47-Year-Old with Brain and Spinal Cord Lesions: An Atypical Presentation of CADASIL

Abstract

This case describes an uncommon CADASIL phenotype with concomitant spinal cord lesions that initially mimicked a neuroinflammatory demyelinating disorder. CADASIL is a NOTCH3-mediated small-vessel arteriopathy classically presenting with migraine with aura, subcortical ischemic events, psychiatric symptoms, and progressive cognitive decline; spinal cord involvement and inflammatory Cerebrospinal Fluid (CSF) profiles are unusual and may lead to misdiagnosis. We report a 47-year-old man with vitiligo, Hashimoto thyroiditis, and tobacco use who presented with right-hand incoordination and facial paresthesia a decade before diagnosis, with brain MRI showing periventricular white matter hyperintensities and cystic encephalomalacia; CSF was non-specific and he was lost to follow-up. Ten years later he developed left-sided weakness and gait instability, with exam demonstrating hyperreflexia, ankle clonus, spasticity, vibratory loss, and a positive Romberg sign. MRI showed an acute right corona radiata infarct with extensive leukoencephalopathy involving the corpus callosum, periventricular regions, and anterior temporal lobes, plus subtle cervical and thoracic cord T2 hyperintensities. CSF revealed mildly elevated protein, three mirror-pattern oligoclonal bands, and mildly elevated anti-SSA antibodies. High-dose intravenous methylprednisolone produced no clinical benefit, and he was initially diagnosed with relapsing-remitting multiple sclerosis. Disclosure of a sister with genetically confirmed CADASIL and a paternal history of early stroke, dementia, and psychiatric illness prompted NOTCH3 testing, which was positive. He was transitioned to secondary stroke prevention as recommended for CADASIL. This case highlights that spinal cord lesions and mild inflammatory biomarkers may occur in CADASIL, and the importance of a detailed patient history to prompt NOTCH3 testing