Martin Dichgans

..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...

..Together these findings provide strong support for a central role of frontal-subcortical circuits in cerebral small vessel disease and vascular cognitive impairment...

..Subclinical hyperthyroidism is associated with adverse cardiovascular events, including stroke and atrial fibrillation. However, its impact on functional outcome after stroke remains unexplored...

..This article highlights some of the advances on cognition in CADASIL...

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

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

..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...

..A substantial subset of treated patients survives with only minor or moderate functional handicap. However, long-term functional outcome and quality of life in these patients have rarely been systematically analyzed...

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

..The results extend the concept of CR to VCI...

..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...

..The purpose of this study was to evaluate the influence of chronic lipid apheresis (LA) on the composition of atherosclerotic carotid plaques...

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..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...

..Vasoreactivity induced by L-arginine, which is the substrate for endothelial nitric oxide synthase, is a parameter of endothelial function and has been shown to be altered in patients with cerebrovascular disease...

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

..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...

..These findings strengthen the view that hippocampal atrophy is an important pathway of cognitive impairment in vascular as well as degenerative disease...

..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 protective effects in an additional animal model of ischemia and reperfusion strongly recommend hypothermia as a potential beneficial treatment for stroke...

..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...

..To test this hypothesis, we analyzed the influence of intravenous thrombolysis on net intervention time in subsequent endovascular mechanical recanalization...

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

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

..These findings in combination with a new assay for single-molecule aggregation analysis provide novel opportunities for the development of therapeutic strategies...

..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...

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

..Brain atrophy is common in subcortical ischemic vascular disease, but the underlying mechanisms are poorly understood. We set out to examine the effects of incident subcortical infarcts on cortical morphology...

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

..While most patients stabilize and have a good recovery, progressing coma associated with poor outcome is seen in a subset of patients who may thus require other treatment options, such as endovascular therapy...

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

..Taken together, our results for the first time provide experimental evidence for N3 self-association and strongly argue for a neomorphic effect of CADASIL mutations in disease pathogenesis...

..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...

..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...

..Acute carotid-T occlusion generally responds poorly to thrombolysis. Endovascular mechanical thrombectomy (EMT) seems to be a promising alternative. However, there are few data on EMT in carotid-T occlusions...

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

..SS can be considered a warning sign of future ICH or SAH, which frequently occur adjacent to pre-existing SS. Prospective studies are needed to confirm these findings...

..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...

..Cortical vein thrombosis (CVT) is a rare disorder, and its diagnosis is challenging. The aim of our study was to evaluate the value of different imaging modalities for the detection of CVT...

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..It mostly reflects first ever ischemic stroke, and follow-up data suggest a rather benign course...

..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...

..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...

..Suboccipital decompressive craniectomy (SDC) is a life-saving intervention for patients with malignant cerebellar infarction. However, long-term outcome has not been systematically analyzed...

..Our goal was to assess the prevalence of complicated American Heart Association (AHA) lesion type VI plaques in the carotid arteries of patients with cryptogenic stroke...

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

..We used contrast-enhanced high-resolution MRI (hrMRI) and positron emission tomography CT (PET-CT) to systematically investigate VWI in spontaneous CAD...

..Choice of analysis approach for this kind of clinical question will be determined by factors other than their robustness and precision, such as a desire to explore subtle localised changes using extensions of these processing tools...

..So far, only single cases of unilateral carotid artery dissection and reversible cerebral vasoconstriction syndrome have been reported...

..3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk...

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

..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...

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..Although many stroke patients are young or middle-aged, risk factor profiles in these age groups are poorly understood...

..This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder...

..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...

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

..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...

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

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

..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...

..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...

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

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

..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...

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

..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...

..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...

..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...

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

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

..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...

..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...