Movement Disorders in Antibody-Associated Neurologic Diseases: A Nationwide Study.

BACKGROUND AND

OBJECTIVES

Antibody-associated neurologic diseases often present with movement disorders (MDs). The frequency and clinical course of specific MDs in most antibody-associated disease subtypes remain largely unknown.

METHODS

We performed a retrospective nationwide observational study on a large cohort of Dutch patients with antibody-associated neurologic diseases between January 2000 and April 2024 to describe associated MDs.

RESULTS

We identified 1,140 patients (56% female; 58/1,140 [5%] aged < 18 years; mean age 56 years [range 1-87]). The most common antibody targets were HuD (n = 212, 19%), NMDA receptor (NMDAR; n = 189, 17%), leucine-rich glioma inactivated 1 (LGI1; n = 187, 16%), and high-concentration glutamic acid decarboxylase 65-kilodalton isoform (GAD65; n = 135, 12%). MDs were present in 459 patients (42%) and represented the predominant and/or first symptom in 56% and 50% of cases, respectively. Cerebellar ataxia was by far the most common MD symptom (n = 235, mainly represented by Yo and GAD65), followed by dyskinesia (n = 61, mainly NMDAR), myoclonus (n = 51, mainly NMDAR), and stiff-person syndrome (n = 51, mainly GAD65). Syndromes associated with Yo- and delta/notch-like epidermal growth factor-related receptor (DNER/Tr) antibodies presented (almost) exclusively with MD (cerebellar ataxia) while the lowest MD frequency was observed in anti-gamma-aminobutyric acid B receptor (GABABR; 6/56, 11%) and anti-LGI1 encephalitis (19/181, 10%; excluding faciobrachial dystonic seizures). Furthermore, we identified MD associations that have not been previously reported, including chorea/dystonia (n = 1) and catatonia (n = 1) in anti-kelch like protein 11-associated brainstem encephalitis, chorea (n = 2) in anti-glycine receptor encephalitis, and episodic ataxia in anti-LGI1 and anti-GAD65-associated neurologic syndrome (both n = 1).

DISCUSSION: MDs are common in antibody-associated neurologic diseases, occurring in 42% of patients, with varying frequencies depending on the specific subtype and antibody. MDs can be the first, predominant, and even only manifestation of these diseases. In addition, we also describe some novel antibody-MD associations. Antibody-associated neurologic diseases should be in the differential diagnosis of new-onset MDs, and we provide recommendations for rational antibody testing in different phenotypes.