CADASIL: pathogenesis, clinical and radiological findings and treatment

Abstract

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.

Anesthetic Management and Postoperative Care of a Patient with CADASIL (Cerebral Arteriopathy, Autosomal Dominant, with Subcortical Infarcts and leukoencephalopathy) for Cesarean Section

“…The disease has a natural history of recurrent ischemic episodes affecting the white substance. The signs and symptoms of the disease are migraine, with or without accompanying neurological signs, cognitive problems, epileptic attacks, psychiatric symptoms, and dementia, which is frequently accompanied by walking difficulties, urinary incontinence and pseudo bulbar syndrome (3)(4)(5). Typical neuroradiological findings on magnetic resonance imaging (MRI): multifocal and bilateral FLAIR, hyperintensities in the periventricular and deep white matter, with lesions mainly affecting the anterior temporal pole, frontal and parietal lobes, external capsule, pons and basal ganglia; focal hyperintensities (lacunar infarcts) and lesions suggestive of micro hemorrhages or gradient-echo (3,4) (Figure 1).…”

“…CADASIL is sometimes not even considered in differential diagnosis for several reasons, especially lack of MRI availability and apparently negative family history. Computed tomography (CT) clearly shows the subcortical infarcts -typically lacunar, but also larger lesions and also shows white matter lesions, especially in more advanced cases (3). No specific treatment is available.…”

“…However, anti-platelet agents such as aspirin, dipyridamole, or clopidogrel might slow down the disease and help prevent strokes. Given the propensity for cardiovascular and cerebrovascular complications, minimizing vascular risk factors and implementing therapy for primary or secondary prevention of stroke and myocardial infarction seems prudent (2,3). It is essential to keep in mind that cerebral arteriography is highly inadvisable, for it is likely to induce vasospasm.…”

Longitudinally extensive transverse myelopathy in a patient with CADASIL

“…Examination disclosed spastic tetraparesis with posterior cord syndrome. Neuroimaging revealed a longitudinally extensive centromedullary hyperintensity in the spinal cord between C2-T1 levels and a diffuse leukoencephalopathy CADASIL is a common hereditary vasculopathy in adults characterized by chronic migraine, subcortical infarcts and cognitive and behavioral disturbances 1,2 . Spinal cord involvement is extremely rare, making this a differential diagnosis of demyelinating diseases 2,3 .…”

New risk factors of stroke in young adults

“…Специфического лечения не существует, рекомен-дован прием аспирина, дипиридамола или клопи-догрела. При когнитивных нарушениях положи-тельных эффект был отмечен при применении до-непезила [90][91][92].…”