The Use of Nitrosative Stress Molecules as Potential Diagnostic Biomarkers in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) of still unclear etiology. In recent years, the search for biomarkers facilitating its diagnosis, prognosis, therapy response, and other parameters has gained increasing attention. In this regard, in a previous meta-analysis comprising 22 studies, we found that MS is associated with higher nitrite/nitrate (NOx) levels in the cerebrospinal fluid (CSF) compared to patients with non-inflammatory other neurological diseases (NIOND). However, many of the included studies did not distinguish between the different clinical subtypes of MS, included pre-treated patients, and inclusion criteria varied. As a follow-up to our meta-analysis, we therefore aimed to analyze the serum and CSF NOx levels in clinically well-defined cohorts of treatment-naïve MS patients compared to patients with somatic symptom disorder. To this end, we analyzed the serum and CSF levels of NOx in 117 patients (71 relapsing-remitting (RR) MS, 16 primary progressive (PP) MS, and 30 somatic symptom disorder). We found that RRMS and PPMS patients had higher serum NOx levels compared to somatic symptom disorder patients. This difference remained significant in the subgroup of MRZ-negative RRMS patients. In conclusion, the measurement of NOx in the serum might indeed be a valuable tool in supporting MS diagnosis.

Immune Checkpoint Inhibition-Related Myasthenia-Myositis-Myocarditis Responsive to Complement Blockade.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but come with immune-related adverse events (irAEs) that provide a novel challenge for treating physicians. Neuromuscular irAEs, including myositis, myasthenia gravis (MG), and demyelinating polyradiculoneuropathy, lead to significant morbidity and mortality. METHODS: We present a case of severe myasthenia-myositis-myocarditis overlap in a patient receiving ICIs for breast cancer. Clinical findings were recorded. RESULTS: A 47-year-old woman developed tetraparesis, dysphagia, and muscle pain during ICI treatment. MG with a thymoma had been diagnosed earlier. Neuromuscular overlap irAEs with cardiac affection was confirmed, and ICI treatment was discontinued. Given a lack of clinical response to standard therapies, a muscle biopsy was performed demonstrating complement deposition. Eculizumab treatment led to rapid improvement in muscle strength and cardiac function. DISCUSSION: Neuromuscular irAEs are associated with a high in-hospital mortality, and specific treatment strategies remain an unmet need. Here, early muscle biopsy enabled targeted therapy after standard approaches failed, thereby highlighting the value of identifying a specific treatment target. To improve therapeutic outcomes, the development of patient-tailored strategies for neuromuscular irAEs requires further studies.