1/12. Thrombophilic risk factors and unusual clinical features in three Italian cadasil patients.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in cadasil patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian cadasil patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of cadasil should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.- - - - - - - - - - ranking = 1keywords = family, family member, member (Clic here for more details about this article) |
2/12. cadasil in a family from north-west india.We here with report a family with two sibs having history of recurrent familial stroke. neuroimaging revealed diffuse hyperintense signals in subcortical white matter and basal ganglia on MR images in younger sib suggestive of cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leucoencephalopathy (cadasil). The diagnosis was further strengthened on skin biopsy showing presence of PAS positive granules with thickening of dermal vessels.- - - - - - - - - - ranking = 4.644625595779keywords = family (Clic here for more details about this article) |
3/12. Arg332Cys mutation of NOTCH3 gene in the first known Taiwanese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.The phenotype and genotype of cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (cadasil) in Caucasians have been well characterized, but cadasil is less recognized in Asian populations. Here we investigated the first known Taiwanese family affected by cadasil and identified an uncommon NOTCH3 mutation. The family had clinical manifestations in affected members including recurrent strokes, early dementia, and depression, but not migraine. A skin biopsy in the proband patient showed characteristic pathological findings of cadasil on electron microscopy. Afterward, genetic analysis found an Arg332Cys mutation at exon 6 of NOTCH3. Neuropsychological evaluation showed vascular dementia in two of four affected people. head MRI showed multiple infarcts in bilateral basal ganglia, thalami, periventricular white matter, external capsules, and brainstem, but involvement of the anterior temporal pole was found only in two people with milder symptoms. To our knowledge, the Arg332Cys NOTCH3 mutation at exon 6, which was identified in the studied family, has not been reported in Asian populations. Our findings emphasize the importance of genetic analysis of NOTCH3 for Asians with a phenotype typical of cadasil.- - - - - - - - - - ranking = 6.5112328444637keywords = family, member (Clic here for more details about this article) |
4/12. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephaloapthy (cadasil): a hereditary cerebrovascular disease, which can be diagnosed by skin biopsy electron microscopy.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is an inherited cerebrovascular disease characterized by recurrent subcortical ischemic strokes starting in the third or fourth decade as a result of mutations in the Notch3 gene. Granular osmiophilic material (GOM) deposition around the vascular smooth muscle cells is a specific feature and electron microscopic observations of skin biopsies are useful for this diagnosis. A 39-year-old female with dizziness, abnormal visual fields, and hemiplegia, and a 42-year-old male with tinnitus and dizziness, were suspected of suffering from cadasil based on MRI findings. Both cases were shown to have characteristic deposits of GOM, 200 to 800 nm in diameter, around the vascular smooth muscle cells of small arteries in the deep dermis, and thus the diagnoses of cadasil were made, although there was no family history of cerebrovascular disorders or dementia. Dermatologists should be aware of these ultra-structural findings because this disease may occur sporadically and might be more common than initially thought.- - - - - - - - - - ranking = 0.92892511915579keywords = family (Clic here for more details about this article) |
5/12. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) presenting with sudden sensorineural hearing loss.cadasil (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an autosomal dominant angiopathy characterized by recurrent cerebrovascular events, migraine and dementia. We describe a case of sensorineural hearing loss as the presenting feature of this condition. We have found no previous reports in the world literature of cadasil presenting with a sudden sensorineural hearing loss. The significance of questioning a patient with regard to family history is exemplified in this case.- - - - - - - - - - ranking = 0.92892511915579keywords = family (Clic here for more details about this article) |
6/12. cadasil with NOTCH3 S180C presenting anticipation of onset age and hallucinations.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is an inherited disease leading to strokes and vascular dementia. The average age of onset for stroke is 45 years with a range of about 30 to 70 years. We describe a Japanese cadasil family showing S180C in the exon 4 of NOTCH3, presenting an anticipation of the onset age for stroke. MRI demonstrated a similar extent of white matter involvement in younger and older individuals, supporting the presence of anticipation. In addition, hallucinations in 71% of affected patients, and delusions in 57% were also described. Our findings in this family suggest that a specific NOTCH3 mutation was related to unique clinical features, although such correlations have seldom been encountered in cadasil.- - - - - - - - - - ranking = 1.8578502383116keywords = family (Clic here for more details about this article) |
7/12. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) in a Greek family.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is an adult-onset inherited disease, characterised by recurrent strokes, migraine and cognitive impairment. We present the first Greek family with cadasil, caused by the R153C mutation at exon 4 of the Notch3 gene. A member of this family carrying this mutation was also found to be heterozygotic for the MTHFR mutation, factor v Leiden mutation and had low serum levels of antithrombin iii, thus resulting in the appearance of recurrent strokes and thrombotic episodes since his early adulthood. The co-existence of these thrombophilic disorders with cadasil in a single person poses serious therapeutic dilemmas, as the administration of anticoagulant agents may correlate with increased risk of potentially fatal intracerebral haemorrhage.- - - - - - - - - - ranking = 5.5823077253079keywords = family, member (Clic here for more details about this article) |
8/12. Neonatal porencephaly and adult stroke related to mutations in collagen IV A1.OBJECTIVE: The objective of this study was to describe leukoencephalopathy, lacunar infarcts, microbleeds and macrobleeds in the context of a collagen IV A1 mutation. methods: We examined a family with autosomal dominant porencephaly, in whom a defect in collagen IV A1 was detected recently. The patients underwent neurological, ophthalmological, and cardiological examinations and magnetic resonance imaging of the brain. Electron microscopy of a skin biopsy was performed. Extensive laboratory screening was performed for thrombophilia and increased bleeding tendency. RESULTS: The porencephaly was symptomatic in the infantile period in two patients, whereas it led to only minor neurological dysfunction in their affected mother. However, she experienced development of recurrent strokes in her 40s. In addition to the porencephaly, all patients had a leukoencephalopathy, which was most severe in the mother. Her magnetic resonance imaging results also showed lacunar infarcts, macrobleeds and a multitude of microbleeds. No other risk factors for recurrent stroke were found. Electron microscopy showed interruptions of the basement membrane of skin capillaries and inhomogeneous thickening of the basement membrane with pools of basement membrane fragments. INTERPRETATION: Leukoencephalopathy, ischemic infarcts, microbleeds, and macrobleeds are indicative of an underlying microangiopathy, of which the best-known causes are hypertension, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral amyloid angiopathy. Mutations in collagen IV A1, a major component of the vascular basement membrane, appear to be another risk factor.- - - - - - - - - - ranking = 0.92892511915579keywords = family (Clic here for more details about this article) |
9/12. cadasil presenting with a movement disorder: a clinical study of a Chilean kindred.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is a hereditary vascular disease that usually begins with migraine, followed by repeated strokes and progressive dementia. We describe an unusual clinical presentation of this condition in members of a Chilean family with an established NOTCH3 mutation. We report early clinical, neuropsychological, transcranial ultrasound, magnetic resonance imaging (MRI), cerebral blood flow, and skin biopsy findings on these patients. Of the patients, 2 presented with facial dystonia, 1 of whom had abnormal single photon emission computed tomography and transcranial ultrasound studies after normal brain MRI scans. Our report emphasizes that cadasil must be considered in the study of patients with secondary dystonia.- - - - - - - - - - ranking = 0.93768212952893keywords = family, member (Clic here for more details about this article) |
10/12. The R110C mutation in Notch3 causes variable clinical features in two Turkish families with cadasil syndrome.Mutations in Notch3 gene are responsible for the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). It is a late onset neurological disorder recognized by recurrent strokes and dementia. We describe here the clinical and molecular findings of three unrelated Turkish families with cadasil syndrome. Two of the families were identified to have the same mutation, p.R110C (c.C328T), located in exon 3 of the Notch3 gene. Interestingly, the phenotypic expression of the disease in these two families was markedly different in severity and age of onset implicating additional genetic and/or non-genetic modulating factors involved in the pathogenesis. In addition, we identified the novel p.C201R (c.T601C) mutation in exon 4 of the Notch3 gene in a proband of the third family with two consecutive stroke-like episodes and typical MRI findings. Mutations described here cause an odd number of cysteines in the N-terminal of the EGF domain of Notch3 protein, which seems to have an important functional effect in the pathophysiology of cadasil. The phenotypic variability in families carrying the same molecular defect as presented here makes the prediction of prognosis inconceivable. Although dna analysis is effective and valuable in diagnosing approximately 90% of the cadasil patients, lack of genotype-phenotype correlation and prognostic parameters makes the presymptomatic genetic counseling very difficult.- - - - - - - - - - ranking = 0.92892511915579keywords = family (Clic here for more details about this article) |
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