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

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

Andrea Sturchio  1   2 , Alok K Dwivedi  3 , Matteo Gastaldi  4 , Maria Barbara Grimberg  1 , Pietro Businaro  4   5 , Kevin R Duque  1 , Joaquin A Vizcarra  6 , Elhusseini Abdelghany  1 , Bettina Balint  7 , Luca Marsili  1 , Alberto J Espay  8
Affiliations

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

Andrea Sturchio et al. J Neurol. 2022 Jul.

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.

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Conflict of interest statement

MBG, PB, KRD, JAV, EA, NW, and BB have nothing to report. AS is cofounder of REGAIN Therapeutics, owner of a provisional patent on compositions and methods for treatment and/or prophylaxis of proteinopathies. AKD is supported as a co-investigator by the NIH (1 R21 HL143030-01) and (R21 AI133207) grants. He is also currently serving as a statistician in CPRIT funded studies (PP200006, PP190058, PP180003, and PP170068). MG has received honoraria from Roche. LM has received honoraria from the International Association of Parkinsonism and Related Disorders (IAPRD) Society. He serves on the Editorial board of the Journal of Clinical Movement Disorders. AJE: has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Adamas, Acadia, Acorda, Kyowa Kirin, Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from USWorldMeds, Acadia, and Sunovion. He serves on the editorial boards of the Journal of Parkinson’s Disease, European Journal of Neurology, and JAMA Neurology. He is cofounder of REGAIN Therapeutics, owner of a provisional patent on compositions and methods for treatment and/or prophylaxis of proteinopathies.

Figures

Fig. 1
Fig. 1
Systematic review flowchart
Fig. 2
Fig. 2
Prevalence of movement disorders and non-movement symptoms according to the autoantibody. Absolute number of patients for each movement disorder: ataxia (n = 320); stiffness/rigidity/spasm (n = 243); dyskinesia (n = 168); myoclonus/jerking (n = 189); dystonia (n = 101); chorea/choreoathetosis (n = 106); tremors (n = 83); parkinsonism (n = 59); opsoclonus (n = 33); startle reaction (n = 32); stereotypies (n = 14); and opisthotonus (n = 19). Opsoclonus was associated with myoclonus in 67% of the cases (22/33); in particular with ANNA-2/Ri (10/19), and ANNA-1/Hu (3/5)
Fig. 3
Fig. 3
Distribution of the most common tumors for each antibody. Percentage was calculated considering only subjects with tumor
See this image and copyright information in PMC

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