SHM Converge Scientific Abstract ePoster Gallery-Unraveling Cadasil: From Clinical Presentation to Genetic Confirmation

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CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is the most common inherited cerebral small-vessel disease, caused by NOTCH3 mutations. It typically begins with migraines, then progresses to recurrent ischemic events, transient neurologic symptoms, and cognitive decline.<br /><br />This case describes a 45-year-old woman who presented with sudden dizziness on sitting up, persistent holocranial pressure headaches, blurry vision, and kaleidoscope-like visual distortions. She had been followed as an outpatient for worsening headaches and cognitive decline. She denied focal weakness, sensory loss, falls, or family history. Initial CT head showed white matter abnormalities, and MRI demonstrated severe leukoencephalopathy involving multiple brain regions, raising concern for CADASIL versus vasculitis. Further evaluation, including cerebrospinal fluid testing and genetic screening, confirmed a heterozygous NOTCH3 mutation, establishing the diagnosis of CADASIL.<br /><br />The underlying pathology involves NOTCH3 protein misfolding and aggregation, with accumulation of granular osmiophilic material in small cerebral vessels. This leads to vessel wall thickening, impaired blood-brain barrier function, and damage to perivascular drainage pathways. On MRI, CADASIL classically produces symmetric bilateral white matter hyperintensities on T2/FLAIR, especially in the frontal, parietal, and anterior temporal regions and the external capsule.<br /><br />The authors emphasize that CADASIL should be considered in patients with new cognitive changes or stroke-like symptoms, particularly when traditional vascular risk factors are absent and imaging suggests the diagnosis. Early recognition and genetic confirmation are important for accurate diagnosis and counseling.

Asset Subtitle

Rodrigo Paredes

Meta Tag

Author List Andre Khazak, Brinda Raval, David Fruchter, Rodrigo Paredes, Sara Heide

Category Clinical Vignettes

Concept CADASIL

Concept White Matter Hyperintensity

Concept NOTCH3 mutation

Concept Cognitive Decline

Concept Stroke

Distinguished Non-Finalist

Presenter Organization Icahn School of Medicine at Mount Sinai, Department of Medicine Mount Sinai Morningside/West

Presenting Author Rodrigo Paredes

Track Adult

Keywords

CADASIL

NOTCH3 mutation

cerebral small-vessel disease

leukoencephalopathy

white matter hyperintensities

migraine

cognitive decline

ischemic events

MRI brain

granular osmiophilic material

CADASIL

White Matter Hyperintensity

NOTCH3 mutation

Cognitive Decline

Stroke