Neuronal Antibodies in Patients With Atypical Parkinsonism

Abstract

Background and Objectives Patients with antibody-associated movement disorders sometimes lack specific features of autoimmune diseases and can therefore be misdiagnosed, for example, as neurodegenerative diseases. A well-known example is anti-IgLON5 disease, which may mimic atypical parkinsonian (AP) syndromes. Our objectives were (1) to test different cohorts of patients with suspected AP for anti-IgLON5 and other neuronal antibodies and (2) to describe the characteristics of AP in anti-IgLON5 disease. Methods We performed a retrospective observational cohort study in which we screened 5 cohorts of patients with AP syndromes for antibodies by immunohistochemistry. Positive results were evaluated with additional techniques including human live neurons. We also reviewed all Dutch patients with anti-IgLON5 disease for parkinsonian features. Results We identified 719 patients with AP syndromes, of which 532 had available serum or CSF. Seven (1.3%) had antibody-associated disorders (2 anti-IgLON5, 1 anti-IgLON5/anti-NMDAR, 1 anti-Caspr2, 1 anti-CV2, 1 anti-Hu, and 1 anti-CV2/anti-Hu). All but 1 of these patients were already suspected of an autoimmune cause. Furthermore, we identified 30 Dutch patients with anti-IgLON5 disease. Twelve (40%) had AP features, but 11 of the 12 patients also had additional features that differentiated them from classical AP (prominent sleep apnea in 10, neuromuscular symptoms in 6, and chorea in 3). The phenotype of the last patient was clinically indistinguishable from idiopathic Parkinson disease (with probable concurrent mild anti-IgLON5 disease). We also found 8 patient cases falsely identified as anti-IgLON5 positive using a commercial cell-based assay. Discussion Routine testing for anti-IgLON5 or other neuronal antibodies in AP is not recommended. Rather, careful clinical phenotyping is essential to uncover additional features that might suggest an underlying antibody-associated disease in selected patient cases.