The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.

Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-12Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analyzed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the Interictal Suppression Hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the Interictal Suppression Hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.

The Interictal Suppression Hypothesis in focal epilepsy: network-level supporting evidence.

Why are people with focal epilepsy not continuously having seizures? Previous neuronal signalling work has implicated gamma-aminobutyric acid balance as integral to seizure generation and termination, but is a high-level distributed brain network involved in suppressing seizures? Recent intracranial electrographic evidence has suggested that seizure-onset zones have increased inward connectivity that could be associated with interictal suppression of seizure activity. Accordingly, we hypothesize that seizure-onset zones are actively suppressed by the rest of the brain network during interictal states. Full testing of this hypothesis would require collaboration across multiple domains of neuroscience. We focused on partially testing this hypothesis at the electrographic network level within 81 individuals with drug-resistant focal epilepsy undergoing presurgical evaluation. We used intracranial electrographic resting-state and neurostimulation recordings to evaluate the network connectivity of seizure onset, early propagation and non-involved zones. We then used diffusion imaging to acquire estimates of white-matter connectivity to evaluate structure-function coupling effects on connectivity findings. Finally, we generated a resting-state classification model to assist clinicians in detecting seizure-onset and propagation zones without the need for multiple ictal recordings. Our findings indicate that seizure onset and early propagation zones demonstrate markedly increased inwards connectivity and decreased outwards connectivity using both resting-state (one-way ANOVA, P-value = 3.13 × 10-13) and neurostimulation analyses to evaluate evoked responses (one-way ANOVA, P-value = 2.5 × 10-3). When controlling for the distance between regions, the difference between inwards and outwards connectivity remained stable up to 80 mm between brain connections (two-way repeated measures ANOVA, group effect P-value of 2.6 × 10-12). Structure-function coupling analyses revealed that seizure-onset zones exhibit abnormally enhanced coupling (hypercoupling) of surrounding regions compared to presumably healthy tissue (two-way repeated measures ANOVA, interaction effect P-value of 9.76 × 10-21). Using these observations, our support vector classification models achieved a maximum held-out testing set accuracy of 92.0 ± 2.2% to classify early propagation and seizure-onset zones. These results suggest that seizure-onset zones are actively segregated and suppressed by a widespread brain network. Furthermore, this electrographically observed functional suppression is disproportionate to any observed structural connectivity alterations of the seizure-onset zones. These findings have implications for the identification of seizure-onset zones using only brief electrographic recordings to reduce patient morbidity and augment the presurgical evaluation of drug-resistant epilepsy. Further testing of the interictal suppression hypothesis can provide insight into potential new resective, ablative and neuromodulation approaches to improve surgical success rates in those suffering from drug-resistant focal epilepsy.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.

Longitudinal CSF Iron Pathway Proteins in Posthemorrhagic Hydrocephalus: Associations with Ventricle Size and Neurodevelopmental Outcomes.

OBJECTIVE: Iron has been implicated in the pathogenesis of brain injury and hydrocephalus after preterm germinal matrix hemorrhage-intraventricular hemorrhage, however, it is unknown how external or endogenous intraventricular clearance of iron pathway proteins affect the outcome in this group. METHODS: This prospective multicenter cohort included patients with posthemorrhagic hydrocephalus (PHH) who underwent (1) temporary and permanent cerebrospinal fluid (CSF) diversion and (2) Bayley Scales of Infant Development-III testing around 2 years of age. CSF proteins in the iron handling pathway were analyzed longitudinally and compared to ventricle size and neurodevelopmental outcomes. RESULTS: Thirty-seven patients met inclusion criteria with a median estimated gestational age at birth of 25 weeks; 65% were boys. Ventricular CSF levels of hemoglobin, iron, total bilirubin, and ferritin decreased between temporary and permanent CSF diversion with no change in CSF levels of ceruloplasmin, transferrin, haptoglobin, and hepcidin. There was an increase in CSF hemopexin during this interval. Larger ventricle size at permanent CSF diversion was associated with elevated CSF ferritin (p = 0.015) and decreased CSF hemopexin (p = 0.007). CSF levels of proteins at temporary CSF diversion were not associated with outcome, however, higher CSF transferrin at permanent CSF diversion was associated with improved cognitive outcome (p = 0.015). Importantly, longitudinal change in CSF iron pathway proteins, ferritin (decrease), and transferrin (increase) were associated with improved cognitive (p = 0.04) and motor (p = 0.03) scores and improved cognitive (p = 0.04), language (p = 0.035), and motor (p = 0.008) scores, respectively. INTERPRETATION: Longitudinal changes in CSF transferrin (increase) and ferritin (decrease) are associated with improved neurodevelopmental outcomes in neonatal PHH, with implications for understanding the pathogenesis of poor outcomes in PHH. ANN NEUROL 2021;90:217-226.

Machine learning predicts risk of cerebrospinal fluid shunt failure in children: a study from the hydrocephalus clinical research network.

PURPOSE: While conventional statistical approaches have been used to identify risk factors for cerebrospinal fluid (CSF) shunt failure, these methods may not fully capture the complex contribution of clinical, radiologic, surgical, and shunt-specific variables influencing this outcome. Using prospectively collected data from the Hydrocephalus Clinical Research Network (HCRN) patient registry, we applied machine learning (ML) approaches to create a predictive model of CSF shunt failure. METHODS: Pediatric patients (age < 19 years) undergoing first-time CSF shunt placement at six HCRN centers were included. CSF shunt failure was defined as a composite outcome including requirement for shunt revision, endoscopic third ventriculostomy, or shunt infection within 5 years of initial surgery. Performance of conventional statistical and 4 ML models were compared. RESULTS: Our cohort consisted of 1036 children undergoing CSF shunt placement, of whom 344 (33.2%) experienced shunt failure. Thirty-eight clinical, radiologic, surgical, and shunt-design variables were included in the ML analyses. Of all ML algorithms tested, the artificial neural network (ANN) had the strongest performance with an area under the receiver operator curve (AUC) of 0.71. The ANN had a specificity of 90% and a sensitivity of 68%, meaning that the ANN can effectively rule-in patients most likely to experience CSF shunt failure (i.e., high specificity) and moderately effective as a tool to rule-out patients at high risk of CSF shunt failure (i.e., moderately sensitive). The ANN was independently validated in 155 patients (prospectively collected, retrospectively analyzed). CONCLUSION: These data suggest that the ANN, or future iterations thereof, can provide an evidence-based tool to assist in prognostication and patient-counseling immediately after CSF shunt placement.

Comparison of anticoagulation and antiplatelet therapy for treatment of blunt cerebrovascular injury in children <10 years of age: a multicenter retrospective cohort study.

PURPOSE: Blunt cerebrovascular injury (BCVI) is uncommon in the pediatric population. Among the management options is medical management consisting of antithrombotic therapy with either antiplatelets or anticoagulation. There is no consensus on whether administration of antiplatelets or anticoagulation is more appropriate for BCVI in children < 10 years of age. Our goal was to compare radiographic and clinical outcomes based on medical treatment modality for BCVI in children < 10 years. METHODS: Clinical and radiographic data were collected retrospectively for children screened for BCVI with computed tomography angiography at 5 academic pediatric trauma centers. RESULTS: Among 651 patients evaluated with computed tomography angiography to screen for BCVI, 17 patients aged less than 10 years were diagnosed with BCVI (7 grade I, 5 grade II, 1 grade III, 4 grade IV) and received anticoagulation or antiplatelet therapy for 18 total injuries: 11 intracranial carotid artery, 4 extracranial carotid artery, and 3 extracranial vertebral artery injuries. Eleven patients were treated with antiplatelets (10 aspirin, 1 clopidogrel) and 6 with anticoagulation (4 unfractionated heparin, 2 low-molecular-weight heparin, 1 transitioned from the former to the latter). There were no complications secondary to treatment. One patient who received anticoagulation died as a result of the traumatic injuries. In aggregate, children treated with antiplatelet therapy demonstrated healing on 52% of follow-up imaging studies versus 25% in the anticoagulation cohort. CONCLUSION: There were no observed differences in the rate of hemorrhagic complications between anticoagulation and antiplatelet therapy for BCVI in children < 10 years, with a nonsignificantly better rate of healing on follow-up imaging in children who underwent antiplatelet therapy; however, the study cohort was small despite including patients from 5 hospitals.

Pediatric Intrathecal Baclofen Pumps: A Descriptive Analysis of Hospital Course and Associated Costs.

INTRODUCTION: The purpose of this study was to identify predictors of increased cost and postoperative length-of-stay (LOS) following intrathecal baclofen pump (ITBP) placement. METHODS: Patients were derived from the 2009/2012 kids' inpatient database. Inclusion criteria were selected for patients with ICD-9 codes 343.X (infantile cerebral palsy), 86.06 (infusion pump insertion), 03.90 (spinal catheter insertion), and elective hospitalizations. Nonparametric univariate analysis and subsequent gamma log-link general linear modeling were used to identify significant predictors of cost/LOS (p < 0.05). RESULTS: 529 unweighted patients (787 with survey weights applied) met criteria. Median LOS was 3.00 days, and median cost was USD 23,284. Following multivariate modeling, predictors of increased LOS (in days) included increased hospital ITBP volume (p = 0.027), small hospital size (+0.55, p = 0.004), device complications (+0.95, p < 0.001), procedural complications (+1.40, p < 0.001), additional procedures (+0.86, p < 0.001), electrolyte abnormalities (+3.74, p < 0.001), and neurological comorbidities (+1.60, p < 0.001). Factors associated with decreased LOS were paralysis (-0.53, p < 0.001), Northeastern hospital region (-0.55, p = 0.018), and investor-owned hospital status (-0.75, p = 0.001). Similarly, predictors of increased cost included race of Hispanic (+USD 1,156, p = 0.033) or "other" (+USD 2,158, p = 0.001), Northeast hospital region (+USD 4,120, p < 0.001), small (+USD 4,139, p < 0.001) or medium (+USD 3,368, p < 0.001) hospital sizes, additional procedures (+USD 1,649, p < 0.001), neurological comorbidities (+USD 3,222, p = 0.003), and increased LOS (p < 0.001). Factors associated with decreased cost included Western hospital region (-USD 1,594, p = 0.001), government hospitals (-USD 1,391, p = 0.019), and investor-owned hospitals (-USD 2,057, p = 0.021). CONCLUSION: This study found multiple variables associated with increased cost/LOS following ITBP placement. Broadly, this analysis demonstrates national trends associated with increased cost following ITBP placement.

Seizure-onset regions demonstrate high inward directed connectivity during resting-state: An SEEG study in focal epilepsy.

OBJECTIVE: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. METHODS: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. RESULTS: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. SIGNIFICANCE: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.

Cerebrospinal fluid alterations following endoscopic third ventriculostomy with choroid plexus cauterization: a retrospective laboratory analysis of two tertiary care centers.

PURPOSE: This study sought to determine the previously undescribed cytologic and metabolic alterations that accompany endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC). METHODS: Cerebrospinal fluid (CSF) samples were collected from infant patients with hydrocephalus at the time of index ETV/CPC and again at each reintervention for persistent hydrocephalus. Basic CSF parameters, including glucose, protein, and cell counts, were documented. A multivariable regression model, incorporating known predictors of ETV/CPC outcome, was constructed for each parameter to inform time-dependent normative values. RESULTS: A total of 187 infants were treated via ETV/CPC for hydrocephalus; initial laboratory values were available for 164 patients. Etiology of hydrocephalus included myelomeningocele (53, 32%), intraventricular hemorrhage of prematurity (43, 26%), aqueductal stenosis (24, 15%), and others (44, 27%). CSF parameters did not differ significantly with age or etiology. Glucose levels initially drop below population average (36 to 32 mg/dL) post-operatively before slowly rising to normal levels (42 mg/dL) by 3 months. Dramatically elevated protein levels post-ETV/CPC (baseline of 59 mg/dL up to roughly 200 mg/dL at 1 month) also normalized over 3 months. No significant changes were appreciated in WBC. RBC counts were very elevated following ETV/CPC and quickly declined over the subsequent month. CONCLUSION: CSF glucose and protein deviate significantly from normal ranges following ETV/CPC before normalizing over 3 months. High RBC values immediately post-ETV/CPC decline rapidly. Age at time of procedure and etiology have little influence on common clinical CSF laboratory parameters. Of note, the retrospective study design necessitates ETV/CPC failure, which could introduce bias in the results.

Deep brain stimulation in pediatric dystonia: a systematic review.

While deep brain stimulation (DBS) treatment is relatively rare in children, it may have a role in dystonia to reduce motor symptoms and disability. Pediatric DBS studies are sparse and limited by small sample size, and thus, outcomes are poorly understood. Thus, we performed a systematic review of the literature including studies of DBS for pediatric (age < 21) dystonia. Patient demographics, disease causes and characteristics, motor scores, and disability scores were recorded at baseline and at last post-operative follow-up. We identified 19 studies reporting DBS outcomes in 76 children with dystonia. Age at surgery was 13.8 ± 3.9 (mean ± SD) years, and 58% of individuals were male. Post-operative follow-up duration was 2.8 ± 2.8 years. Sixty-eight percent of patients had primary dystonia (PD), of whom 56% had a pathological mutation in DYT1 (DYT1+). Across all patients, regardless of dystonia type, 43.8 ± 36% improvement was seen in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor (-M) scores after DBS, while 43.7 ± 31% improvement was observed in BFMDRS disability (-D) scores. Patients with PD were more likely to experience ≥ 50% improvement (56%) in BFMDRS-M scores compared to patients with secondary causes of dystonia (21%, p = 0.004). DYT1+ patients were more likely to achieve ≥ 50% improvement (65%) in BFMDRS-D than DTY1- individuals (29%, p = 0.02), although there was no difference in BFMDRS-M ≥ 50% improvement rates between DYT1+ (66%) or DYT1- (43%) children (p = 0.11). While DBS is less common in pediatric patients, individuals with severe dystonia may receive worthwhile benefit with neuromodulation treatment.

Mechatronic Design of a Two-Arm Concentric Tube Robot System for Rigid Neuroendoscopy.

Open surgical approaches are still often employed in neurosurgery, despite the availability of neuroendoscopic approaches that reduce invasiveness. The challenge of maneuvering instruments at the tip of the endoscope makes neuroendoscopy demanding for the physician. The only way to aim tools passed through endoscope ports is to tilt the entire endoscope; but, tilting compresses brain tissue through which the endoscope passes and can damage it. Concentric tube robots can provide necessary dexterity without endoscope tilting, while passing through existing ports in the endoscope and carrying surgical tools in their inner lumen. In this paper we describe the mechatronic design of a new concentric tube robot that can deploy two concentric tube manipulators through a standard neuroendoscope. The robot uses a compact differential drive and features embedded motor control electronics and redundant position sensors for safety. In addition to the mechatronic design of this system, this paper contributes experimental validation in the context of colloid cyst removal, comparing our new robotic system to standard manual endoscopy in a brain phantom. The robotic approach essentially eliminated endoscope tilt during the procedure (17.09° for the manual approach vs. 1.16° for the robotic system). The robotic system also enables a single surgeon to perform the procedure - typically in a manual approach one surgeon aims the endoscope and another operates the tools delivered through its ports.

X-ray vs. CT in identifying significant C-spine injuries in the pediatric population.

PURPOSE: Evaluation of cervical spine injury (CSI) in children requires rapid, yet accurate assessment of damage. Given concerns of radiation exposure, expert consensus advises that computed tomography (CT) should be used sparingly. However, CT can provide superior image resolution and detection of pathology. Herein, we evaluate if X-ray offers equal diagnostic accuracy compared to CT imaging in identifying CSI in children. METHODS: We conducted a retrospective study between October 2000 and March 2012 of pediatric patients evaluated for cervical spine injury at a level 1 trauma center. All patients included in this study were imaged with cervical spine X-rays and CT at the time of injury. Demographic information, mechanism of injury, significant versus non-significant injury (as defined by the NEXUS criteria), radiographic findings, level of the injury, presence of spinal cord injury, treatment, clinical outcome, and length of follow-up were collected. Chi-squared (χ 2) and Fisher's exact tests were used as appropriate and means and standard deviations were reported. RESULTS: We identified 1296 patients who were screened for CSI. Of those, 164 patients were diagnosed with spinal cord/column injuries (CSI). Eighty-nine patients were excluded for only having a CT or X-ray imaging without the other modality. Thus, a total of 75 patients with CSI were included in the final cohort. Using the NEXUS definitions, 78% of patients had clinically significant injuries while 22% had non-significant injuries. There were no injuries detected on X-ray that were not also detected on CT. For all injuries, X-ray sensitivity was 50.7%. X-rays were more sensitive to significant injuries (62.3%) compared in non-significant injuries, which were missed on all X-rays (0%). Therefore, X-rays did not identify 24 significant cervical spine injuries (32%) as defined by NEXUS. CONCLUSIONS: CT is superior to X-rays in detecting both clinically significant and insignificant cervical spine injuries. These results were not dependent on patient age or location of the injury. We recommend CT imaging in the evaluation of suspected cervical spine injuries in children. LEVEL OF EVIDENCE: III.

The Global Rise of Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization in Pediatric Hydrocephalus.

In the quest to identify the optimal means of cerebrospinal fluid diversion free of shunt dependency, endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) has been proposed as a promising procedure in select children. Supplementing traditional ETV with obliteration of the choroid plexus has been shown to decrease the likelihood of ultimate shunt dependency by roughly 20%. Originally devised to treat hydrocephalus in infants in sub-Saharan Africa, ETV/CPC has gained eager attention and cautious support in the developed world. Herein, we offer a comprehensive review of ETV/CPC beginning with the history and theory behind the operation. Next, we delve into the data supporting its use across heterogeneous pediatric populations, and finally we discuss clinical outcomes and future directions.

Pseudoprogression of low-grade gliomas after radiotherapy.

BACKGROUND: Increasing mass effect following radiation therapy (RT) in patients with low-grade gliomas (LGGs) can be mistaken for tumor progression and/or malignant degeneration. Distinguishing pseudoprogression (PP) from true progression is crucial, with vastly different treatment approaches and prognoses. PROCEDURE: Patients treated with RT for LGGs through the Children's Hospital of Pittsburgh Neuro-Oncology Program are considered to have PP and managed conservatively if they develop increased mass effect within 3 years of RT. Pre-RT tumor area was compared to the maximum tumor size following RT and the size on the last follow-up scan by a central reviewer. RESULTS: Twenty-four children, median age 13 years, received external beam RT for LGG between March 2000 and August 2011. Thirteen patients (54.2%) developed an increase in tumor size compared to baseline beginning at a median of 6 months after RT and lasting for a median of 2.1 years (range 6.5 months to 5.1 years). Maximum tumor enlargement occurred at a median of 8 months after RT, with a range (5 months to 4.2 years). In all 13 cases, the tumor eventually decreased in size without additional anti-tumor therapy. Two patients (8.3%) developed true tumor progression. With a median follow-up of 4.9 years (range 1.0-12.4 years), all patients are alive. CONCLUSIONS: Pseudoprogression occurred in more than half of the children with LGG following RT, typically beginning within 8 months and often running a very protracted course. Late presentations can also occur.

Treatment of hydrocephalus following fetal repair of myelomeningocele: comparing endoscopic third ventriculostomy with choroid plexus cauterization to ventricular shunting.

OBJECTIVE: The aim of this study was to compare clinical and craniometric outcomes of patients treated for hydrocephalus following fetal myelomeningocele repair (fMMR) via a ventriculoperitoneal shunt (VPS) or endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC). METHODS: This was a retrospective cohort study of children who were treated for hydrocephalus following fMMR via VPS or ETV with or without CPC (ETV ± CPC) at Vanderbilt between 2012 and 2021. The primary outcomes were treatment failure and time to failure (TTF). Secondary outcomes included changes in hydrocephalus metrics (fronto-occipital horn ratio [FOHR] and head circumference measurements) and healthcare resource utilization (number of hospital admissions, clinic visits, and neuroimaging findings). RESULTS: Among 88 patients who underwent fMMR, 37 (42%) required permanent CSF diversion, of whom 19 received treatment at the authors' institution. Twelve patients underwent ETV ± CPC, and 7 underwent VPS placement at a median corrected age of 23 weeks versus 1 week (p = 0.002). The preoperative median head circumference percentiles and z-scores for patients in the ETV ± CPC cohort were similar to those of the VPS cohort (percentiles: 98.5 vs 94.0, p = 0.064; z-scores: 2.32 vs 1.60, p = 0.111). There was no difference in preoperative median FOHR measurements between the two cohorts (0.57 vs 0.59, p = 0.53). At 6 months postoperatively, the median head circumference percentile and z-score for the ETV ± CPC cohort remained similar between the two cohorts (percentiles: 98.0 vs 67.5, p = 0.315; z-scores: 2.12 vs 0.52, p = 0.307). There was no difference in the change in FOHR (-0.06 vs -0.09, p = 0.37) and change in head circumference percentile (-1.33 vs -28.6, p = 0.058) between the cohorts 6 months after the index CSF diversion procedure. One patient in the ETV ± CPC cohort experienced a seizure and a nonoperative subdural hemorrhage postoperatively; no other complications were observed. Six of the 7 patients in the VPS cohort required shunt revision with a median TTF of 9.8 months while 2 of the 12 ETV ± CPC patients required a repeat ETV at a median of 17.5 months (86% vs 17%, p = 0.013). The median number of hydrocephalus-related hospital readmissions was significantly lower in the ETV ± CPC cohort than in the VPS cohort (0 vs 1, p = 0.006). The ETV ± CPC cohort had fewer CT scans (0 vs 2, p = 0.004) and radiographs (0 vs 2, p < 0.001) than the VPS cohort. CONCLUSIONS: In a single-center cohort, hydrocephalic fMMR patients treated via ETV ± CPC remained shunt free, while a majority of patients receiving an upfront shunt required revision. This is the first study comparing ETV ± CPC with VPS in the fMMR hydrocephalus population. While larger, multicenter studies are needed, these results suggest that ETV/CPC may be a preferred means of CSF diversion following fMMR.

Comparing ventriculoatrial and ventriculopleural shunts in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort. METHODS: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months. RESULTS: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013). CONCLUSIONS: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.

Progression of Chiari I malformations while on growth hormone replacement: a report of two cases.

PURPOSE: The effect of growth hormone replacement on Chiari I malformation (CIM) associated with growth hormone deficiency is not clear. CASE REPORTS: Two patients are presented, who were found to have CIM and growth hormone deficiency. While on hormone replacement therapy, both experienced disease progression with development of syringomyelia and required surgical intervention. CONCLUSION: Growth hormone replacement for CIM associated with growth hormone deficiency does not uniformly halt or reverse syrinx progression. If a trial of hormone replacement is attempted, patients should be followed closely for progression of syringomyelia or the development of symptoms.

Multi-Center Validation of the McGovern Pediatric Blunt Cerebrovascular Injury Screening Score.

Blunt cerebrovascular injury (BCVI) is defined as blunt trauma to the head and neck leading to damage to the vertebral and/or carotid arteries; debate exists regarding which children are considered at high risk for BCVI and in need of angiographic/vessel imaging. We previously proposed a screening tool, the McGovern score, to identify pediatric trauma patients at high risk for BCVI, and we aim to validate the McGovern score by pooling data from multiple pediatric trauma centers. This is a multi-center, hospital-based, cohort study from all prospectively registered pediatric (<16 years of age) trauma patients who presented to the emergency department (ED) between 2003 and 2017 at six Level 1 pediatric trauma centers. The registry was retrospectively queried for patients who received a computed tomography angiogram (CTA) as a screening method for BCVI. Age, length of follow-up, mechanism of injury (MOI), arrival Glasgow Coma Scale (GCS) score, and focal neurological deficit were recorded. Radiological variables queried were the presence of a carotid canal fracture, petrous temporal bone fracture, and CT presence of infarction. Patients with BCVI were queried for mode of treatment, type of intracranial injury, artery damaged, and BCVI injury grade. The McGovern score was calculated for all patients who underwent CTA across all data groups. A total of 1012 patients underwent CTA; 72 of these patients were found to have BCVI, 51 of which were in the validation cohort. Across all data groups, the McGovern score has a >80% sensitivity (SN) and >98% negative predictive value (NPV). The McGovern score for pediatric BCVI is an effective, generalizable screening tool.

SEEG Functional Connectivity Measures to Identify Epileptogenic Zones: Stability, Medication Influence, and Recording Condition.

BACKGROUND AND OBJECTIVES: Functional connectivity (FC) measures can be used to differentiate epileptogenic zones (EZs) from non-EZs in patients with medically refractory epilepsy. Little work has been done to evaluate the stability of stereo-EEG (SEEG) FC measures over time and their relationship with antiseizure medication (ASM) use, a critical confounder in epilepsy FC studies. We aimed to answer the following questions: Are SEEG FC measures stable over time? Are they influenced by ASMs? Are they affected by patient data collection state? METHODS: In 32 patients with medically refractory focal epilepsy, we collected a single 2-minute prospective SEEG resting-state (awake, eyes closed) data set and consecutive 2-minute retrospective pseudo-rest (awake, eyes open) data sets for days 1-7 postimplantation. ASM dosages were recorded for days 1-7 postimplantation and drug load score (DLS) per day was calculated to standardize and compare across patients. FC was evaluated using directed and nondirected measures. Standard clinical interpretation of ictal SEEG was used to classify brain regions as EZs and non-EZs. RESULTS: Over 7 days, presumed EZs consistently had higher FC than non-EZs when using between imaginary coherence (ImCoh) and partial directed coherence (PDC) inward strength, without accounting for DLS. These measures were demonstrated to be stable over a short-term period of 3 consecutive days with the same DLS. Between ImCoh FC differences between EZs and non-EZs were reduced with DLS decreases, whereas other measures were not affected by DLS. FC differences between EZs and non-EZs were seen during both resting-state and pseudo-rest conditions; ImCoh values were strongly correlated between the 2 conditions, whereas PDC values were not. DISCUSSION: Inward and nondirected SEEG FC is higher in presumed EZs vs non-EZs and measures are stable over time. However, certain measures may be affected by ASM dose, as between ImCoh differences between EZs and non-EZs are less pronounced with lower doses, and other measures such as PDC are poorly correlated across recording conditions. These findings allow novel insight into how SEEG FC measures may aid surgical localization and how they are influenced by ASMs and other factors.

Endoscopic third ventriculostomy in previously shunt-treated patients.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) is an option for treatment of hydrocephalus, including for patients who have a history of previous treatment with CSF shunt insertion. The purpose of this study was to report the success of postshunt ETV by using data from a multicenter prospective registry. METHODS: Prospectively collected data in the Hydrocephalus Clinical Research Network (HCRN) Core Data Project (i.e., HCRN Registry) were reviewed. Children who underwent ETV between 2008 and 2019 and had a history of previous treatment with a CSF shunt were included. A Kaplan-Meier survival curve was created for the primary outcome: time from postshunt ETV to subsequent CSF shunt placement or revision. Univariable Cox proportional hazards models were created to evaluate for an association between clinical and demographic variables and subsequent shunt surgery. Postshunt ETV complications were also identified and categorized. RESULTS: A total of 203 children were included: 57% male and 43% female; 74% White, 23% Black, and 4% other race. The most common hydrocephalus etiologies were postintraventricular hemorrhage secondary to prematurity (56, 28%) and aqueductal stenosis (42, 21%). The ETV Success Score ranged from 10 to 80. The median patient age was 4.1 years. The overall success of postshunt ETV at 6 months was 41%. Only the surgeon's report of a clear view of the basilar artery was associated with a lower likelihood of postshunt ETV failure (HR 0.43, 95% CI 0.23-0.82, p = 0.009). None of the following variables were associated with postshunt ETV success: age at the time of postshunt ETV, etiology of hydrocephalus, sex, race, ventricle size, number of previous shunt operations, ETV performed at time of shunt infection, and use of external ventricular drainage. Overall, complications were reported in 22% of patients, with CSF leak (8.6%) being the most common complication. CONCLUSIONS: Postshunt ETV was successful in treating hydrocephalus, without subsequent need for a CSF shunt, in 41% of patients, with a clear view of the basilar artery being the only variable significantly associated with success. Complications occurred in 22% of patients. ETV is an option for treatment of hydrocephalus in children who have previously undergone shunt placement, but with a lower than expected likelihood of success.