Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL)

Hutchinson, Michael; O'Riordan, J I; Javed, Mohammed; Quin, Etain; MacErlaine, Donal P.; Willcox, Teresa; Parfrey, Nollaig A.; Nagy, Tamás; Tournier‐Lasserve, Elisabeth

doi:10.1002/ana.410380517

Cited by 82 publications

(27 citation statements)

References 19 publications

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“…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).…”

Section: Discussionmentioning

confidence: 54%

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

et al. 2000

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Objective More than 80 unrelated, but all Caucasian, patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), originating from various communities around the world, have been molecularly identified. To clarify the occurrence of CADASILin Orientals, we investigated Japanese families presenting as CADASIL. Methods Weperformed the PCR-SSCPand sequence analyses using genomic DNA,isolated from venous blood of participants under informed consent. Patients Weidentified two unrelated Japanese families with CADASIL,including 5 affected members through 2 generations.Results Each of the affected individuals developed recurrent strokes without risk factors resulting in progressive dementia, pseudobulbar palsy, and gait disturbances which started after the fifth decade of life. Although affected individuals had no vascular risk factors, they showed various degrees of narrowing of retinal arteries. Their MRI/ CTs showed characteristics of the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem, and deep white matter in addition to the findings of leukoaraiosis. On SPECTimaging, there was severe hypoperfusion in the cortex as well as in the white matter. Ultrastructural studies revealed an abnormal deposition of granular osmiophilic materials (GOM)within the basal lamina of pericytes in muscular capillaries. On PCR-SSCPand sequence analyses, a heterozygous Argl33Cys mutation was present, in the affected individuals, in the exon 4 of Notch3 gene which is the hot spot region for CADASILmutations in Caucasian families. None of the non-affected membersnor the 50 Japanese normal controls revealed this mutation. Conclusion Thus, our results confirm that CADASIL is a geographically widespread disorder caused by a Notch3 mutation. (Internal Medicine 39: 732-737, 2000)

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Section: Discussionmentioning

confidence: 54%

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

et al. 2000

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“…Five to 10% of the CADASIL patients develop epileptic seizures which may require treatment. There have been single reports on spinal cord signs [17] or infarcts [1, 18] as well as intracerebral hemorrhages [1, 19]. However, these are single observations.…”

Section: Clinical Phenotypementioning

confidence: 94%

CADASIL: A Monogenic Condition Causing Stroke and Subcortical Vascular Dementia

Dichgans

2002

Cerebrovasc Dis

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Mutations in Notch3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited small vessel disease leading to subcortical strokes and vascular dementia. The phenotypic presentation is variable but remarkable for a high frequency of migraine with aura. Magnetic resonance images show a microangiopathic pattern of lesions. Prominent involvement of the temporopolar white matter and involvement of the temporopolar arcuate fibers are conspicuous findings seen in many patients. The underlying angiopathy is characterized by a unique type of ultrastructural basal lamina deposits and by degeneration of vascular smooth muscle cells which are the major source of Notch3 expression. In line with these findings there is evidence for a functional impairment of vascular smooth muscle cells. CADASIL has opened a new perspective in studying basic mechanisms of vessel wall degeneration and ischemic tissue damage related to small vessel disease.

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“…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 .…”

Section: Migrainementioning

confidence: 99%

CADASIL: pathogenesis, clinical and radiological findings and treatment

André

2010

Arq. Neuro-Psiquiatr.

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of ischemic strokes and a most important model for the study of subcortical vascular dementia. This unrelentlessly progressive disease affects many hundreds of families all over the world but is not well studied in Brazil. This manuscript reviews pathogenetic, clinical, radiological and therapeutic features of CADASIL. The causal mutations are now very well known, but the same can not be said about its intimate pathogenetic mechanisms. The variable clinical presentation should lead physicians to actively pursue the diagnosis in many settings and to more thouroughly investigate family history in first degree relatives. A rational approach to genetic testing is however needed. Treatment of CADASIL is still largely empiric. Highquality therapeutic studies involving medications and cognitive interventions are strongly needed in CADASIL. Key words: CADASIL, etiology, genetics, diagnosis, therapeutics.cADAsIL: patogênese, achados clínicos e radiológicos e tratamento resumo CADASIL é a causa genética mais freqüente de infartos cerebrais e constitui modelo importante de estudo de demências vasculares subcorticais. De natureza inexoravelmente progressiva, afeta milhares de pessoas em todo o mundo. Sua importância é pouco reconhecida entre nós, o que nos levou à presente revisão dos principais aspectos patogenéticos, clínicos, neuroradiológicos e terapêuticos da doença. As mutações causais são hoje bem conhecidas, mas os mecanismos patogenéticos íntimos ainda permanecem misteriosos. A apresentação clínica variável deve fazer com que os médicos considerem o diagnóstico em vários contextos clínicos e investiguem de forma mais extensa que o usual a história familial deparentes de primeiro grau. Além disso, uma abordagem racional é necessária para reduzir custos e aumentar a eficiência do diagnóstico genético. O tratamento atual de pacientes com CADASIL é basicamente empírico. Estudos clínicos sobre medicamentos e intervenções cognitivas de alto nível metodológico constituem uma necessidade urgente.

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Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL)

Cited by 82 publications

References 19 publications

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

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

CADASIL: A Monogenic Condition Causing Stroke and Subcortical Vascular Dementia

CADASIL: pathogenesis, clinical and radiological findings and treatment

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