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.