Toward rational use of repeat imaging in children with mild traumatic brain injuries and intracranial injuries.

OBJECTIVE: Limited evidence exists on the utility of repeat neuroimaging in children with mild traumatic brain injuries (mTBIs) and intracranial injuries (ICIs). Here, the authors identified factors associated with repeat neuroimaging and predictors of hemorrhage progression and/or neurosurgical intervention. METHODS: The authors performed a multicenter, retrospective cohort study of children at four centers of the Pediatric TBI Research Consortium. All patients were ≤ 18 years and presented within 24 hours of injury with a Glasgow Coma Scale score of 13-15 and evidence of ICI on neuroimaging. The outcomes of interest were 1) whether patients underwent repeat neuroimaging during index admission, and 2) a composite outcome of progression of previously identified hemorrhage ≥ 25% and/or repeat imaging as an indication for subsequent neurosurgical intervention. The authors performed multivariable logistic regression and report odds ratios and 95% confidence intervals. RESULTS: A total of 1324 patients met inclusion criteria; 41.3% of patients underwent repeat imaging. Repeat imaging was associated with clinical change in 4.8% of patients; the remainder of the imaging tests were for routine surveillance (90.9%) or of unclear prompting (4.4%). In 2.6% of patients, repeat imaging findings were reported as an indication for neurosurgical intervention. While many factors were associated with repeat neuroimaging, only epidural hematoma (OR 3.99, 95% CI 2.22-7.15), posttraumatic seizures (OR 2.95, 95% CI 1.22-7.41), and age ≥ 2 years (OR 2.25, 95% CI 1.16-4.36) were significant predictors of hemorrhage progression and/or neurosurgery. Of patients without any of these risk factors, none underwent neurosurgical intervention. CONCLUSIONS: Repeat neuroimaging was commonly used but uncommonly associated with clinical deterioration. Although several factors were associated with repeat neuroimaging, only posttraumatic seizures, age ≥ 2 years, and epidural hematoma were significant predictors of hemorrhage progression and/or neurosurgery. These results provide the foundation for evidence-based repeat neuroimaging practices in children with mTBI and ICI.

Predictors of Seizure Freedom in Pediatric Low-Grade Gliomas.

OBJECTIVE: Pediatric low-grade gliomas (LGGs) are found in approximately one to three percent of patients with childhood epilepsy. Epilepsy in these patients is often medically refractory and therefore represents a unique cohort with significant morbidity from concomitant pathology. Similar studies in adult patients with low-grade gliomas have identified predictors of seizure freedom including gross-total resection, preoperative seizure control on antiepileptic medication and duration of seizures of less than one year. This study aims to identify similar predictors of seizure freedom in operatively managed pediatric LGGs. METHODS: A retrospective chart review was performed for patients diagnosed with World Health Organization (WHO) Grade I and II gliomas in patients ≤18 years old at a single institution (Indiana University School of Medicine at Riley Hospital for Children in Indianapolis, IN) from 2007-2017. Infratentorial and purely intraventricular lesions were excluded. WHO classification and histologic diagnosis were based on surgical pathology. Tumor grade, location, laterality, seizure status at presentation, and AED requirements pre- and post-operatively were recorded. Chi-squared analyses for independence were performed controlling for age at presentation, resection extent, seizure type, and Engel Class for seizure freedom post-operatively. RESULTS: Forty-two patients met the inclusion criteria. Preoperative seizures were observed in 23 patients (55%). Presentation with preoperative seizures was highly associated with continued seizure burden post-operatively, independent of the extent of surgical resection. Supratentorial location and the administration of prophylactic pre- and post-operative AEDs were associated with Engel Class I seizure freedom. Temporal location was not significantly associated with medically refractory epilepsy compared with extra-temporal locations. CONCLUSIONS: In our cohort of pediatric LGGs, we find that patients that did not initially present with seizures and those who were treated with prophylactic pre- and post-operative AEDs, were more likely to achieve Engel Class I seizure freedom post-operatively. Tumors located in the temporal location were not significantly associated with a higher seizure burden than other supratentorial, extra-temporal tumors. Neither extent of resection nor electrocorticography-guided resection correlated with improved seizure freedom outcomes during glioma resection.

Measures of Intracranial Injury Size Do Not Improve Clinical Decision Making for Children With Mild Traumatic Brain Injuries and Intracranial Injuries.

BACKGROUND: When evaluating children with mild traumatic brain injuries (mTBIs) and intracranial injuries (ICIs), neurosurgeons intuitively consider injury size. However, the extent to which such measures (eg, hematoma size) improve risk prediction compared with the kids intracranial injury decision support tool for traumatic brain injury (KIIDS-TBI) model, which only includes the presence/absence of imaging findings, remains unknown. OBJECTIVE: To determine the extent to which measures of injury size improve risk prediction for children with mild traumatic brain injuries and ICIs. METHODS: We included children ≤18 years who presented to 1 of the 5 centers within 24 hours of TBI, had Glasgow Coma Scale scores of 13 to 15, and had ICI on neuroimaging. The data set was split into training (n = 1126) and testing (n = 374) cohorts. We used generalized linear modeling (GLM) and recursive partitioning (RP) to predict the composite of neurosurgery, intubation >24 hours, or death because of TBI. Each model's sensitivity/specificity was compared with the validated KIIDS-TBI model across 3 decision-making risk cutoffs (<1%, <3%, and <5% predicted risk). RESULTS: The GLM and RP models included similar imaging variables (eg, epidural hematoma size) while the GLM model incorporated additional clinical predictors (eg, Glasgow Coma Scale score). The GLM (76%-90%) and RP (79%-87%) models showed similar specificity across all risk cutoffs, but the GLM model had higher sensitivity (89%-96% for GLM; 89% for RP). By comparison, the KIIDS-TBI model had slightly higher sensitivity (93%-100%) but lower specificity (27%-82%). CONCLUSION: Although measures of ICI size have clear intuitive value, the tradeoff between higher specificity and lower sensitivity does not support the addition of such information to the KIIDS-TBI model.

Development and external validation of the KIIDS-TBI tool for managing children with mild traumatic brain injury and intracranial injuries.

BACKGROUND: Clinical decision support (CDS) may improve the postneuroimaging management of children with mild traumatic brain injuries (mTBI) and intracranial injuries. While the CHIIDA score has been proposed for this purpose, a more sensitive risk model may have broader use. Consequently, this study's objectives were to: (1) develop a new risk model with improved sensitivity compared to the CHIIDA model and (2) externally validate the new model and CHIIDA model in a multicenter data set. METHODS: We analyzed children ≤18 years old with mTBI and intracranial injuries included in the PECARN head injury data set (2004-2006). We used binary recursive partitioning to predict the composite outcome of neurosurgical intervention, intubation for > 24 h due to TBI, or death due to TBI. The new model was externally validated in a separate data set that included children treated at any one of six centers from 2006 to 2019. RESULTS: Based on 839 patients from the PECARN data set, a new risk model, the KIIDS-TBI model, was developed that incorporated imaging (e.g., midline shift) and clinical (e.g., Glasgow Coma Scale score) findings. Based on the model-predicted probability of the composite outcome, three cutoffs were evaluated to classify patients as "high risk" for level of care decisions. In the external validation data set consisting of 1,630 patients, the most conservative cutoff (i.e., any predictor present) identified 119 of 119 children with the composite outcome (sensitivity = 100%), but had the lowest specificity (26.3%). The other two decision-making cutoffs had worse sensitivity (94.1%-96.6%) but improved specificity (67.4%-81.3%). The CHIIDA model lacked the most conservative cutoff and otherwise showed the same or slightly worse performance compared to the other two cutoffs. CONCLUSIONS: The KIIDS-TBI model has high sensitivity and moderate specificity for risk stratifying children with mTBI and intracranial injuries. Use of this CDS tool may help improve the safe, resource-efficient management of this important patient population.

Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development.

Endocannabinoid (eCB) signaling system (ECS), encompassing cannabinoid receptors and enzymes involved in the synthesis and degradation of the endogenous cannabinoid signaling lipids, is highly expressed in the cerebellar cortex of adult humans and rodents. In addition to their well-established role in neuromodulation, eCBs have been shown to play key roles in aspects of neurodevelopment in the fore- and mid-brain, including neurogenesis, cell migration, and synapse specification. However, little is known about the role of ECS in cerebellar development. In this study, we conducted immunohistochemical characterization of ECS components through key stages of cerebellar development in mice using antibodies for 2-arachidonoylglycerol (2-AG) synthetizing and degrading enzymes and the major brain cannabinoid receptor, cannabinoid receptor 1 (CB1), in combination with cerebellar cell markers. Our results reveal a temporally, spatially, and cytologically dynamic pattern of expression. Production, receptor binding, and degradation of eCBs are tightly controlled, thus localization of eCB receptors and the complementary cannabinoid signaling machinery determines the direction, duration, and ultimately the outcome of eCB signaling. To gain insights into the role of eCB signaling in cerebellar development, we characterized gross anatomy of cerebellar midvermis in CB1 knock-out (CB1 KO) mice, as well as their performance in cerebellar-influenced motor tasks. Our results show persistent and selective anatomic and behavioral alterations in CB1 KOs. Consequently, the insights gained from this study lay down the foundation for investigating specific cellular and molecular mechanisms regulated by eCB signaling during cerebellar development.

PedsQL for prediction of postoperative patient-reported outcomes following Chiari decompression surgery.

OBJECTIVE: The purpose of this study is to determine if the preoperative Pediatric Quality of Life Inventory (PedsQL) score is predictive of short- and intermediate-term PedsQL outcomes following Chiari decompression surgery. The utility of preoperative patient-reported outcomes (PROs) in predicting pain, opioid consumption, and long-term PROs has been demonstrated in adult spine surgery. To the best of the authors' knowledge, however, there is currently no widely accepted tool to predict short-, intermediate-, or long-term outcomes after pediatric Chiari decompression surgery. METHODS: A prospectively maintained database was retrospectively reviewed. Patients who had undergone first-time decompression for symptomatic Chiari malformation were identified and grouped according to their preoperative PedsQL scores: mild disability (score 80-100), moderate disability (score 60-79), and severe disability (score < 60). PedsQL scores at the 6-week, 3-month, and/or 6-month follow-ups were collected. Preoperative PedsQL subgroups were tested for an association with demographic and perioperative characteristics using one-way ANOVA or chi-square analysis. Preoperative PedsQL subgroups were tested for an association with improvements in short- and intermediate-term PedsQL scores using one-way ANOVA and a paired Wilcoxon signed-rank test controlling for statistically different demographic characteristics when appropriate. RESULTS: A total of 87 patients were included in this analysis. According to their preoperative PedsQL scores, 28% of patients had mild disability, 40% had moderate disability, and 32% had severe disability. There was a significant difference in the prevalence of comorbidities (p = 0.009) and the presenting symptoms of headaches (p = 0.032) and myelopathy (p = 0.047) among the subgroups; however, in terms of other demographic or operative factors, there was no significant difference. Patients with greater preoperative disability demonstrated statistically significantly lower PedsQL scores at all postoperative time points, except in terms of the parent-reported PedsQL at 6 months after surgery (p = 0.195). Patients with severe disability demonstrated statistically significantly greater improvements (compared to preoperative scores) in PedsQL scores at all time points after surgery, except in terms of the 6-week and 6-month PROs and the 6-month parent-reported outcomes (p = 0.068, 0.483, and 0.076, respectively). CONCLUSIONS: Patients with severe disability, as assessed by the PedsQL, had lower absolute PedsQL scores at all time points after surgery but greater improvement in short- and intermediate-term PROs. The authors conclude that the PedsQL is an efficient and accurate tool that can quickly assess patient disability in the preoperative period and predict both short- and intermediate-term surgical outcomes.