Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia.

Madeline Garza,Amanda L. Piquet

doi:10.3389/fneur.2021.683048

Madeline Garza, Amanda L. Piquet

Open Access

https://doi.org/10.3389/fneur.2021.683048

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Abstract

Movement disorders are a common feature of many antibody-associated neurological disorders. In fact, cerebellar ataxia is one of the most common manifestations of autoimmune neurological diseases. Some of the first autoantibodies identified against antigen targets include anti-neuronal nuclear antibody type 1 (ANNA-1 or anti-Hu) and Purkinje cell cytoplasmic antibody (PCA-1) also known as anti-Yo have been identified in paraneoplastic cerebellar degeneration. Historically these antibodies have been associated with an underlying malignancy; however, recently discovered antibodies can occur in the absence of cancer as well, resulting in the clinical syndrome of autoimmune cerebellar ataxia. The pace of discovery of new antibodies associated with autoimmune or paraneoplastic cerebellar ataxia has increased rapidly over the last few years, and pathogenesis and potential treatment options remains to be explored. Here we will review the literature on recently discovered antibodies associated with autoimmune and paraneoplastic cerebellar ataxia including adaptor protein-3B2 (AP3B2); inositol 1,4,5-trisphophate receptor type 1 (ITPR1); tripartite motif-containing (TRIM) proteins 9, 67, and 46; neurochondrin; neuronal intermediate filament light chain (NIF); septin 5; metabotropic glutamate receptor 2 (mGluR2); seizure-related 6 homolog like 2 (SEZ6L2) and homer-3 antibodies. We will review their clinical characteristics, imaging and CSF findings and treatment response. In addition, we will discuss two clinical case examples of autoimmune cerebellar ataxia.

Highlights

Cerebellar ataxia has a broad differential diagnosis including both acquired and genetic causes, autoimmune etiologies or paraneoplastic cerebellar degeneration (PCD) should be considered in most case, in adults [1]
This is in contrast to neuronal antibodies that have already been shown to be directly involved in the pathogenesis of ataxia
We have reviewed recently described autoantibodies associated with cerebellar ataxia including anti-adaptor protein-3B2 (AP3B2), antiITPR1, anti-tripartite motif-containing (TRIM), anti-neurochondrin, anti-neuronal intermediate filament light chain (NIF), anti-septin 5,anti-metabotropic glutamate receptor 2 (mGluR2), anti-seizure-related 6 homolog like 2 (SEZ6L2), and anti-homer 3

Summary

INTRODUCTION

Cerebellar ataxia has a broad differential diagnosis including both acquired and genetic causes, autoimmune etiologies or paraneoplastic cerebellar degeneration (PCD) should be considered in most case, in adults [1]. Patients who present with subacute onset cerebellar ataxia but in the absence of malignancy or a known pathogenic antibody are deemed to have primary autoimmune cerebellar ataxia (PACA) [6] This is in contrast to neuronal antibodies that have already been shown to be directly involved in the pathogenesis of ataxia (e.g. dipeptidyl-peptidase-like-6 [DPPX], metabotropic glutamate receptor 1 [mGluR1], glutamic acid decarboxylase [GAD]-65). The aim of this review article is to focus on recently discovered autoantibodies against neuronal targets identified in syndromes cerebellar ataxia and includes two clinical case examples of adaptor protein-3B2 (AP3B2) and tripartite motif-containing (TRIM)-46 In these the majority cases, an associated antibody has been identified, but it is not yet clear whether there is a direct.

METHODS

Findings

DISCUSSION