1/7. Arg133Cys mutation of Notch3 in two unrelated Japanese families with cadasil.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 cadasil in Orientals, we investigated Japanese families presenting as cadasil. methods: We performed the PCR-SSCP and sequence analyses using genomic dna, isolated from venous blood of participants under informed consent. patients: We identified 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 SPECT imaging, 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-SSCP and sequence analyses, a heterozygous Arg133Cys mutation was present, in the affected individuals, in the exon 4 of Notch3 gene which is the hot spot region for cadasil mutations in Caucasian families. None of the non-affected members nor 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.- - - - - - - - - - ranking = 1keywords = pseudobulbar, pseudobulbar palsy, palsy (Clic here for more details about this article) |
2/7. Progressive supranuclear palsy phenotype secondary to cadasil.BACKGROUND AND PURPOSE: To report a unique case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy manifesting as a progressive supranuclear palsy phenotype, thereby expanding its recognized presentations. methods: review of the pertinent literature from medline, cross-referencing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, progressive supranuclear palsy, and parkinsonism. Description of a 60-year-old woman who presented with a several year history of step-wise, progressive parkinsonism secondary to cerebral autosomal dominant arteriopathy. RESULTS: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present with a progressive supranuclear phenotype. CONCLUSION: Parkinsonism, including a progressive supranuclear palsy phenotype, is one of a growing number of recognized ways that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present.- - - - - - - - - - ranking = 0.00057119063111241keywords = palsy (Clic here for more details about this article) |
3/7. An Italian case of cadasil with mutation CGC-TCG in codon 1006, exon 19 Notch3 gene.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in cadasil is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in italy and the second reported in the literature.- - - - - - - - - - ranking = 2keywords = pseudobulbar, pseudobulbar palsy, palsy (Clic here for more details about this article) |
4/7. Multi-infarct progressive supranuclear palsy--case report.A patient with supranuclear upward gaze palsy, pseudobulbar palsy, dementia, asymmetrical pyramidal signs, and atypical parkinsonism that developed after recurrent strokes was reported. The clinical features closely resembled idiopathic progressive supranuclear palsy (PSP). Computerised tomography of the brain showed, in addition to dilated third ventricle and prominent quadrigeminal plate and ambient cisterns, multiple infarcts at the thalamus, striatum, frontal subcortex and corona radiata. Multi-infarct PSP (MI-PSP) was thought to be the most likely diagnosis rather than coincidental idiopathic PSP with recurrent cerebral infarcts.- - - - - - - - - - ranking = 1.0004895919695keywords = pseudobulbar, pseudobulbar palsy, palsy (Clic here for more details about this article) |
5/7. Diffuse white matter involvement seen in patients in longstanding bedridden state from cerebrovascular dementia.We report here two autopsied cases of patients who had been in a longstanding bedridden state from cerebrovascular dementia. They showed a clinical history of persistent hypertension, a history of acute strokes, a lengthy clinical course with long plateau periods and a gradual accumulation of focal neurological symptoms and signs, including dementia and prominent motor disturbances and pseudobulbar palsy. They had been in a bedridden state for the last several years and had to be fed. The pathology seemed to predominently affect the perforating vessels to the subcortical gray and white matter. Demyelination, loss of axons, patchy gliosis and infiltration by macrophages were noted in the involved regions. The long penetrating vessels of the white matter showed advanced arteriosclerotic changes. There was a relative sparing of the cortex. The low attenuation of the white matter with moderate to severe atrophy, and an infarction might well be significant features on a CT-scan of these conditions. One of the possible mechanisms on the pathogenesis of chronic vascular disease includes diffuse ischemia related to hypertensive vasculopathy.- - - - - - - - - - ranking = 1keywords = pseudobulbar, pseudobulbar palsy, palsy (Clic here for more details about this article) |
6/7. Binswanger's disease presenting as levodopa-responsive parkinsonism: clinicopathologic study of three cases.We report three cases of autopsy-proven Binswanger's disease (subcortical arteriosclerotic encephalopathy) with unusual clinical features. Two patients had supranuclear gaze disturbances, early gait dysfunction, and speech disorders suggestive of progressive supranuclear palsy. One of these patients was not demented at the time of death. The third patient had features typical of Parkinson's disease. All three patients were responsive to treatment with levodopa. The clinical spectrum of Binswanger's disease should be expanded to include levodopa-responsive parkinsonism.- - - - - - - - - - ranking = 8.1598661587487E-5keywords = palsy (Clic here for more details about this article) |
7/7. Autosomal dominant leukoencephalopathy and subcortical ischemic stroke. A clinicopathological study.BACKGROUND AND PURPOSE: We recently described an autosomal dominant syndrome characterized mainly by recurrent strokes and neuroimaging evidence of leukoencephalopathy. We now report the pathological findings in one of the affected subjects. CASE DESCRIPTION: A 40-year-old woman experienced her first grand mal seizure in 1971. From 1983 on she suffered recurrent strokes, seizures, and psychiatric disturbances with depressions, manic episodes, and dementia. In 1988, after her fourth stroke, she became tetraplegic with a severe pseudobulbar palsy, and she died in 1990. Pathological examination disclosed a recent capsulolenticular hematoma, multiple small deep infarcts, a diffuse myelin loss and pallor of the hemispheric white matter, and a widespread vasculopathy of the small arteries penetrating the white matter. The arterial wall was markedly thickened with an extensive nonamyloid eosinophilic deposit in the media and reduplication of the internal elastic lamella. CONCLUSIONS: The underlying lesion of this hereditary disorder is located in the small arteries and is of unknown etiology. It differs from arteriosclerotic and amyloid angiopathies but is similar to that described in some cases of hereditary multi-infarct dementia.- - - - - - - - - - ranking = 0.6097883012248keywords = pseudobulbar, palsy (Clic here for more details about this article) |