Neurology. 2026 Jun 9;106(11):e218061. doi: 10.1212/WNL.0000000000218061. Epub 2026 May 8.
ABSTRACT
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive metabolic disorder that can cause premature atherosclerosis and ischemic stroke in young adults. We report a 23-year-old man who had recurrent strokes even after patent foramen ovale (PFO) closure. Initial evaluation for his first cryptogenic stroke revealed a PFO with a high Risk of Paradoxical Embolism (RoPE) score, leading to closure. Three years later, he experienced a recurrent stroke with right M1 segment occlusion. High-resolution magnetic resonance vessel wall imaging demonstrated intracranial atherosclerotic plaque, prompting reconsideration of the etiology. Further history taking revealed chronic diarrhea since infancy and juvenile cataracts. Examination showed borderline intellectual functioning, bilateral ankle clonus, and Achilles tendon xanthomas. Brain MRI exhibited characteristic bilateral dentate nucleus hyperintensities. Genetic testing confirmed CYP27A1 pathogenic variants, consistent with a diagnosis of CTX. Through highlighting CTX underlying premature atherosclerosis and stroke in a young man, this case emphasizes the importance of rare metabolic disorders in stroke, even when a common cause such as PFO is identified. Early recognition enables targeted therapy and improves outcomes.
PMID:42102332 | DOI:10.1212/WNL.0000000000218061