A clinically applicable functional MRI memory paradigm for use with pediatric patients.

OBJECTIVE: Clinically employable functional MRI (fMRI) memory paradigms are not yet established for pediatric patient epilepsy surgery workups. Seeking to establish such a paradigm, we evaluated the effectiveness of memory fMRI tasks we developed by quantifying individual activation in a clinical pediatric setting, analyzing patterns of activation relative to the side of temporal lobe (TL) pathology, and comparing fMRI and Wada test results. METHODS: We retrospectively identified 72 patients aged 6.7-20.9 years with pathology (seizure focus and/or tumor) limited to the TL who had attempted memory and language fMRI tasks over a 9-year period as part of presurgical workups. Memory fMRI tasks required visualization of autobiographical memories in a block design alternating with covert counting. Language fMRI protocols involved verb and sentence generation. Scans were both qualitatively interpreted and quantitatively assessed for blood oxygenation level dependent (BOLD) signal change using region of interest (ROI) masks. We calculated the percentage of successfully scanned individual cases, compared 2 memory task activation masks in cases with left versus right TL pathology, and compared fMRI with Wada tests when available. Patients who had viable fMRI and Wada tests had generally concordant results. RESULTS: Of the 72 cases, 60 (83%), aged 7.6-20.9 years, successfully performed the memory fMRI tasks and 12 (17%) failed. Eleven of 12 unsuccessful scans were due to motion and/or inability to perform the tasks, and the success of a twelfth was indeterminate due to orthodontic metal artifact. Seven of the successful 60 cases had distorted anatomy that precluded employing predetermined masks for quantitative analysis. Successful fMRI memory studies showed bilateral mesial temporal activation and quantitatively demonstrated: (1) left activation (L-ACT) less than right activation (R-ACT) in cases with left temporal lobe (L-TL) pathology, (2) nonsignificant R-ACT less than L-ACT in cases with right temporal lobe (R-TL) pathology, and (3) lower L-ACT plus R-ACT activation for cases with L-TL versus R-TL pathology. Patients who had viable fMRI and Wada tests had generally concordant results. SIGNIFICANCE: This study demonstrates evidence of an fMRI memory task paradigm that elicits reliable activation at the individual level and can generally be accomplished in clinically involved pediatric patients. This autobiographical memory paradigm showed activation in mesial TL structures, and cases with left compared to right TL pathology showed differences in activation consistent with extant literature in TL epilepsy. Further studies will be required to assess outcome prediction.

Increased complications without neurological benefit are associated with prophylactic spinal cord untethering prior to scoliosis surgery in children with myelomeningocele.

PURPOSE: Children with myelomeningocele (MMC) are at increased risk of developing neuromuscular scoliosis and spinal cord re-tethering (Childs Nerv Syst 12:748-754, 1996; Neurosurg Focus 16:2, 2004; Neurosurg Focus 29:1, 2010). Some centers perform prophylactic untethering on asymptomatic MMC patients prior to scoliosis surgery because of concern that additional traction on the cord may place the patient at greater risk of neurologic deterioration peri-operatively. However, prophylactic untethering may not be justified if it carries increased surgical risks. The purpose of this study was to determine if prophylactic untethering is necessary in asymptomatic children with MMC undergoing scoliosis surgery. METHODS: A multidisciplinary, retrospective cohort study from seven children's hospitals was performed including asymptomatic children with MMC < 21 years old, managed with or without prophylactic untethering prior to scoliosis surgery. Patients were divided into three groups for analysis: (1) untethering at the time of scoliosis surgery (concomitant untethering), (2) untethering within 3 months of scoliosis surgery (prior untethering), and (3) no prophylactic untethering. Baseline data, intra-operative reports, and 90-day post-operative outcomes were analyzed to assess for differences in neurologic outcomes, surgical complications, and overall length of stay. RESULTS: A total of 208 patients were included for analysis (mean age 9.4 years, 52% girls). No patient in any of the groups exhibited worsened motor or sensory function at 90 days post-operatively. However, comparing the prophylactic untethering groups with the group that was not untethered, there was an increased risk of surgical site infection (SSI) (31.3% concomitant, 28.6% prior untethering vs. 12.3% no untethering; p = 0.0104), return to the OR (43.8% concomitant, 23.8% prior untethering vs. 17.4% no untethering; p = 0.0047), need for blood transfusion (51.6% concomitant, 57.1% prior untethering vs. 33.8% no untethering; p = 0.04), and increased mean length of stay (LOS) (13.4 days concomitant, 10.6 days prior untethering vs. 6.8 days no untethering; p < 0.0001). In multivariable logistic regression analysis, prophylactic untethering was independently associated with increased adjusted relative risks of surgical site infection (aRR = 2.65, 95% CI 1.17-5.02), unplanned re-operation (aRR = 2.17, 95% CI 1.02-4.65), and any complication (aRR = 2.25, 95% CI 1.07-4.74). CONCLUSION: In this study, asymptomatic children with myelomeningocele who underwent scoliosis surgery developed no neurologic injuries regardless of prophylactic untethering. However, those who underwent prophylactic untethering were more likely to experience SSIs, return to the OR, need a blood transfusion, and have increased LOS than children not undergoing untethering. Based on these data, prophylactic untethering in asymptomatic MMC patients prior to scoliosis surgery does not provide any neurological benefit and is associated with increased surgical risks.

Bilateral occipital endoscopic choroid plexus cauterization for persistent hydrocephalus following frontal endoscopic third ventriculostomy and choroid plexus cauterization--the "bowling ball" technique.

Endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) as a primary treatment for hydrocephalus is gaining popularity in North America, particularly among the infant population. Unfortunately, despite considerable experience with ETV/CPC at several centers, treatment failures still exist. Early reports have suggested that greater than 90 % cauterization of the choroid plexus is associated with improved clinical outcomes. However, individual patient anatomy and smaller overall ventricular size can limit the amount of choroid plexus cauterization that is technically possible through a single frontal burr hole. Furthermore, the degree of cauterization achieved by surgeons using this technique is difficult to quantify objectively. In this report, we describe the case of an infant who failed initial ETV/CPC but then had successful resolution of hydrocephalus after additional choroid plexus cauterization performed through bilateral occipital burr holes. The child remains shunt-free over a year after treatment, suggesting that this three-pronged CPC approach (the "bowling ball" technique) may be successful in some young children with persistent hydrocephalus after ETV/CPC from a single frontal burr hole.

Intraoperative neuromonitoring potentials and evidence of preserved neuronal circuitry below the anatomical and functional level in patients with complex spinal dysraphism undergoing detethering reoperations.

OBJECTIVE: Spina bifida represents one of the most common birth defects, occurring in approximately 1-2 children per 1000 live births worldwide. The functional level of patients with spina bifida is highly variable and believed to be correlated with the anatomical level of the lesion. The variable clinical picture is well established, but the correlation with anatomical level and intraoperative neuromonitoring (IONM) data has not been investigated. Furthermore, the potential for preserving function beyond the apparent clinical level has also not been investigated. The objective of this research was to determine the presence and level of intraoperative transcranial motor evoked potential (tcMEP) and triggered electromyography (tEMG) responses, and the association of these responses with preoperative clinical function and radiographic data in pediatric cases of complex tethered cord release reoperations. METHODS: A single-center retrospective review of pediatric patients with complex spinal dysraphism undergoing detethering reoperations was conducted. Preoperative demographic and clinical data, including the radiographic and clinical level of dysraphism, were collected. IONM, including tcMEPs and tEMG responses, were obtained and compared with preoperative clinical data. Descriptive analysis was performed, by patient for demographics and by case for surgeries performed. RESULTS: In 100% of 21 cases of complex detethering reoperations, representing 20 patients, intraoperative tcMEPs could be generated at (4.8%) or below (95.2%) the level of clinical function. Compared with the preoperative clinical examination, 5 cases (23.8%) demonstrated tcMEP responses that were 1 level below the clinical function level, 11 cases (52.4%) were 2 levels below, and 4 cases (19.0%) were 3 levels below. Overall, 18 of 21 cases showed tEMG responses at or below the level of clinical function; of these, 7 cases (33%) were 1 level below and 3 (14%) were ≥ 2 levels below the clinical function level. CONCLUSIONS: The presence of positive stimulation potentials below the level of clinical function in patients with complex spinal dysraphism undergoing detethering reoperations indicates a degree of preserved neuronal connectivity. These findings suggest novel future treatment approaches for these patients, including using devices targeted to stimulation of these neurological pathways.

Cerebrospinal fluid liquid biopsy by low-pass whole genome sequencing for clinical disease monitoring in pediatric embryonal tumors.

Background: Liquid biopsy assays that detect cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) are a promising tool for disease monitoring in pediatric patients with primary central nervous system (CNS) tumors. As a compliment to tissue-derived molecular analyses, CSF liquid biopsy has the potential to transform risk stratification, prognostication, and precision medicine approaches. Methods: In this pilot study, we evaluated a clinical pipeline to determine feasibility and sensitivity of low-pass whole genome sequencing (LP-WGS) of CSF-derived cfDNA from patients with CNS embryonal tumors. Thirty-two longitudinal CSF samples collected from 17 patients with molecularly characterized medulloblastoma (12), embryonal tumor with multilayered rosettes (2), CNS embryonal tumor, not elsewhere classified (NEC) (2), and atypical teratoid/rhabdoid tumor (1) were analyzed. Results: Adequate CSF-derived cfDNA for LP-WGS analysis was obtained in 94% of samples (30/32). Copy number variants compatible with neoplasia were detected in 90% (27/30) and included key alterations, such as isodicentric ch17, monosomy 6, and MYCN amplification, among others. Compared to tissue specimens, LP-WGS detected additional aberrations in CSF not previously identified in corresponding primary tumor specimens, suggesting a more comprehensive profile of tumor heterogeneity or evolution of cfDNA profiles over time. Among the 12 CSF samples obtained at initial staging, only 2 (17%) were cytologically positive, compared to 11 (92%) that were copy number positive by LP-WGS. Conclusions: LP-WGS of CSF-derived cfDNA is feasible using a clinical platform, with greater sensitivity for tumor detection compared to conventional CSF cytologic analysis at initial staging. Large prospective studies are needed to further evaluate LP-WGS as a predictive biomarker.

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

Timing of intraoperative neurophysiological monitoring (IONM) recovery and clinical recovery after termination of pediatric spinal deformity surgery due to loss of IONM signals.

BACKGROUND CONTEXT: Intraoperative neurophysiological monitoring (IONM) is used to reduce the risk of spinal cord injury during pediatric spinal deformity surgery. Significant reduction and/or loss of IONM signals without immediate recovery may lead the surgeon to acutely abort the case. The timing of when monitorable signals return remains largely unknown. PURPOSE: The goal of this study was to investigate the correlation between IONM signal loss, clinical examination, and subsequent normalization of IONM signals after aborted pediatric spinal deformity surgery to help determine when it is safe to return to the operating room. STUDY DESIGN/SETTING: This is a multicenter, multidisciplinary, retrospective study of pediatric patients (<18 years old) undergoing spinal deformity surgery whose surgery was aborted due to a significant reduction or loss of IONM potentials. PATIENT SAMPLE: Sixty-six patients less than 18 years old who underwent spinal deformity surgery that was aborted due to IONM signal loss were enrolled into the study. OUTCOME MEASURES: IONM data, operative reports, and clinical examinations were investigated to determine the relationship between IONM loss, clinical examination, recovery of IONM signals, and clinical outcome. METHODS: Information regarding patient demographics, deformity type, clinical history, neurologic and ambulation status, operative details, IONM information (eg, quality of loss [SSEPs, MEPs], laterality, any recovery of signals, etc.), intraoperative wake-up test, postoperative neurologic exam, postoperative imaging, and time to return to the operating were all collected. All factors were analyzed and compared with univariate and multivariate analysis using appropriate statistical analysis. RESULTS: Sixty-six patients were enrolled with a median age of 13 years [IQR 11-14], and the most common sex was female (42/66, 63.6%). Most patients had idiopathic scoliosis (33/66, 50%). The most common causes of IONM loss were screw placement (27/66, 40.9%) followed by rod correction (19/66, 28.8%). All patients had either complete bilateral (39/66, 59.0%), partial bilateral (10/66, 15.2%) or unilateral (17/66, 25.8%) MEP loss leading to termination of the case. Overall, when patients were returned to the operating room 2 weeks postoperatively, nearly 75% (40/55) had monitorable IONM signals. Univariate analysis demonstrated that bilateral SSEP loss (p=.019), bilateral SSEP and MEP loss (p=.022) and delayed clinical neurologic recovery (p=.008) were significantly associated with having unmonitorable IONM signals at repeat surgery. Multivariate regression analysis demonstrated that delayed clinical neurologic recovery (> 72 hours) was significantly associated with unmonitorable IONM signals when returned to the operating room (p=.006). All patients ultimately made a full neurologic recovery. CONCLUSIONS: In children whose spinal deformity surgery was aborted due to intraoperative IONM loss, there was a strong correlation between combined intraoperative SSEP/MEP loss, the magnitude of IONM loss, the timing of clinical recovery, and the time of electrophysiological IONM recovery. The highest likelihood of having a prolonged postoperative neurological deficit and undetectable IONM signals upon return to the OR occurs with bilateral complete loss of SSEPs and MEPs.

Perioperative complications and secondary retethering after pediatric tethered cord release surgery.

OBJECTIVE: Tethered cord syndrome refers to a constellation of symptoms characterized by neurological, musculoskeletal, and urinary symptoms, caused by traction on the spinal cord, which can be secondary to various etiologies. Surgical management of simple tethered cord etiologies (e.g., fatty filum) typically consists of a single-level lumbar laminectomy, intradural exploration, and coagulation and sectioning of the filum. More complex etiologies such as lipomyelomeningoceles or scar formation after myelomeningocele repair involve complex dissection and dural reconstruction. The purpose of this study was to evaluate operative complications and long-term outcomes of secondary retethering related to pediatric tethered cord release (TCR) at a tertiary children's hospital. METHODS: Medical records of children who underwent surgery for TCR from July 2014 to March 2023 were retrospectively reviewed. Data collected included demographics, perioperative characteristics, surgical technique, and follow-up duration. Primary outcomes were 60-day postoperative complications and secondary retethering requiring repeat TCR surgery. Univariate and multivariate analyses were performed to identify risk factors associated with complications and secondary retethering. RESULTS: A total of 363 TCR surgeries (146 simple, 217 complex) in 340 patients were identified. The mean follow-up was 442.8 ± 662.2 days for simple TCRs and 733.9 ± 750.3 days for complex TCRs. The adjusted 60-day complication-free survival rate was 96.3% (95% CI 91.3%-98.4%) for simple TCRs and 88.7% (95% CI 82.3%-91.4%) for complex TCRs. Lower weight, shorter surgical times, and intensive care unit admission were associated with complications for simple TCRs. Soft-tissue drains increased complications for complex TCRs. The secondary retethering rates were 1.4% for simple TCRs and 11.9% for complex TCRs. The 1-, 3-, and 5-year progression-free survival rates in complex cases were 94.7% (95% CI 89.1%-97.4%), 77.7% (95% CI 67.3%-85.3%), and 62.6% (95% CI 46.5%-75.1%), respectively. Multivariate analysis revealed that prior detethering (OR 8.15, 95% CI 2.33-28.50; p = 0.001) and use of the operative laser (OR 10.43, 95% CI 1.36-80.26; p = 0.024) were independently associated with secondary retethering in complex cases. CONCLUSIONS: This is the largest series to date examining postoperative complications and long-term secondary retethering in TCR surgery. Simple TCR surgeries demonstrated safety, rare complications, and low secondary retethering rates. Complex TCR surgeries presented higher risks of complications and secondary retethering. Modifiable risk factors such as operative laser use influenced secondary retethering in complex cases.

Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety.

Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. Based on adoptive cellular therapy's clinical success against childhood leukemia and the preclinical efficacy against pediatric CNS tumors, chimeric antigen receptor (CAR) T cells offer hope of improving outcomes for recurrent tumors and universally fatal diseases such as diffuse intrinsic pontine glioma (DIPG). However, a major obstacle for tumors of the brain and spine is ineffective T cell chemotaxis to disease sites. Locoregional CAR T cell delivery via infusion through an intracranial catheter is currently under study in multiple early phase clinical trials. Here, we describe the Seattle Children's single-institution experience including the multidisciplinary process for the preparation of successful, repetitive intracranial T cell infusion for children and the catheter-related safety of our 307 intracranial CAR T cell doses.

Chondroblastoma of the Occipital Bone With Atypical Genetic Markers: A Case Report.

Chondroblastoma is a rare bone tumor, most often found in epiphyseal plates of long bones. It has infrequently been reported in the skull, most often in the temporal bone. We present a case of chondroblastoma of the occipital bone in a pediatric patient presenting with a bony protuberance of the occiput and imaging consistent with obstructive hydrocephalus, which persisted even after removal of the obstructing tumor. Pathological examination demonstrated that this unusually placed tumor also lacked the classic genetic markers typically associated with chondroblastoma.

Concordance of functional MRI memory task and resting-state functional MRI connectivity used in surgical planning for pediatric temporal lobe epilepsy.

OBJECTIVE: Assessing memory is often critical in surgical evaluation, although difficult to assess in young children and in patients with variable task abilities. While obtaining interpretable data from task-based functional MRI (fMRI) measures is common in compliant and awake patients, it is not known whether functional connectivity MRI (fcMRI) data show equivalent results. If this were the case, it would have substantial clinical and research generalizability. To evaluate this possibility, the authors evaluated the concordance between fMRI and fcMRI data collected in a presurgical epilepsy cohort. METHODS: Task-based fMRI data for autobiographical memory tasks and resting-state fcMRI data were collected in patients with epilepsy evaluated at Seattle Children's Hospital between 2010 and 2017. To assess memory-related activation and laterality, signal change in task-based measures was computed as a percentage of the average blood oxygen level-dependent signal over the defined regions of interest. An fcMRI data analysis was performed using 1000 Functional Connectomes Project scripts based on Analysis of Functional NeuroImages and FSL (Functional Magnetic Resonance Imaging of the Brain Software Library) software packages. Lateralization indices (LIs) were estimated for activation and connectivity measures. The concordance between these two measures was evaluated using correlation and regression analysis. RESULTS: In this epilepsy cohort studied, the authors observed concordance between fMRI activation and fcMRI connectivity, with an LI regression coefficient of 0.470 (R2 = 0.221, p = 0.00076). CONCLUSIONS: Previously published studies have demonstrated fMRI and fcMRI overlap between measures of vision, attention, and language. In the authors' clinical sample, task-based measures of memory and analogous resting-state mapping were similarly linked in pattern and strength. These results support the use of fcMRI methods as a proxy for task-based memory performance in presurgical patients, perhaps including those who are more limited in their behavioral compliance. Future investigations to extend these results will be helpful to explore how the magnitudes of effect are associated with neuropsychological performance and postsurgical behavioral changes.

Precision medicine in pediatric temporal epilepsy surgery: optimization of outcomes through functional MRI memory tasks and tailored surgeries.

OBJECTIVE: The goal of epilepsy surgery is both seizure cessation and maximal preservation of function. In temporal lobe (TL) cases, the lack of functional MRI (fMRI) tasks that effectively activate mesial temporal structures hampers preoperative memory risk assessment, especially in children. This study evaluated pediatric TL surgery outcome optimization associated with tailored resection informed by an fMRI memory task. METHODS: The authors identified focal onset TL epilepsy patients with 1) TL resections; 2) viable fMRI memory scans; and 3) pre- and postoperative neuropsychological (NP) evaluations. They retrospectively evaluated preoperative fMRI memory scans, available Wada tests, pre- and postoperative NP scores, postoperative MRI scans, and postoperative Engel class outcomes. To assess fMRI memory task outcome prediction, the authors 1) overlaid preoperative fMRI activation onto postoperative structural images; 2) classified patients as having "overlap" or "no overlap" of activation and resection cavities; and 3) compared these findings with memory improvement, stability, or decline, based on Reliable Change Index calculations. RESULTS: Twenty patients met the inclusion criteria. At a median of 2.1 postoperative years, 16 patients had Engel class IA outcomes and 1 each had Engel class IB, ID, IIA, and IID outcomes. Functional MRI activation was linked to NP memory outcome in 19 of 20 cases (95%). Otherwise, heterogeneity characterized the cohort. CONCLUSIONS: Functional MRI memory task activation effectively predicted individual NP outcomes in the context of tailored TL resections. Patients had excellent seizure and overall good NP outcomes. This small study adds to extant literature indicating that pediatric TL epilepsy does not represent a single clinical syndrome. Findings support individualized surgical intervention using fMRI memory activation to help guide this precision medicine approach.

The Putative Role of mTOR Inhibitors in Non-tuberous Sclerosis Complex-Related Epilepsy.

Epilepsy affects ~5 out of every 10,000 children per year. Up to one-third of these children have medically refractory epilepsy, with limited to no options for improved seizure control. mTOR, a ubiquitous 289 kDa serine/threonine kinase in the phosphatidylinositol 3-kinase (PI3K)-related kinases (PIKK) family, is dysregulated in a number of human diseases, including tuberous sclerosis complex (TSC) and epilepsy. In cell models of epilepsy and TSC, rapamycin, an mTOR inhibitor, has been shown to decrease seizure frequency and duration, and positively affect cell growth and morphology. Rapamycin has also been shown to prevent or improve epilepsy and prolong survival in animal models of TSC. To date, clinical studies looking at the effects of mTOR inhibitors on the reduction of seizures have mainly focused on patients with TSC. Everolimus (Novartis Pharmaceuticals), a chemically modified rapamycin derivative, has been shown to reduce seizure frequency with reasonable safety and tolerability. Mutations in mTOR or the mTOR pathway have been found in hemimegalencephaly (HME) and focal cortical dysplasias (FCDs), both of which are highly correlated with medically refractory epilepsy. Given the evidence to date, a logical next step is to investigate the role of mTOR inhibitors in the treatment of children with medically refractory non-TSC epilepsy, particularly those children who have also failed resective surgery.

Opioid-Sparing Multimodal Analgesia After Selective Dorsal Rhizotomy.

OBJECTIVES: Multimodal analgesia (MMA) may reduce opioid use among children who are hospitalized, and may contribute toward enhanced recovery after selective dorsal rhizotomy (SDR) for patients with spasticity in pediatric cerebral palsy. In this retrospective cohort study, we assess an MMA protocol consisting of scheduled nonsteroidal antiinflammatory drug doses (ketorolac or ibuprofen), alternating with scheduled acetaminophen and diazepam doses, with as-needed opioids. It was hypothesized that protocol use would be associated with reductions in opioid requirements and other clinical improvements. METHODS: Data were obtained for 52 patients undergoing SDR at an academic tertiary care pediatric hospital (2012-2017, with the protocol implemented in 2014). Using a retrospective cohort design, we compared outcomes between protocol and nonprotocol patients, employing both univariate t test and Wilcoxon rank test comparisons as well as multivariable regression methods. The primary outcome was total as-needed opioid requirements over postoperative days (PODs) 0 to 2, measured in oral morphine milligram equivalents per kilogram. Additional outcomes included antiemetic medication doses, discharge opioid prescriptions, total direct cost, and length of stay. RESULTS: Twelve patients received the MMA protocol, and 40 patients did not. POD-0 MMA initiation was independently associated with a reduction of 0.14 morphine milligram equivalents per kilogram in mean opioid requirements over PODs 0 to 2 in the multiple regression analysis (95% confidence interval 0.01 to 0.28; P = .04). No statistically significant differences were demonstrated in doses of antiemetic medications, discharge opioid prescriptions, total direct cost, and length of stay. CONCLUSIONS: This MMA protocol may help reduce opioid use after SDR. Improving protocol implementation in a prospective, multisite study will help elucidate further MMA effects on pain, costs, and recovery.

Multimodal Analgesia After Posterior Fossa Decompression With and Without Duraplasty for Children With Chiari Type I.

BACKGROUND: Multimodal analgesia (MMA) may reduce opioid use after surgery for Chiari malformation type I. An MMA protocol was implemented after both posterior fossa decompression without dural opening (PFD) and posterior fossa decompression with duraplasty (PFDD). METHODS: Scheduled nonsteroidal antiinflammatory drugs (ketorolac or ibuprofen) and diazepam were alternated with acetaminophen, and as-needed oxycodone or intravenous morphine. The primary outcome was total opioid requirement over postoperative days 0 to 2. RESULTS: From 2012 to 2017, 49 PFD and 29 PFDD procedures were performed, and 46 of 78 patients used the protocol. Patients with PFD required less opioids than patients with PFDD. Among patients with PFDD, patients with MMA protocol usage had a lower mean opioid requirement than patients with no MMA protocol usage (0.53 ± 0.49 mgEq/kg versus 1.4 ± 1.0 mgEq/kg, P = .0142). In multivariable analysis, MMA protocol usage status independently predicted a mean decrease in opioid requirement of 0.146 mg equivalents/kg (P = .0497) after adjustment for procedure and surgeon. Statistically significant differences were not demonstrated in antiemetic requirements, discharge opioid prescriptions, total direct cost, and length of stay. CONCLUSIONS: A protocol of scheduled nonsteroidal antiinflammatory drugs alternating with scheduled acetaminophen and diazepam was associated with opioid use reductions.

Risk of seizures induced by intracranial research stimulation: analysis of 770 stimulation sessions.

OBJECTIVE: Patients with medically refractory epilepsy often undergo intracranial electroencephalography (iEEG) monitoring to identify a seizure focus and determine their candidacy for surgical intervention. This clinically necessary monitoring period provides an increasingly utilized research opportunity to study human neurophysiology, however ethical concerns demand a thorough appreciation of the associated risks. We measured the incidence of research stimulation-associated seizures in a large multi-institutional dataset in order to determine whether brain stimulation was statistically associated with seizure incidence and identify potential risk factors for stimulation-associated seizures. APPROACH: 188 subjects undergoing iEEG monitoring across ten institutions participated in 770 research stimulation sessions over 3.5 yr. Seizures within 30 min of a stimulation session were included in our retrospective analysis. We analyzed stimulation parameters, seizure incidence, and typical seizure patterns, to assess the likelihood that recorded seizures were stimulation-induced, rather than events that occurred by chance in epilepsy patients prone to seizing. MAIN RESULTS: In total, 14 seizures were included in our analysis. All events were single seizures, and no adverse events occurred. The mean amplitude of seizure-associated stimulation did not differ significantly from the mean amplitude delivered in sessions without seizures. In order to determine the likelihood that seizures were stimulation induced, we used three sets of analyses: visual iEEG analysis, statistical frequency, and power analyses. We determined that three of the 14 seizures were likely stimulation-induced, five were possibly stimulation-induced, and six were unlikely stimulation-induced. Overall, we estimate a rate of stimulation-induced seizures between 0.39% and 1.82% of sessions. SIGNIFICANCE: The rarity of stimulation-associated seizures and the fact that none added morbidity or affected the clinical course of any patient are important findings for understanding the feasibility and safety of intracranial stimulation for research purposes.

Safety and efficacy of stereoelectroencephalography in pediatric focal epilepsy: a single-center experience.

OBJECTIVE: Patients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients. METHODS: The authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed. RESULTS: Twenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3-19 days). Nearly all patients were discharged home on the day following electrode explantation. There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics. SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV. CONCLUSIONS: SEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.

Identifying Factors Predictive of Atlantoaxial Fusion Failure in Pediatric Patients: Lessons Learned From a Retrospective Pediatric Craniocervical Society Study.

STUDY DESIGN: Multicenter retrospective cohort study with multivariate analysis. OBJECTIVE: To determine factors predictive of posterior atlantoaxial fusion failure in pediatric patients. SUMMARY OF BACKGROUND DATA: Fusion rates for pediatric posterior atlantoaxial arthrodesis have been reported to be high in single-center studies; however, factors predictive of surgical non-union have not been identified by a multicenter study. METHODS: Clinical and surgical details for all patients who underwent posterior atlantoaxial fusion at seven pediatric spine centers from 1995 to 2014 were retrospectively recorded. The primary outcome was surgical failure, defined as either instrumentation failure or fusion failure seen on either plain x-ray or computed tomography scan. Multiple logistic regression analysis was undertaken to identify clinical and technical factors predictive of surgical failure. RESULTS: One hundred thirty-one patients met the inclusion criteria and were included in the analysis. Successful fusion was seen in 117 (89%) of the patients. Of the 14 (11%) patients with failed fusion, the cause was instrumentation failure in 3 patients (2%) and graft failure in 11 (8%). Multivariate analysis identified Down syndrome as the single factor predictive of fusion failure (odds ratio 14.6, 95% confidence interval [3.7-64.0]). CONCLUSION: This retrospective analysis of a multicenter cohort demonstrates that although posterior pediatric atlantoaxial fusion success rates are generally high, Down syndrome is a risk factor that significantly predicts the possibility of surgical failure. LEVEL OF EVIDENCE: 3.

Growth and alignment of the pediatric subaxial cervical spine following rigid instrumentation and fusion: a multicenter study of the Pediatric Craniocervical Society.

OBJECTIVE The long-term effects of surgical fusion on the growing subaxial cervical spine are largely unknown. Recent cross-sectional studies have demonstrated that there is continued growth of the cervical spine through the teenage years. The purpose of this multicenter study was to determine the effects of rigid instrumentation and fusion on the growing subaxial cervical spine by investigating vertical growth, cervical alignment, cervical curvature, and adjacent-segment instability over time. METHODS A total of 15 centers participated in this multi-institutional retrospective study. Cases involving children less than 16 years of age who underwent rigid instrumentation and fusion of the subaxial cervical spine (C-2 and T-1 inclusive) with at least 1 year of clinical and radiographic follow-up were investigated. Charts were reviewed for clinical data. Postoperative and most recent radiographs, CT, and MR images were used to measure vertical growth and assess alignment and stability. RESULTS Eighty-one patients were included in the study, with a mean follow-up of 33 months. Ninety-five percent of patients had complete clinical resolution or significant improvement in symptoms. Postoperative cervical kyphosis was seen in only 4 patients (5%), and none developed a swan-neck deformity, unintended adjacent-level fusion, or instability. Of patients with at least 2 years of follow-up, 62% demonstrated growth across the fusion construct. On average, vertical growth was 79% (4-level constructs), 83% (3-level constructs), or 100% (2-level constructs) of expected growth. When comparing the group with continued vertical growth to the one without growth, there were no statistically significant differences in terms of age, sex, underlying etiology, surgical approach, or number of levels fused. CONCLUSIONS Continued vertical growth of the subaxial spine occurs in nearly two-thirds of children after rigid instrumentation and fusion of the subaxial spine. Failure of continued vertical growth is not associated with the patient's age, sex, underlying etiology, number of levels fused, or surgical approach. Further studies are needed to understand this dichotomy and determine the long-term biomechanical effects of surgery on the growing pediatric cervical spine.

Epidemiology of cavernous malformations.

Cavernous malformations, accounting for approximately 5-15% of all vascular abnormalities in the central nervous system, are angiographically occult lesions which most often present with seizures, rather than acute hemorrhage. Widely variable across populations, the incidence of cavernous malformations has been reported to be 0.15-0.56 per 100 000 persons per year, with an annual hemorrhage rate of 0.6-11% per patient-year. Seen in 0.17-0.9% of the population, up to one-half are familial, and at least three gene loci have been associated with a familial form, more common among Hispanic Americans. Most cavernous malformations are supratentorial, with 10-23% in the posterior fossa, and approximately 5% found in the spine.