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Abstract Details

Clinical Spectrum of SEZ6L2 Autoimmunity: A Case Report and Systematic Review
Autoimmune Neurology
P9 - Poster Session 9 (5:00 PM-6:00 PM)
1-003

To describe a case of seizure-related 6 homolog-like 2 (SEZ6L2) autoimmunity and conduct a systematic review to characterize this rare disease.

Since the initial report of SEZ6L2 autoimmunity in a patient with cerebellar ataxia and retinopathy, SEZ6L2 autoimmunity has also been recognized to present with parkinsonism and cognitive impairment. Although rare, timely recognition is essential because it is immunotherapy-responsive.

We present a case of SEZ6L2 autoimmunity and describe the clinical course, diagnostic evaluation, and treatment. A PubMed search from 2014 to 2025 identified English and Japanese articles with individual patient data. Clinical data, treatments, and outcomes were analyzed. Categorical variables were summarized as frequencies, and continuous variables as medians with range.

A previously independent 87-year-old man presented with progressive gait difficulty and cognitive decline. He declined from independent ambulation to wheelchair dependence over 4 months. Examination showed dysarthria, appendicular and axial ataxia, bilateral dysmetria, action tremor, bradykinesia, and postural instability. Brief Ataxia Rating Scale (BARS) was 19.5. CSF revealed normal cell count, protein, and glucose. Oligoclonal bands were negative. Brain MRI was unremarkable, but FDG-PET demonstrated diffusely decreased cerebellar uptake. Malignancy workup was negative. Initial autoimmune and infectious workup was negative except for antinuclear antibody (1:80, homogeneous). He empirically received IVIg 2 g/kg and continued monthly IVIg 2 g/kg. Later, tissue-based immunofluorescence and a cell-based assay detected SEZ6L2 antibodies in serum and CSF. At 1 month, tremor and dysarthria improved and gait and cognition stabilized. At 6 months, balance improved and he ambulated short distances with assistance (BARS 18). We identified 11 articles reporting 18 patients. Together with our case, clinical courses of 19 patients (median age 60 years, range 34–87, 12 [63%] female) were analyzed.

SEZ6L2 autoimmunity is a rare but distinct and immunotherapy-responsive cause of subacute cerebellar ataxia, often with parkinsonism and cognitive changes.
Authors/Disclosures
Goh Kobayashi, MD
PRESENTER
Mr. Kobayashi has nothing to disclose.
Yoji Hoshina, MD (University of Utah Health) Dr. Hoshina has nothing to disclose.
Haatem M. Reda, MD (Massachusetts General Hospital) Dr. Reda has nothing to disclose.