Anti-Ma1/Ma2 Paraneoplastic Neurological Syndrome Associated with Malignant Mesothelioma: A Case Study

Anti-Ma1/Ma2 paraneoplastic neurological syndromes (PNS) are rare immune-mediated disorders classically associated with testicular germ cell tumours but increasingly recognised in a broader range of malignancies. We report a 74-year-old left-handed man who initially presented with progressive yet mild gait ataxia. Brain MRI revealed T2 hyperintensity in the right amygdala and hippocampus, as well as in the left caudate head. Both serum and cerebrospinal fluid samples tested positive for anti-Ma1/Ma2 antibodies. Despite extensive initial imaging and tumour-marker screening, no malignancy was identified. Over the next two months, his deficits progressed rapidly, with severe gait ataxia, opsoclonus, and left distal arm weakness in an ulnar nerve distribution. Nerve conduction studies demonstrated demyelinating large-fibre sensorimotor polyneuropathy. High-dose corticosteroids, intravenous immunoglobulin, mycophenolate, and rituximab led to clinical stabilisation. However, four months later, he re-presented with insidious respiratory distress due to a right parapneumonic effusion, and pleural biopsy confirmed mesothelioma. This case reinforces the rare association between anti-Ma1/Ma2 PNS and mesothelioma. To our knowledge, only three other published cases have reported anti-Ma1/Ma2 PNS preceding the diagnosis of mesothelioma, including one in which the malignancy was identified only after several years of surveillance. This case highlights that disabling neurological symptoms may precede detectable tumour burden. Early immunosuppression can offer temporary clinical benefit; nevertheless, sustained clinical stability, which is often difficult to achieve in PNS, relies on timely identification and treatment of the underlying malignancy. Our report underscores the importance of prolonged, multimodal surveillance even when initial cancer screening is negative, as oncological treatment remains central to long-term management.