(Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)

Created 12/05/2023, last revision 21/07/2023


  • CARASIL is a very rare (probably underdiagnosed) hereditary disease affecting the small cerebral vessels, spine, and hair follicles
  • caused by a mutation in the HTRA1 gene on chromosome 10q (10q25.3-q26.2)
  • there are 2 forms (Onodera, 2010)
    • classic CARASIL – with biallelic pathogenic variants  (AR inheritance)
    • HTRA1-CSVD – with heterozygous HTRA1 pathogenic variant (AD inheritance)
  • classic CARASIL is characterized by early-onset changes in the deep white matter on MRI and associated neurologic symptoms (early-onset gait disturbance, scalp alopecia, cognitive impairment)
  • HTRA1-CSVD may be oligosymptomatic or asymptomatic (with positive neuroimaging only)

Clinical presentation


  • premature alopecia (starting in the teenage years; one of the initial symptoms)
  • musculoskeletal symptoms (before the age of 30)

    • deforming spondylosis (cervical spine and/or thoracolumbar spine), disc herniation
    • knee or elbow osteoarthritis
  • spastic gait (between 20 and 40 years of age)
  • recurrent ischemic stroke-like episodes (typically before age 40) with gradually progressive vascular dementia and mood changes (apathy)
  • symptomatic poststroke epilepsy
  • in contrast to CADASIL, migraine is not present


  • slowly progressive gait disturbance and stroke-like episodes (usually after age 40)
  • may be followed by mood changes and cognitive dysfunction
  • spondylosis and alopecia are less common

Diagnostic evaluation

CARASIL should be suspected if the combination of diffuse vascular leukoencephalopathy, alopecia, and disk herniations occur at a young age


  • CT shows nonspecific hypodensities in the white matter (leukoaraiosis)
  • MRI detects hypointensities on T1 and hyperintensities on T2
    • white matter lesions (WML)
      • U-fibers are relatively preserved
      • it is not clear whether the anterior temporal pole and external capsule lesions are observed in the early stages of CARASIL
    • lacunar infarcts in the basal ganglia, thalamus, and pons
    • arc sign – increased T2 signal across the pons at the level of middle cerebellar peduncles  (Röben, 2016)
    • cerebral microbleeds (CMBs) → see here
CARASIL - arc sign (Roeben, 2016)

Laboratory tests

  • genetic testing – the gold standard for definitive diagnosis
    • mutation affects the HTRA1 gene on chromosome 10q (10q25.3-q26.2
    • once the HTRA1 pathogenic variant(s) have been identified in family members, prenatal and preimplantation testing is possible
  • skin biopsy does not help establish the diagnosis

Differential diagnosis

  • Binswanger´s disease
    • in elderly individuals with multiple vascular risk factors
    • absence of typical temporal lobe lesions
    • symptoms appear 10-15 years earlier in patients with classic CARASIL
    • migraine and depression are not present in CARASIL
  • Susac syndrome 
    • no temporal lobe involvement
    • retinopathy, hearing impairment
  • primary angiitis of the CNS (PACNS)
  • progressive multiple sclerosis
  • COL4A1 cerebral small-vessel disease
  • CARASAL (cathepsin A-related arteriopathy with strokes and leukoencephalopathy)


  • no causal or disease-modifying treatment is available
  • therapy is similar to that of traditional small vessel disease
  • management of modifiable vascular risk factors
  • antiplatelets and statins
    • clinical efficacy is not proven
  • symptomatic treatment of psychiatric disorders and spasticity
  • risk/benefit ratio of tPA and anticoagulation is uncertain
  • physical therapy, walking aids, cognitive training
  • standard treatment of spinal spondylosis and mood disorders
  • genetic counseling

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