New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature.

Abstract

A survey was carried out on a large family presenting the symptoms of familial arteriopathy (CADASIL) recently mapped to chromosome 19. This is characterised clinically by recurrent subcortical infarcts developing into pseudobulbar palsy and subcortical dementia, and radiologically by early MRI abnormalities.To characterise this familial condition, 43 members older than 20 years and spreading over four generations were studied clinically (31 living, 12 deceased), genetically, and radiologically by MRI (n = 31).Twenty out of 43 were found to be clinically symptomatic and of these 13 out of 31 had MRI abnormalities. Genetic studies mapped this condition to the locus of CADASIL (lod score > 3). The natural history suggests a chronological clinicoradiological staging of this phenotype of CADASIL: stage I between 20 and 40 years with frequent migraine-like episodes and well delineated lesions of the white matter; stage II between 40 and 60 years with stroke-like episodes, bipolar or monopolar-like psychotic disorders, coalescent lesions of the white matter, and well delineated lesions of the basal ganglia; and stage III over 60 years with subcortical dementia, pseudobulbar palsy, diffuse leukoencephalopathy, and multiple well delineated lesions of the basal ganglia.This phenotype differs from the other two previously described by high frequency of migraine, frequency of psychotic disorders, and early neurological manifestations.

Arg133Cys Mutation of Notch3 in Two Unrelated Japanese Families with CADASIL.

“…Considering the clinical features, the present Japanese patients did not have attacks of migraine with aura, which was frequently present in the Caucasian patients as the clinical onset (2,13,14). Although the presence of epileptic seizures has been documentedas a rare neurologic manifestation in French families (2), it was one of the major features in the probands of our Japanese families, as also seen in an Italian family (15).…”

CADASIL: pathogenesis, clinical and radiological findings and treatment

“…Neuroradiological abnormalities, which may be present from childhood 41 , are often already detected at symptom onset and are almost universally present in symptomatic patients (possible exception in individuals with migraine only) or around 35 years 42,43 . CADASIL may be classified in three clinical/radiological stages 44 : I: generally between 20 to 40 years of age, with migraine and MRI showing white matter-defined lesions 42 . II: age between 40 and 60, characterized by transient or permanent ischemic insults leading to motor disorders, sensory, sensory and cognitive impairments, with or without psychiatric disorders.…”

“…There are other families in which migraine and later insidiously progressive cognitive disorders are the sole manifestations of the disease, but the final diagnosis of CADASIL in these cases is still uncertain 53 . The first migraine attacks occur before 20 years of age 44,54 and may precede or be linked to early neuroradiological changes -punctate hyperintensities in deep hemisphere or periventricular white matter -that may also be present in some individuals with primary migraine 30 . Women with CADASIL and migraine with aura tend to have symptom onset earlier than affected men 43 .…”

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

“…[105][106][107] One CADASIL family has been described with typical FHM attacks, 108 and another family, linked to the CADASIL locus, with migraine and CADASIL-like white matter lesions on magnetic resonance imaging. 109 All these observations contributed to the clinical spectrum of migraine-FHM-CADASIL.…”