General description

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare hereditary small vessel disease caused by mutations in the HTRA1 gene on chromosome 10. It is inherited in an autosomal recessive manner and primarily affects young adults, typically presenting in the 20s or 30s. Most reported cases have been from Asia, though instances in European families suggest a broader global distribution.

CARASIL is characterized by a classic triad:

1. Premature alopecia: Often the earliest symptom, appearing as diffuse hair thinning in the teenage years. Unlike male-pattern baldness, it involves a generalized thinning of scalp hair without affecting body or pubic hair.
2. Vascular brain disease: Patients experience recurrent ischemic stroke-like episodes, typically starting in the third decade, often accompanied by progressive vascular dementia.
3. Spinal involvement: Severe low back pain due to early-onset deforming spondylosis, sometimes preceding neurological symptoms.

CARASIL involves small vessel pathology characterized by smooth muscle cell degeneration and intimal thickening in the cerebral vasculature. White matter lesions, visible on imaging, often precede neurological symptoms. The degenerative changes in spinal structures contribute to deforming spondylosis and chronic back pain.

Over time, patients experience gradual neurological decline, with many becoming bedridden after several decades due to progressive cognitive and motor impairments. Incomplete forms of CARASIL have been reported, where patients may lack one of the triad symptoms, such as alopecia.

References

1. Nozaki, Hiroaki, et al. "Characteristic features and progression of abnormalities on MRI for CARASIL." Neurology 85.5 (2015): 459-463.