A polymorphic neurologic syndrome with recurrent
infarctions in the white matter resulting in a wide range of neurologic
symptoms (depression, dementia, seizures, pseudobulbar paralysis). CADASIL
is an acronym for cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy.
Hereditary Multi-Infarct Dementia; Familial Vascular
More than 50 affected families have been described. No
sexual predilection has been reported.
Autosomal dominant. The gene defect has been
mapped to the NOTCH3 gene (which encodes a transmembrane receptor with a
large number of epidermal growth factor-like repeats), located on
Not clearly understood. The disease is related to mutations in the NOTCH3
gene. Dense osmiophilic granular material in contact with arteriolar smooth muscle cells can be revealed
by electron microscopy.
Based on clinical findings characterized by the
acronymic association and a positive family history. Prominent signal
abnormalities on magnetic resonance imaging include hyperintense lesions on
T2-weighted images of the subcortical white matter, especially in the
anterior part of the temporal lobes, the periventricular portion of the
occipital lobes, and the basal ganglia. Small linear and punctate lacunas
can be detected in the periventricular white matter, brainstem, thalamus,
external capsule, and corpus callosum. Based on the abnormal accumulation of
NOTCH3-positive material within small vessels, immunostaining of skin biopsy samples using a
monoclonal antibody specific for NOTCH3 is the basis of a reliable and easy
diagnostic test. Skin biopsy revealing granular osmiophilic material can be
used for the diagnosis.
The onset of symptoms occurs generally in young
adults of both sexes, with complete penetrance of the disorder between 30
and 40 years of age. The most consistent findings are cerebrovascular
ischemic episodes (most often classic transient ischemic attacks or lacunar
strokes, but occasionally insidious deficits developing over several days).
Recurrent subcortical ischemic events occur in more than 80% of patients,
and a progressive or stepwise subcortical dementia with pseudobulbar palsy
can be found in almost one third of the patients. Clinical symptoms result
from (nonarteriosclerotic, nonamyloidotic) vasoocclusive cerebral infarcts
in the white matter that can cause a wide range of neurologic signs:
relapsing strokes, seizures, pseudobulbar palsy, gait anomalies, dementia,
urinary incontinence, hemiparesis or hemiplegia, and even tetraplegia.
Sensorineuronal dysfunctions may lead to speech defect, deafness, visual
loss, and insensitivity to pain. The behavior is severely affected and may
present as mood disorders, manic episodes, depression, and dementia.
Approximately 60% of patients have cognitive deficits, almost 40% have
migraine (usually with aura), and 10% have epilepsy. The mean age at death of
males is approximately 53 years versus 59 years for females.
Obtain a full neurologic status and
history (review electroencephalography reports, computed tomography scans,
and magnetic resonance images). Some patients may be on acetazolamide
therapy, so preoperative acid-base status and serum electrolytes should be
checked. If mental retardation is clinically significant, anxiolytic and
sedative premedication and/or presence of the primary caregiver ...