M Dichgans

..Genetic studies have established an association with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar involvement are largely unknown...

..Our purposes were (1) to determine the frequency, extent, and pattern of MBs in CADASIL; (2) to analyze the relationship between MBs and T2-hyperintense lesions; and (3) to evaluate the histopathology of brain tissue affected by MBs...

..These data are consistent with the hypothesis that the change toward an odd number of cysteine residues within a given EGF repeat and therefore an unpaired, reactive cysteine residue is the common and critical molecular event in CADASIL...

..This article gives a brief overview on the phenotypic spectrum of the disease and discusses some of the relevant disease mechanisms that lead from Notch3 mutations to ischemic infarcts...

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..Mutation carriers almost invariably develop cognitive deficits and eventually dementia. The current study describes the profile of cognitive abnormalities in CADASIL subjects...

..CADASIL has opened a new perspective in studying basic mechanisms of vessel wall degeneration and ischemic tissue damage related to small vessel disease...

..To study the potential effects of these mutations 3D homology models of the first six EGF domains were generated on the basis of NMR data from human fibrillin-1. These models predict domain misfolding for a subset of mutations...

..The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus...

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..This suggests a possible causal link between cerebellar and cognitive disturbances in this patient; in addition to these pathophysiological aspects, we review of the role of the cerebellum in cognition...

..Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials...

..The reduction of CO(2) reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease...

..In particular, we speculate that ET may increase the susceptibility of cervical vessels to spontaneous dissection, for example, by disturbing the microcirculation within the vessel wall...

..Because noncontrast cranial CT (NCCT) is still the imaging technique of choice in most emergency departments, we aimed to investigate its value in the diagnosis of SVT and DVT...

..We aimed to assess the value of SS for the in vivo diagnosis of CAA, and tested whether the inclusion of SS as a criterion alters the sensitivity and specificity of the Boston criteria for CAA-related hemorrhage...

..To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI)...

..For future studies on treatment of neurogenic-cardial disorders, the classification of the differently defined disorders based on their common pathophysiology will be essential...

..Susac syndrome is a rare disease of unknown pathogenesis. It consists of retinal arterial occlusion, hearing loss and encephalopathy (triad)...

..This review focuses on current developments in the diagnosis and treatment of acute basilar artery occlusion...

..Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD...

..We further discuss the roles of CACNA1A, ATP1A2, and SCN1A in the pathophysiology of cortical spreading depression, which is the likely correlate of migraine aura...

..The findings suggest that the delayed cortical edema was vasogenic in the severe migraine aura variant of this ATP1A2 mutation carrier...

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..Thus, we propose that these 2 findings might be valuable as noninvasive diagnostic markers for CAA...

..99. The observation of key recombinations in one family refined the disease locus to a 7.2 cM region flanked by the markers D7S652 and D7S2480...

..Their diagnosis which is based on family history, typical clinical features and genetic analysis often has implications for treatment and genetic counselling...

..Therefore, brain biopsies are often needed to confirm the diagnosis. Recent reports have shown that MRI is able to visualise contrast enhancement in subjects with known primary CNS arteritis...

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..Findings included bilateral peripapillary arteriolar sheathing (30%), arteriolar narrowing (80%), and arteriovenous nicking (90%). No retinal infarcts, vascular occlusions, exudation, or hypoperfusion of affected vessels were found...

..Attacks recurred after treatment was stopped; subsequent treatment alleviated the symptoms (mean follow-up time 6 months). These effects might be due to an improvement of the impaired functioning of Purkinje cells...

..These results suggest that, in this assay, the cytoprotective effect of parkin might result not only from its E3-ligase activity, but also from direct or indirect modulation of gene expression in a time-dependent manner...

..1% vs. 2.6%, p < 0.05). Our study shows that patients with hereditary RLS may experience an earlier onset of the disease. Hereditary and non-hereditary RLS present with similiar clinical signs and symptoms...

..The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial...

..The absence of Purkinje cell staining suggests that the cis elements required for this expression must be located outside of the sequences used in this study...

..Despite various benefits, rt-PA is responsible for a dose-dependent increase of edema and hemorrhage after cerebral ischemia. Clinicians should consider using the lowest effective dose of rt-PA in stroke patients...

..CADASIL is a monogenic form of SVD caused by mutations in the Notch3 gene. Treatment options are limited and little is known about the therapeutic role of statins in CADASIL...

..We investigated whether initial admission to telemedically linked general hospitals with subsequent stroke-center transfer is related to poorer outcome than direct admission to stroke centers...

..This approach will contribute to the identification of additional genes, novel pathways, and eventually novel therapeutic approaches to ischaemic stroke...

..A pathophysiological model explaining this cooccurrence as well as the significance of prothrombotic risk factors ("hypercoaguable state") in the setting of inflammatory bowel disease and stroke are discussed...

..The prominent capillary vulnerability contributes significantly to the impairment of the microvascular integrity and after ischemia and reperfusion...

..We did a multicentre, 18-week, placebo-controlled, double-blind, randomised parallel-group trial to determine whether the cholinesterase inhibitor donepezil improves cognition in patients with CADASIL...

..The combination of IVT with consecutive on-demand EMT may allow for early treatment initiation with high recanalization rates but has never been systematically tested in patients with BAO...

..This association seems to be mediated predominantly by large-vessel disease...

..Using a case control replication methodology, all members of the leukotriene synthesis pathway and their receptors were examined for genetic variants, which may act as risk factors for all ischemic stroke and stroke subtypes...

..Meta-analysis provides a method to combine this data and determine in a larger sample size whether the association with PDE4D can be replicated...

..These results suggest that the examination of cortical morphology may be of high clinical relevance in SVDB...

..1 defects can cause FHM3. Our results also emphasize the complex relationship between migraine and epilepsy and provide further evidence that both disorders may share common molecular mechanisms...

..Application of these criteria in CADASIL, a genetic model of SIVD, may help to better assess their significance. The aim of this study was to compare different sets of diagnostic criteria of VaD in a population of CADASIL patients...

..Studies comparing CADASIL subjects with other patient populations seem warranted to determine possible differences in CTT between different types of small-vessel disease...

..A large number of candidate gene association studies have attempted to identify genes implicated in stroke, but there have been few replicable and robust associations reported...

..Mutations are typically located within epidermal growth factor-like repeat domains in the extracellular part of the Notch3 receptor. Identification of the mutation is critical for genetic counseling and testing of relatives at risk...

..The aim of the present study was to explore the role of these genes in a central European population of stroke patients...

..Our findings suggest possible genotype-phenotype correlations with regard to disease progression. The data presented may serve as source material for counselling CADASIL patients and for designing future interventional trials...

..Moreover, the data suggest that ligand-induced receptor shedding may not be required for N3ECD deposition in CADASIL...

..To assess histopathological findings in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)...

..Sample size calculations emphasize the need for surrogate markers of disease progression for future interventional trials...

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..The purpose of this study was to evaluate with (18)F-FDG PET whether regional cerebral metabolic rate of glucose (rCMRglc) is altered in CADASIL patients and, if so, whether there is evidence of subcortically induced disconnection...

..So far, mutations in two genes regulating ion translocation-CACNA1A and ATP1A2-have been identified in pedigrees with this disease...

..Also, their family history suggests further evidence of possible manifestation of FXTAS in women...

..Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress...

..In this study, we assessed the role of quantitative MRI (T2-lesion volume and diffusion tensor imaging [DTI]-derived metrics) in monitoring and predicting disease progression...

..These lesions have a potential clinical impact in CADASIL. These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease...

..553 +/- 47%, P < 0.01). Pravastatin pretreatment resulted in a reduction of microvascular basal lamina damage and hemoglobin extravasation following transient ischemia. Pravastatin seems to protect the cerebral microvascular system...

..Our report emphasizes that CADASIL must be considered in the study of patients with secondary dystonia...

..The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL...

..This sign may serve as an indicator of meningeal carcinomatosis and should raise the suspicion of this disease entity...

..Our findings establish the role of neuronal Na(v)1.1 sodium channels in FHM and reinforce the involvement of ion channel dysfunction in the pathogenesis of this episodic brain disorder...

..These findings justify a systematic search for genetic variants that modify disease progression...

..The segregation pattern found in our families argues for an autosomal allele acting dominantly in RLS families with an early age at onset of symptoms and suggests that RLS is a causative heterogeneous disease...

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..These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias...

..15). We found a SORL1 haplotype which was associated with CSF levels of amyloid-beta cleavage products, measured as altered levels of Abeta42. Thus our data suggest that SORL1 gene variants might influence AD pathology...

..This strongly supports use of the lowest effective dosage of rt-PA available...

..These results raise the possibility that the increased expression of EMMPRIN, the increase in MMPs and the damage of the basal lamina following cerebral ischemia are connected and part of a network of related changes...

..Thus, this method increases the validity of data comparisons and reduces significantly the number of animals needed in various experimental settings...

..Hemoglobin extravasation was also significantly reduced. Our results suggest that doxycycline may have a potential use as an anti-ischemic compound since it provides microvascular protection by inhibiting the plasminogen system...