Investigators examined whether circulating blood biomarkers might help explain fatigue in acetylcholine receptor–positive myasthenia gravis (MG). Among 116 patients, fatigue was very common, with nearly two-thirds meeting criteria for severe fatigue. Fatigue was associated with greater MG severity and more depressive symptoms. However, the main biomarker finding was a positive correlation between fatigue and C-reactive protein (CRP), even though CRP levels were generally only mildly elevated and not linked to MG disease severity itself. Fatigue was also negatively associated with hemoglobin, consistent with the known contribution of anemia to fatigue. Most other tested biomarkers, including AChR antibody levels, complement measures, and many cytokines, were not associated with fatigue.

The authors interpret these findings as suggesting that chronic low-grade inflammation may contribute to fatigue in MG, similar to what has been observed in other autoimmune diseases and in the general population. However, CRP did not predict future fatigue, and the CRP-fatigue association was not clearly replicated at the second study visit, likely because of lower statistical power and some data limitations. The study therefore supports low-grade inflammation as one possible part of fatigue pathophysiology in MG, but not the whole explanation. Overall, the authors conclude that fatigue in MG is likely multifactorial, with inflammation, disease burden, mood symptoms, and other patient factors all playing a role.

Reference: Ruiter AM, van Meijgaarden KE, Joosten SA, et al. Correlation of C-Reactive Protein With Severe Fatigue in Patients With Myasthenia Gravis. Neurol Neuroimmunol Neuroinflamm. 2025;12(6):e200468. doi: 10.1212/NXI.0000000000200468.

Authors of this review describe how genomic technologies such as genome-wide association studies (GWAS) and next-generation sequencing (NGS) have expanded understanding of neurodegenerative disease genetics, with a particular focus on amyotrophic lateral sclerosis (ALS). GWAS has been useful for identifying common risk variants. NGS has made it possible to detect rarer, higher-impact variants, supporting the view that both common and rare genetic changes contribute to complex disease. In ALS, this work has helped define key familial and sporadic disease genes, including SOD1, FUS, TARDBP, and C9orf72. It has further clarified major pathogenic pathways such as RNA dysregulation, protein aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, and excitotoxicity. These discoveries have also strengthened the push toward genotype-based stratification and precision medicine in ALS, where treatment may increasingly be tailored to the patient’s specific mutation.

The review also highlights how genetics is shaping ALS biomarker and therapy development. Gene-targeted therapies such as antisense oligonucleotides, RNA interference, and viral gene-delivery approaches are already being tested or used in mutation-defined ALS, including approved and investigational therapies aimed at SOD1, FUS, ATXN2, and other targets. In parallel, blood-based biomarkers such as neurofilament light chain and SOD1-related measures, as well as regulatory RNAs such as microRNAs and long noncoding RNAs, are being studied for earlier diagnosis, prognosis, patient stratification, and therapeutic targeting. MicroRNAs may help reflect disease activity and progression, while long noncoding RNAs may influence motor neuron development, degeneration, and autophagy pathways. Overall, the authors conclude that genetic discoveries are opening new avenues for earlier diagnosis and precision therapy in ALS. However, major challenges remain, including blood-brain barrier delivery, model development, biomarker validation, and translating RNA-based strategies into routine clinical care.

Reference: Ruffo P, Traynor BJ, Conforti FL. Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects. J Neurol. 2025;272(3):233. doi: 10.1007/s00415-025-12975-8.

Authors of this case report describe a 30-year-old woman with biopsy-confirmed idiopathic small fiber neuropathy whose symptoms began abruptly after a viral upper respiratory infection and recurred over time in a relapsing-remitting pattern. Her manifestations included distal numbness, lancinating pain, allodynia, erythromelalgia, and severe sensory discomfort without motor or autonomic involvement. Extensive testing for known causes was unrevealing, supporting an idiopathic diagnosis, yet the clinical course strongly suggested an immune-mediated process. Early episodes responded dramatically to prednisone, with complete remissions lasting months to years. Later flares were often temporally associated with viral infections, pregnancy, miscarriage, or vaccination. Serial symptom tracking and skin biopsy findings supported true disease fluctuation rather than a fixed or degenerative process.

The patient’s treatment responses further pointed toward dysimmune small fiber neuropathy. Multiple immunotherapies were tried over the years, with varying benefit: corticosteroids, intravenous immunoglobulin/subcutaneous immunoglobulin, rituximab, daratumumab, plasmapheresis, and belimumab all provided at least partial improvement, whereas cyclosporine was ineffective. Daratumumab produced rapid near-complete remissions, suggesting an important role for antibody-producing plasma cells in this patient’s disease. Belimumab was ultimately used during breastfeeding with continued symptom control, despite occasional mild flares triggered by infections. Overall, the case highlights that some apparently idiopathic small fiber polyneuropathy cases may follow an immune-mediated, relapsing course and may respond meaningfully to immunotherapy. It also underscores the need for better biomarkers, disease measures, and guidance for management during pregnancy and postpartum.

Reference: Oaklander AL, Allen J, Dietliker N, Wilder-Smith EP. Relapsing-Remitting Immunotherapy Responsive Small-Fiber Neuropathy: Longitudinal Tracking Through 10 Years Including Pregnancies. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200286. doi: 10.1212/NXI.0000000000200286.