Indications for cerebral revascularization for moyamoya syndrome in pediatric sickle cell disease determined by Delphi methodology.

OBJECTIVE: Cerebral revascularization surgery (CRS) has been used to prevent stroke in children with sickle cell disease (SCD) and cerebral vasculopathy (e.g., moyamoya syndrome). While results suggest that it may be an effective treatment, surgical indications have not been well defined. This study sought to determine indications for offering revascularization surgery in centers with established sickle cell programs in the US. METHODS: Three sequential surveys utilizing the Delphi methodology were administered to neurosurgeons participating in the Stroke in Sickle Cell Revascularization Surgery study. Respondents were presented with clinical scenarios of patients with SCD and varying degrees of ischemic presentation and vasculopathy, and the group's agreement to offer surgical revascularization was measured. Consensus was defined as ≥ 75% similar responses. RESULTS: The response rate to all 3 surveys was 100%. Seventeen neurosurgeons from 16 different centers participated. The presence of moyamoya collaterals (MMCs) and arterial stenosis matching an ischemic distribution yielded the strongest recommendations to offer surgery. There was consensus to offer revascularization in the presence of MMCs and at least 50% arterial stenosis matching an ischemic distribution. In contrast, there was no consensus to offer revascularization with 50%-70% stenosis not matching an ischemic presentation in the absence of MMCs. The presence of the ivy sign in the distribution of the stenotic artery also contributed to the consensus to offer surgery in certain scenarios. CONCLUSIONS: There were several clinical scenarios that attained consensus to offer surgery; the strongest was moderate to severe arterial stenosis that matched the distribution of ischemic presentation in the presence of MMCs. Radiological findings of decreased cerebral flow or perfusion also facilitated attaining consensus to offer surgery. The findings of this study reflect expert opinion about questions that deserve prospective clinical research. Determination of indications for CRS can guide clinical practice and aid the design of prospective studies.

Postoperative outcomes and stimulation responses for sectioned nerve roots during selective dorsal rhizotomy in cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is the most cause of motor dysfunction in children. Selective dorsal rhizotomy (SDR) plays a major role in long term spasticity control. However, limited data exists on the effect of SDR on postoperative spasticity treatment requirements and supraspinal effects, and the stimulation responses of dorsal nerve roots in those with CP. METHODS: The current study included the outcome for 35 individuals undergoing SDR for motor functional outcome, spasticity, baclofen dose changes, botulinum toxin injection frequency, and spasticity related orthopedic procedures. We also report on the stimulation responses in 112 individuals who underwent SDR at our institution. RESULTS: There was a significant difference in gross motor function measures (GMFM)-66 scores at last follow up that remained present when considering only ambulatory children but not with non-ambulatory children. Ashworth scores were significantly decreased for both upper and lower extremities after SDR at all follow up points. There was a significant decrease in Baclofen dose and botulinum toxin injections requirements after SDR, but no significant difference in the need for orthopedic intervention. A total of 5502 dorsal nerve roots were tested showing a decrease in stimulation intensity and increase in grade on the right side and for descending lumbosacral levels. CONCLUSIONS: SDR improves gross motor scores during short term follow up but has additional benefits in decreasing baclofen dosing and botulinum toxin injections requirements after surgery. They stimulation responses of sectioned dorsal nerve roots adds to the limited available data and our understanding of the pathological changes that occur in CP.

PECARN prediction rule for cervical spine imaging of children presenting to the emergency department with blunt trauma: a multicentre prospective observational study.

BACKGROUND: Cervical spine injuries in children are uncommon but potentially devastating; however, indiscriminate neck imaging after trauma unnecessarily exposes children to ionising radiation. The aim of this study was to derive and validate a paediatric clinical prediction rule that can be incorporated into an algorithm to guide radiographic screening for cervical spine injury among children in the emergency department. METHODS: In this prospective observational cohort study, we screened children aged 0-17 years presenting with known or suspected blunt trauma at 18 specialised children's emergency departments in hospitals in the USA affiliated with the Pediatric Emergency Care Applied Research Network (PECARN). Injured children were eligible for enrolment into derivation or validation cohorts by fulfilling one of the following criteria: transported from the scene of injury to the emergency department by emergency medical services; evaluated by a trauma team; and undergone neck imaging for concern for cervical spine injury either at or before arriving at the PECARN-affiliated emergency department. Children presenting with solely penetrating trauma were excluded. Before viewing an enrolled child's neck imaging results, the attending emergency department clinician completed a clinical examination and prospectively documented cervical spine injury risk factors in an electronic questionnaire. Cervical spine injuries were determined by imaging reports and telephone follow-up with guardians within 21-28 days of the emergency room encounter, and cervical spine injury was confirmed by a paediatric neurosurgeon. Factors associated with a high risk of cervical spine injury (>10%) were identified by bivariable Poisson regression with robust error estimates, and factors associated with non-negligible risk were identified by classification and regression tree (CART) analysis. Variables were combined in the cervical spine injury prediction rule. The primary outcome of interest was cervical spine injury within 28 days of initial trauma warranting inpatient observation or surgical intervention. Rule performance measures were calculated for both derivation and validation cohorts. A clinical care algorithm for determining which risk factors warrant radiographic screening for cervical spine injury after blunt trauma was applied to the study population to estimate the potential effect on reducing CT and x-ray use in the paediatric emergency department. This study is registered with ClinicalTrials.gov, NCT05049330. FINDINGS: Nine emergency departments participated in the derivation cohort, and nine participated in the validation cohort. In total, 22 430 children presenting with known or suspected blunt trauma were enrolled (11 857 children in the derivation cohort; 10 573 in the validation cohort). 433 (1·9%) of the total population had confirmed cervical spine injuries. The following factors were associated with a high risk of cervical spine injury: altered mental status (Glasgow Coma Scale [GCS] score of 3-8 or unresponsive on the Alert, Verbal, Pain, Unresponsive scale [AVPU] of consciousness); abnormal airway, breathing, or circulation findings; and focal neurological deficits including paresthesia, numbness, or weakness. Of 928 in the derivation cohort presenting with at least one of these risk factors, 118 (12·7%) had cervical spine injury (risk ratio 8·9 [95% CI 7·1-11·2]). The following factors were associated with non-negligible risk of cervical spine injury by CART analysis: neck pain; altered mental status (GCS score of 9-14; verbal or pain on the AVPU; or other signs of altered mental status); substantial head injury; substantial torso injury; and midline neck tenderness. The high-risk and CART-derived factors combined and applied to the validation cohort performed with 94·3% (95% CI 90·7-97·9) sensitivity, 60·4% (59·4-61·3) specificity, and 99·9% (99·8-100·0) negative predictive value. Had the algorithm been applied to all participants to guide the use of imaging, we estimated the number of children having CT might have decreased from 3856 (17·2%) to 1549 (6·9%) of 22 430 children without increasing the number of children getting plain x-rays. INTERPRETATION: Incorporated into a clinical algorithm, the cervical spine injury prediction rule showed strong potential for aiding clinicians in determining which children arriving in the emergency department after blunt trauma should undergo radiographic neck imaging for potential cervical spine injury. Implementation of the clinical algorithm could decrease use of unnecessary radiographic testing in the emergency department and eliminate high-risk radiation exposure. Future work should validate the prediction rule and care algorithm in more general settings such as community emergency departments. FUNDING: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration of the US Department of Health and Human Services in the Maternal and Child Health Bureau under the Emergency Medical Services for Children programme.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Unraveling the complexity of the senescence-associated secretory phenotype in adamantinomatous craniopharyngioma using multimodal machine learning analysis.

BACKGROUND: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed. METHODS: We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining. RESULTS: We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells. CONCLUSIONS: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.

Full-length isoform concatenation sequencing to resolve cancer transcriptome complexity.

BACKGROUND: Cancers exhibit complex transcriptomes with aberrant splicing that induces isoform-level differential expression compared to non-diseased tissues. Transcriptomic profiling using short-read sequencing has utility in providing a cost-effective approach for evaluating isoform expression, although short-read assembly displays limitations in the accurate inference of full-length transcripts. Long-read RNA sequencing (Iso-Seq), using the Pacific Biosciences (PacBio) platform, can overcome such limitations by providing full-length isoform sequence resolution which requires no read assembly and represents native expressed transcripts. A constraint of the Iso-Seq protocol is due to fewer reads output per instrument run, which, as an example, can consequently affect the detection of lowly expressed transcripts. To address these deficiencies, we developed a concatenation workflow, PacBio Full-Length Isoform Concatemer Sequencing (PB_FLIC-Seq), designed to increase the number of unique, sequenced PacBio long-reads thereby improving overall detection of unique isoforms. In addition, we anticipate that the increase in read depth will help improve the detection of moderate to low-level expressed isoforms. RESULTS: In sequencing a commercial reference (Spike-In RNA Variants; SIRV) with known isoform complexity we demonstrated a 3.4-fold increase in read output per run and improved SIRV recall when using the PB_FLIC-Seq method compared to the same samples processed with the Iso-Seq protocol. We applied this protocol to a translational cancer case, also demonstrating the utility of the PB_FLIC-Seq method for identifying differential full-length isoform expression in a pediatric diffuse midline glioma compared to its adjacent non-malignant tissue. Our data analysis revealed increased expression of extracellular matrix (ECM) genes within the tumor sample, including an isoform of the Secreted Protein Acidic and Cysteine Rich (SPARC) gene that was expressed 11,676-fold higher than in the adjacent non-malignant tissue. Finally, by using the PB_FLIC-Seq method, we detected several cancer-specific novel isoforms. CONCLUSION: This work describes a concatenation-based methodology for increasing the number of sequenced full-length isoform reads on the PacBio platform, yielding improved discovery of expressed isoforms. We applied this workflow to profile the transcriptome of a pediatric diffuse midline glioma and adjacent non-malignant tissue. Our findings of cancer-specific novel isoform expression further highlight the importance of long-read sequencing for characterization of complex tumor transcriptomes.

Intradural Pituitary Hemitransposition: Technical Note and Case Series Illustration.

BACKGROUND AND OBJECTIVES: Lesions located in the retrosellar region, interpeduncular cistern, and petroclival region are among the most difficult to access in neurosurgery. Transcranial approaches are useful; however, the large distance between the surgeon and the lesion as well as the presence of major neurovascular structures surrounding the lesion may limit surgical exposure. A midline transsphenoidal route avoids transgression of the neurovascular plane and provides direct access to the interpeduncular cistern. To safely access the interpeduncular fossa, it requires mobilization of the pituitary gland. The pituitary hemitransposition technique permits mobilization of the gland, while preserving its venous drainage and arterial supply to the gland on one of its sides, preserving gland function. The authors aim to describe the intradural pituitary hemitransposition technique and to demonstrate its safe application for resection of skull base tumors in the retrosellar space. METHODS: The authors describe the surgical technique and illustrate its application in 5 cases of different types of skull base tumors, including a video demonstrating all the steps to perform this approach. In addition, the authors discuss the advantages and limitations of this technique compared with other approaches to the retrosellar space. RESULTS: The intradural pituitary hemitransposition technique was used to safely resect a chondrosarcoma, chordoma, craniopharyngioma, teratoma, and meningioma involving the parasellar and retrosellar spaces, while minimizing endocrine morbidity. We had one patient with mild, albeit permanent hyperprolactinemia and hypothyroidism after surgery. No other patients had permanent dysfunction related to surgery. CONCLUSION: The endonasal endoscopic intradural pituitary hemitransposition approach is an effective technique for resection of lesions located within the retrosellar and petroclival regions, allowing adequate exposure while potentially optimizing the preservation of the pituitary function.

Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy.

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development.

Epileptic versus neuro-oncological focus of management in pediatric patients with concurrent primary brain lesion and seizures: a systematic review.

OBJECTIVE: Seizures can be a debilitating manifestation of underlying neoplastic intracranial pathology. Existing literature offers a paucity of scientific consensus regarding risk factors, seizure semiology, operative techniques, and tumor characteristics in pediatric patients with a concurrent diagnosis of primary intracranial neoplasm and seizures. To address the limited evidence in current literature, the authors systematically reviewed published literature on current clinical characteristics and management strategies for patients presenting concurrently with seizures and a newly diagnosed brain lesion, while aiming to synthesize a potential management protocol or set of recommendations for these patients. METHODS: An initial search revealed 792 papers, of which 196 studies were excluded, leaving 596 studies available for abstract review. After further stratification, 546 studies were eliminated, leaving 50 studies for eligibility assessment. Of the 50 studies, 12 met the criteria for outcome extraction. RESULTS: The results indicate that patients with a mean age of 9 years with a newly diagnosed brain tumor and presenting symptoms of seizure are likely to present with daily seizures of the complex partial subtype, with the most likely primary epileptogenic and neoplastic foci occurring in the temporal lobe. The most common tumor subtypes were low-grade gliomas, ganglioglioma, dysembryoplastic neuroepithelial tumor, or astrocytoma. With the aim of gross-total resection, 77.54% of patients are likely to achieve seizure freedom. CONCLUSIONS: This study highlights the demographic, clinical, seizure, tumor, and postoperative outcomes for pediatric patients presenting with a primary brain tumor and concurrent seizures. Further prospective multicenter studies are necessary to understand and compare varying treatment approaches and to develop standardized guidelines for these patients, with the goal of optimizing neuro-oncological and seizure-related outcomes.

Long-Term Functional Outcome Following Neurosurgical Intervention for Suspected Abusive Head Trauma.

BACKGROUND: The purpose of this study was to evaluate the long-term functional and neurodevelopmental outcomes in pediatric patients who underwent neurosurgical intervention following suspected abusive head trauma (AHT). METHODS: We performed a single-center retrospective review (January 1, 2007, to December 31, 2019) of patients aged less than three years who had intracranial injury suspicious for AHT and received a neurosurgical procedure. Long-term functional outcome was measured using the Pediatric Cerebral Performance Category (PCPC), Pediatric Overall Performance Category (POPC), and the Mullen Scales of Early Learning (MSEL). RESULTS: Seventy-seven patients were identified; 53 survived to discharge and had at least one-year follow-up. To examine long-term functional outcome, PCPC at the last available visit was examined and found to be 1 or 2 (normal to mild disability) for 64% of patients and 3 or 4 (moderate to severe disability) for 36%. The last available MSEL composite score for neurodevelopmental assessment also demonstrated that 13% of patients scored in the "average" range, 17% in the "below average" range, and 70% in the "very low" range. There was no statistical difference in the last available PCPC or POPC score or the last available MSEL score for patients who received a craniotomy when compared with those who received an intracranial shunt. CONCLUSIONS: For patients with AHT who survived to discharge, functional improvements over time were noted in both patients who received craniotomy or who simply required shunt placement. These results suggest that, for patients who survive to discharge, operative management of AHT can lead to reasonable long-term functional outcomes.

The development of a pediatric skull base team: how, where and why?

PURPOSE OF REVIEW: The purpose of this review is to describe the development of pediatric skull base surgical techniques and illustrate the advantages of pediatric endonasal skull base surgery (ESBS) when applied in appropriate settings. Additionally, this manuscript endeavors to define the pediatric skull base team components, highlight circumstances amenable to the development of a pediatric skull base surgery team, and describe the relative advantages of independent pediatric teams versus incorporation with adult skull base practices. RECENT FINDINGS: Multiple series published within the last decade have described the application of ESBS to the pediatric population, demonstrating adoption of these interventions in many academic centers. Most series include relatively small numbers of patients, highlighting the relative infrequency of anterior skull base pathology in the pediatric patient. Given the relatively low volume and high technical demands of this skillset, general guidelines for the timing, suggested training, and volume necessary to support a pediatric skull base team are offered. SUMMARY: The interest in pediatric ESBS continues to expand though case volumes may limit maintenance of skills in lower volume centers. The development of a dedicated pediatric skull base team in areas where sufficient volume exists facilitates concentration of expertise and interdisciplinary relationships necessary to provide the highest level of care. Collaborating with adult skull base teams can enhance the pediatric team experience, increasing exposure to complex surgical planning and radiologic nuances. However, a pediatric-focused skull base team can tailor treatment to meet the specific psychosocial and developmental needs of children.

Oncolytic virus-driven immune remodeling revealed in mouse medulloblastomas at single cell resolution.

Oncolytic viruses, modified for tumor-restricted infection, are a promising cancer immunotherapeutic, yet much remains to be understood about factors driving their activity and outcome in the tumor microenvironment. Here, we report that oncolytic herpes simplex virus C134, previously found to exert T cell-dependent efficacy in mouse models of glioblastoma, exerts T cell-independent efficacy in mouse models of medulloblastoma, indicating this oncolytic virus uses different mechanisms in different tumors. We investigated C134's behavior in mouse medulloblastomas, using single cell RNA sequencing to map C134-induced gene expression changes across cell types, timepoints, and medulloblastoma subgroup models at whole-transcriptome resolution. Our work details substantial oncolytic virus-induced transcriptional remodeling of medulloblastoma-infiltrating immune cells, 10 subpopulations of monocytes and macrophages collectively demonstrating M1-like responses to C134, and suggests C134 be investigated as a potential new therapy for medulloblastoma.

Selective Dorsal Rhizotomy: Patient Demographics and Postoperative Physical Therapy.

BACKGROUND: Selective dorsal rhizotomy (SDR) is a surgical procedure that permanently alters lower extremity spasticity, common in children with spastic cerebral palsy (CP). Intensive postoperative physical therapy (PT) is recommended following SDR. The first purpose of this study is to describe and compare patient demographics between children who received SDR and the population of children with CP at one institution. The second purpose of this study is to compare the completed dose of postoperative PT with the clinically recommended dose for a subset of ambulatory children who underwent SDR. METHODS: This retrospective, observational study included 60 children with spastic CP following SDR. A subset (n = 12 ambulatory children) was included to describe the dose of postoperative PT. Information gathered from electronic medical records included age at the time of SDR, sex, Gross Motor Function Classification System level, anatomic distribution, race, county-level habitancy, health insurance provider, timed current procedural terminology codes, and location for postoperative PT encounters within a single institution. RESULTS: Black or African American children (P = 0.002), children living in large central metro areas (P = 0.033), and children with public insurance (P ≤ 0.001) were significantly less likely to receive SDR. Children undergoing SDR do not achieve the recommended dose of PT after hospital discharge. CONCLUSION: SDR is not equally accessed by patient populations, and postoperative PT frequency is below current recommendations throughout the rehabilitation process. Future studies need to investigate why these disparities exist and what prevents children from meeting the clinically recommended dose of postoperative PT after SDR.

Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Impact of Etiology on Seizure and Quantitative Functional Outcomes in Children with Cerebral Palsy and Medically Intractable Epilepsy Undergoing Hemispherotomy/Hemispherectomy.

OBJECTIVE: To compare functional and seizure outcomes in children with vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy following functional hemispherotomy or anatomic hemispherectomy. METHODS: Consecutive patients satisfying inclusion criteria from 07/01/2015 to 12/01/2019 were reviewed for demographic data and seizure (Engel classification) and functional (Functional Independence Measure for Children) outcomes. RESULTS: After a mean follow-up of 2 years 8 months (1 year 2 months), 11 of 18 patients achieved post-operative seizure freedom without significant difference between vascular (5/7) and dysplastic (6/11) etiologies (P = 0.64). Functional assessments were completed for 15 of 18 of subjects, split comparably between groups. Mean change in the Functional Independence Measure for Children from pre-operative baseline to inpatient rehabilitation admission (vascular, -35.3 [13.2]; malformation of cortical development{MCD}, -34.5 [25.0]; P = 0.69), inpatient rehabilitation admission to discharge (vascular, 18.7 [9.0]; MCD, 20.8 [11.4]; P = 0.60), and pre-operative evaluation to clinic follow-up (vascular, -7.6 [9.7]; MCD, -3.6 [19.3]; P = 0.61) did not differ between groups. CONCLUSION: Quantitative functional and seizure outcomes following functional hemispherotomy or anatomic hemispherectomy did not differ significantly between vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy in this study. Hemispheric surgery resulted in minor functional declines from baseline following comprehensive multidisciplinary therapy.

Building consensus for the medical management of children with moderate and severe acute spinal cord injury: a modified Delphi study.

OBJECTIVE: The focus of this modified Delphi study was to investigate and build consensus regarding the medical management of children with moderate and severe acute spinal cord injury (SCI) during their initial inpatient hospitalization. This impetus for the study was based on the AANS/CNS guidelines for pediatric SCI published in 2013, which indicated that there was no consensus provided in the literature describing the medical management of pediatric patients with SCIs. METHODS: An international, multidisciplinary group of 19 physicians, including pediatric neurosurgeons, orthopedic surgeons, and intensivists, were asked to participate. The authors chose to include both complete and incomplete injuries with traumatic as well as iatrogenic etiologies (e.g., spinal deformity surgery, spinal traction, intradural spinal surgery, etc.) due to the overall low incidence of pediatric SCI, potentially similar pathophysiology, and scarce literature exploring whether different etiologies of SCI should be managed differently. An initial survey of current practices was administered, and based on the responses, a follow-up survey of potential consensus statements was distributed. Consensus was defined as ≥ 80% of participants reaching agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). A final meeting was held virtually to generate final consensus statements. RESULTS: Following the final Delphi round, 35 statements reached consensus after modification and consolidation of previous statements. Statements were categorized into the following eight sections: inpatient care unit, spinal immobilization, pharmacological management, cardiopulmonary management, venous thromboembolism prophylaxis, genitourinary management, gastrointestinal/nutritional management, and pressure ulcer prophylaxis. All participants stated that they would be willing or somewhat willing to change their practices based on consensus guidelines. CONCLUSIONS: General management strategies were similar for both iatrogenic (e.g., spinal deformity, traction, etc.) and traumatic SCIs. Steroids were recommended only for injury after intradural surgery, not after acute traumatic or iatrogenic extradural surgery. Consensus was reached that mean arterial pressure ranges are preferred for blood pressure targets following SCI, with goals between 80 and 90 mm Hg for children at least 6 years of age. Further multicenter study of steroid use following acute neuromonitoring changes was recommended.

A multicenter initiative to reduce intrathecal baclofen pump surgical site infection: a Cerebral Palsy Research Network quality improvement project.

OBJECTIVE: Intrathecal baclofen (ITB) therapy is an effective treatment for spasticity and dystonia in children with cerebral palsy (CP). However, ITB pump surgery is associated with one of the highest rates of surgical site infection (SSI) in medicine, leading to significant morbidity and expense. Surgical protocols have reduced the rate of SSI in children with other CNS implants, and single-center protocols have been effective in ITB surgery in pediatrics. The authors describe the first multicenter quality improvement (QI)-driven standardized protocol for ITB pump surgery in children with CP across the Cerebral Palsy Research Network (CPRN), implemented with the aim of reducing ITB-associated SSI. METHODS: SSI was defined as a culture-positive infection, ITB pump system removal for suspected infection, or wound dehiscence with exposed hardware. Each center reported historical infection rates for at least 3 years before initiating the SSI protocol (preintervention phase). After initiation of a 13-step surgical protocol, a consecutive series of 130 patients undergoing 149 surgical procedures for ITB at four CPRN tertiary pediatric neurosurgery centers were prospectively enrolled at surgery during a 2-year study period (intervention phase). QI methodology was used, including development of a key driver diagram and tracking performance using run and control charts. The primary process measure goal was documented compliance with 80% of the protocol steps, and the primary outcome measure goal was a 20% reduction in 90-day infection rate. Patient characteristics were collected from the CPRN Research Electronic Data Capture registry, including age at surgery, BMI, Gross Motor Function Classification System level, and pattern of spasticity. RESULTS: The aggregated preintervention 90-day ITB SSI rate was 4.9% (223 procedures) between 2014 and 2017. During the intervention phase, 136 of 149 ITB surgeries performed met inclusion criteria for analysis. The mean documented compliance rate with protocol steps was 75%, and the 90-day infection rate was 4.4%, with an average of 42 days from index surgery to infection. CONCLUSIONS: This is the first multicenter QI initiative designed to reduce SSI in ITB surgery in children with CP. Ongoing enrollment and expansion of the protocol to other CPRN centers will facilitate identification of patient- and procedure-specific risk factors for SSI, and iterative plan-do-study-act cycles incorporating these data will further decrease the risk of SSI for ITB surgery in children.