We performed a nested case series within multicenter cohorts of patients with Ma/Ma2-associated neurological syndromes, confirmed by tissue-based assay and line-blot. We included patients with isolated peripheral nervous system clinical presentation with or without concomitant spinal cord involvement (if peripheral nervous system predominated).
Among 212 patients with Ma/Ma2 antibody-associated neurologic syndromes, 7 (3%) presented with isolated peripheral nervous system involvement (median age, 68 years; 4/7 female). The onset was subacute in 5/7 (71%) patients, and at the nadir, 5 (71%) required assistance for ambulation (median mRS 4, range 2-4). Clinical phenotypes were consistent with involvement of the proximal components of the peripheral nervous sytem in 6 (86%) patients, presenting as sensory neuronopathy (n = 3), myeloradiculopathy (n = 1), radiculoplexopathy (n = 1), and motor neuronopathy (n = 1). The remaining patient had multiple mononeuropathy. All patients were anti-Ma2-positive whereas Ma antibodies (reactive against Ma1 and Ma2 proteins) were detected in 2 (33%)/6 tested patients. CSF examination showed pleocytosis in all but one patient (5/6, 83%), the latter being sampled 24 months after symptom onset. None of the samples showed additional neuronal antibodies in tissue-based assays. An associated cancer was identified in 6 (86%)/7 patients: pleural mesothelioma, oral squamous cell, testicular, lung, and breast cancer, and B-cell lymphoma. Five patients received immunotherapy, cancer treatment, or both. After a median follow-up of 23 months, symptoms improved or stabilized in 3 patients and progressed in 4.
Isolated peripheral nervous system involvement is a rare manifestation of Ma/Ma2 associated autoimmunity. Ma/Ma2 antibody testing should be considered in neuronopathies and unexplained non–length-dependent neuropathies.