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CADASIL
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CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Genetics & Pathophysiology
Autosomal dominant condition:
  • Mutation in the NOTCH3 gene located on chromosome 19.
    • The NOTCH3 gene is critical for the survival of vascular smooth muscle cells; mutation of it leads to apoptosis of vascular smooth muscle cells, which leads to blood vessel damage and stroke.
  • Although CADASIL is a generalized vasculopathy, the vascular patholology is mostly limited to the brain.
Clinical Manifestations
Generally, first manifests in adulthood: Recurrent ischemic strokes (mainly* small subcortical strokes)
    • Anterior temporal lobe white matter changes.
    • Often in the basal ganglia; thalamus (pure sensory stroke, sensorimotor strokes); or brainstem (ataxic-hemiparesis, pure motor stroke), particularly the pons (dysarthria–clumsy hand syndrome).
  • Migraine with aura
    • Migraine is often the presenting symptom of CADASIL.
    • The auras are typically visuosensory aura but ~ 50% will have atypical auras (eg, hemiplegic, confusion, etc…).
  • Neuropsychiatric manifestations
    • Major depression and apathy
  • Cognitive impairment
    • Recurrent nature of the strokes leads to cognitive deterioration.
    • Commonly stepwise decline with pronounced deficits in executive function, cognitive processing speed, and verbal fluency.
Radiographic Findings
Characteristically causes leukoencephalopathy in the anterior temporal lobes.
  • Less commonly, causes white matter lesions in the external capsule and corpus callosum.
  • Subcortical strokes
  • Microhemorrhages
  • Brain atrophy
    • In large part, due to neurodegeneration of the cortical regions that connect with the areas of subcortical infarct.
Diagnosis
  • Genetic Screening
  • Skin Biopsy
Image Reference
  • Special thanks to Bohlega S, Al Shubili A, Edris A, Alreshaid A, Alkhairallah T, AlSous MW, Farah S, Abu-Amero KK for use the associated radiographs. From: CADASIL in Arabs: clinical and genetic findings. BMC Medical Genetics 2007, 8:67doi:10.1186/1471-2350-8-67
REFERENCES
Chabriat H, Joutel A, Dichgans M, et al. Cadasil. Lancet Neurol 2009; 8:643.
Dichgans M. Cognition in CADASIL. Stroke 2009; 40:S45.
Fattapposta F, Restuccia R, Pirro C, et al. Early diagnosis in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): the role of MRI. Funct Neurol 2004; 19:239.
Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383:707.
Ling Y, De Guio F, Duering M, et al. Predictors and Clinical Impact of Incident Lacunes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy. Stroke 2017; 48:283.
Moreton FC, Razvi SS, Davidson R, Muir KW. Changing clinical patterns and increasing prevalence in CADASIL. Acta Neurol Scand 2014; 130:197.
https://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy#genes

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