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See detailWhole brain and regional hyperintense white matter volume and blood pressure: overlap of genetic loci produced by bivariate, whole-genome linkage analyses.
Kochunov, Peter; Glahn, David; Lancaster, Jack et al

in Stroke (2010), 41(10), 2137-42

BACKGROUND AND PURPOSE: The volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity with a demonstrated high heritability. Pathophysiology studies have shown ... [more ▼]

BACKGROUND AND PURPOSE: The volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity with a demonstrated high heritability. Pathophysiology studies have shown that the regional, ependymal, and subcortical HWM lesions are associated with elevated arterial pulse pressure and arterial blood pressure (BP), respectively. We performed bivariate, whole-genome linkage analyses for HWM volumes and BP measurements to identify chromosomal regions that contribute jointly to both traits in a population of healthy Mexican Americans. Our aims were to localize novel quantitative trait loci acting pleiotropically on these phenotypes and to replicate previous genetic findings on whole brain HWM volume and BP measurements. METHODS: BP measurements and volumes of whole-brain (WB), subcortical, and ependymal HWM lesions, measured from high-resolution (1 mm(3)) 3-dimensional fluid-attenuated inversion recovery images, served as focal quantitative phenotypes. Data were collected from 357 (218 females; mean age=47.9+/-13.2 years) members of large extended families who participated in the San Antonio Family Heart Study. RESULTS: Bivariate genomewide linkage analyses localized a significant quantitative trait locus influencing WB and regional (ependymal) HWM volumes and pulse pressure and systolic BP to chromosomal location 1q24 between markers D1S196 and D1S1619. Several other chromosomal regions (1q42, 10q24-q26, and 15q26) exhibited suggestive linkages. The results of the post hoc analyses that excluded 55 subjects taking antihypertensive medication showed no substantive differences from the results obtained in the full cohort. CONCLUSIONS: This study confirms several previously observed quantitative trait loci influencing BP and cerebral integrity and identifies a novel significant quantitative trait locus at chromosome 1q24. The genetic results strongly support a role for pleiotropically acting genes jointly influencing BP and cerebral white matter integrity. [less ▲]

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See detailBelgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease.
Brouns, Raf; Thijs, Vincent; Eyskens, Francois et al

in Stroke (2010), 41(5), 863-8

BACKGROUND AND PURPOSE: Data on the prevalence of Fabry disease in patients with central nervous system pathology are limited and controversial. In this study, we assessed the prevalence of Fabry disease ... [more ▼]

BACKGROUND AND PURPOSE: Data on the prevalence of Fabry disease in patients with central nervous system pathology are limited and controversial. In this study, we assessed the prevalence of Fabry disease in young patients presenting with cerebrovascular disease in Belgium. METHODS: In this national, prospective, multicenter study, we screened for Fabry disease in 1000 patients presenting with ischemic stroke, transient ischemic attack, or intracranial hemorrhage; unexplained white matter lesions; or vertebrobasilar dolichoectasia. In male patients, we measured alpha-galactosidase A (alpha-GAL A) activity in dried blood spots. Female patients were screened for mutations by exonic DNA sequencing of the alpha-GAL A gene. RESULTS: alpha-GAL A activity was deficient in 19 men (3.5%), although all had normal alpha-GAL A gene sequences. Enzymatic deficiency was confirmed on repeat assessment in 2 male patients (0.4%). We identified missense mutations in 8 unrelated female patients (1.8%): Asp313Tyr (n=5), Ala143Thr (n=2), and Ser126Gly (n=1). The pathogenicity of the 2 former missense mutations is controversial. Ser126Gly is a novel mutation that can be linked to late-onset Fabry disease. CONCLUSIONS: alpha-GAL A deficiency may play a role in up to 1% of young patients presenting with cerebrovascular disease. These findings suggest that atypical variants of Fabry disease with late-onset cerebrovascular disease exist, although the clinical relevance is unclear in all cases. [less ▲]

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See detailAnalysis of genetic variability and whole genome linkage of whole-brain, subcortical, and ependymal hyperintense white matter volume.
Kochunov, Peter; Glahn, David; Winkler, Anderson ULiege et al

in Stroke (2009), 40(12), 3685-90

BACKGROUND AND PURPOSE: The cerebral volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity. Pathophysiology studies identified that subcortical and ... [more ▼]

BACKGROUND AND PURPOSE: The cerebral volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity. Pathophysiology studies identified that subcortical and ependymal HWM are produced by 2 different mechanisms but shared a common risk factor: high arterial pulse pressure. Recent studies have demonstrated high heritability of the whole-brain HMW volume and reported significant and suggestive evidence of genetic linkage. We performed heritability and whole-genome linkage analysis to replicate previous reported findings and to study shared genetic variance, and possible overlap for specific loci, between subcortical and ependymal HWM volumes in a population of healthy Mexican Americans. METHODS: The volumes of subcortical and ependymal HWM regions were measured from high-resolution (1 mm(3)), 3-dimensional fluid-attenuated inversion recovery images acquired for 459 (283 females, 176 males) active participants in the San Antonio Family Heart Study. Subjects ranged in age from 19 to 85 years of age (47.9+/-13.5 years) and were part of 49 families (9.4+/-8.5 individuals per family). RESULTS: The volumes of whole-brain, subcortical, and ependymal HWM were highly heritable (h(2)=0.72, 0.66, and 0.73, respectively). The subcortical and ependymal HWM volumes shared 21% of genetic variability indicating significant pleiotropy. Genomewide linkage analysis showed only a suggestive bivariate linkage for subcortical and ependymal HWM volumes (log of odds=2.12) on chromosome 1 at 288 cM. CONCLUSIONS: We replicated previous findings of high heritability for the whole-brain HWM volume. We also showed that subcortical and ependymal volume shared a significant portion of genetic variability and the bivarate linkage analysis produced a suggestive linkage near the locus previously identified in a study of whole-brain HWM volume and arterial pulse pressure. [less ▲]

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See detailTherapeutic use of high-frequency repetitive transcranial magnetic stimulation in stroke.
Hotermans, Christophe; Peigneux, Philippe ULiege; Moonen, Gustave ULiege et al

in Stroke (2007), 38(2), 253254

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See detailIpsilateral motor responses to focal transcranial magnetic stimulation in healthy subjects and acute-stroke patients
Alagona, Giovanna; DELVAUX, Valérie ULiege; GERARD, Pascale ULiege et al

in Stroke (2001), 32(6), 1304-1309

BACKGROUND AND PURPOSE: Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) were compared in healthy subjects ... [more ▼]

BACKGROUND AND PURPOSE: Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) were compared in healthy subjects and patients with acute stroke. METHODS: Sixteen healthy subjects and 25 patients with acute stroke underwent focal TMS at maximum stimulator output over motor and premotor cortices. If present, MEPs evoked in muscles ipsilateral to TMS were analyzed for latency, amplitude, shape, and center of gravity (ie, preferential coil location to elicit them). In stroke patients, possible relationships between early ipsilateral responses and functional outcome at 6 months were sought. RESULTS: With relaxed or slightly contracting target muscle, maximal TMS over the motor cortex failed to elicit ipsilateral MEPs in the first dorsal interosseous (FDI) or biceps of any of 16 normal subjects. In 5 of 8 healthy subjects tested, ipsilateral MEPs with latencies longer than contralateral MEPs were evoked in FDI muscle (in biceps, 6 of 8 subjects) during strong (>50% maximum) contraction of the target muscle. In 15 of 25 stroke patients, ipsilateral MEPs in the unaffected relaxed FDI (in biceps, 6 of 25 stroke patients) were evoked by stimulation of premotor areas of the affected hemisphere. Their latencies were shorter than those that MEPs evoked in the same muscle by stimulation of the motor cortex of the contralateral unaffected hemisphere. Such responses were never obtained in normal subjects and were mostly observed in patients with subcortical infarcts. Patients harboring these responses had slightly better bimanual dexterity after 6 months. CONCLUSIONS: Ipsilateral MEPs obtained in healthy individuals and stroke patients have different characteristics and probably different origins. In the former, they are probably conveyed via corticoreticulospinal or corticopropriospinal pathways, whereas in the latter, early ipsilateral MEPs could originate in hyperexcitable premotor areas. [less ▲]

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See detailAbsence of response to early transcranial magnetic stimulation in ischemic stroke patients: prognostic value for hand motor recovery.
Pennisi, Giovanni; Rapisarda, Giuseppe; Bella, R. et al

in Stroke (1999), 30(12), 2666-70

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been proposed as a prognostic tool in stroke patients. Most of the previous studies agree in considering the presence of motor-evoked ... [more ▼]

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been proposed as a prognostic tool in stroke patients. Most of the previous studies agree in considering the presence of motor-evoked potentials (MEPs) in the first days after a stroke as an indicator of good outcome. In the present study, we have assessed the prognostic value of the absence of response to early TMS on hand motor recovery in stroke patients with complete hand palsy at onset due to ischemia in the area of the middle cerebral artery. METHODS: Fifteen patients submitted to TMS within 48 hours of stroke onset (defined as day 1) and again after 1 year. They were also evaluated clinically on day 1 by a scale derived from the Medical Research Council (MRC) and by the National Institutes of Health (NIH) stroke scale; they were reevaluated by the same scales and by Barthel Index on day 365. RESULTS: On day 1, all the patients had complete hand palsy and no response to TMS; their NIH scores showed great variability. After 1 year, 6 of 15 patients regained small and prolonged MEPs, together with a very poor and not functionally useful motor recovery. NIH scores were significantly improved. Barthel Index scores showed large interindividual differences and were not correlated with MRC scores. CONCLUSIONS: We conclude that in patients with complete hand palsy, the absence of response to TMS in the first hours is predictive of absent or very poor, not useful, hand motor recovery. [less ▲]

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See detailCan Motor Recovery in Stroke Patients Be Predicted by Early Transcranial Magnetic Stimulation ?
Rapisarda, Giuseppe; Bastings, Eric; MAERTENS DE NOORDHOUT, Alain ULiege et al

in Stroke (1996), 27(12), 2191-2196

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