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PURPOSE - Cerebral amyloid angiopathy is a vasculopathy caused by β-amyloid deposition in cerebral arterioles and capillaries. It is closely linked to Alzheimer's disease and predisposes elderly patients to intracerebral hemorrhage, transient focal neurological episodes, and cognitive impairment. Because of a predilection for symptomatic hemorrhage, particularly in the frontal lobes, cerebral amyloid angiopathy may also cause a dysexecutive syndrome.
RECENT FINDINGS - In this case series, we describe presentations of classic clinical dementia syndromes which are not are widely thought to be associated with cerebral amyloid angiopathy, namely logopenic variant primary progressive aphasia (n = 3), normal pressure hydrocephalus (n = 3), and Lewy body dementia (n = 2). In every case, after a clinical diagnosis was established, neuroimaging, brain biopsy, and/or autopsy confirmed the presence of cerebral amyloid angiopathy. Cerebral amyloid angiopathy has significant clinical implications, and its ability to mimic and/or contribute to other clinical dementia syndromes can complicate its diagnosis. This series of cases broadens the range of clinical scenarios associated with cerebral amyloid angiopathy.
BACKGROUND AND PURPOSE - Intracerebral hemorrhage is a considerable source of morbidity and mortality. This 3-center study describes outcomes of pediatric intracerebral hemorrhage and identifies 2-year neurological outcome predictors.
METHODS - Children 29 days to 18 years of age presenting with intracerebral hemorrhage from March 2007 to May 2015 were enrolled prospectively. Exclusion criteria included trauma; intracranial tumor; hemorrhagic transformation of arterial ischemic stroke or cerebral sinovenous thrombosis; isolated subdural, epidural, or subarachnoid hemorrhage; and abnormal baseline neurological function. Intracerebral hemorrhage and total brain volumes were measured on neuroimaging. The Pediatric Stroke Outcome Measure assessed outcomes.
RESULTS - Sixty-nine children were included (median age: 9.7 years; interquartile range: 2.2-14). Six children (9%) died during hospitalization. Outcomes in survivors were assessed at early follow-up in 98% (median 3.1 months; interquartile range: 3.1-3.8) and at later follow-up in 94% (median: 2.1 years; interquartile range: 1.3-2.8). Over a third had a significant disability at 2 years (Pediatric Stroke Outcome Measure >2). Total Pediatric Stroke Outcome Measure score improved over time (=0.0003), paralleling improvements in the sensorimotor subscore (=0.0004). Altered mental status (odds ratio, 13; 95% confidence interval, 3.9-46; <0.001), hemorrhage volume ≥4% of total brain volume (odds ratio, 17; 95% confidence interval, 1.9-156; =0.01), and intensive care unit length of stay (odds ratio, 1.1; 95% confidence interval, 1.0-1.2; =0.002) were significantly associated with poor 2-year outcome.
CONCLUSIONS - Over one third of children experienced significant disability at 2 years. Improvements in outcomes were driven by recovery of sensorimotor function. Altered mental status, hemorrhage volume ≥4% of total brain volume, and intensive care unit length of stay were independent predictors of significant disability at 2 years.
© 2018 American Heart Association, Inc.
AIM - Previous research investigating outcomes after pediatric intracerebral hemorrhage (ICH) has generally been limited to global and sensorimotor outcomes. This study examined cognitive outcomes after spontaneous ICH in school-aged children with serial assessments over 2 years after stroke.
METHOD - Seven children (age range 6-16y, median 13; six males, one female; 57% white, 43% black) presenting with spontaneous ICH (six arteriovenous malformations) were assessed at 3 months, 12 months, and 24 months after stroke. The Pediatric Stroke Outcome Measure (PSOM) quantified neurological outcome and Wechsler Intelligence Scales measured cognitive outcomes: verbal comprehension, perceptual reasoning, working memory, and processing speed.
RESULTS - PSOM scales showed improved neurological function over the first 12 months, with mild to no sensorimotor deficits and moderate overall deficits at 1- and 2-year follow-ups (median 2-year sensorimotor PSOM=0.5, total PSOM=1.5). Changes in cognitive function indicated a different trajectory; verbal comprehension and perceptual reasoning improved over 24 months; low performance was sustained in processing speed and working memory. Age-normed centile scores decreased between 1- and 2-year follow-ups for working memory, suggesting emerging deficits compared with peers.
INTERPRETATION - Early and serial cognitive testing in children with ICH is needed to assess cognitive functioning and support children in school as they age and cognitive deficits become more apparent and important for function.
WHAT THIS PAPER ADDS - In children with intracerebral hemorrhage (ICH), motor function improved between 3 months and 24 months. Improvements in cognitive function were variable between 3 months and 24 months. Working memory centiles declined, suggesting emerging deficits compared with peers. Processing speed improved but remained significantly below the 50th centile. Cognitive impact of ICH may increase with age in children.
© 2017 Mac Keith Press.
The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept. In contrast, the potential contribution of CSF secretion to PHH has received little attention. In a rat model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and NF-κB-dependent inflammatory response in the CPE that is associated with a ∼3-fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the CPE apical membrane. Genetic depletion of TLR4 or SPAK normalizes hyperactive CSF secretion rates and reduces PHH symptoms, as does treatment with drugs that antagonize TLR4-NF-κB signaling or the SPAK-NKCC1 co-transporter complex. These data uncover a previously unrecognized contribution of CSF hypersecretion to the pathogenesis of PHH, demonstrate a new role for TLRs in regulation of the internal brain milieu, and identify a kinase-regulated mechanism of CSF secretion that could be targeted by repurposed US Food and Drug Administration (FDA)-approved drugs to treat hydrocephalus.
The authors present a case of monozygotic twins with hereditary hemorrhagic telangiectasia (HHT) who experienced cerebral arteriovenous malformation (AVM) hemorrhage at a very young age. The clinical variables influencing HHT-related AVM rupture are discussed, and questions surrounding the timing of screening and intervention are explored. This is only the second known case of monozygotic HHT twins published in the medical literature, and the youngest pair of first-degree relatives to experience AVM-related cerebral hemorrhage. Evidence guiding the screening and management of familial HHT is lacking, and cases such as this underscore the need for objective and validated protocols.
BACKGROUND - This study describes educational placement of school-aged children after spontaneous intracerebral hemorrhage and examines whether educational placement is associated with severity of neurological deficits.
METHODS - Children with spontaneous intracerebral hemorrhage presenting from 2007 to 2013 were prospectively enrolled at three tertiary children's hospitals. The Pediatric Stroke Outcome Measure and parental interview gathered information about neurological outcome, school attendance, and educational placement.
RESULTS - The cohort of 92 enrolled children included 42 school-aged children (6 to 17 years) with intracerebral hemorrhage. Four children died; one was excluded because of preexisting cognitive deficits. Thirty-seven children completed three-month follow-up, and 30 completed 12-month follow-up. At 12 months, 14 children (46.7%) received regular age-appropriate programming, 12 (40%) attended school with in-class services, three (10%) were in special education programs, and one child (3.3%) received home-based services because of intracerebral hemorrhage-related deficits. Of 30 children with three- and 12-month follow-up, 14 (46.7%) improved their education status, 13 (43.3%) remained at the same education level, and three (10%) began to receive in-class services. An increasing Pediatric Stroke Outcome Measure score predicted the need for educational modifications at three months (odds ratio, 3.3; 95% confidence interval, 1.4 to 7.9; P = 0.007) and at 12 months (odds ratio, 2.1; 95% confidence interval, 1.1 to 3.9; P = 0.025).
CONCLUSIONS - Most children returned to school within a year after intracerebral hemorrhage, and many had a reduction in the intensity of educational support. However, a great need for educational services persisted at 12 months after intracerebral hemorrhage with fewer than half enrolled in regular age-appropriate classes. Worse deficits on the Pediatric Stroke Outcome Measure were associated with remedial educational placement.
Copyright © 2016 Elsevier Inc. All rights reserved.
With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ∼11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA (3% and 10%, respectively). In high-income countries, RCTs (Stroke Prevention in Sickle Cell Anemia [STOP], STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TCD With Transfusions Changing to Hydroxyurea [TWiTCH]). Also in high-income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (Stroke With Transfusions Changing to Hydroxyurea [SWiTCH]) or silent cerebral infarcts (Silent Infarct Transfusion [SIT] Trial). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention.
© 2016 by The American Society of Hematology.
We assessed factors associated with mortality and potential targets for intervention in a large national sample of children with nontraumatic intracerebral hemorrhage. Using Healthcare Cost and Utilization Project Kids' Inpatient Database ICD-9-CM code 431 identified children aged 1 to 18 years with nontraumatic intracerebral hemorrhage in 2003, 2006 and 2009. Intracerebral hemorrhage was the primary diagnosis for 1172 children (ages 1-18 years) over the 3-year sample. Factors associated with mortality based on multivariable logistic regression included Hispanic ethnicity (odds ratio 1.9, 95% confidence interval 1.1-3.3), older age (11-18 vs 1-10 years, odds ratio 2.5, 95% confidence interval 1.3-5.0), coagulopathy (odds ratio 3.0, 95% confidence interval 1.6-6.0), and coma (odds ratio 9.0, 95% confidence interval 3.2-24.6). From 2003 to 2009, there was a non-significant decrease in mortality with a significant increase in length of stay from 9 to 11 days (P < .003). In children with intracerebral hemorrhage, coma and coagulopathy had the strongest association with mortality; coagulopathy is a potentially modifiable risk factor.
© The Author(s) 2014.
BACKGROUND - The rates and outcomes of treatments for intracranial aneurysms have not been exclusively determined within the pediatric population. We determined the rates of endovascular and microsurgical treatments for unruptured intracranial aneurysms (UIA) and associated rates of favorable outcome in patients aged <18 years.
METHODS - We analyzed data obtained as part of the Kids' Inpatient Database between 2003 and 2009 with primary diagnosis of UIA. Patients undergoing endovascular treatment were compared to those undergoing microsurgical treatment. We determined rates of intracerebral hemorrhage, subarachnoid hemorrhage, neurological complications, and favorable outcome.
RESULTS - There were 818 cases of UIA during the study period. A total of 111 patients (mean age 14 ± 6 years, 37.6 % female) underwent microsurgical treatment, and another 200 patients (mean age 13 ± 7 years, 42.5 % female) underwent endovascular treatment. A high rate of favorable outcome was observed in patients who received either treatment (microsurgical treatment 87.7 % versus endovascular treatment 91.6 %, p = 0.4). There was a trend towards a significantly shorter mean hospitalization stay among those who received endovascular treatment compared with microsurgical treatment (6 ± 12 versus 9 ± 11 days, p = 0.06). There was a significant trend towards higher utilization of endovascular treatment as opposed to microsurgical treatment from 2003 to 2009 (p = 0.02).
CONCLUSIONS - Although outcomes except for length of stay were comparable between endovascular treatment and microsurgical treatment patients, there was a trend towards higher utilization of endovascular treatment among children with UIAs from 2003 to 2009.