683 research outputs found
CADASIL: A monogenic condition causing stroke and subcortical vascular dementia
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. Copyright (C) 2002 S. Karger AG, Basel
Familial hemiplegic migraine with cerebellar ataxia and paroxysmal psychosis
Familial hemiplegic migraine is a rare autosomal dominant disorder associated with stereotypic neurologic au ra phenomena including hemiparesis, So far two chromosomal loci have been identified. Families linked to the chromosome 19 locus display missense mutations within the CACNL1A4 gene. Here we report on a family with familial hemiplegic migraine and cerebellar ataxia with recurrent episodes of acute paranoid psychosis with anxiety and visual hallucinations associated with migraine attacks. Based on the clinical and haplotype evidence indicating linkage to chromosome 19 in this family, we hypothesize that a dysfunction of the mutated calcium channel may be involved not only in the development of hemiplegic migraine but also in the acute psychotic episodes observed in these patients
Vascular Cognitive Impairment
Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts
APP Expression in Primary Neuronal Cell Cultures fromP6 Mice during in vitro Differentiation
Primary neuronal cell cultures from P6 mice were investigated in order to study amyloid protein precursor (APP) gene expression in differentiating neurons. Cerebellar granule cells which strongly express APP 695 allowed the identification of three distinct isoforms of neuronal APP 695. The high-molecular-weight form of APP 695 is sialylated. The expression pattern of neuronal APP 695 changes during in vitro differentiation. Sialylated forms become more abundant upon longer cultivation time. The secreted forms of sialylated, neuronal APP 695 are shown to comigrate with APP isolated from cerebrospinal fluid. We suggest that the different sialylation states of APP 695 may reflect the modulation of cell-cell and cell-substrate interactions during in vitro differentiation and regeneration
NIHSS Scores in Ischemic Small Vessel Disease: A Study in CADASIL
Background: The National Institutes of Health Stroke Scale (NIHSS) is widely used to measure neurological deficits, evaluate the effectiveness of treatment and predict outcome in acute ischemic stroke. It has also been used to measure the residual neurological deficit at the chronic stage after ischemic events. However, the value of NIHSS in ischemic cerebral small vessel disease has not been specifically evaluated. The purpose of this study was to investigate the link between the NIHSS score and clinical severity in a large population of subjects with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a unique model to investigate the pathophysiology and natural history of ischemic small vessel disease. Methods: Demographic and clinical data of 220 patients with one or more lacunar infarcts confirmed by MRI examination and enrolled from a prospective cohort study were analyzed. Detailed neurological examinations, including evaluation of the NIHSS and modified Rankin Scale score (mRS) for evaluating the clinical severity, were performed in all subjects. The sensitivity, specificity, positive and negative predictive values of various NIHSS thresholds to capture the absence of significant disability (mRS = 3, but only 16 (7.3%) had NIHSS >5. All but 1 subject with NIHSS >5 showed mRS >= 3. NIHSS = 3 showed a lower MMSE score than those with mRS = 3 presented either with gait disturbances or MMSE score <25. Conclusions: The present results suggest that the NIHSS cannot reflect the extent of neurological deficit and clinical severity in subjects with lacunar infarctions in the context of a chronic and diffuse small vessel disease. A specific and global neurological scale, including the assessment of cognitive and gait performances, should be developed for ischemic cerebral microangiopathy. Copyright (C) 2012 S. Karger AG, Base
Confluent Thalamic Hyperintensities in CADASIL
Background: CADASIL is responsible for diffuse hyperintensities in the white matter on FLAIR images. These lesions are often associated with focal lesions in the basal ganglia such as lacunar infarctions. The prevalence and significance of diffuse or confluent thalamic hyperintensities (CTH) remain unknown. Methods: The frequency of hyperintensities on FLAIR images in the thalamus was assessed in 147 CADASIL patients, and signal abnormalities on both FLAIR and T(1)-weighted images were categorized as focal/punctuate or diffuse/confluent by the same reader. The areas of increased diffusion were also analyzed on apparent diffusion coefficient maps. The association of CTH with vascular risk factors, the main clinical manifestations of the disease and MRI markers (brain parenchymal fraction, volume of white matter hyperintensities, volume of lacunar infarcts and number of microbleeds) was analyzed with generalized linear regression models. Results: CTH were detected in 12% of the CADASIL subjects in association with hypointensities on T(1)-weighted images. CTH corresponded to areas of increased diffusion apparent diffusion coefficient maps. CTH were found significantly associated with age and independently related to the volume of white matter hyperintensities but not to that of lacunar infarctions or to cerebral atrophy after adjustment for age and sex. No significant association was found between CTH and global cognitive performances. Conclusion: CTH are observed on FLAIR images in a sizeable proportion of CADASIL patients. They are mainly related to the extent of white matter hyperintensities and do not correlate with cognitive decline. Demyelination and/or loss of glial cells appear to be the most plausible cause of these confluent signal changes in the thalamus. Copyright (C) 2010 S. Karger AG, Base
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