Movement disorders associated with neuronal antibodies: a data-driven approach

Andrea Sturchio; Alok K Dwivedi; Matteo Gastaldi; Maria Barbara Grimberg; Pietro Businaro; Kevin R Duque; Joaquin A Vizcarra; Elhusseini Abdelghany; Bettina Balint; Luca Marsili; Alberto J Espay

doi:10.1007/s00415-021-10934-7

Movement disorders associated with neuronal antibodies: a data-driven approach

J Neurol. 2022 Jul;269(7):3511-3521. doi: 10.1007/s00415-021-10934-7. Epub 2022 Jan 13.

Authors

Affiliations

¹ Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
² Department of Clinical Neuroscience, Neuro Svenningsson, Karolinska Institute, 171 76, Stockholm, Sweden.
³ Division of Biostatistics and Epidemiology, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
⁴ Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy.
⁵ Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
⁶ Department of Neurology, Emory University, Atlanta, USA.
⁷ Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁸ Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA. espayaj@ucmail.uc.edu.

Abstract

Background: Movement disorders can be associated with anti-neuronal antibodies.

Methods: We conducted a systematic review of cases with documented anti-neuronal antibodies in serum and/or cerebrospinal fluid published in PubMed before April 1, 2020. Only patients with at least one movement disorder were included. We used random forests for variable selection and recursive partitioning and regression trees for the creation of a data-driven decision algorithm, integrated with expert's clinical feedback.

Results: Three hundred and seventy-seven studies met eligibility criteria, totaling 844 patients and 13 antibodies: amphiphysin, GAD, GlyR, mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, NMDAR, LGI-1, CRMP5/CV2, ANNA-1/Hu, IgLON5, and DPPX. Stiffness/rigidity/spasm spectrum symptoms were more frequently associated with amphiphysin, GAD, and GlyR; ataxia with mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, and ANNA-1/Hu; dyskinesia with NMDAR and paroxysmal movement with LGI1; chorea/choreoathetosis with CRMP5/CV2, IgLON5, and NMDAR; myoclonus with GlyR and DPPX; tremors with ANNA2/Ri and anti-DPPX; and parkinsonism with IgLON5 and NMDAR. Data-driven classification analysis determined the following diagnostic predictions (with probability selection): psychiatric symptoms and dyskinesia predicted NMDAR (71% and 87%, respectively); stiffness/rigidity/spasm and ataxia, GAD (67% and 47%, respectively); ataxia and opsoclonus, ANNA-2/Ri (68%); chorea/choreoathetosis, CRMP5/CV2 (41%). These symptoms remained the top predictors in random forests analysis. The integration with an expert opinion analysis refined the precision of the approach. Breast and lung tumors were the most common tumors. On neuroimaging, cerebellar involvement was associated with GAD and Yo/PCA-1; temporal involvement with Caspr2, LGI-1, ANNA-1/Hu.

Conclusion: Selected movement disorders are associated with specific anti-neuronal antibodies. The combination of data-driven and expert opinion approach to the diagnosis may assist early management efforts.

Keywords: Movement disorders; Neuronal antibodies; Systematic review.

Publication types

Systematic Review

MeSH terms

Autoantibodies
Cell Adhesion Molecules, Neuronal
Cerebellar Ataxia*
Chorea*
Humans
Movement Disorders*
Spasm

Substances

Autoantibodies
Cell Adhesion Molecules, Neuronal
IgLON5 protein, human