Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a major risk factor for stroke and dementia and is associated with white matter hyperintensities (WMH) and reduced brain volumes. We measured the increase in WMH volume, and rate of cerebral atrophy over two years, in hypertensive subjects participating in the Study on COgnition and Prognosis in the Elderly (SCOPE), receiving candesartan or placebo, and normotensive controls. We recruited 163 subjects who had MRI (FLAIR and volumetric T1) at 2 and 4 years after baseline assessment. From these two scans, volumetric change in WMH (n = 133) and brain atrophy rates (n = 95) were determined. Total WMH fraction increased in both normotensive and treated hypertensive groups (p < 0.01) median change: 0.05% of brain volume [range: -0.45% to 1.51%]. Deep WMH increased in hypertensive (p = 0.001) but not the normotensive group. The number of subjects with an increase of total WMH in the 5(th) quintile differed between the treatment groups (chi square p = 0.006), being greatest in the placebo group (32%), then candesartan (20%) then normotensive (5%). Regression analysis found significant predictors of change in WMH to be blood pressure and initial deep WMH, but not treatment group. Increased atrophy rate was predicted by baseline systolic blood pressure (p = 0.02) but was not associated with measures of WMH. Similar to WMH, there was a trend with treatment, with atrophy in normotensive < Candesartan < Placebo (Spearman's rho = 0.23, p = 0.026). Hypertension in older people is associated with increased rates of progressive whole brain atrophy and an increase in WMH. These changes are independent. Successful hypertension treatment was associated with reduced risk of WMH progression and possibly brain atrophy.
 ...
PMID:Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure. Brain atrophy, WMH change and blood pressure. 1744 97

The natural history of Sturge-Weber Syndrome is variable where some patients have refractory epilepsy and persistent neurologic deficits while others do well. Also, evolution of MRI abnormalities is largely unknown. This long-term follow-up study tries to address these two issues. This retrospective and later prospective study followed 9 children with confirmed SWS. Clinical details of seizures, stroke-like episodes, neurologic and developmental deficits were ascertained specifically. Patients were divided into those with onset below or after 6 months of age for analysis. Disease was classified as active or inactive and correlations were made with the use of aspirin. All past, as well as prospectively acquired imaging was reviewed by two independent blinded neuroradiologists and the images were analysed as ictal (temporally related to seizure/stroke-like event) or interictal. Degree and extent of leptomeningeal enhancement was specifically looked for. Four boys and five girls were followed up for a mean of 6.1 years. Disease activity subsided in 8/9. Early-onset patients had a severe early course with significant residual deficits while late-onset patients did uniformly well. In 6 patients where aspirin was used, a stable course ensued. There was a significant increase in degree/extent of leptomeningeal enhancement during an ictus which returned to the baseline in the interictal state in all 7 patients where both images were available. Focal cerebral atrophy worsened in early-onset cases. In conclusion, SWS patients with onset of seizures/stroke-like events before 6 months of age seem to do worse with a severe early course and persistent neurologic deficits. However the course stabilizes after 5 years of age in most. Late-onset SWS patients have a benign course. Aspirin use is associated with a stable course though further studies are needed. The leptomeningeal enhancement appears to increase during acute events before returning to baseline suggesting that extent of the disease is probably best judged during the interictal state.
 ...
PMID:Natural history and magnetic resonance imaging follow-up in 9 Sturge-Weber Syndrome patients and clinical correlation. 1762 34

Brain atrophy and small vessel disease increase the risk of dementia and stroke. In a population-based cohort study (n=490; 60-90 years) we investigated how volumetric measures of atrophy and small vessel disease were related to mortality and whether this was independent of incident dementia or stroke. Brain volume and hippocampal volume were considered as measures of atrophy, whereas white matter lesions (WML) and lacunar infarcts reflected small vessel disease. We first investigated all-cause mortality in the whole cohort. In subsequent analyses we censored persons at incident dementia or incident stroke. Finally, we separately investigated cardiovascular mortality. The average follow-up was 8.4 years, during which 191 persons died. Brain atrophy and hippocampal atrophy, as well as WML increased the risk of death. The risks associated with hippocampal atrophy attenuated when censoring persons at incident dementia, but not at incident stroke. Censoring at either incident dementia or stroke did not change the risk associated with brain atrophy and WML. Moreover, WML were particularly associated with cardiovascular mortality.
 ...
PMID:Brain tissue volumes and small vessel disease in relation to the risk of mortality. 1776 13

Neonatal stroke presents with seizures and results in neurologic morbidity, including epilepsy, hemiparesis, and cognitive deficits. Stem cell-based therapy offers a possible therapeutic strategy for neonatal stroke. We developed an immature mouse model of stroke with acute seizures and ischemic brain injury. Postnatal day 12 CD1 mice received right-sided carotid ligation. Two or 7 days after ligation, mice received an intrastriatal injection of B5 embryonic stem cell-derived neural stem cells. Four weeks after ligation, hemispheric brain atrophy was measured. Pups receiving stem cells 2 days after ligation had less severe hemispheric brain atrophy compared with either noninjected or vehicle-injected ligated controls. Transplanted cells survived, but 3 out of 10 pups injected with stem cells developed local tumors. No difference in hemispheric brain atrophy was seen in mice injected with stem cells 7 days after ligation. Neural stem cells have the potential to ameliorate ischemic injury in the immature brain, although tumor development is a serious concern.
 ...
PMID:Neural stem cells reduce brain injury after unilateral carotid ligation. 1820 88

Stroke is a major cause of neurologic morbidity in neonates and children. Because neonatal and pediatric stroke frequently present with seizures, the question of which anticonvulsant best blocks acute ischemic seizures and reduces injury is clinically relevant. The purpose of this study was to determine the extent to which gabapentin is neuroprotective and suppresses acute seizures in this model of ischemic injury in the immature brain. Postnatal day 12 CD1 mice underwent right common carotid artery ligation and immediately after ligation received a 0, 50, 100, 150, or 200 mg/kg dose of gabapentin intraperitoneally. Acute seizure activity was behaviorally scored and hemispheric brain atrophy measured. In vehicle-treated mice, severity of acute seizures correlated with hemispheric brain atrophy 4 wks later. Gabapentin significantly decreased acute seizures at 200 mg/kg and reduced brain atrophy at doses of 150 and 200 mg/kg but not at lower doses. These results suggest that gabapentin effectively reduces acute seizures and injury after ischemia in the immature brain. When analyzed by animal sex, the data suggest that gabapentin may more effectively reduce acute seizures and injury in male pups vs. female pups.
 ...
PMID:Gabapentin neuroprotection and seizure suppression in immature mouse brain ischemia. 1839 49

Intracerebral hemorrhage (ICH) is a subtype of stroke with very high mortality. Experiments have indicated that clot lysis and iron play an important role in ICH-induced brain injury. Iron overload occurs in the brain after ICH in rats. Intracerebral infusion of iron causes brain edema and neuronal death. Deferoxamine, an iron chelator, is an FDA-approved drug for the treatment of acute iron intoxication and chronic iron overload due to transfusion-dependent anemia. Deferoxamine can rapidly penetrate the blood-brain barrier and accumulate in the brain tissue in significant concentration after systemic administration. We have demonstrated that deferoxamine reduces ICH-induced brain edema, neuronal death, brain atrophy, and neurological deficits. Iron chelation with deferoxamine could be a new therapy for ICH.
 ...
PMID:Deferoxamine therapy for intracerebral hemorrhage. 1906 72

The aim of our study was to investigate the effects of silent brain lesions on cognitive function of community-dwelling elderly individuals. Brain magnetic resonance imaging and other medical examinations were performed on 350 nondemented elderly individuals (121 male and 229 female, average age 72.4 years) who resided in the rural community of Sefuri Village, Saga, Japan. The mini mental state examination and modified Stroop test (MST) were used to identify cognitive impairment. White matter lesions (WMLs) and cerebral atrophy on magnetic resonance imaging were measured quantitatively. Multivariate analyses were done using a logistic regression model with a software package. Cognitive impairment defined by mini mental state examination score less than 24 was present in 55 individuals (15.7%). They had a lower educational level, significantly larger quantity of WMLs, and more remarkable cerebral atrophy. Frontal lobe dysfunction was detected in 52 individuals (14.9%) through prolonged MST score (>36 seconds). Impaired frontal lobe function was related to number of silent lacunar infarcts, larger WMLs, and more prominent cerebral atrophy. MST score in individuals with two or more infarcts was significantly more prolonged compared with MST score in those without infarction. These results suggest that WMLs may cause rather diffuse cognitive decline, whereas multiple lacunar infarcts are specifically involved in frontal lobe dysfunction. Silent ischemic lesions in apparently healthy elderly individuals seem to form a distinctive group of people with vascular cognitive impairment without dementia. This group should be the primary target of prevention of vascular dementia.
J Stroke Cerebrovasc Dis 2009 Jan
PMID:Cognitive consequences of multiple lacunes and leukoaraiosis as vascular cognitive impairment in community-dwelling elderly individuals. 1911 Jan 42

The critical question as to the respective role of Alzheimer's disease (AD) and cerebrovascular disease in dementia of the Alzheimer's type (DAT), the most common form of dementia, is still debated. But there has been considerable progress in understanding cerebral hemodynamics and the relationship between structural brain damage and cognitive decline, in routine neuro imaging techniques. These advances now allow the proposition of a novel MR classification of DAT including indicators of both cerebrovascular function and regional brain atrophy. MR indicators of windkessel function include the arterial pulsatility index, the intracranial blood stroke volume, the cerebral relative venous outflow rates and a relative index of craniospinal compliance. MR indicators of vascular conduct function include total arterial and superficial venous flow rates that are closely related to brain metabolism. Structural MR sequences allow the detection of structural markers of windkessel dysfunction and, beyond the non specific hippocampal atrophy, a more extensive AD-like MR pattern of atrophy. The first illustration of this MR classification in elderly patients that later progressed to dementia converges with recent neuropathological observations to suggest that the major enemy to combat in late-life dementia is not AD but cerebrovascular dysfunction.
 ...
PMID:Assessing cerebrovascular contribution to late dementia of the Alzheimer's type: the role of combined hemodynamic and structural MR analysis. 1926 12

The C10orf2 gene encodes the mitochondrial DNA helicase Twinkle, which is one of the proteins important for mitochondrial DNA maintenance. Dominant mutations cause multiple mitochondrial DNA deletions and progressive external ophthalmoplegia, but recent findings associate recessive mutations with mitochondrial DNA depletion and encephalopathy or hepatoencephalopathy. The latter clinical phenotypes resemble those associated with recessive POLG1 mutations. We have previously described patients with infantile onset spinocerebellar ataxia (MIM271245) caused either by homozygous (Y508C) or compound heterozygous (Y508C and A318T) Twinkle mutations. Our earlier reports focused on the spinocerebellar degeneration, but the 20-year follow-up of 23 patients has shown that refractory status epilepticus, migraine-like headaches and severe psychiatric symptoms are also pathognomonic for the disease. All adolescent patients have experienced phases of severe migraine, and seven patients had antipsychotic medication. Epilepsia partialis continua occurred in 15 patients leading to generalized epileptic statuses in 13 of them. Eight of these patients have died. Valproate treatment was initiated on two patients, but had to be discontinued because of a severe elevation of liver enzymes. The patients recovered, and we have not used valproate in infantile onset spinocerebellar ataxia since. The first status epilepticus manifested between 15 and 34 years of age in the homozygotes, and at 2 and 4 years in the compound heterozygotes. The epileptic statuses lasted from several days to weeks. Focal, stroke-like lesions were seen in magnetic resonance imaging, but in infantile onset spinocerebellar ataxia these lesions showed no predilection. They varied from resolving small cortical to large hemispheric oedematous lesions, which reached from cerebral cortex to basal ganglia and thalamus and caused permanent necrotic damage and brain atrophy. Brain atrophy with focal laminar cortical necrosis and hippocampal damage was confirmed on neuropathological examination. The objective of our study was to describe the development and progression of encephalopathy in infantile onset spinocerebellar ataxia syndrome, and compare the pathognomonic features with those in other mitochondrial encephalopathies.
 ...
PMID:Recessive twinkle mutations cause severe epileptic encephalopathy. 1930 94

Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in developing countries. Brain involvement in CD has been attributed to left ventricular dysfunction, resulting in chronic brain ischemia due to hypoperfusion and/or embolic infarcts. However, cognitive impairment in CD may occur independently of cardiac disease. Therefore, we aimed to investigate head computed tomography (CT) findings in patients with Chagas disease cardiomyopathy (CDC) in comparison with other cardiomyopathies (OC). We studied 73 patients with CDC (n = 41) or OC (n = 32) matched for age and gender. These patients underwent head CT, rated by an investigator blinded to all clinical information. Head CT was rated for the presence of lacunar or territorial infarcts, as well as for measuring the total volumes of the brain, cerebellum and ventricles. Total brain volume was smaller in CDC as compared to OC patients (1,135 +/- 150 vs. 1,332 +/- 198 cm(3), P < 0.001). Cerebellar and ventricular volumes did not differ between the groups. The prevalence of brain infarcts did not differ significantly between the groups. Chagas disease was the only independent predictor of brain atrophy in the multivariable analysis (OR = 1.38; 95% CI = 1.06-1.79, P = 0.017). Chagas disease is associated with brain atrophy independent of structural cardiac disease related to cardiomyopathy. Brain atrophy, rather than multiple infarcts, may represent the main anatomical substrate of cognitive impairment in Chagas disease.
 ...
PMID:Chagas disease is independently associated with brain atrophy. 1936 36


<< Previous 1 2 3 4 5 6 7 8 9 10