1/24. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (cadasil): a case report with review of literature. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (cadasil) is an inherited arterial disease, commonly overlooked or misdiagnosed. We report a case of cadasil in a 51 years old woman who presented with progressive subcortical dementia, recurrent ischemic events and seizures in the absence of known vascular risk factors of five years' duration. Her mother had a history of similar illness. magnetic resonance imaging (MRI) of brain revealed subcortical and deep white matter hyperintense lesions within the cerebral white matter on T2-weighted images. dna mutation of Notch 3 gene confirmed the diagnosis of cadasil. ( info) |
2/24. 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. ( info) |
| 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. ( info) |
4/24. 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. ( info) |
5/24. cadasil-an unusual manifestation with prominent cutaneous involvement. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucencephalopathy (cadasil) is a rare vascular disorder affecting mainly the central nervous system with transient ischaemic attacks, strokes, psychiatric symptoms and dementia. It is a progressive familial disease owing to mutations in the Notch3 gene. Clinically apparent skin involvement is usually absent. Electron microscopy of seemingly uninvolved skin reveals characteristic granular deposits in the basal lamina of vessels and adnexals. We report on a case of cadasil with generalized haemorrhagic macules and patches. Typical neurological symptoms as well as classical findings in histopathology and electron microscopy confirmed the diagnosis. Immunofluorescence showed an increased number of vessels with walls markedly thickened by deposits of fibrin, complement and immunoglobulins. This method could serve as an additional method for accurate diagnosis of cadasil. ( info) |
6/24. 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. ( info) |
7/24. cadasil: underdiagnosed in psychiatric patients? OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is exclusively related to symptoms of the central nervous system. Retrospectively in up to 15% the initial presentation is psychiatric disturbances. In these cases the diagnosis often is delayed or missed. METHOD: Two cases of cadasil diagnosed in a psychiatric hospital are presented. RESULTS: Both patients were admitted to the gerontopsychiatric department (one because of a suicidal attempt and a depressive episode, the other because of cognitive decline and progressive personal neglect). brain magnetic resonance imaging (MRI) showed severe leukoencephalopathy in the absence of cardiovascular risk factors. In both cases, diagnosis of cadasil was made by the identification of specific granular osmiophilic material in skin biopsies. CONCLUSION: brain MRI should be performed in all cases of late onset of severe psychiatric symptoms. cadasil should be considered as a possible differential diagnosis whenever a marked leukoencephalopathy is detectable. diagnosis can be verified by taking a skin biopsy or by specific genetic testing. ( info) |
8/24. Peripheral neuropathy in cadasil. BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (cadasil) is a hereditary cerebral microangiopathy associated with mutations in the Notch 3 gene. The clinical phenotype is characterized by cerebral impairment even though typical microvascular changes are diffuse. OBJECTIVE: To assess peripheral neuropathy in patients with cadasil. patients AND methods: We enrolled eleven cadasil patients with variable phenotype including clinical signs of peripheral nerve involvement. In all patients electromyography and nerve conduction velocities were performed. Peripheral nerve biopsy was performed in three cases. RESULTS: We found sensory motor neuropathy in 7/11 patients. Nerve biopsy revealed axonal and demyelinated findings. CONCLUSION: Our findings suggest that peripheral neuropathy may be part of the cadasil phenotype. ( info) |
9/24. 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. ( info) |
10/24. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is an adult-onset hereditary syndrome characterized by recurrent TIAs and strokes, cognitive decline and dementia, migraine with aura ( /-40% of patients), and psychiatric disturbances ( /-30% of patients). Affected individuals have prominent signal abnormalities on brain MRI. Symmetrical white matter abnormalities are invariably seen and often small subcortical infarcts are also present. The extent of the MRI lesions increases with age, from subtle white matter abnormalities in the anterior temporal poles in the early 20 years to confluent white matter lesions with subcortical infarcts and microbleeds in the 6(th) decade. A typical arteriopathy with electron dense granular depositions in the media of small cerebral arteries underlies this disorder. These arterial lesions can be found, to a lesser extent, in extra-cerebral arteries such as skin arterioles. In 1996, the defective gene in cadasil was discovered to be NOTCH3. NOTCH3 encodes a 300-kd transmembrane protein with a receptor and cell signal transduction function. Mutations are almost always missense mutations causing the loss or gain of a cysteine residue and are detected in over 90% of patients. How alterations in NOTCH3 lead to the cadasil phenotype has yet to be elucidated. ( info) |