Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.

BackgroundNeonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.MethodsThis is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.ResultsIn a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.ConclusionsElevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers

Population-based study of ischemic stroke risk after trauma in children and young adults.

OBJECTIVE:To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort. METHODS:We electronically identified trauma patients (<50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997-2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression. RESULTS:From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0-5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1-14.9) and neck (OR 5.6, CI 1.03-30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation). CONCLUSIONS:Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

Cerebral palsy research funding from the National Institutes of Health, 2001 to 2013.

AimCerebral palsy (CP) is a poorly understood disorder with no cure. We determined the landscape of National Institutes of Health (NIH) funding for CP-related research.MethodWe searched NIH databases Research Portfolio Online Reporting Tools Expenditures and Results, and Research, Condition, and Disease Categorization for keywords 'cerebral palsy' among all NIH-funded studies, 2001 to 2013. We classified grants by type and area of study.ResultsNIH funding, averaging $30 million per year, supported clinical ($215 million), basic ($187 million), and translational ($26.3 million) CP-related research. Clinical intervention studies comprised 19% of funding, and focused on treatments ($60.3 million), early parent intervention ($2.7 million), and CP prevention ($2.5 million). Among grants that specified gestational age, more funds were devoted to preterm ($166 million) than term infants ($15 million). CP in adulthood was the main focus of 4$3.6 to $66.7 million. However, funding for clinical intervention studies peaked in 2008, and has since decreased.InterpretationAdditional research funds are needed to improve the treatment and prevention of CP. Topics that have been relatively underfunded include clinical interventions, prevention, and term infants and adults with CP

Cerebral palsy research funding from the National Institutes of Health, 2001 to 2013.

AimCerebral palsy (CP) is a poorly understood disorder with no cure. We determined the landscape of National Institutes of Health (NIH) funding for CP-related research.MethodWe searched NIH databases Research Portfolio Online Reporting Tools Expenditures and Results, and Research, Condition, and Disease Categorization for keywords 'cerebral palsy' among all NIH-funded studies, 2001 to 2013. We classified grants by type and area of study.ResultsNIH funding, averaging $30 million per year, supported clinical ($215 million), basic ($187 million), and translational ($26.3 million) CP-related research. Clinical intervention studies comprised 19% of funding, and focused on treatments ($60.3 million), early parent intervention ($2.7 million), and CP prevention ($2.5 million). Among grants that specified gestational age, more funds were devoted to preterm ($166 million) than term infants ($15 million). CP in adulthood was the main focus of 4$3.6 to $66.7 million. However, funding for clinical intervention studies peaked in 2008, and has since decreased.InterpretationAdditional research funds are needed to improve the treatment and prevention of CP. Topics that have been relatively underfunded include clinical interventions, prevention, and term infants and adults with CP

Intraoperative rerupture during surgical treatment of aneurysmal subarachnoid hemorrhage is not associated with an increased risk of vasospasm

OBJECT: Intraoperative rerupture during open surgical clipping of cerebral aneurysms in subarachnoid hemorrhage (SAH) is a relatively frequent and potentially catastrophic occurrence. Patients who suffer rerupture have been shown to have worse outcomes at discharge compared with those who do not have rerupture. Perioperative injury likely plays a large part in the clinical worsening of these patients. However, due to the increased vessel manipulation and repeat exposure to acute hemorrhage, it is possible that secondary injury from increased incidence of vasospasm also contributes. Identifying an increased rate of vasospasm in these patients would justify early aggressive treatment with measures to prevent delayed cerebral ischemia. The authors investigated whether patients who suffer intraoperative rerupture during surgical treatment of ruptured cerebral aneurysms are at increased risk of developing vasospasm. METHODS: Five hundred consecutive patients treated with open surgical clipping for SAH were reviewed, and clinical and imaging data were collected. Angiographic vasospasm was defined as vessel narrowing believed to be consistent with vasospasm on angiography. Symptomatic vasospasm was defined as angiographic vasospasm in the setting of a clinical change attributable to vasospasm. Rates of angiographic and symptomatic vasospasm among patients with and without intraoperative rerupture were compared. RESULTS: There were no significant differences between the groups with and without rupture with respect to age, sex, modified Fisher grade, history of hypertension, or smoking. The group with intraoperative rupture had more patients with Hunt and Hess Grade I. Angiographic vasospasm was noted in 279 (66%) of the 425 patients without rerupture compared with 49 (65%) of the 75 patients with rerupture (p = 1.0, Fisher\u27s exact test). Symptomatic vasospasm was noted in 154 (36%) of the 425 patients without rerupture, compared with 31 (41%) of the 75 patients with rerupture (p = 0.44, Fisher\u27s exact test). In multivariate analysis, higher modified Fisher grade was significantly predictive of vasospasm, whereas older age and male sex were protective. CONCLUSIONS: This study found no significant influence of intraoperative rerupture during open surgical clipping on the rate of angiographic or symptomatic vasospasm. Brief exposure to acute hemorrhage and vessel manipulation associated with rerupture events did not affect the rate of vasospasm. Risk of vasospasm was related to increased modified Fisher grade, and inversely related to age and male sex. These results do not justify early, targeted vasospasm therapy in patients with intraoperative rerupture