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

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Abstract

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.

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Acknowledgements

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).

Funding

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.

Author information

Authors and Affiliations

  1. French Reference Center of Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Lyon, France

    Alberto Vogrig, Bastien Joubert, Aurélien Maureille, Laure Thomas, Francois Ducray & Jérome Honnorat

  2. SynatAc Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France

    Alberto Vogrig, Bastien Joubert, Aurélien Maureille, Laure Thomas, Francois Ducray & Jérome Honnorat

  3. University Claude Bernard Lyon 1, Université de Lyon, Lyon, France

    Alberto Vogrig, Bastien Joubert, Aurélien Maureille, Laure Thomas, Francois Ducray & Jérome Honnorat

  4. Department of Neurosciences, Santa Maria della Misericordia University Hospital, Udine, Italy

    Alberto Vogrig

  5. Department of Neurology, Lille University Hospital, Lille, France

    Aurélien Maureille

  6. Department of Electroneuromyography and Neuromuscular Diseases, Hospices Civils de Lyon, Lyon, France

    Emilien Bernard

  7. Centre de Neuropathologie Est, Hospices Civils de Lyon, Université Claude Bernard Lyon1, Institut NeuroMyogène, CNRS UMR 5310, INSERM U1217, Lyon, France

    Nathalie Streichenberger

  8. Service de Radiologie, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France

    Francois Cotton

  9. CREATIS-CNRS UMR 5220 & INSERM U1044, University Claude Bernard Lyon 1, Lyon, France

    Francois Cotton

  10. Centre de Référence National pour les Syndromes Neurologiques Paranéoplasique, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France

    Jérome Honnorat

Authors
  1. Alberto Vogrig
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  2. Bastien Joubert
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  3. Aurélien Maureille
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  4. Laure Thomas
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  5. Emilien Bernard
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  6. Nathalie Streichenberger
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  7. Francois Cotton
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  8. Francois Ducray
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  9. Jérome Honnorat
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Contributions

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.

Corresponding author

Correspondence to Jérome Honnorat.

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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.

Ethical standards

All procedures were performed in accordance with the institutional ethics committee and the Declaration of Helsinki.

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Vogrig, A., Joubert, B., Maureille, A. et al. Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome. J Neurol 266, 398–410 (2019). https://doi.org/10.1007/s00415-018-9143-x

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  • DOI: https://doi.org/10.1007/s00415-018-9143-x

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