical immunosuppressants (primarily azathioprine) are the basic immunotherapeutics to treat mild/moderate to (highly) active generalized MG/young MG and ocular MG. Thymectomy is indicated as a treatment for thymoma-associated MG and generalized MG with acetylcholine receptor antibody (AChR-Ab)-positive status. In (highly) active generalized MG, complement inhibitors (currently eculizumab and ravulizumab) or neonatal Fc receptor modulators (currently efgartigimod) are recommended for AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase (MuSK)-Ab-positive status. Specific treatment for myasthenic crises requires plasmapheresis, immunoadsorption, or IVIG. Specific aspects of ocular, juvenile, and congenital myasthenia are highlighted. The guideline will be further developed based on new study results for other immunomodulators and biomarkers that aid the accurate measurement of disease activity.

Background: Large language models (LLMs) have demonstrated impressive performances in various medical domains, prompting an exploration of their potential utility within the high-demand setting of emergency department (ED) triage. This study evaluated the triage proficiency of different LLMs and ChatGPT, an LLM-based chatbot, compared to professionally trained ED staff and untrained personnel. We further explored whether LLM responses could guide untrained staff in effective triage. Objective: This study aimed to assess the efficacy of LLMs and the associated product ChatGPT in ED triage compared to personnel of varying training status and to investigate if the models’ responses can enhance the triage proficiency of untrained personnel. Methods: A total of 124 anonymized case vignettes were triaged by untrained doctors; different versions of currently available LLMs; ChatGPT; and professionally trained raters, who subsequently agreed on a consensus set according to the Manchester Triage System (MTS). The prototypical vignettes were adapted from cases at a tertiary ED in Germany. The main outcome was the level of agreement between raters’ MTS level assignments, measured via quadratic-weighted Cohen κ. The extent of over- and undertriage was also determined. Notably, instances of ChatGPT were prompted using zero-shot approaches without extensive background information on the MTS. The tested LLMs included raw GPT-4, Llama 3 70B, Gemini 1.5, and Mixtral 8x7b. Results: GPT-4–based ChatGPT and untrained doctors showed substantial agreement with the consensus triage of professional raters (κ=mean 0.67, SD 0.037 and κ=mean 0.68, SD 0.056, respectively), significantly exceeding the performance of GPT-3.5–based ChatGPT (κ=mean 0.54, SD 0.024; P<.001). When untrained doctors used this LLM for second-opinion triage, there was a slight but statistically insignificant performance increase (κ=mean 0.70, SD 0.047; P=.97). Other tested LLMs performed similar to or worse than GPT-4–based ChatGPT or showed odd triaging behavior with the used parameters. LLMs and ChatGPT models tended toward overtriage, whereas untrained doctors undertriaged. Conclusions: While LLMs and the LLM-based product ChatGPT do not yet match professionally trained raters, their best models’ triage proficiency equals that of untrained ED doctors. In its current form, LLMs or ChatGPT thus did not demonstrate gold-standard performance in ED triage and, in the setting of this study, failed to significantly improve untrained doctors’ triage when used as decision support. Notable performance enhancements in newer LLM versions over older ones hint at future improvements with further technological development and specific training.

Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, we demonstrate oligoclonal expansion of terminally differentiated activated cytotoxic CD8⁺T cells (CTLs). Neuropathological data derived from both SuS patients and a newly-developed transgenic mouse model recapitulating the disease indicate that CTLs adhere to CNS microvessels in distinct areas and polarize granzyme B, which most likely results in the observed endothelial cell injury and microhemorrhages. Blocking T-cell adhesion by anti-α4 integrin-intervention ameliorates the disease in the preclinical model. Similarly, disease severity decreases in four SuS patients treated with natalizumab along with other therapy. Our study identifies CD8⁺T-cell-mediated endotheliopathy as a key disease mechanism in SuS and highlights therapeutic opportunities.

Objective To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic. Methods In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020). Results Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09–13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695–2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19⁺ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19⁺ B-cell repopulation. Conclusion Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic. Classification of Evidence This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.

(1) Background: Dysphagia is a clinical hallmark and part of the current American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) diagnostic criteria for idiopathic inflammatory myopathy (IIM). However, the data on dysphagia in IIM are heterogenous and partly conflicting. The aim of this study was to conduct a systematic review on epidemiology, pathophysiology, outcome and therapy and a meta-analysis on the prevalence of dysphagia in IIM. (2) Methods: Medline was systematically searched for all relevant articles. A random effect model was chosen to estimate the pooled prevalence of dysphagia in the overall cohort of patients with IIM and in different subgroups. (3) Results: 234 studies were included in the review and 116 (10,382 subjects) in the meta-analysis. Dysphagia can occur as initial or sole symptom. The overall pooled prevalence estimate in IIM was 36% and with 56% particularly high in inclusion body myositis. The prevalence estimate was significantly higher in patients with cancer-associated myositis and with NXP2 autoantibodies. Dysphagia is caused by inflammatory involvement of the swallowing muscles, which can lead to reduced pharyngeal contractility, cricopharyngeal dysfunction, reduced laryngeal elevation and hypomotility of the esophagus. Swallowing disorders not only impair the quality of life but can lead to serious complications such as aspiration pneumonia, thus increasing mortality. Beneficial treatment approaches reported include immunomodulatory therapy, the treatment of associated malignant diseases or interventional procedures targeting the cricopharyngeal muscle such as myotomy, dilatation or botulinum toxin injections. (4) Conclusion: Dysphagia should be included as a therapeutic target, especially in the outlined high-risk groups.

Objectives To evaluate prevalence, clinical characteristics, and predictors of pain, depression, and their impact on the quality of life (QoL) in a large neuromyelitis optica spectrum disorder (NMOSD) cohort. Methods We included 166 patients with aquaporin-4–seropositive NMOSD from 13 tertiary referral centers. Patients received questionnaires on demographic and clinical characteristics, PainDetect, short form of Brief Pain Inventory, Beck Depression Inventory–II, and Short Form 36 Health Survey. Results One hundred twenty-five (75.3%) patients suffered from chronic NMOSD-associated pain. Of these, 65.9% had neuropathic pain, 68.8% reported spasticity-associated pain and 26.4% painful tonic spasms. Number of previous myelitis attacks (OR = 1.27, p = 0.018) and involved upper thoracic segments (OR = 1.31, p = 0.018) were the only predictive factors for chronic pain. The latter was specifically associated with spasticity-associated pain (OR = 1.36, p = 0.002). More than a third (39.8%) suffered from depression, which was moderate to severe in 51.5%. Pain severity (OR = 1.81, p < 0.001) and especially neuropathic character (OR = 3.44, p < 0.001) were associated with depression. Pain severity and walking impairment explained 53.9% of the physical QoL variability, while depression and walking impairment 39.7% of the mental QoL variability. No specific medication was given to 70.6% of patients with moderate or severe depression and 42.5% of those with neuropathic pain. Two-thirds (64.2%) of patients with symptomatic treatment still reported moderate to severe pain. Conclusions Myelitis episodes involving upper thoracic segments are main drivers of pain in NMOSD. Although pain intensity was lower than in previous studies, pain and depression remain undertreated and strongly affect QoL. Interventional studies on targeted treatment strategies for pain are urgently needed in NMOSD.