Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events, including myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS). This syndrome poses notable management challenges and has high mortality rates. Due to limited data, its clinical features and optimal treatment strategies remain poorly understood. The present study aims to clarify these aspects and share clinical management experiences. A total of 6 patients with IM3OS were retrospectively analyzed, collecting demographic, clinical, laboratory, electrophysiological, therapeutic and outcome data. Additionally, the relevant literature was reviewed to contextualize the findings. The 6 patients, all male, with a median age of 70.5 years (range, 63-83 years), developed symptoms a median of 30.5 days post-ICI initiation. Common symptoms included fluctuating ptosis, neck weakness, fatigue, myalgia, diplopia, dysphagia, dysarthria and limb weakness. Of the 6 patients, 3 required ventilation support. Elevated creatine kinase (CK) and cardiac troponin I (cTnI) were observed in all patients, with CK and cTnI levels decreasing rapidly post-treatment. Cardiac troponin T levels remained elevated for 3 months. Myotonic discharge and increased jitter were noted in 2 patients. Treatments included corticosteroids, intravenous immunoglobulin (IVIG), plasmapheresis and rituximab. Pyridostigmine was discontinued in 2 out of 4 patients due to severe cardiac adverse effects. Despite interventions, 2 patients died and 1 was bedridden, with only 3 showing favorable outcomes. In conclusion, IM3OS has a high fatality rate, highlighting the need for prompt intervention in ICI-treated patients with neuromuscular symptoms. Serum cTnI is a reliable cardiac injury marker, and early treatment with IVIG, plasmapheresis and high-dose methylprednisolone is recommended. Pyridostigmine should be administered with caution in patients with IM3OS, particularly in the presence of bradyarrhythmic ICI-related myocarditis. Given the high mortality and disability rates associated with IM3OS, novel biological targeted therapies such as eculizumab and efgartigimod may reduce fatal outcomes.

Background: Myasthenia gravis is an autoimmune disorder of the neuromuscular junction characterized by fluctuating skeletal muscle weakness. Late-onset MG (onset ≥ 50 and <65 years) and very late-onset MG (VLOMG; onset ≥ 65 years) are increasingly recognized subgroups, and diagnosis in very elderly patients remains challenging because symptoms frequently overlap with age-related conditions and comorbidities. Case Presentation: An 88-year-old man with very late-onset myasthenia gravis (symptom onset at approximately age 85) was urgently referred because of a several-day history of rapidly worsening dysphagia and dysarthria, superimposed on fluctuating diplopia, dysphagia, dysarthria, and fatigable bulbar symptoms that had progressively worsened over the preceding three years. Initial diagnostic evaluation was challenging because of advanced age, previous lacunar infarctions, and multiple comorbidities, including pulmonary thromboembolism, chronic kidney disease, and permanent pacemaker implantation (which precluded brain MRI). Neurological examination and the characteristic fluctuation of symptoms raised suspicion of myasthenia gravis. Serological testing confirmed markedly elevated acetylcholine receptor antibodies, whereas MuSK antibodies were negative. Repetitive nerve stimulation was not performed given the high antibody titer and unambiguous clinical presentation. Thoracic computed tomography excluded thymoma. Treatment with pyridostigmine, azathioprine (maintenance dose kept lower than standard due to chronic kidney disease stage IIIB), and low-dose prednisone (selected due to age and comorbidity profile) resulted in early, patient-reported clinical improvement (approximately 60% in speech and swallowing) over eight weeks of follow-up; a validated severity scale (MG-ADL) showed a score of six (scoring range 0-24). Conclusions: Myasthenia gravis should remain an important differential diagnosis in very elderly patients presenting with fluctuating ocular and bulbar symptoms, even in the presence of multiple comorbidities that may obscure the diagnosis. In this patient, early recognition, antibody testing, and individualised initiation of therapy were followed by meaningful short-term improvement; a single case with eight weeks of follow-up cannot establish that such therapy prevents disease progression or myasthenic crisis, and longer follow-up and additional cases are needed.

Gastrointestinal (GI) symptoms are a prominent feature of Gulf War Illness (GWI). Animal models attribute them to pyridostigmine bromide (PB) exposure, which induces smooth muscle hypertrophy, neuroinflammation, and motility impairment. However, animal studies only provide static snapshots of disease progression and can only partially resolve how inflammatory, neuronal, and biomechanical processes interact dynamically over time. To address this gap, we developed a computational model that couples cytokine kinetics, macrophage activation, and an excitatory-inhibitory neuronal imbalance to predict smooth muscle hypertrophy and colonic motility changes in GWI. The model was calibrated using data from mice exposed to PB under acute (7-day exposure and measurement) and chronic (7-day exposure and day-30 measurement) conditions, reproducing measured cytokine IL-6 elevations, macrophage accumulation, circular muscle thickening, and shifts in excitatory and inhibitory neuronal signaling. Simulations captured reduced excitatory stress, and sustained loss of inhibitory relaxation, consistent with organ-bath recordings. Sensitivity analyses identified macrophage persistence as a dominant regulator of chronic inhibitory dysfunction, whereas excitatory pathways exhibited relative robustness and recovery. Thus, the proposed framework integrates inflammatory, neuronal, and biomechanical processes into a unified computational model of PB-induced colonic dysfunction, providing a systems-level platform for hypothesis generation, exposure-duration prediction, and future evaluation of therapeutic interventions in Gulf War Illness and related neuroimmune gastrointestinal disorders.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive prion disorder whose heterogeneous manifestations may overlap with potentially treatable neurological conditions. We report an atypical sCJD phenotype dominated by progressive dysarthria and an opsoclonus-myoclonus-ataxia-plus (OMAS-plus) phenotype, highlighting the diagnostic pitfalls relative to treatable mimics.

Trible-seronegative myasthenia gravis (tSNMG) is defined as myasthenia gravis (MG) without detectable or low affinity antibodies to acetylcholine receptor (AChR), muscle-specific kinase (MuSK) andlipoprotein related protein 4(LRP-4). This article reports a case of a 39-year-old married female patient with thymoma-associated seronegative myasthenia gravis (tSNMG), which was accompanied by multiple positive autoantibodies and a benign mediastinal lesion. The primary manifestation was generalized muscle weakness, involving the limbs, bulbar muscles, and respiratory muscles. After admission, the patient showed poor responses to treatments including pyridostigmine bromide, human immunoglobulin, glucocorticoids, and tacrolimus. Ultimately, following therapy with efgartigimod followed by rituximab, significant symptomatic improvement was observed. By analyzing the diagnosis and treatment process of this case alongside relevant literature, this report explores the therapeutic value of efgartigimod followed by rituximab for tSNMG, key points for individualized regimen adjustments, and the challenges in diagnosis and treatment, thereby providing a reference for the clinical management of such refractory cases.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic neuromuscular junction disorder that may be mistaken for peripheral neuropathy, radiculopathy, inflammatory myopathy, or myasthenia gravis. We report a female in her early 40s with two months of progressive, predominantly proximal lower-limb weakness, areflexia, and dry mouth, without ocular or bulbar symptoms. Routine laboratory testing and creatine kinase were unremarkable, while spinal imaging showed degenerative abnormalities that did not explain the clinical pattern. Nerve conduction studies demonstrated low compound muscle action potential amplitudes with preserved sensory responses and no demyelinating features. Low-frequency repetitive nerve stimulation produced a decrement, whereas brief exercise caused a marked increase in compound muscle action potential amplitude. Serum P/Q-type voltage-gated calcium channel antibodies were positive, confirming LEMS. Pyridostigmine produced partial symptomatic improvement. Amifampridine was subsequently initiated, followed by intravenous immunoglobulin, after which the patient demonstrated marked improvement in lower-limb strength and walking ability. Initial malignancy screening was negative, and longitudinal surveillance was planned. This case emphasizes that a decrement on low-frequency stimulation is not specific for myasthenia gravis and that low resting motor amplitudes with marked post-exercise facilitation strongly indicate a presynaptic neuromuscular junction disorder.