6.8.1 Headache attributed to Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Description:

Headache recurring in attacks resembling 1.2 Migraine with aura, except for an unusual frequency of prolonged aura, caused by Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). It is associated with the other clinical features of CADASIL or, often, the first symptom of it.

Diagnostic criteria:
  1. Recurrent attacks of migraine with typical, hemiplegic or prolonged aura, fulfilling criterion C
  2. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) has been demonstrated1
  3. Either or both of the following:
    1. migraine with aura was the earliest clinical manifestation of CADASIL
    2. attacks of migraine with aura improve or cease when other manifestations of CADASIL (eg, ischaemic stroke, mood disturbances and/or cognitive dysfunction) appear and worsen
  4. Not better accounted for by another ICHD-3 diagnosis.
Note:

The diagnosis is made by screening for NOTCH-3 mutations, by a simple skin biopsy with immunostaining of NOTCH-3 antibodies, or with electron microscopy to assess for extracellular granular osmiophilic material (GOM) within the arterial media.

Comments:

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an autosomal dominant disease, with some sporadic cases, involving the smooth muscle cells in the media of small arteries of the brain. It is due to mutations of the NOTCH-3 gene.

CADASIL is characterized clinically by recurrent small deep infarcts, subcortical dementia, mood disturbances and, in one third of cases, by attacks typical of 1.2 Migraine with aura except for an unusual frequency of prolonged aura. In such cases, these are usually the first symptom of the disease, appearing at a mean age of 30 years, some 15 years before ischaemic strokes and 20-30 years before death.

MRI is always abnormal, with striking white matter changes on T2-weighted images.