Anti-KLHL11 antibody encephalitis without detectable malignancy: a case report and literature review

Abstract

Background Anti-Kelch-like protein 11 (KLHL11) antibody encephalitis, first reported in 2019, is a rare autoimmune disorder typically associated with seminoma. This disorder exhibits a striking male predominance, with cerebellar ataxia as the hallmark manifestation, whereas seizures and altered consciousness occur less frequently. Cases without detectable malignancy account for fewer than 20% of reports, and their clinical manifestations, treatment responses, and outcomes have not been systematically characterized. Methods We report a case of a 62-year-old male with anti-KLHL11 encephalitis and no detectable malignancy, who initially presented with recurrent generalized tonic-clonic seizures (GTCS), followed by intermittent seizures and progressive neurological deterioration. A systematic search of published cases with narrative synthesis was conducted to analyze the clinical presentation, neuroimaging features, treatment responses, and outcomes of similar reported cases. Results We analyzed 13 cases of anti-KLHL11 encephalitis without detectable malignancy. The most common clinical manifestations were ataxia (9/13), dysarthria (8/13), and gaze palsy/nystagmus (6/13). Intracranial pressure (ICP) (median: 165 mmH2O, range: 60–200 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 9 × 106/L, range: 1–46 × 106/L), and CSF protein level (median: 0.50 g/L, range: 0.27–1.32 g/L) were also measured. The median serum anti-KLHL11 antibody titer was 1:100 (range: 1:30–1:160,000), while CSF anti-KLHL11 antibody titer was 1:10 (range: 1:1–1:32). Electroencephalography (EEG) was normal in 2 cases, showed epileptiform discharges in 2, diffuse background slowing in 2, and sleep-related central hypoventilation in 1. Brain magnetic resonance imaging (MRI) was unremarkable in 3 cases. Seven cases (53.8%) presented with T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities, 4 cases (30.8%) showed cerebellar/brainstem atrophy, 1 case (7.7%) presented with acute cerebral infarction. Following immunotherapy, 6 patients achieved clinical improvement, 3 patients remained clinically stable, 4 deteriorated clinically, of whom 2 died of central respiratory failure. Conclusion Anti-KLHL11 encephalitis without detectable malignancy cannot be reliably distinguished from tumor-positive cases based solely on clinical symptoms and neuroimaging findings. The gold standard for differential diagnosis remains comprehensive tumor screening and long-term follow-up. Extensive white matter and deep gray matter involvement, together with prominent seizures, may be more prevalent in patients without detectable malignancy, although these observations require validation in larger comparative cohorts.