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Transient Neurological Symptoms Preceding Cerebellar Ataxia with Glutamic Acid Decarboxylase Antibodies

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Abstract

A prompt diagnosis and treatment of patients with autoimmune cerebellar ataxia (CA) with antibodies against glutamic acid decarboxylase (GAD-Abs) may lead to a better prognosis. Herein, we report prodromal transient neurological symptoms that should raise clinical suspicion of CA with GAD-Abs. We initially identified a 70-year-old man who presented a first acute episode of vertigo, diplopia, and ataxia lasting 2 weeks. Two months later, he experienced a similar episode along with new-onset gaze-evoked nystagmus. After 4 months, downbeat nystagmus, left limb dysmetria, and gait ataxia progressively appeared, and an autoimmune CA was diagnosed based on the positivity of GAD-Abs in serum and cerebrospinal fluid (CSF). We searched retrospectively for similar presentations in a cohort of 31 patients diagnosed with CA and GAD-Abs. We found 11 (35.4%) patients (all women, median age 62 years; 8/11 [72.7%] with autoimmune comorbidities) with transient neurological symptoms antedating CA onset by a median of 3 months, including vertigo in 9 (81.8%; described as paroxysmal in 8) and fluctuating diplopia in 3 (27.3%) patients. The identification of transient neurological symptoms of unknown etiology, such as paroxysmal vertigo and fluctuating diplopia, should lead to GAD-Abs testing in serum and CSF, especially in patients with autoimmune comorbidities.

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Acknowledgments

We thank NeuroBioTec Hospices Civils de Lyon BRC (France, AC-2013-1867, NFS96-900) for banking sera and CSF samples. We thank Philip Robinson for his help in the manuscript preparation (Direction de la Recherche Clinique, Hospices Civils de Lyon).

Funding

This study is supported by research grants from the Fondation pour la recherche médicale (reference DQ20170336751) and has been developed within the BETPSY project, which is supported by a public grant overseen by the French national research agency (Agence nationale de la recherche, ANR), as part of the second “Investissements d’Avenir” program (reference ANR-18-RHUS-0012). SM-C was supported by a clinical fellowship grant from the European Academy of Neurology (2017).

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Authors and Affiliations

  1. French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France

    Sergio Muñiz-Castrillo, Alberto Vogrig, Bastien Joubert, Anne-Laurie Pinto, Véronique Rogemond, Géraldine Picard & Jérôme Honnorat

  2. Institut NeuroMyoGène, INSERM U1217/CNRS UMR 5310, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France

    Sergio Muñiz-Castrillo, Alberto Vogrig, Bastien Joubert, Anne-Laurie Pinto, Véronique Rogemond, Géraldine Picard & Jérôme Honnorat

  3. Neurology Department, Hospital Universitario Infanta Cristina, Madrid, Spain

    Sergio Muñiz-Castrillo

  4. Immunology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Lyon, France

    David Gonçalves & Nicole Fabien

  5. Neurology Department, Centre Hospitalier Universitaire de la Guadeloupe, Point-à-Pitre, France

    Hugo Chaumont

  6. Service de Neuro-Oncologie, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France

    Jérôme Honnorat

Authors
  1. Sergio Muñiz-Castrillo
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  2. Alberto Vogrig
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  3. Bastien Joubert
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  4. Anne-Laurie Pinto
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  5. David Gonçalves
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  6. Hugo Chaumont
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  7. Véronique Rogemond
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  8. Géraldine Picard
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  9. Nicole Fabien
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  10. Jérôme Honnorat
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Contributions

Sergio Muñiz-Castrillo and Jérôme Honnorat conceptualized and designed the study. Sergio Muñiz-Castrillo, Alberto Vogrig, Bastien Joubert, Anne-Laurie Pinto, David Gonçalves, Hugo Chaumont, Véronique Rogemond, Géraldine Picard, Nicole Fabien, and Jérôme Honnorat collected, analyzed, and interpreted the data. Sergio Muñiz-Castrillo and Jérôme Honnorat drafted the manuscript. Sergio Muñiz-Castrillo, Alberto Vogrig, Bastien Joubert, Anne-Laurie Pinto, David Gonçalves, Hugo Chaumont, Véronique Rogemond, Géraldine Picard, Nicole Fabien, and Jérôme Honnorat revised the manuscript. Jérôme Honnorat supervised the study.

Corresponding author

Correspondence to Jérôme Honnorat.

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The authors declare that they have no conflict of interest.

Ethical Approval

This study followed the Declaration of Helsinki and was performed according to the guidelines of the Institutional Review Board of the Université Claude Bernard Lyon 1 and Hospices Civils de Lyon.

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Muñiz-Castrillo, S., Vogrig, A., Joubert, B. et al. Transient Neurological Symptoms Preceding Cerebellar Ataxia with Glutamic Acid Decarboxylase Antibodies. Cerebellum 19, 715–721 (2020). https://doi.org/10.1007/s12311-020-01159-x

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