Journal of Neurology

, Volume 266, Issue 2, pp 398–410 | Cite as

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

  • Alberto Vogrig
  • Bastien Joubert
  • Aurélien Maureille
  • Laure Thomas
  • Emilien Bernard
  • Nathalie Streichenberger
  • Francois Cotton
  • Francois Ducray
  • Jérome HonnoratEmail author
Original Communication



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.


Paraneoplastic 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).

Author 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.


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.

Ethical standards

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


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alberto Vogrig
    • 1
    • 2
    • 3
    • 4
  • Bastien Joubert
    • 1
    • 2
    • 3
  • Aurélien Maureille
    • 1
    • 2
    • 3
    • 5
  • Laure Thomas
    • 1
    • 2
    • 3
  • Emilien Bernard
    • 6
  • Nathalie Streichenberger
    • 7
  • Francois Cotton
    • 8
    • 9
  • Francois Ducray
    • 1
    • 2
    • 3
  • Jérome Honnorat
    • 1
    • 2
    • 3
    • 10
    Email author
  1. 1.French Reference Center of Paraneoplastic Neurological SyndromeHospices Civils de Lyon, Hôpital NeurologiqueLyonFrance
  2. 2.SynatAc TeamNeuroMyoGene Institute, INSERM U1217/CNRS UMR5310LyonFrance
  3. 3.University Claude Bernard Lyon 1, Université de LyonLyonFrance
  4. 4.Department of NeurosciencesSanta Maria della Misericordia University HospitalUdineItaly
  5. 5.Department of NeurologyLille University HospitalLilleFrance
  6. 6.Department of Electroneuromyography and Neuromuscular DiseasesHospices Civils de LyonLyonFrance
  7. 7.Centre de Neuropathologie Est, Hospices Civils de LyonUniversité Claude Bernard Lyon1, Institut NeuroMyogène, CNRS UMR 5310, INSERM U1217LyonFrance
  8. 8.Service de Radiologie, Centre Hospitalier Lyon-Sud, Hospices Civils de LyonPierre-BéniteFrance
  9. 9.CREATIS-CNRS UMR 5220 & INSERM U1044, University Claude Bernard Lyon 1LyonFrance
  10. 10.Centre de Référence National pour les Syndromes Neurologiques Paranéoplasique, Hôpital NeurologiqueBron CedexFrance

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