Continuous irrigation with thrombolytics for intraventricular hemorrhage: case-control study.

Intraventricular hemorrhage (IVH) is a complication of a spontaneous intracerebral hemorrhage. Standard treatment is with external ventricular drain (EVD). Intraventricular thrombolysis may improve mortality but does not improve functional outcomes. We present our initial experience with a novel irrigating EVD (IRRAflow) that automates continuous irrigation with thrombolysis.Single-center case-control study including patients with IVH treated with EVD compared to IRRAflow. We compared standard demographics, treatment, and outcome parameters between groups. We developed a brain phantom injected with a human clot and assessed clot clearance using EVD/IRRAflow approaches with CT imaging.Twenty-one patients were treated with standard EVD and 9 patients with IRRAflow. Demographics were similar between groups. Thirty-three percent of patients with EVD also had at least one dose of t-PA and 89% of patients with IRRAflow received irrigation with t-PA (p = 0.01). Mean drain days were 8.8 for EVD versus 4.1 for IRRAflow (p = 0.02). Days-to-clearance of ventricular outflow was 5.8 for EVD versus 2.5 for IRRAflow (p = 0.02). Overall clearance was not different. Thirty-seven percent of EVD patients achieved good outcome (mRS ≥ 3) at 90 days versus 86% of IRRAflow patients (p = 0.03). Assessing only t-PA, reduction in mean days-to-clearance (p = 0.0004) and ICU days (p = 0.04) was observed. In the benchtop model, the clot treated with IRRAflow and t-PA showed a significant reduction of volume compared to control.Irrigation with IRRAflow and t-PA is feasible and safe for patients with IVH. Improving clot clearance with IRRAflow may result in improved clinical outcomes and should be incorporated into randomized trials.

Impact of insurance status, hospital ownership type, and children's hospital designation on outcomes for pediatric neurosurgery patients following spasticity procedures in the USA.

PURPOSE: This study aims to examine the relationship between insurance status, hospital ownership type, and children's hospital designation with outcomes for pediatric patients undergoing neurosurgical treatment for spasticity. METHODS: This retrospective cohort study utilized the Healthcare Cost and Utilization Project Kids' Inpatient Database and included 11,916 pediatric patients (≤ 17 years of age) who underwent neurosurgical treatment for spasticity between 2006 and 2012 using ICD-9-CM procedure codes. RESULTS: Uninsured patients had a significantly shorter hospital length of stay compared to Medicaid patients (-1.42 days, P = 0.030) as did privately insured patients (-0.74 days; P = 0.035). Discharge disposition and inpatient mortality rate were not associated with insurance status. There were no significant associations with hospital ownership type. Free-standing children's hospitals retained patients significantly longer compared to non-children's hospitals (+1.48 days; P = 0.012) and had a significantly higher likelihood of favorable discharge disposition (P = 0.004). Mortality rate was not associated with children's hospital designation. CONCLUSION: Pediatric patients undergoing neurosurgical treatment for spasticity were more likely to stay in the hospital longer if they were insured by Medicaid or treated in a free-standing children's hospital. In addition, patients in free standing children's hospitals were more likely to be discharged with a favorable disposition.

Profile of Patients Receiving Computed Tomography Scans for Mild Traumatic Brain Injury in a Tertiary Care Hospital in Ethiopia.

BACKGROUND: Traumatic brain injury (TBI) is a leading contributor to emergency department (ED) mortalities in Ethiopia. Mild TBI patients comprise half of all TBI patients presenting for care in Ethiopia and have a high potential for recovery. As such, context-specific care-improving strategies may be highly impactful for this group of patients. OBJECTIVE: This study examines the presentation and disposition of mTBI patients who received a computed tomography scan of the head upon arrival at the largest teaching hospital in Ethiopia. METHODS: A retrospective cohort study was conducted from 2018 to2021 including patients >13 years old with a head injury and a Glasgow Coma Score of 13-15 who obtained a computed tomography scan of the head. Variables were collected from medical charts and single and multivariable analyses assessed outcomes of clinically important TBI (ciTBI) requiring a neurosurgical procedure or admission. RESULTS: A total of 193 patients were included. They were predominantly young men with no comorbidities, injured in road traffic accidents or by assault, had stable vital signs and were treated in lower-acuity ED areas. A minority demonstrated focal deficits, and 29.5% of patients had ciTBI. Most patients were discharged from the ED, but 13% were taken for operative neurosurgical procedures and 10.4% were admitted to the neurosurgery ward for observation. ED stays ranged from 8 hours to 10 days, as patients waited for CT availability, neurosurgical decision, or transportation. Female sex was independently protective of ciTBI. Self-referral status was independently protective against operative intervention. Female sex and self-referral status were independently protective of a disposition of admission and/or going to the operating room. CONCLUSIONS: This study characterizes the mTBI subgroup of head injury patients in Ethiopia's busiest ED: predominantly healthy young men with low-acuity presentations and only a fraction with abnormal neurological examinations. Nonetheless, about one-third had ciTBI and a minority were taken for neurosurgical procedures or admission, with female sex and self-referral identified as protective factors. Meanwhile, many patients stayed in the ED for days due to social or other nonmedical reasons. As TBI care in Ethiopia continues to improve, optimizing care for the mTBI subgroup is tantamount given their high recovery potential. This care will benefit from efficiently identifying those who need intervention or hospital level of care, and discharging those who do not.

The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact.

Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the genetic architecture and molecular pathogenesis of HC. Without this knowledge, the development of preventive, diagnostic, and therapeutic measures is impeded. However, the genetics of HC is extraordinarily complex, based on studies of varying size, scope, and rigor. This review serves to provide a comprehensive overview of genes, pathways, mechanisms, and global impact of genetics contributing to all etiologies of HC in humans.

Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA. METHODS: The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study's initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment. RESULTS: Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists. CONCLUSIONS: The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated. TRIAL REGISTRATION: NCT04539964; August 31, 2020.

Advances in myelin imaging with potential clinical application to pediatric imaging.

White matter development and myelination are critical processes in neurodevelopment. Myelinated white matter facilitates the rapid and coordinated brain messaging required for higher-order cognitive and behavioral processing. Whereas several neurological disorders such as multiple sclerosis are associated with gross white matter damage and demyelination, other disorders such as epilepsy may involve altered myelination in the efferent or afferent white matter pathways adjoining epileptic foci. Current MRI techniques including T1 weighting, T2 weighting, FLAIR, diffusion tensor imaging, and MR spectroscopy permit visualization of gross white matter abnormalities and evaluation of underlying white matter fiber architecture and integrity, but they provide only qualitative information regarding myelin content. Quantification of these myelin changes could provide new insight into disease severity and prognosis, reveal information regarding spatial location of foci or lesions and the associated affected neural systems, and create a metric to evaluate treatment efficacy. Multicomponent analysis of T1 and T2 relaxation data, or multicomponent relaxometry (MCR), is a quantitative imaging technique that is sensitive and specific to myelin content alteration. In the past, MCR has been associated with lengthy imaging times, but a new, faster MCR technique (mcDESPOT) has made quantitative analysis of myelin content more accessible for clinical research applications. The authors briefly summarize traditional white matter imaging techniques, describe MCR and mcDESPOT, and discuss current and future clinical applications of MCR, with a particular focus on pediatric epilepsy.

Validation of the Canadian CT Head Rule and the New Orleans Criteria for Mild Traumatic Brain Injury in Ethiopia.

BACKGROUND: Traumatic brain injury (TBI) is a major public health problem worldwide. Although computed tomography (CT) scans are often used for TBI workup, clinicians in low-income countries are limited by fewer radiographic resources. The Canadian CT Head Rule (CCHR) and the New Orleans Criteria (NOC) are widely used screening tools to rule out clinically important brain injury without CT imaging. Although these tools are well validated in studies from upper- and middle-income countries, it is important to study these tools in low-income countries. This study sought to validate the CCHR and NOC in a tertiary teaching hospital population in Addis Ababa, Ethiopia. METHODS: This single-center retrospective cohort study included patients older than 13 years presenting from December 2018 to July 2021 with a head injury and a Glasgow Coma Scale score of 13-15. Retrospective chart review collected demographic, clinical, radiographic, and hospital course variables. Proportion tables were constructed to determine the sensitivity and specificity of these tools. RESULTS: A total of 193 patients were included. Both tools showed 100% sensitivity for identifying patients requiring neurosurgical intervention and abnormal CT scans. The specificity for the CCHR was 41.5% and 26.5% for the NOC. Male gender, falling accidents, and headaches had the strongest association with abnormal CT findings. CONCLUSIONS: The NOC and the CCHR are highly sensitive screening tools that can help rule out clinically important brain injury in mild TBI patients without a head CT in an urban Ethiopian population. Their implementation in this low-resource setting may help spare a significant number of CT scans.

Baseline frailty status, not advanced patient age, predicts epilepsy surgery outcomes: An analysis of 696 patients from the NSQIP database.

OBJECTIVE: Preoperative risk stratification of patients undergoing epilepsy surgery remains challenging. Recently, the efforts to look beyond age alone as an outcomes predictor has resulted in the development of measures of physiological reserve, or 'frailty indices.' The most frequently cited index in neurosurgery is the 11-item or 5-item modified frailty index (mFI11 or mFI-5). The present study aimed to use a large national registry to evaluate the effect of frailty (as measured by mFI-5 versus age on postoperative outcomes of patients undergoing epilepsy surgery. METHODS: The National Surgical Quality Improvement Program (NSQIP) database, overseen by the American College of Surgeons (ACS), was used to extract data for patients undergoing epilepsy surgery from 2015 to 2019. Univariate and multivariate analyses for age and mFI-5 were performed for the following 30-day outcomes of extended length of hospital stay (eLOS) and non-home discharge (NHD). The effect sizes were summarized by odds ratio and associated 95 % confidence intervals. Receiver operating characteristic (ROC) curve analysis, including area under the curve (AUC), was used to quantify the discrimination. RESULTS: Univariate and multivariate analyses demonstrated that frailty statuses from mFI-5, not age, were significantly predictive of eLOS and NHD. On ROC curve analysis, mFI-5 was a stronger predictor of eLOS (C = 0.59, 95 % CI 0.54-0.64, p < 0.001) and NHD (C = 0.69, 95 % CI 0.64-0.76, p < 0.001) than age (C = 0.53, 95 % CI 0.48-0.58, p = 0.21 and C = 0.53, 95 % CI 0.46-0.59, p = 0.44, respectively). CONCLUSION: Frailty, not age, is an independent risk factor for poor postoperative outcomes, particularly eLOS and NHD, in patients undergoing epilepsy surgery. Usage of mFI-5 for preoperative risk stratification of epilepsy surgery patients can help in prognostication.

Frailty Measured by the Risk Analysis Index Predicts Nonhome Discharge and Mortality After Resection in Refractory Epilepsy: Analysis of 1236 Patients From a Prospective Surgical Registry, 2012 to 2020.

BACKGROUND: Risk stratification of epilepsy surgery patients remains difficult. The Risk Analysis Index (RAI) is a frailty measurement that augments preoperative risk stratification. OBJECTIVE: To evaluate RAI's discriminative threshold for nonhome discharge disposition (NHD) and mortality (or discharge to hospice within 30 days of operation) in epilepsy surgery patients. METHODS: Patients were queried from the American College of Surgeons-National Surgical Quality Improvement Program database (2012-2020) using diagnosis/procedure codes. Linear-by-linear trend tests assessed RAI's relationship with NHD and mortality. Discriminatory accuracy was assessed by C-statistics (95% CI) in receiver operating characteristic curve analysis. RESULTS: Epilepsy resections (N = 1236) were grouped into temporal lobe (60.4%, N = 747) and nontemporal lobe (39.6%, N = 489) procedures. Patients were stratified by RAI tier: 76.5% robust (RAI 0-20), 16.2% normal (RAI 21-30), 6.6% frail (RAI 31-40), and 0.8% severely frail (RAI 41 and above). The NHD rate was 18.0% (N = 222) and positively associated with increasing RAI tier: 12.5% robust, 34.0% normal, 38.3% frail, and 50.0% severely frail ( P < .001). RAI had robust predictive discrimination for NHD in overall cohort (C-statistic 0.71), temporal lobe (C-statistic 0.70), and nontemporal lobe (C-statistic 0.71) cohorts. The mortality rate was 2.7% (N = 33) and significantly associated with RAI frailty: 1.1% robust, 8.0% normal, 6.2% frail, and 20.0% severely frail ( P < .001). RAI had excellent predictive discrimination for mortality in overall cohort (C-statistic 0.78), temporal lobe (C-statistic 0.80), and nontemporal lobe (C-statistic 0.74) cohorts. CONCLUSION: The RAI frailty score predicts mortality and NHD after epilepsy surgery. This is accomplished with a user-friendly calculator: https://nsgyfrailtyoutcomeslab.shinyapps.io/epilepsy/ .

An In Vitro Study of Magnetic Field Interference with an Electronic Shunt Programmer.

BACKGROUND: Programmable shunts play a valuable role in the treatment of hydrocephalus. However, the use of magnets in programming these valves has caused obstacles in today's magnetized world. Previous studies have reported problems with magnetic toys and electronics unintentionally reprogramming shunt valves. This study investigated how an Apple Watch can interfere with the Codman CERTAS Plus electronic programmer. METHODS: In this in vitro study, we tested the magnetic field emitted by Apple Watch Series 3, 4, 5, and 6 using an electromagnetic field tester at distances of 0-50 mm. We conducted 20 trials of shunt programming and shunt setting reading with and without each watch. RESULTS: All 4 watches generated significant magnetic fields. Maximum magnetic fields were Series 3, 165.73 millitesla (mT); Series 4, 144.91 mT; Series 5, 131.09 mT; and Series 6, 130.68 mT. All 4 watches interfered with the programmer's ability to correctly read and program the valve setting. CONCLUSIONS: The Codman CERTAS Plus electronic programmer detects the magnetic field emitted from an Apple Watch and mistakes it for the valve, rendering programming difficult. These smartwatches and similar electronic devices should be kept away from the programmer and not worn by health care providers to avoid inappropriate readings and setting changes.

Neuroinvasive Onchocerca lupi Infection in a Ten-Year-Old Girl.

The nematode Onchocerca lupi is an emerging human pathogen. Though its life cycle is not well studied, it likely infects humans after a bite from a black fly vector, which in turn acquires infective microfilariae from an infected canid. These microfilariae mature into an infective larval stage within the fly. Among six reported cases in the United States, five involved children, and all occurred in the southwest. In this report, we present a case of O. lupi infection with cervical spine invasion in a healthy 10-year-old girl. She presented with five months of neurological symptoms from a rural and medically underserved area, highlighting a need for clinical vigilance in such settings for this emerging infectious threat in the American southwest.

Trends in United States pediatric neurosurgical practice during the COVID-19 pandemic.

There is minimal information on COVID-19 pandemic's national impact on pediatric neurosurgical operative volumes. In this study, using a national database, TriNetX, we compared the overall and seasonal trends of pediatric neurosurgical procedure volumes in the United States during the pandemic to pre-pandemic periods. In the United States, the incidence of COVID-19 began to rise in September 2020 and reached its maximum peak between December 2020 and January 2021. During this time, there was an inverse relationship between pediatric neurosurgical operative volumes and the incidence of COVID-19 cases. From March 2020 to May 2021, there was a significant decrease in the number of pediatric shunt (-11.7% mean change, p = 0.006), epilepsy (-16.6%, p < 0.001), and neurosurgical trauma (-13.8%, p < 0.001) surgeries compared to pre-pandemic years. The seasonal analysis also yielded a broad decrease in most subcategories in spring 2020 with significant decreases in pediatric spine, epilepsy, and trauma cases. To the best of our knowledge, this is the first study to report a national decline in pediatric shunt, epilepsy, and neurosurgical trauma operative volumes during the pandemic. This could be due to fear-related changes in health-seeking behavior as well as underdiagnosis during the COVID-19 pandemic.

Association of hospital characteristics and insurance type with quality outcomes for pediatric craniosynostosis patients.

OBJECTIVE: Our study aimed to assess the association of insurance status and hospital ownership type with inpatient hospital outcomes among a nationally representative population of pediatric craniosynostosis neurosurgery patients. METHODS: This retrospective cohort study utilized data from the Healthcare Cost and Utilization Project 2006-2012 Kids Inpatient Database. Primary outcomes including length of stay, and favorable discharge disposition were assessed for all pediatric neurosurgery patients who underwent a neurosurgical procedure for craniosynostosis. RESULTS: Pediatric neurosurgery patients with private insurance had a reduced length of stay of 0.75 days compared to patients insured by Medicaid. Compared to private, investor-owned hospitals, Government, non-federal, and private, not for profit hospital ownership types were associated with an increased length of stay greater than 1 day. CONCLUSIONS: Our finding of increased LOS for craniosynostosis patients seen in other hospital ownership types compared to those seen in private, investor-owned hospitals is indicative of the possible role that financial incentives may play in influencing quality metrics. Although we observed a shortened LOS for privately-insured patients compared to patients insured by Medicaid, we found no difference in favorable discharge disposition based on insurance status. This suggests that patients with shorter LOS have similar outcomes and are likely not being prematurely discharged.

Association of hospital characteristics with outcomes for pediatric neurosurgical accidental trauma patients.

OBJECTIVE: In the pediatric population, few studies have examined outcomes for neurosurgical accidental trauma care based on hospital characteristics. The purpose of this study was to explore the relationship between hospital ownership type and children's hospital designation with primary outcomes. METHODS: This retrospective cohort study utilized data from the Healthcare Cost and Utilization Project 2006, 2009, and 2012 Kids' Inpatient Database. Primary outcomes, including inpatient mortality, length of stay (LOS), and favorable discharge disposition, were assessed for all pediatric neurosurgery patients who underwent a neurosurgical procedure and were discharged with a primary diagnosis of accidental traumatic brain injury. RESULTS: Private, not-for-profit hospitals (OR 2.08, p = 0.034) and freestanding children's hospitals (OR 2.88, p = 0.004) were predictors of favorable discharge disposition. Private, not-for-profit hospitals were also associated with reduced inpatient mortality (OR 0.34, p = 0.005). A children's unit in a general hospital was associated with a reduction in hospital LOS by almost 2 days (p = 0.004). CONCLUSIONS: Management at freestanding children's hospitals correlated with more favorable discharge dispositions for pediatric patients with accidental trauma who underwent neurosurgical procedures. Management within a children's unit in a general hospital was also associated with reduced LOS. By hospital ownership type, private, not-for-profit hospitals were associated with decreased inpatient mortality and more favorable discharge dispositions.

Impact of Telephone Follow-Up on Patient Satisfaction in a Pediatric Neurosurgery Clinic.

Patient satisfaction is a key metric used to measure quality in health care. However, patient satisfaction measures in the pediatric population are less studied and understood than in the adult population. The purpose of this study was to evaluate the impact of telephone follow-up on patient satisfaction in an outpatient pediatric neurosurgery clinic. A standardized telephone follow-up call was performed within 1 week of a child's clinic visit. Pearson's χ2 or Fisher's exact tests were used to assess changes in patient satisfaction measures after implementation of the telephone follow-up call initiative. The proportion of overall "top-box" physician rating significantly increased from 85.5% in 2017 to 95.6% in 2018 (P = .04). There was also a nonsignificant upward trend in the proportion of respondents noting that they would recommend this provider, as well as in all measures of physician communication quality and office staff quality. A simple telephone call to new patients after an outpatient pediatric neurosurgery clinic visit resulted in statistically significant and clinically meaningful changes in patient satisfaction scores.

Inpatient Hospital Outcomes and its Association with Insurance Type Among Pediatric Neurosurgery Trauma Patients.

OBJECTIVE: To assess the association of insurance status and inpatient hospital outcomes among a nationally representative population of pediatric trauma neurosurgery patients. METHODS: The 2006, 2009, and 2012 Healthcare Cost and Utilization Project Kids' Inpatient Database was queried for all pediatric neurosurgery patients (birth through 17 years) with primary International Classification of Diseases, Ninth Edition, Clinical Modification, procedure codes for trauma or hematoma. RESULTS: Self-pay patients were 2.5 times more likely to die during hospitalization. Results also showed that pediatric neurosurgery patients with private insurance had a reduced length of stay and were more likely to have a favorable disposition at discharge. CONCLUSIONS: Insurance status is significantly associated with mortality, length of stay, and favorable discharge disposition among pediatric neurosurgery trauma patients. Further studies are needed to examine the underlying mechanism of the observed associations.

Using the neutrophil-to-lymphocyte ratio to predict outcomes in pediatric patients with traumatic brain injury.

OBJECTIVE: The brain's inflammatory reaction to traumatic brain injury (TBI) generally peaks between 24 and 48 h after injury. This inflammatory cascade can be neuroprotective or may mediate secondary brain injury beyond the initial TBI. Therefore, circulating inflammatory markers may be useful for predicting outcomes in pediatric TBI. The goal of this study was to determine whether elevations in peripheral blood neutrophil-to-lymphocyte ratios (NLRs) are associated with adverse outcomes in pediatric TBI patients. PATIENTS AND METHODS: 188 pediatric patients (0-18 years) presenting to our institution with TBI from 2007 to 2017 were retrospectively reviewed. Absolute neutrophil and lymphocyte counts from a complete blood count (CBC) were used to calculate NLRs on admission (<12 h) and approximately 24, 48, and 72 h after injury. Data points included Glasgow Coma Scale (GCS) on admission, presence of post-traumatic amnesia (PTA), loss of consciousness (LOC), and Glasgow Outcome Scale Extended Pediatric Version (GOS-E Peds) with a median outcome span of 86 days. RESULTS: A one-way ANOVA demonstrated statistically significant differences in NLR at 24 h (p = 0.004) and 48 h (p=0.003) among patients stratified by GOS-E Peds. No significant differences in NLR were observed at any time point based on GCS or PTA. Patients who experienced LOC had a significantly higher NLR on admission (p=0.013) and at 24 h (p<0.001) than those who did not. CONCLUSION: In this study, relatively higher NLRs at 24 and 48 h post-TBI were associated with worse outcomes in pediatric patients. This suggests that NLR may be a useful and cost-effective outcome predictor in pediatric TBI as well as a possible future target for therapeutic intervention, warranting larger prospective trials.

Peripheral blood neutrophil-to-lymphocyte ratio in preterm infants with intraventricular hemorrhage.

OBJECTIVES: Intraventricular hemorrhage (IVH) remains a major complication of prematurity, affecting 20-25% of premature infants of very low birth weight. Preterm infants with IVH are at risk for developing significant complications, including posthemorrhagic hydrocephalus and seizures. Multiple studies have reported an association between the neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and outcomes after acute intracranial hemorrhage in adults. However, the prognostic value of the NLR in preterm infants, particularly those with IVH, has not been investigated previously. PATIENTS AND METHODS: This retrospective, observational cohort study included premature infants with IVH and a neonatal reservoir placed between January 2013 and January 2018. For each patient, peripheral blood and available cerebrospinal fluid laboratory results within 50 days of IVH diagnosis were averaged. NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Differences in NLR levels for patients with seizures or shunt placement were analyzed. RESULTS: Data for 13 surviving preterm infants (mean gestational age, 26.5 ± 3.0 weeks) were analyzed. The mean peripheral NLR (n = 13) was 1.6 ± 1.3 for all patients. Patients who experienced seizures had significantly higher peripheral blood NLR (p = 1.2 × 10-6, t-test) than those who did not, and an NLR > 3 correlated with seizure outcomes (p = 0.0035, Fisher's exact). Patients with sepsis or meningitis also had NLR values >3 (p = 0.01 and 0.005, respectively) but there was no correlation between the sepsis/meningitis and seizures patients. No significant correlation was found between NLR and the development of hydrocephalus. CONCLUSION: The development of seizures in preterm infants with IVH is known to significantly increase morbidity. In this study, higher peripheral blood NLR (>3) correlated with the development of seizures, independent of sepsis or meningitis. Further prospective validation of the role of NLR as a predictive marker for seizures in preterm infants is warranted.

Myelin water fraction changes in febrile seizures.

OBJECTIVE: The objective of this feasibility study was to investigate whether myelin water fraction (MWF) patterns can differentiate children presenting with febrile seizures who will go on to develop nonfebrile epilepsy from those who will not. PATIENTS AND METHODS: As part of a prospective study of myelination patterns in pediatric epilepsy, seven subjects with febrile seizures underwent magnetic resonance imaging (MRI) including the following standard sequences-T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR)-and an additional experimental sequence, multicomponent-derived equilibrium single-pulse observation of T1 and T2 (mcDESPOT) to quantify MWF. For each of these subjects, MWF maps were derived and compared with an age-matched population-averaged MWF atlas. RESULTS: All seven subjects (<5 years old) initially presented with febrile seizures. Of the seven, four had complex seizures and three had simple seizures. All of the children with simple febrile seizures had higher MWF compared with model-derived controls and did not develop epilepsy. All of the children with complex febrile seizures had lower MWF than their model-derived control, and two of these subjects later developed epilepsy. CONCLUSION: This is the first study in which MWF maps were used to study children with febrile *seizures. This data suggests that relatively higher or stable MWF compared with normative data indicates a lower risk of nonfebrile epilepsy while relatively lower MWF may indicate a pathological condition that could lead to nonfebrile epilepsy.

Prospective study of myelin water fraction changes after mild traumatic brain injury in collegiate contact sports.

OBJECTIVE: Mild traumatic brain injury (mTBI) in athletes, including concussion, is increasingly being found to have long-term sequelae. Current imaging techniques have not been able to identify early damage caused by mTBI that is predictive of long-term symptoms or chronic traumatic encephalopathy. In this preliminary feasibility study, the authors investigated the use of an emerging magnetic resonance imaging (MRI) technique, multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT), in visualizing acute and chronic white matter changes after mTBI in collegiate football and rugby players. METHODS: This study was a nonrandomized, nonblinded prospective trial designed to quantify changes in the myelin water fraction (MWF), used as a surrogate MRI measure of myelin content, in a group of male collegiate football and rugby players, classified here as a contact sport player (CSP) cohort, at the time of mTBI diagnosis and 3 months after injury when the acute symptoms of the injury had resolved. In addition, differences in the MWF between the CSP cohort and a control cohort of noncontact sport players (NCSPs) were quantified. T-tests and a threshold-free cluster enhancement (TFCE) statistical analysis technique were used to identify brain structures with significant changes in the MWF between the CSP and NCSP cohorts and between immediately postinjury and follow-up images obtained in the CSP cohort. RESULTS: Brain MR images of 12 right-handed male CSPs were analyzed and compared with brain images of 10 right-handed male NCSPs from the same institution. A comparison of CSP and NCSP baseline images using TFCE showed significantly higher MWFs in the bilateral basal ganglia, anterior and posterior corpora callosa, left corticospinal tract, and left anterior and superior temporal lobe (p < 0.05). At the 3-month follow-up examination, images from the CSP cohort still showed significantly higher MWFs than those identified on baseline images from the NCSP cohort in the bilateral basal ganglia, anterior and posterior corpora callosa, and left anterior temporal lobe, and also in the bilateral corticospinal tracts, parahippocampal gyrus, and bilateral juxtapositional (previously known as supplemental motor) areas (p < 0.05). In the CSP cohort, a t-test comparing the MWF at the time of injury and 3 months later showed a significant increase in the overall MWF at follow-up (p < 0.005). These increases were greatest in the bilateral basal ganglia and deep white matter. MWF decreases were seen in more superficial white matter (p < 0.005). CONCLUSIONS: In this preliminary study, MWF was found to be increased in the brains of CSPs compared with the brains of controls, suggesting acute/chronic MWF alterations in CSPs from previous injuries. Increases in the MWF were also demonstrated in the brains of CSPs 3 months after the players sustained an mTBI. The full clinical significance of an increased MWF and whether this reflects axon neuropathology or disorderly remyelination leading to hypermyelination has yet to be determined.