CADASIL

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 Leukoencephalopathy.

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 19p13.2-p13.1.

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 for induction of anesthesia may be helpful.

Maintaining cerebral perfusion pressure and unobstructed cerebral venous drainage (avoid Trendelenburg position), preventing hypocapnia, and avoiding cerebral vasoconstrictive drugs (e.g., propofol) are the main goals of anesthesia. Regional anesthesia is not contraindicated per se (although some patients are on acetylsalicylic acid), but central neuraxial blockade should probably be avoided given the neurologic symptoms. If used, however, care should be taken to maintain mean arterial pressure.

Consider the interaction between anesthetic and antiepileptic drugs. Avoid epileptogenic drugs. In patients with hemiparesis/hemiplegia or tetraplegia, succinylcholine should be avoided because of a possible exaggerated hyperkalemic response due to muscular denervation.

Moyamoya Syndrome: A progressive disease that affects the cerebral vasculature. The disease is characterized by narrowing and/or complete obstruction of the carotids. Headaches, various vision problems, mental retardation, paralysis, seizures, and psychiatric problems may occur. Cerebral hemorrhage (subarachnoid), cerebral infarction, severe headaches, speech disorders, and sudden onsets of recurrent paralysis are part of the presentation and most often occur in juvenile Moyamoya patients.