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CARASAL

Summary

  • Cathepsin A-Related Arteriopathy with Strokes And Leukoencephalopathy: a hereditary cerebral small vessel disease
  • Autosomal dominant, caused by mutations in CTSA (cathepsin A)
  • MRI shows a diffuse confluent leukoencephalopathy with characteristic brainstem and internal capsule involvement and lacunar infarcts

Pathophysiology

  • Autosomal dominant mutation in CTSA (chromosome 20)
  • Cathepsin A dysfunction disturbs vasoregulation (endothelin-1 and bradykinin handling), producing a non-amyloid small vessel arteriopathy
  • Chronic white matter ischaemia and lacunar infarction result

Demographics

  • Very rare; originally described in a large Dutch pedigree
  • Adult onset, typically from middle age

Diagnosis

  • Clinical features: treatment-resistant hypertension, ischaemic stroke, cognitive decline, migraine and prominent muscle cramps
  • Confirmed by CTSA genetic testing

Imaging

  • MRI:
    • Diffuse, confluent T2/FLAIR leukoencephalopathy of the cerebral white matter and internal/external capsules
    • Characteristic brainstem (pons) and superior cerebellar peduncle involvement
    • Lacunar infarcts
    • Relatively few microhaemorrhages, unlike CADASIL or amyloid angiopathy1

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  • A 50-year-old patient presented with a homonymous hemianopia and motor and sensory disturbance.
  • MRI showed an acute left thalamic infarct on a background of a diffuse leukoencephalopathy affecting the cerebral and capsular white matter, the brainstem and superior cerebellar peduncles.
  • There were no microhaemorrhages.

Treatment

  • Supportive; vascular risk-factor and blood-pressure management

Differential diagnosis

Imaging differential Differentiating feature
CADASIL Anterior temporal pole and external capsule white matter hyperintensities; NOTCH3 mutation
CARASIL Similar confluent white matter pattern; autosomal recessive HTRA1 mutation; early-onset spondylosis and alopecia
Hypertensive microangiopathy Deep white matter and basal ganglia hyperintensities; spares the anterior temporal poles
COL4A1-related small vessel disease Deep cerebral microhaemorrhages; lacunar infarcts; porencephaly; COL4A1/COL4A2 mutations
MELAS Stroke-like lesions not conforming to vascular territories; elevated serum/CSF lactate
Cerebral amyloid angiopathy Lobar microhaemorrhages; posterior predominance; cortical superficial siderosis
CSF1R-related leukoencephalopathy Confluent white matter disease with calcifications on CT; thalamic involvement
Susac syndrome Corpus callosum "snowball" lesions at the central fibres; hearing loss; branch retinal artery occlusions

  1. Bugiani et al. Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL). 2016. Neurology - Open in new tab. ↩