1,537 research outputs found
Confluent Thalamic Hyperintensities in CADASIL
No full textBackground: 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
CADASIL: A monogenic condition causing stroke and subcortical vascular dementia
No full textMutations 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
Biological effects of low-dose TBI on chronic-progressive MS patients: preliminary results of a double blind study.
No full textsj-docx-2-eso-10.1177_23969873231219416 – Supplemental material for European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke
No full textSupplemental material, sj-docx-2-eso-10.1177_23969873231219416 for European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke by Joanna M Wardlaw, Hugues Chabriat, Frank-Erik de Leeuw, Stéphanie Debette, Martin Dichgans, Fergus Doubal, Hanna Jokinen, Aristeidis H Katsanos, Raffaele Ornello, Leonardo Pantoni, Marco Pasi, Aleksandra M Pavlovic, Salvatore Rudilosso, Reinhold Schmidt, Julie Staals, Martin Taylor-Rowan, Salman Hussain and Arne G Lindgren in European Stroke Journal</p
sj-docx-1-eso-10.1177_23969873231219416 – Supplemental material for European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke
No full textSupplemental material, sj-docx-1-eso-10.1177_23969873231219416 for European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke by Joanna M Wardlaw, Hugues Chabriat, Frank-Erik de Leeuw, Stéphanie Debette, Martin Dichgans, Fergus Doubal, Hanna Jokinen, Aristeidis H Katsanos, Raffaele Ornello, Leonardo Pantoni, Marco Pasi, Aleksandra M Pavlovic, Salvatore Rudilosso, Reinhold Schmidt, Julie Staals, Martin Taylor-Rowan, Salman Hussain and Arne G Lindgren in European Stroke Journal</p
sj-docx-3-eso-10.1177_23969873231219416 – Supplemental material for European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke
No full textSupplemental material, sj-docx-3-eso-10.1177_23969873231219416 for European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke by Joanna M Wardlaw, Hugues Chabriat, Frank-Erik de Leeuw, Stéphanie Debette, Martin Dichgans, Fergus Doubal, Hanna Jokinen, Aristeidis H Katsanos, Raffaele Ornello, Leonardo Pantoni, Marco Pasi, Aleksandra M Pavlovic, Salvatore Rudilosso, Reinhold Schmidt, Julie Staals, Martin Taylor-Rowan, Salman Hussain and Arne G Lindgren in European Stroke Journal</p
Restless legs syndrome in spinocerebellar ataxia types 1, 2, and 3
No full textTo identify the prevalence and determinants of restless legs syndrome (RLS) in spinocerebellar ataxia (SCA) we studied 58 patients with a molecular diagnosis of SCA1, SCA2 and SCA3. Data on the symptoms of RLS were collected by a standardized questionnaire, and RLS was diagnosed when patients met the four minimal criteria of the syndrome as recently defined by an international study group. In addition, we studied the relationship between RLS and age, age at ataxia onset, CAG repeat length, and nerve conduction and evoked potentials data. RLS was significantly more frequent in SCA patients than in controls (28% vs. 10%). Age at RLS onset in SCA was 49.0 +/- 10.9 years. There were no significant differences in nerve conduction or evoked potentials between RLS and non-RLS SCA patients. The probability of developing RLS increased with age but not with CAG repeat length or higher age of ataxia onset. The data provide evidence that patients with SCAI, SCA2 and SCA3 are per se more susceptible to RLS than non-affected individuals. The probability of developing RLS is related principally to the period over which the CAG repeat mutation exerts its effect and not to CAG repeat length or age of ataxia onset
Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
No full textGenetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10<sup>−11</sup>; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28–1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes
Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity
No full textGlioblastoma multiforme is a lethal neoplasm refractory to radiochemotherapy, Although glioma cells undergo apoptosis when exposed to the death ligand, CD95 (Fas/APO-1) ligand, the therapeutic use of CD95L is considered impossible because of lethal side effects. Here, we report that the locoregional application of Apoa ligand (Apo2L) exerts strong antitumor activity on preestablished intracranially growing human U87MG glioma xenografts in athymic mice. Two repetitive intratumoral injections of 2 mu g Apo2L resulted in long-term survival of mice (>100 days), whereas the median survival of mock-treated mice was 36 days. The assessment of tumor volumes at 21 and 35 days after inoculation showed complete eradication of glioma xenografts in Apo2L-treated mice. Histology and TUNEL assay confirmed the induction of apoptosis by Apo2L in glioma cells in vivo. Importantly, the intracerebral injection of Apo2L does not result in acute or delayed neurotoxicity. We propose that a phase 1 trial of intralesional Apo2L therapy for human glioblastoma multiforme is warranted. (C) 1999 Academic Press
RLS3: Fine-mapping of an autosomal dominant locus in a family with intrafamilial heterogeneity
No full textA new locus for restless legs syndrome (RLS3) was identified on chromosome 9p24-22. The authors analyzed transmission disequilibrium tests (TDTs) and affecteds-only linkage analysis in one large family of Bavarian origin, taking into account age at onset. P values were 0.0054 for marker D9S1810 for TDT and 0.0009 for the affecteds-only linkage analysis, providing a confirmation of RLS3. This study narrows the region containing the autosomal dominant RLS3 locus to 11.1 cM (16.6 Mbp)
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