Advances in intracerebral hemorrhage management

Peer reviewe

Migraine and risk of haemorrhagic stroke in women: prospective cohort study

Objectives To examine the association between migraine and migraine aura status with risk of haemorrhagic stroke

Genetic Correlates of Brain Aging on MRI and Cognitive Test Measures: A Genome-Wide Association and Linkage Analysis in the Framingham Study

BACKGROUND: Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. METHODS: A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. RESULTS: The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1). CONCLUSION: Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.National Institutes of Health National Center for Research Resources Shared Instrumentation grant (ISI0RR163736-01A1); National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institute of Aging (5R01-AG08122, 5R01-AG16495); National Institute of Neurological Disorders and Stroke (5R01-NS17950

Intra-Arterial Treatment Methods in Acute Stroke Therapy

Acute revascularization is associated with improved outcomes in ischemic stroke patients. It is unclear which method of intra-arterial intervention, if any, is ideal. Promising approaches in acute stroke treatment are likely a combination of intravenous and endovascular revascularization efforts, combining early treatment initiation with direct clot manipulation and/or PTA/stenting. In this review, we will discuss available thrombolytic therapies and endovascular recanalization techniques, beginning with chemical thrombolytic agents, followed by mechanical devices, and a review of ongoing trials. Further randomized studies comparing medical therapy, intravenous and endovascular treatments are essential, and their implementation will require the wide support and enthusiasm from the neurologic, neuroradiologic, and neurosurgical stroke communities

Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study

Purpose We examined the incidence of seizures following ischemic stroke in a community-based sample. Methods All subjects with incident ischemic strokes in the Framingham Original and Offspring cohorts between 1982 and 2003 were identified and followed for up to 20 years to determine incidence of seizures. Seizure-type was based on the 2010 International League Against Epilepsy (ILAE) classification. Disability was stratified into mild/none, moderate and severe, based on post-stroke neurological deficit documentation according to the Framingham Heart Study (FHS) protocol and functional status was determined using the Barthel Index. Results An initial ischemic stroke occurred in 469 subjects in the cohort and seizures occurred in 25 (5.3%) of these subjects. Seizure incidence was similar in both large artery atherosclerosis (LAA) (6.8%) and cardio-embolic (CE) (6.2%) strokes. No seizures occurred following lacunar strokes. The predominant seizure type was focal seizure with or without evolution to bilateral convulsive seizure. One third of participants had seizures within the first 24 h from stroke onset and half of all seizures occurred within the first 30 days. On multivariate analysis, moderate and severe disability following stroke was associated with increased risk of incident seizure. Conclusions Seizures occurred in approximately 5% of subjects after an ischemic stroke. One third of these seizures occurred in the first 24 h after stroke and none followed lacunar strokes. Focal seizures with or without evolution in bilateral convulsive seizures were the most common seizure type. Moderate and severe disability was predictive of incident seizures

Caudate Infarcts

Eighteen Patients Had Caudate Nucleus Infarcts (10 Left-Sided; 8 Right-Sided). Infarcts Extended into the Anterior Limb of the Internal Capsule in 9 Patients, and Also the Anterior Putamen in 5 Patients. Thirteen Patients Had Motor Signs, Most Often a Slight Transient Hemiparesis. Dysarthria Was Common (11 Patients). Cognitive and Behavioral Abnormalities Were Frequent, and Included Abulia (10 Patients), Agitation and Hyperactivity (7 Patients), Contralateral Neglect (3 Patients, All Right Caudate), and Language Abnormalities (2 Patients, Both Left Caudate). the Majority of Patients Had Risk Factors for Penetrating Artery Disease. Branch Occlusion of Heubner\u27s Artery, or Perforators from the Proximal Anterior or Middle Cerebral Arteries Were the Posited Mechanism of Infarction. © 1990, American Medical Association. All Rights Reserved

Interobserver Agreement in the Diagnosis of Stroke Type

Interobserver Agreement is Essential to the Reliability of Clinical Data from Cooperative Studies and Provides the Foundation for Applying Research Results to Clinical Practice. in the Stroke Data Bank, a Large Cooperative Study of Stroke, We Sought to Establish the Reliability of a Key Aspect of Stroke Diagnosis: The Mechanism of Stroke. Seventeen Patients Were Evaluated by Six Neurologists. Interobserver Agreement Was Measured When Diagnosis Was based on Patient History and Neurologic Examination Only, as Well as When It Was based on Results of a Completed Workup, Including a Computed Tomographic Scan. Initial Clinical Impressions, based Solely on History and One Neurologic Examination, Were Fairly Reliable in Establishing the Mechanism of Stroke (Ie, Distinguishing among Infarcts, Subarachnoid Hemorrhages, and Parenchymatous Hemorrhages). Classification into One of Nine Stroke Subtypes Was Substantially Reliable When Diagnoses Were based on a Completed Workup. Compared with Previous Findings for the Same Physicians and Patients, the Diagnosis of Stroke Type Was Generally More Reliable Than Individual Signs and Symptoms. These Results Suggest that Multicentered Studies Can Rely on the Independent Diagnostic Choices of Several Physicians When Common Definitions Are Employed and Data from a Completed Workup Are Available. Furthermore, Reliability May Be Less for Individual Measurements Such as Signs or Symptoms Than for More-Complex Judgments Such as Diagnoses. © 1986, American Medical Association. All Rights Reserved

Interobserver Reliability in the Interpretation of Computed Tomographic Scans of Stroke Patients

Interobserver Reliability in Interpretation of Computed Tomographic Images Was Studied by Six Senior Neurologists Who Independently Evaluated on a Standardized Stroke Data Bank Form the Brain Lesions of 17 Patients. the Results Analyzed with K Statistics Yielded Moderate to Substantial Agreement on Most Items of Interest Including the Stroke Pathology and Anatomy. in General, the Levels of Agreement Were as High as Previously Reported for the Diagnosis of the Mechanism of the Stroke, and Much Higher Than on Many Stroke History Items and Items of Neurologic Examination. Excellent Agreement Was Obtained for the Detection of Infarcts and Intracerebral Hemorrhage, and Substantial Agreement Was Obtained on Whether the Computed Tomographic Images Were Normal or Indicative of Small Deep Infarcts, Superficial and Deep Infarcts, and Aneurysms. the Level of Agreement on Anatomy of the Lesions Was Best for the Frontal, Parietal, and Temporal Lobes, Putamen, Cerebellum, and Subarachnoid Space. Implications for Clinical Research and Diagnosis Are Discussed. © 1987 American Medical Association All Rights Reserved

Interobserver Variability in the Assessment of Neurologic History and Examination in the Stroke Data Bank

Interobserver Reliability in Obtaining Neurologic Histories and Examinations Was Investigated among Neurologists Collaborating in the Stroke Data Bank (SDB). Seventeen In-Hospital Stroke Patients Were Examined by Six Neurologists Experienced in Stroke over the Course of Three Days. Patients Were Examined Twice a Day for Two Successive Days, with Each Patient Seen by Four Different Neurologists. Data Were Recorded on SDB Forms, According to Definitions and Procedures Established for the SDB. Percent Agreement and Κ Coefficients Were Calculated to Assess the Levels of Agreement for Each Item. Important Differences in Levels of Agreement Were Found among Items on Both Neurologic History and Examination. Agreement among Neurologists Was Higher for Neurologic Examination Than for History. Patterns of Agreement for Items with Low Prevalence or with Numerous Unknown Ratings Are Discussed. Improvement in Interobserver Agreement Due to Data Editing for Intra-Observer Consistency Was Shown. © 1985, American Medical Association. All Rights Reserved

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status