Movement Disorders in Antibody-associated Neurological Diseases: A Nationwide Study
Jeroen Kerstens1, Juna De Vries1, Juliette Brenner1, Yvette Crijnen1, Robin van Steenhoven1, Marienke De Bruijn2, Agnes Van Sonderen3, Marleen van Coevorden-Hameete1, Anna Bastiaansen1, Marie Vermeiren1, Rinze F Neuteboom1, Sharon Veenbergen1, Peter Sillevis Smitt1, Agnita Boon1, Maarten Titulaer1
1Erasmus University Medical Center, 2Elisabeth-TweeSteden Hospital, 3Haaglanden Medical Center
Objective:

To describe movement disorders (MD) in a large nationwide cohort of autoimmune encephalitis (AIE) and paraneoplastic neurological syndromes (PNS).

Background:

Although a large variety of MD has been described in different antibody-associated syndromes, frequency and clinical course of specific MD remains unknown for most antibodies. This knowledge is important to aid in early diagnosis and develop rational antibody testing strategies.

Design/Methods:
We performed a retrospective nationwide observational study on a large cohort of all Dutch patients diagnosed with antibody-associated AIE/PNS between January 2000 and April 2024 and described associated MD. 
Results:

We identified 1,140 patients (56% female, 58/1,140 [5%] <18 years, mean age 56 years [range 1-87]). The most common antibody targets were HuD (n=212, 19%), NMDAR (n=189, 17%), LGI1 (n=187, 16%) and high-concentration GAD65 (n=135, 12%). MD were present in 459 patients (42%) and were the predominant or first symptom in 56% and 50% of these, respectively. Cerebellar ataxia was the most common (n=235, mainly Yo and GAD65), followed by dyskinesia (n=61, mainly NMDAR), myoclonus (n=51, mainly NMDAR) and stiff-person syndrome (n=51, mainly GAD65). Patients with Yo- and DNER/Tr-antibodies presented (almost) exclusively with MD (cerebellar ataxia), while the lowest MD frequency was observed in anti-GABABR (6/56, 11%) and anti-LGI1 (19/181, 10%; excluding faciobrachial dystonic seizures). Furthermore, we identified MD associations not previously reported, i.e. chorea/dystonia (n=1) and catatonia (n=1) in anti-KLHL11-associated encephalitis, chorea (n=2) in anti-GlyR encephalitis and episodic ataxia in anti-LGI1 and anti-GAD65-associated neurological syndrome (both n=1).

Conclusions:

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

10.1212/WNL.0000000000212900
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