EP17.01 LAMBERT-EATON MYASTHENIC SYNDROME ASSOCIATED WITH ANTI-HU AND ANTI-SOX1 ANTIBODIES IN SMALL-CELL LUNG CANCER: A CHALLENGING NEUROIMMUNO-ONCOLOGICAL MANAGEMENT

Abstract BACKGROUND Lambert-Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic autoimmune disorder affecting neuromuscular transmission, most commonly associated with small-cell lung cancer (SCLC). Although anti-voltage-gated calcium channel (VGCC) antibodies are present in the majority of cases, their absence does not rule out the diagnosis. The presence of anti-Hu and anti-SOX1 antibodies supports a paraneoplastic origin and may indicate broader neurological involvement. However, whether follow-up antibody titers correlate with clinical evolution remains unclear. METHODS We present a case report of a patient with suspected LEMS, detailing the clinical presentation, complementary tests and serial measurements of onconeuronal antibody titers. RESULTS A 76-year-old man presented with one month of progressive general deterioration, including proximal muscle weakness impairing both ambulation and upper limb elevation, dysarthria, dysphagia for solids, dysphonia, resting dyspnea, severe asthenia, cognitive impairment, weight loss, imbalance-type dizziness. Electromyography showed severe neuromuscular transmission dysfunction in the right periorbital muscles and a greater than 10% decrement in low-frequency repetitive stimulation of distal muscles. Onconeuronal antibodies revealed positive anti-Hu (+++) and anti-SOX1(+++). Thoracic imaging identified a right hilar mass, confirmed as stage IV SCLC. A diagnosis of probable LEMS was established and the patient was treated with pyridostigmine, high-dose intravenous methylprednisolone, and five sessions of plasmapheresis, followed by systemic chemotherapy using carboplatin (AUC 3) and gemcitabine (1000 mg/m² biweekly) resulting in mild clinical improvement with a decrease in SOX-1 and Hu antibody levels. Within the subsequent six months, the patient suffered a left proximal segment middle cerebral artery ischemic stroke, successfully treated with mechanical thrombectomy, complicated by early seizures and a right lower limb hemorrhage, leading to the withdrawal of anticoagulation. At present, the patient continues in partial response, and persistent imbalance-type dizziness and fatigue. CONCLUSIONS This case highlights the co-occurrence of anti-Hu and anti-SOX1 antibodies in a patient with paraneoplastic LEMS associated with SCLC with a notable correlation between decreasing antibody titers and partial neurological improvement following immunomodulatory therapy and chemotherapy with succesfully treated systemic complications achieving oncological partial response at six months. These findings underscore the importance of early recognition of paraneoplastic syndromes, comprehensive antibody profiling with longitudinal follow-up, and a multidisciplinary approach to optimize outcomes.