COL4A1 brain small-vessel disease
COL4A1 brain small-vessel disease is an autosomal dominant monogenic COL4A1-related disorder that primarily causes cerebral small vessel disease.
Epidemiology
The exact prevalence is unknown, but the condition is likely under-diagnosed.
Clinical presentation
The clinical presentation is varied but generally presents during adulthood (30-50 years of age) with CNS features, including :
- hemorrhagic stroke: generally subcortical in location, involving the centrum semiovale, deep grey matter, or brainstem
- ischemic stroke: generally lacunar infarcts
- migraine with aura
- seizures
- subarachnoid hemorrhage
Notably, dementia is not a feature of COL4A1 brain small-vessel disease . Furthermore, multi-organ involvement (including features of other COL4A1-related disorders) has also been rarely reported in patients with COL4A1 brain small-vessel disease, including cataracts, retinal hemorrhages, Axenfeld-Rieger anomaly, nephropathy, muscle cramps, mitral valve prolapse, arrhythmias, and Raynaud phenomenon .
Pathology
COL4A1 brain small-vessel disease is an autosomal dominant condition resulting from a mutation to the COL4A1 gene, located on the long arm of chromosome 13, that normally encodes for the alpha-1 chain of type IV collagen . Type IV collagen is an important component of basement membranes in many tissues, especially blood vessels .
A similar syndrome is seen in patients with mutation to the COL4A2 gene .
Histology
Histological analysis of affected blood vessels reveals interruption and thickening of basement membrane .
Radiographic features
CT
CT is non-specific, demonstrating white matter regions of low attenuation .
MRI
MRI is the investigation of choice and demonstrates the following features:
- widespread confluent, bilateral, symmetric white matter hyperintensities on T2-weighted sequences, with relative sparing of subcortical U-fibers
- dilated perivascular spaces
- cerebral microhemorrhages, predominantly involving the centrum semiovale, deep grey matter, or brainstem
- intracerebral hemorrhage in the same distribution as cerebral microhemorrhages
- ischemic stroke, most commonly lacunar infarcts
- porencephalic cysts, often unilateral
CTA / MRA
Angiographic studies may demonstrate the presence of intracranial cerebral aneurysms, most commonly affecting the intracranial internal carotid artery or middle cerebral artery .
Treatment and prognosis
No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended .
Differential diagnosis
General imaging differential considerations include:
