Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome
To present clinical, radiological, and pathological features of a cohort of patients with motor neuron involvement in association with anti-Ma2 antibodies (Ma2-Ab).
Retrospective case-series of patients with definite paraneoplastic neurological syndrome (PNS) and Ma2-Ab, and cases identified from a review of the literature.
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.
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.
KeywordsParaneoplastic syndromes Motor neuron syndrome Amyotrophic lateral sclerosis Anti-Ma Myelopathy Radiculopathy
We thank NeuroBioTec Hospices Civils de Lyon BRC (France, AC-2013-1867, NFS96-900) for banking sera and CSF samples. We gratefully acknowledge Philip Robinson for English language editing (Direction de la Recherche Clinique, Hospices civils de Lyon).
Study concept and design: AV, JH. Acquisition of data: AV, BJ, AM, LT, EB, NS, FC, FD, and JH. Analysis and interpretation of data: AV, BJ, AM, LT, EB, NS, FC, FD, and JH. Drafting of the manuscript: AV, JH. Critical revision of the manuscript for important intellectual content: AV, BJ, AM, LT, EB, NS, FC, FD, and JH. Study supervision: Honnorat.
This study is supported by research grants from ANR (ANR-14-CE15-0001-MECANO), FRM (Fondation pour la recherche médicale) DQ20170336751 and CSL Behring France.
Compliance with ethical standards
Data access, responsibility, and analysis
The corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Conflicts of interest
Dr Vogrig reported receiving a fellowship grant from the European Academy of Neurology (EAN). No other disclosures were reported.
All procedures were performed in accordance with the institutional ethics committee and the Declaration of Helsinki.
- 31.Dauvilliers Y, Bauer J, Rigau V et al (2013) Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy. JAMA Neurol 70:1305–1310Google Scholar
- 33.Osborn B (2004) Salzman, et al. Diagnostic imaging brain, 1st edn. Amyrsis, Salt Lake CityGoogle Scholar
- 40.Konagaya M, Iida M (1991) A case of HTLV-1 associated myelopathy with diffuse white matter lesion of the frontal lobe and continuous lesion of the pyramidal tract on cranial MRI. Rinsho Shinkeigaku 31:875–877Google Scholar
- 41.Tan MB, McAdory LE (2016) Capecitabine-induced leukoencephalopathy involving the bilateral corticospinal tracts. J Radiol Case Rep 10:1–10Google Scholar