Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome

Objective: To present clinical, radiological, and pathological features of a cohort of patients with motor neuron involvement in association with anti-Ma2 antibodies (Ma2-Ab). Methods: Retrospective case-series of patients with definite paraneoplastic neurological syndrome (PNS) and Ma2-Ab, and cases identified from a review of the literature. Results: Among 33 Ma2-Ab patients referred between 2002 and 2016, we retrospectively identified three patients (9.1%) with a motor neuron syndrome (MNS). Seven additional cases were retrieved among the 75 Ma2-patients reported in the literature (9.3%). A total of ten patients are, therefore, described herein. MNS was evident as combined upper and lower MNS in four patients, isolated upper MNS in two, and isolated lower MNS in one; three patients were diagnosed with myeloradiculopathy. The most common MNS signs/symptoms were: hyperreflexia (80%), proximal weakness (60%), proximal upper-limb fasciculations (50%), head drop (40%), and dysarthria/dysphagia (30%). Brain MRI abnormalities included bilateral pyramidal tract T2-weighted/FLAIR hyperintensities (three patients). Spine MRI found bilateral, symmetric, T2-weighted signal abnormalities in the anterior horn in two patients. CSF examination was abnormal in nine patients. Cancer was found in seven patients (four testicular, two lung, and one mesothelioma). Eight patients underwent first-line immunotherapy. Second-line immunotherapy was adopted in all our patients and in none of those identified in the literature. Motor improvement was observed in 33% of our patients, and 20% in the literature series. Conclusions: Motor neuron involvement could complicate Ma2-Ab-associated PNS in almost 10% of patients and must be carefully studied to adapt treatment. This disorder differs from amyotrophic lateral sclerosis.