Project description:Seizures are believed to be common presenting symptoms in neonates and children with spontaneous intracerebral hemorrhage (ICH). However, few data are available on the epidemiology of acute symptomatic seizures or the risk for later epilepsy.To define the incidence of and explore risk factors for seizures and epilepsy in children with spontaneous ICH. Our a priori hypotheses were that younger age at presentation, cortical involvement of ICH, acute symptomatic seizures after presentation, ICH due to vascular malformation, and elevated intracranial pressure requiring urgent intervention would predict remote symptomatic seizures and epilepsy.Prospective cohort study conducted between March 1, 2007, and January 1, 2012.Three tertiary care pediatric hospitals.Seventy-three pediatric subjects with spontaneous ICH including 20 perinatal (?37 weeks' gestation to 28 days) and 53 childhood subjects (>28 days to <18 years at presentation).Acute symptomatic seizures (clinically evident and electrographic-only seizures within 7 days), remote symptomatic seizures, and epilepsy.Acute symptomatic seizures occurred in 35 subjects (48%). Acute symptomatic seizures as a presenting symptom of ICH occurred in 12 perinatal (60%) and 19 childhood (36%) subjects (P = .07). Acute symptomatic seizures after presentation occurred in 7 children. Electrographic-only seizures were present in 9 of 32 subjects (28%) with continuous electroencephalogram monitoring. One-year and 2-year remote symptomatic seizure-free survival rates were 82% (95% CI, 68-90) and 67% (95% CI, 46-82), respectively. One-year and 2-year epilepsy-free survival rates were 96% (95% CI, 83-99) and 87% (95% CI, 65-95), respectively. Elevated intracranial pressure requiring acute intervention was a risk factor for seizures after presentation (P = .01; Fisher exact test), remote symptomatic seizures, and epilepsy (P = .03, and P = .04, respectively; log-rank test).Presenting seizures are common in perinatal and childhood ICH. Continuous electroencephalography may detect electrographic seizures in some subjects. Single remote symptomatic seizures occur in many, and development of epilepsy is estimated to occur in 13% of patients at 2 years. Elevated intracranial pressure requiring acute intervention is a risk factor for acute seizures after presentation, remote symptomatic seizures, and epilepsy.

Project description:Importance:Age-related hearing loss (HL) is a common and treatable condition that has been associated with cognitive impairment. The level of hearing at which this association begins has not been studied to date. Objective:To investigate whether the association between hearing and cognition is present among individuals traditionally classified as having normal hearing. Design, Setting, and Participants:Cross-sectional study of 2 US epidemiologic studies (Hispanic Community Health Study [HCHS], 2008-2011, and National Health and Nutrition Examination Study [NHANES], 1999-2000, 2001-2002, and 2011-2012 cycles). The dates of analysis were November 2018 to August 2019. Multivariable generalized additive model (GAM) regression and linear regression were used to assess the association between HL (exposure) and cognition (outcome). Participants included 6451 individuals aged 50 years or older from the general Hispanic population (HCHS [n?=?5190]) and the general civilian, noninstitutionalized US population (NHANES [n?=?1261]). Exposures:Audiometric HL (4-frequency pure-tone average). Main Outcomes and Measures:Neurocognitive performance measured by the Digit Symbol Substitution Test (DSST) (score range, 0-113), Word Frequency Test (range, 0-49), Spanish-English Verbal Learning Test (SEVLT) 3 trials (range, 5-40), SEVLT recall (range, 0-15), and Six-Item Screener (range, 0-6); higher scores indicated better cognitive performance. Results:Among 6451 individuals, the mean (SD) age was 59.4 (6.1) years, and 3841 (59.5%) were women. The GAM regression showed a significant inverse association between hearing and cognition across the entire spectrum of hearing after adjusting for demographics and cardiovascular disease. In separate multivariable linear regressions stratified by the classic binary definition of HL, decreased hearing was independently associated with decreased cognition in adults with normal hearing (pure-tone average ?25 dB) across all cognitive tests in the HCHS. For example in this group, a 10-dB decrease in hearing was associated with a clinically meaningful 1.97-point (95% CI, 1.18-2.75) decrease in score on the DSST. When using a stricter HL cut point (15 dB), an association was also present in NHANES. The associations between hearing and cognition were stronger or equivalent in individuals with normal hearing than among those with HL. For example, there was a 2.28-point (95% CI, 1.56-3.00) combined cohort DSST score decrease per 10-dB decrease among individuals with normal hearing vs a 0.97-point (95% CI, 0.20-1.75) decrease among those with HL, with a significant interaction term between continuous and binary hearing. Conclusions and Relevance:An independent association was observed between cognition and subclinical HL. The association between hearing and cognition may be present earlier in HL than previously understood. Studies investigating whether treating HL can prevent impaired cognition and dementia should consider a lower threshold for defining HL than the current 25-dB threshold.

Project description:Background: Poststroke cognitive impairment (PSCI) has been increasingly recognized in patients, but some stroke survivors appear to show cognitive improvement beyond the acute stage. The risk factors associated with cognitive recovery after spontaneous intracerebral hemorrhage (ICH) onset have not yet been sufficiently investigated in prospective studies. Objective: We aimed to identify the trajectory of post-ICH cognitive impairment and the association of potential prognostic factors with follow-up cognitive recovery beyond early PSCI. Methods: In this stroke center-based cohort study, 141 consecutive dementia-free patients with spontaneous ICH were included and underwent Montreal Cognitive Assessment (MoCA) evaluation for cognitive function at baseline (within 2 weeks of ICH onset) and the shortened MoCA (short-MoCA) at a 6-month follow-up. To explore the prognostic factors associated with trajectory of cognition after an ICH onset, we adjusted for demographic and vascular risk factors, using multivariate logistic regression analysis. Results: Of the 141 ICH patients, approximately three quarters (106/141) were diagnosed with early PSCI (MoCA score <26) within 2 weeks of ICH onset. The multiple logistic regression indicated independent positive associations between risk of early PSCI and dominant-hemisphere hemorrhage [odd's ratio (OR): 8.845 (3.347-23.371); P < 0.001], mean corpuscular volume (MCV) [OR: 1.079 (1.002-1.162); P = 0.043], admission systolic blood pressure (sBP) [OR: 1.021 (1.005-1.038); P = 0.012]. Furthermore, 36% (33/90) of ICH survivors who had early PSCI exhibited cognitive recovery at the 6-month follow-up. After examining potential predictors through multiple linear regression based on stepwise, there were independent negative associations between cognitive recovery and dominant hemisphere hemorrhage [OR: 6.955 (1.604-30.162); P < 0.01], lobar ICH [OR: 8.363 (1.479-47.290); P = 0.016], years of education ? 9 [OR: 5.145 (1.254-21.105); P = 0.023], and MCV [OR: 1.660 (1.171-2.354); P = 0.004]. Baseline cognitive performance in the domains of visuospatial/executive function, attention, orientation, and language showed positive correlations with cognitive improvement (P < 0.05). Conclusion: In this cohort study of dementia-free survivors of ICH, our results show that one in three early PSCI survivors exhibit cognitive recovery, in relation to dominant-hemisphere hematoma, lobar ICH, educational history, and MCV levels. Future clinical trials including ICH survivors with cognitive dysfunction should assess these factors.

Project description:BackgroundCognitive impairment seems to be frequent in intracerebral hemorrhage (ICH) survivors, but remains widely understudied. In this study, we investigated the frequency and patterns of vascular cognitive disorders (VCDs) in patients with cerebral amyloid angiopathy (CAA)-related and deep ICH compared to patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) and healthy controls.MethodsWe prospectively recruited 20 patients with CAA-related lobar ICH, 20 with deep ICH, 20 with MCI-AD and 17 healthy controls. Patients with cognitive decline pre-ICH were excluded from the analysis. Each participant underwent a comprehensive neuropsychological assessment and a structural brain MRI. Cognitive assessment was performed at a median delay of 4 months after the acute phase in ICH patients, and more than 6 months after the first complaint in MCI-AD patients. Cognitive profiles were compared between groups. The prevalence of VCDs in the ICH groups was estimated using the recent VASCOG criteria.Results"Mild" and "major VCDs" were respectively observed in 87.5% and 2.5% of all ICH patients. Every patient in the CAA group had mild VCDs. No significant difference was observed in cognitive functioning between CAA-related and deep ICH patients. The most impaired process in the CAA group was naming, with a mean (±standard deviation) z-score of -5.2 ±5.5, followed by processing speed (-4.1±3.3), executive functioning (-2.6 ±2.5), memory (-2.4 ±3.5) and attention (-0.9 ±1.3). This cognitive pattern was different from the MCI-AD patients, but the groups were only different in gestural praxis, and by construction, in memory processes.ConclusionsVCDs are frequent after ICH. Cognitive patterns of patients with deep or CAA-related ICH did not differ, but there was impaired performance in specific domains distinct from the effects of Alzheimer's disease.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01619709.

Project description:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that lacks effective therapy and reliable prognosis. Neovascularization following ICH is an essential compensatory response that mediates brain repair and modulates the clinical outcome of stroke patients. However, the mechanism that dictates this process is unknown. Bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. The human Tp53 gene harbors a common single-nucleotide polymorphism (SNP) at codon 72, which yields an arginine-to-proline amino-acidic substitution (Arg72Pro) that modulates the apoptotic activity of the p53 protein. Previously, we found that this SNP controls neuronal susceptibility to ischemia-induced apoptosis in vitro. Here, we evaluated the impact of the Tp53 Arg72Pro SNP on vascular repair and functional recovery after ICH. We first analyzed EPC mobilization and functional outcome based on the modified Rankin scale scores in a hospital-based cohort of 78 patients with non-traumatic ICH. Patients harboring the Pro allele of the Tp53 Arg72Pro SNP showed higher levels of circulating EPC-containing CD34+ cells, EPC-mobilizing cytokines - vascular endothelial growth factor and stromal cell-derived factor-1? - and good functional outcome following ICH, when compared with the homozygous Arg allele patients, which is compatible with increased neovascularization. To assess directly whether Tp53 Arg72Pro SNP regulated neovascularization after ICH, we used the humanized Tp53 Arg72Pro knock-in mice, which were subjected to the collagenase-induced ICH. The brain endothelial cells of the Pro allele-carrying mice were highly resistant to ICH-mediated apoptosis, which facilitated cytokine-mediated EPC mobilization, cerebrovascular repair and functional recovery. However, these processes were not observed in the Arg allele-carrying mice. These results reveal that the Tp53 Arg72Pro SNP determines neovascularization, brain repair and neurological recovery after ICH. This study is the first in which the Pro allele of Tp53 is linked to vascular repair and ability to functionally recover from stroke.

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Association of Symptomatic Hearing Loss with Functional and Cognitive Recovery 1 Year after Intracerebral Hemorrhage.

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