Journal Article

DZNE-2026-00620

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Clinical Spectrum of Anti-SEZ6L2 Syndrome: A Case Report With Brain Volumetry and Systematic Literature Review.

Habicht, J. L. ; Cammá, G. ; Wurdack, K. ; Teegen, B. ; Prüss, H.DZNE* ; Finke, C.

2026
Wolters Kluwer Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1212/NXI.0000000000200614

Abstract: Anti-seizure-related 6 homolog like 2 (SEZ6L2) antibodies are a rare cause of immune-mediated cerebellar syndromes. The clinical phenotype, diagnostic features, and outcomes have not been systematically synthesized, and the evidence is limited to case reports and case series. We, therefore, aimed to (1) characterize the clinical course and longitudinal brain volumetric changes in a patient with anti-SEZ6L2 syndrome and (2) systematically review the published evidence regarding clinical features, diagnostics, treatment, and outcomes.We performed a single-patient observational study with serial clinical assessments and cross-sectional and longitudinal MRI volumetry and compared the findings with those from age-matched and sex-matched healthy controls. In addition, we conducted a PRISMA-compliant systematic review of MEDLINE and EMBASE from 1964 to December 1, 2025, including published reports of patients with anti-SEZ6L2 antibodies. Data were synthesized descriptively, and because of disease rarity, this case was included in aggregated analyses.A 45-year-old man developed a severe subacute cerebellar syndrome with cognitive, psychiatric, pyramidal, and parkinsonian features. The peak SARA score was 30, and the peak modified Rankin Scale (mRS) score was 5. Despite sequential immunotherapy, only mild improvement occurred and substantial disability persisted. Longitudinal MRI volumetry demonstrated progressive cerebellar atrophy relative to healthy controls, while whole-brain and subcortical volumes remained within normal range. The systematic review identified 21 previously reported patients, yielding 22 including the current case. Cerebellar syndrome was present in all patients; cognitive symptoms were reported in 14 of 22 (64%), parkinsonism in 8 of 22 (36%), and psychiatric symptoms in 6 of 22 (27%). Cerebellar atrophy was reported in 19 of 22 (86%). Two patients had temporally associated tumors. CSF pleocytosis was present in 7 of 21 (33%). The median peak SARA score was 27 (interquartile range [IQR] 23-30; n = 7) and improved to 20 (IQR 18-22), whereas the median mRS score remained 4 at both peak disease and follow-up (n = 11). Among 21 patients with outcome data, 2 (9.5%) died of tumor-related complications, 2 (9.5%) deteriorated neurologically, 8 (38.1%) stabilized, and 9 (42.9%) improved.Anti-SEZ6L2 syndrome is characterized by severe cerebellar dysfunction frequently accompanied by parkinsonism, cognitive, and psychiatric features. This case demonstrated progressive cerebellar atrophy on longitudinal volumetry despite immunotherapy. Our systematic synthesis highlights that noncerebellar manifestations are common, and that substantial long-term disability often persists despite partial improvement in ataxia severity.

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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