Project description:About half of patients survive intracerebral hemorrhage (ICH), but most are left with significant disability. Rehabilitation after ICH is the mainstay of treatment to reduce impairment, improve independence in activities, and return patients to meaningful participation in the community. The authors discuss the neuroplastic mechanisms underlying recovery in ICH, preclinical and clinical interventional studies to augment recovery, and the rehabilitative and medical management of post-ICH patients.
Project description:Background and purposeVagus nerve stimulation (VNS) delivered during rehabilitative training enhances neuroplasticity and improves recovery in models of cortical ischemic stroke. However, VNS therapy has not been applied in a model of subcortical intracerebral hemorrhage (ICH). We hypothesized that VNS paired with rehabilitative training after ICH would enhance recovery of forelimb motor function beyond rehabilitative training alone.MethodsRats were trained to perform an automated, quantitative measure of forelimb function. Once proficient, rats received an intrastriatal injection of bacterial collagenase to induce ICH. Rats then underwent VNS paired with rehabilitative training (VNS+Rehab; n=14) or rehabilitative training without VNS (Rehab; n=12). Rehabilitative training began ≥9 days after ICH and continued for 6 weeks.ResultsVNS paired with rehabilitative training significantly improved recovery of forelimb function when compared with rehabilitative training without VNS. The VNS+Rehab group displayed a 77% recovery of function, whereas the Rehab group only exhibited 29% recovery. Recovery was sustained after cessation of stimulation. Both groups performed similar amounts of trials during rehabilitative, and lesion size was not different between groups.ConclusionsVNS paired with rehabilitative training confers significantly improved forelimb recovery after ICH compared to rehabilitative training without VNS.
Project description:ImportanceSeizures 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.ObjectiveTo 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.DesignProspective cohort study conducted between March 1, 2007, and January 1, 2012.SettingThree tertiary care pediatric hospitals.ParticipantsSeventy-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).Main outcome measuresAcute symptomatic seizures (clinically evident and electrographic-only seizures within 7 days), remote symptomatic seizures, and epilepsy.ResultsAcute 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).Conclusions and relevancePresenting 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:ImportanceAge-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.ObjectiveTo investigate whether the association between hearing and cognition is present among individuals traditionally classified as having normal hearing.Design, setting, and participantsCross-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]).ExposuresAudiometric HL (4-frequency pure-tone average).Main outcomes and measuresNeurocognitive 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.ResultsAmong 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 relevanceAn 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:We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. The relationship between changes in bacterial flora and the prognosis of spontaneous cerebral hemorrhage was studied in two cohort studies. Fecal samples from healthy volunteers and patients with intracerebral hemorrhage were subjected to 16S rRNA sequencing at three time points: T1 (within 24 hours of admission), T2 (3 days post-surgery), and T3 (7 days post-surgery) using Illumina high-throughput sequencing technology.
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:Macrophages are a source of both proinflammatory and restorative functions in damaged tissue through complex dynamic phenotypic changes. Here, we sought to determine whether monocyte-derived macrophages (MDMs) contribute to recovery after acute sterile brain injury. By profiling the transcriptional dynamics of MDMs in the murine brain after experimental intracerebral hemorrhage (ICH), we found robust phenotypic changes in the infiltrating MDMs over time and demonstrated that MDMs are essential for optimal hematoma clearance and neurological recovery. Next, we identified the mechanism by which the engulfment of erythrocytes with exposed phosphatidylserine directly modulated the phenotype of both murine and human MDMs. In mice, loss of receptor tyrosine kinases AXL and MERTK reduced efferocytosis of eryptotic erythrocytes and hematoma clearance, worsened neurological recovery, exacerbated iron deposition, and decreased alternative activation of macrophages after ICH. Patients with higher circulating soluble AXL had poor 1-year outcomes after ICH onset, suggesting that therapeutically augmenting efferocytosis may improve functional outcomes by both reducing tissue injury and promoting the development of reparative macrophage responses. Thus, our results identify the efferocytosis of eryptotic erythrocytes through AXL/MERTK as a critical mechanism modulating macrophage phenotype and contributing to recovery from ICH.
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:Background and objectivesIL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH).MethodsWe performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes.ResultsOf 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; P=0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P=0.002), with a stronger association seen in lobar (β, 12.51 [95% CI, 6.47-18.55], P<0.001) versus nonlobar (β 5.32 [95% CI, 3.36-7.28], P<0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (β 1.22 [95% CI, 0.15-2.29], P=0.03). Treatment group was not associated with IL-6 levels or outcome.ConclusionsIn the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.