Coexisting cerebellar ataxia and Lambert-Eaton myasthenic syndrome without malignancy: insights from a case and systematic literature review.

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder often associated with small-cell lung carcinoma (SCLC). Cerebellar degeneration can coexist with LEMS, although their simultaneous presentation in the non-neoplastic setting is uncommon. METHODS: We describe a 75-year-old man with progressive cerebellar ataxia followed by bilateral ptosis, ophthalmoparesis, and proximal weakness. LEMS was confirmed by positive P/Q-type VGCC antibodies and electrophysiology. Extensive malignancy screening, including PET-CT, was negative, and immunotherapy produced marked neuromuscular and partial cerebellar improvement. To contextualize this case, we systematically reviewed the published literature (January 1991- August 2025) for this association, including cohorts, case reports and series providing individual patient-level details. RESULTS: We identified 37 studies reporting 67 patients with coexistent LEMS and cerebellar ataxia. Malignancy was present in 71.6% (48/67), predominantly SCLC (35/67, 52.2%). The median interval from neurological symptom onset to cancer diagnosis was 3 months (IQR 0.5–6.0; range − 60 to 39 months). Anti-VGCC antibodies were detected in 83.6% (56/67), anti-SOX1 in 7.5% (5/67), and anti-Hu in 3.0% (2/67), while 6.0% (4/67) were seronegative. Notably, 28.4% (19/67) had no malignancy during follow-up, suggesting a non-paraneoplastic autoimmune subset. Neurological improvement was comparable between paraneoplastic and non-paraneoplastic cases, but mortality was significantly higher in malignancy-associated cases (27.1% vs. 5.3%, p = 0.04). CONCLUSION: Coexistent LEMS and cerebellar ataxia is not invariably paraneoplastic. Early immunotherapy may improve neurological outcomes even in cancer-negative cases, but long-term oncologic surveillance remains essential.