Ventricular catheter tissue obstruction and shunt malfunction in 9 hydrocephalus etiologies.

OBJECTIVE: Hydrocephalus is a neurological disorder with an incidence of 80-125 per 100,000 births in the United States. The most common treatment, ventricular shunting, has a failure rate of up to 85% within 10 years of placement. The authors aimed to analyze the association between ventricular catheter (VC) tissue obstructions and shunt malfunction for each hydrocephalus etiology. METHODS: Patient information was collected from 5 hospitals and entered into a REDCap (Research Electronic Data Capture) database by hydrocephalus etiology. The hardware samples were fixed, and each VC tip drainage hole was classified by tissue obstruction after macroscopic analysis. Shunt malfunction data, including shunt revision rate, time to failure, and age at surgery, were correlated with the degree of tissue obstruction in VCs for each etiology. RESULTS: Posthemorrhagic hydrocephalus was the most common etiology (48.9% of total cases). Proximal catheter obstruction was the most frequent cause of hardware removal (90.4%). Myelomeningocele (44% ± 29%), other congenital etiologies (48% ± 40%), hydrocephalus with brain tumors (45% ± 35%), and posthemorrhagic hydrocephalus (41% ± 35%) showed tissue aggregates in more than 40% of the VC holes. A total of 76.8% of samples removed because of symptoms of obstruction showed cellular or tissue aggregates. No conclusive etiological associations were detected when correlating the percentage of holes with tissue for each VC and age at surgery, shunt revision rates, or time between shunt implantation and removal. CONCLUSIONS: The proximal VC obstruction was accompanied by tissue aggregates in 76.8% of cases. However, the presence of tissue in the VC did not seem to be associated with hydrocephalus etiology.

Intracranial Germinoma in Two Caucasian American Siblings With Autism Spectrum Disorder.

Intracranial germ cell tumors (IGCTs) comprise 3% to 5% of all pediatric brain tumors in the West, with a significantly higher prevalence in Asia. Although these tumors are histologically diverse, repeated somatic variants have been demonstrated. Chromosomal aneuploidies, such as Klinefelter and Down syndromes, are associated with IGCTs, but no familial germline tumor syndromes are currently known. Here, we report the novel case of 2 American siblings with underlying autism spectrum disorder who developed intracranial germinoma within months of each other, in the absence of external risk factors. Extensive genetic testing was performed, including karyotyping, chromosomal microarray, and whole exome and whole genome sequencing, and did not identify any variants accounting for the phenotypes. Despite the absence of overlapping variants, a recent retrospective review demonstrated a threefold greater prevalence of autism spectrum disorder in patients with intracranial germinoma compared with national prevalence. This report highlights the complexity of tumor development, as well as the need for further research regarding IGCTs in a neurodivergent population.

Developmental atlas of phase-amplitude coupling between physiologic high-frequency oscillations and slow waves.

We investigated the developmental changes in high-frequency oscillation (HFO) and Modulation Index (MI) - the coupling measure between HFO and slow-wave phase. We generated normative brain atlases, using subdural EEG signals from 8251 nonepileptic electrode sites in 114 patients (ages 1.0-41.5 years) who achieved seizure control following resective epilepsy surgery. We observed a higher MI in the occipital lobe across all ages, and occipital MI increased notably during early childhood. The cortical areas exhibiting MI co-growth were connected via the vertical occipital fasciculi and posterior callosal fibers. While occipital HFO rate showed no significant age-association, the temporal, frontal, and parietal lobes exhibited an age-inversed HFO rate. Assessment of 1006 seizure onset sites revealed that z-score normalized MI and HFO rate were higher at seizure onset versus nonepileptic electrode sites. We have publicly shared our intracranial EEG data to enable investigators to validate MI and HFO-centric presurgical evaluations to identify the epileptogenic zone.

Exploration of clinical predictors of the degree of ventricular catheter obstruction: a multicenter retrospective study.

OBJECTIVE: The aim of this study was to explore how clinical factors, including the number of lifetime revision surgeries and the duration of implantation, affect the degree of obstruction and failure rates of ventricular catheters (VCs) used to manage hydrocephalus. METHODS: A total of 343 VCs and their associated clinical data, including patient demographics, medical history, and surgical details, were collected from 5 centers and used for this analysis. Each VC was classified by the degree of obstruction after macroscopic analysis. Univariate, multivariate, and binned analyses were conducted to test for associations between clinical data and degree of VC obstruction. RESULTS: VCs from patients with 0 to 2 lifetime revisions had a larger proportion of VC holes obstructed than VCs from patients with 10 or more revisions (p = 0.0484). VCs implanted for less than 3 months had fewer obstructed holes with protruding tissue aggregates than VCs implanted for 13 months or longer (p = 0.0225). Neither duration of implantation nor the number of lifetime revisions was a significant predictor of the degree of VC obstruction in the regression models. In the multinomial regression model, contact of the VCs with the ventricular wall robustly predicted the overall obstruction status of a VC (p = 0.005). In the mixed-effects model, the age of the patient at their first surgery emerged as a significant predictor of obstruction by protruding tissue aggregates (p = 0.002). VCs implanted through the parietal entry site were associated with more holes with nonobstructive growth and fewer empty holes than VCs implanted via other approaches (p = 0.001). CONCLUSIONS: The number of lifetime revisions and duration of implantation are correlated with the degree of VC obstruction but do not predict it. Contact of the VC with the ventricular wall and the age of the patient at their first surgery are predictors of the degree of VC obstruction, while the entry site of the VC correlates with it.

Central Nervous System Tumor With BCL6 Corepressor Internal Tandem Duplication: Treatment Course of a Long-term Survivor.

Central nervous system (CNS) tumor with BCL6 corepressor (BCOR) internal tandem duplication (ITD) is a newly described CNS tumor, characterized by in-frame ITDs of the BCOR gene. There is no standard practice regarding the management of this tumor. We report the clinical course of a 6-year-old boy who presented to the hospital with worsening headaches. Computed tomography scan showed a large right-sided parietal supratentorial mass and brain magnetic resonance imaging confirmed a 6×8×6.7 cm lobulated, solid but heterogeneous mass in the right parieto-occipital region. While initial pathology suggested a WHO grade 3 anaplastic meningioma, additional investigation with molecular analysis confirmed the diagnosis of high-grade neuroepithelial tumor with BCOR exon 15 ITD. This diagnosis was renamed CNS tumor with BCOR ITD in the 2021 WHO CNS tumor classification. The patient received 54 Gy of focal radiation and has no evidence of disease recurrence after 48 months from the end of treatment. As this is a newly discovered entity with only a few previous reports in the scientific literature, this report presents a unique treatment for this CNS tumor compared with those previously described.

Dynamic cortical and tractography atlases of proactive and reactive alpha and high-gamma activities.

Alpha waves-posterior dominant rhythms at 8-12 Hz reactive to eye opening and closure-are among the most fundamental EEG findings in clinical practice and research since Hans Berger first documented them in the early 20th century. Yet, the exact network dynamics of alpha waves in regard to eye movements remains unknown. High-gamma activity at 70-110 Hz is also reactive to eye movements and a summary measure of local cortical activation supporting sensorimotor or cognitive function. We aimed to build the first-ever brain atlases directly visualizing the network dynamics of eye movement-related alpha and high-gamma modulations, at cortical and white matter levels. We studied 28 patients (age: 5-20 years) who underwent intracranial EEG and electro-oculography recordings. We measured alpha and high-gamma modulations at 2167 electrode sites outside the seizure onset zone, interictal spike-generating areas and MRI-visible structural lesions. Dynamic tractography animated white matter streamlines modulated significantly and simultaneously beyond chance, on a millisecond scale. Before eye-closure onset, significant alpha augmentation occurred at the occipital and frontal cortices. After eye-closure onset, alpha-based functional connectivity was strengthened, while high gamma-based connectivity was weakened extensively in both intra-hemispheric and inter-hemispheric pathways involving the central visual areas. The inferior fronto-occipital fasciculus supported the strengthened alpha co-augmentation-based functional connectivity between occipital and frontal lobe regions, whereas the posterior corpus callosum supported the inter-hemispheric functional connectivity between the occipital lobes. After eye-opening offset, significant high-gamma augmentation and alpha attenuation occurred at occipital, fusiform and inferior parietal cortices. High gamma co-augmentation-based functional connectivity was strengthened, whereas alpha-based connectivity was weakened in the posterior inter-hemispheric and intra-hemispheric white matter pathways involving central and peripheral visual areas. Our results do not support the notion that eye closure-related alpha augmentation uniformly reflects feedforward or feedback rhythms propagating from lower to higher order visual cortex, or vice versa. Rather, proactive and reactive alpha waves involve extensive, distinct white matter networks that include the frontal lobe cortices, along with low- and high-order visual areas. High-gamma co-attenuation coupled to alpha co-augmentation in shared brain circuitry after eye closure supports the notion of an idling role for alpha waves during eye closure. These normative dynamic tractography atlases may improve understanding of the significance of EEG alpha waves in assessing the functional integrity of brain networks in clinical practice; they also may help elucidate the effects of eye movements on task-related brain network measures observed in cognitive neuroscience research.

Intra- and inter-hemispheric network dynamics supporting object recognition and speech production.

We built normative brain atlases that animate millisecond-scale intra- and inter-hemispheric white matter-level connectivity dynamics supporting object recognition and speech production. We quantified electrocorticographic modulations during three naming tasks using event-related high-gamma activity from 1,114 nonepileptogenic intracranial electrodes (i.e., non-lesional areas unaffected by epileptiform discharges). Using this electrocorticography data, we visualized functional connectivity modulations defined as significant naming-related high-gamma modulations occurring simultaneously at two sites connected by direct white matter streamlines on diffusion-weighted imaging tractography. Immediately after stimulus onset, intra- and inter-hemispheric functional connectivity enhancements were confined mainly across modality-specific perceptual regions. During response preparation, left intra-hemispheric connectivity enhancements propagated in a posterior-to-anterior direction, involving the left precentral and prefrontal areas. After overt response onset, inter- and intra-hemispheric connectivity enhancements mainly encompassed precentral, postcentral, and superior-temporal (STG) gyri. We found task-specific connectivity enhancements during response preparation as follows. Picture naming enhanced activity along the left arcuate fasciculus between the inferior-temporal and precentral/posterior inferior-frontal (pIFG) gyri. Nonspeech environmental sound naming augmented functional connectivity via the left inferior longitudinal and fronto-occipital fasciculi between the medial-occipital and STG/pIFG. Auditory descriptive naming task enhanced usage of the left frontal U-fibers, involving the middle-frontal gyrus. Taken together, the commonly observed network enhancements include inter-hemispheric connectivity optimizing perceptual processing exerted in each hemisphere, left intra-hemispheric connectivity supporting semantic and lexical processing, and inter-hemispheric connectivity for symmetric oral movements during overt speech. Our atlases improve the currently available models of object recognition and speech production by adding neural dynamics via direct intra- and inter-hemispheric white matter tracts.

Endoscopy in Craniosynostosis Surgery: Evolution and Current Trends.

Over the past 30 years, advances in endoscopic technology and advancing interest in the benefits of minimally invasive approaches for craniofacial surgery have resulted in these techniques becoming a part of the standard of care in the treatment of craniosynostosis. In this review, we discuss the evolution and adoption of endoscopic-assisted strip craniectomy procedures. In addition to reviewing the studies describing various nuances and modifications to minimally invasive strip craniectomy, attention to comparisons in outcomes between traditional or open cranial vault reconstructions and endoscopic-assisted techniques is highlighted for different craniosynostosis diagnoses.

The effect of A1 and A2 reactive astrocyte expression on hydrocephalus shunt failure.

BACKGROUND: The composition of tissue obstructing neuroprosthetic devices is largely composed of inflammatory cells with a significant astrocyte component. In a first-of-its-kind study, we profile the astrocyte phenotypes present on hydrocephalus shunts. METHODS: qPCR and RNA in-situ hybridization were used to quantify pro-inflammatory (A1) and anti-inflammatory (A2) reactive astrocyte phenotypes by analyzing C3 and EMP1 genes, respectively. Additionally, CSF cytokine levels were quantified using ELISA. In an in vitro model of astrocyte growth on shunts, different cytokines were used to prevent the activation of resting astrocytes into the A1 and A2 phenotypes. Obstructed and non-obstructed shunts were characterized based on the degree of actual tissue blockage on the shunt surface instead of clinical diagnosis. RESULTS: The results showed a heterogeneous population of A1 and A2 reactive astrocytes on the shunts with obstructed shunts having a significantly higher proportion of A2 astrocytes compared to non-obstructed shunts. In addition, the pro-A2 cytokine IL-6 inducing proliferation of astrocytes was found at higher concentrations among CSF from obstructed samples. Consequently, in the in vitro model of astrocyte growth on shunts, cytokine neutralizing antibodies were used to prevent activation of resting astrocytes into the A1 and A2 phenotypes which resulted in a significant reduction in both A1 and A2 growth. CONCLUSIONS: Therefore, targeting cytokines involved with astrocyte A1 and A2 activation is a promising intervention aimed to prevent shunt obstruction.

Women in Neurosurgery: A PRISMA-Compliant Systematic Review of Where We Stand and a Pilot Study on How to Move Forward.

BACKGROUND: Surgical specialties struggle to recruit women. In this study, the authors performed a systematic review to describe progress of women in neurosurgery and highlight areas where further research is needed. METHODS: PubMed, Embase, and Cochrane Library were queried with "women in neurosurgery" OR "female neurosurgeon," and publications with empiric research were included. Bias was assessed on the basis of study designs. RESULTS: We found 127 papers, and 36 met inclusion criteria. Much of this research is recent-85% has been published within the past 3 years. These papers detail differences between genders and examine possible causes, but they do not test interventions to remedy inequities. The authors designed an intervention focusing on medical students' perceptions of gender issues within neurosurgery. A seminar was designed with 2 objectives: inform medical students about changes within neurosurgery and introduce them to a female neurosurgery attending who could serve as a potential future mentor. Student attitudes were assessed before and after the seminar by survey. Fourteen students completed both surveys: 10 females and 4 males. CONCLUSIONS: The 1-hour seminar significantly reduced the mean perceived difficulty to enter neurosurgery from 4.4 to 4.1 (P = 0.014); additionally, the mean perceived additional difficulty for career advancement faced by women in neurosurgery decreased from 3.6 to 2.8 (P = 0.026). Much research has gone into documenting the advancement and potential impediments for women in neurosurgery. Less research has tested solutions. Our pilot was small and susceptible to bias, but given that some results achieved significance, it merits more rigorous study.

A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus.

BACKGROUND: Implantation of ventricular catheters (VCs) to drain cerebrospinal fluid (CSF) is a standard approach to treat hydrocephalus. VCs fail frequently due to tissue obstructing the lumen via the drainage holes. Mechanisms driving obstruction are poorly understood. This study aimed to characterize the histological features of VC obstructions and identify links to clinical factors. METHODS: 343 VCs with relevant clinical data were collected from five centers. Each hole on the VCs was classified by degree of tissue obstruction after macroscopic analysis. A subgroup of 54 samples was analyzed using immunofluorescent labelling, histology and immunohistochemistry. RESULTS: 61.5% of the 343 VCs analyzed had tissue aggregates occluding at least one hole (n = 211) however the vast majority of the holes (70%) showed no tissue aggregates. Mean age at which patients with occluded VCs had their first surgeries (3.25 yrs) was lower than in patients with non-occluded VCs (5.29 yrs, p < 0.02). Mean length of time of implantation of occluded VCs, 33.22 months was greater than for non-occluded VCs, 23.8 months (p = 0.02). Patients with myelomeningocele had a greater probability of having an occluded VC (p = 0.0426). VCs with occlusions had greater numbers of macrophages and astrocytes in comparison to non-occluded VCs (p < 0.01). Microglia comprised only 2-6% of the VC-obstructing tissue aggregates. Histologic analysis showed choroid plexus occlusion in 24%, vascularized glial tissue occlusion in 24%, prevalent lymphocytic inflammation in 29%, and foreign body giant cell reactions in 5% and no ependyma. CONCLUSION: Our data show that age of the first surgery and length of time a VC is implanted are factors that influence the degree of VC obstruction. The tissue aggregates obstructing VCs are composed predominantly of astrocytes and macrophages; microglia have a relatively small presence.

Biographies of international women leaders in neurosurgery.

We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as "first" of their country or color or other achievement. All of them are included as outstanding-in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life's work, they chose service, often of the most neglected-those with pain, trauma, and disability. These women inspire and point the way to a time when the term "women leaders" as an exception is unnecessary.-Katharine J. Drummond, MD, on behalf of this month's topic editors.

Reversible Cerebral Vasoconstriction Syndrome and Sickle Cell Disease: A Case Report.

Reversible cerebral vasoconstriction syndrome (RCVS), is rare in the pediatric population and is characterized by severe headaches and other neurologic symptoms. We present a case of RCVS occurring concomitantly with posterior reversible encephalopathy syndrome in an 8-year-old African American child with sickle cell disease (HbSS). Imaging studies including computed tomography, magnetic resonance imaging and cerebral angiography of the brain showed acute hemorrhagic stroke and a beaded appearance of peripheral cerebral vessels. In this report, we focus on the typical features of RCVS and discuss the underlying risk factors that may increase the risk in patients with HbSS disease.

Investigation of ventriculoperitoneal shunt disconnection for hydrocephalus treatment.

OBJECTIVE: This investigation is aimed at gaining a better understanding of the factors that lead to mechanical failure of shunts used for the treatment of hydrocephalus, including shunt catheter-valve disconnection and shunt catheter fracture. METHODS: To determine the root cause of mechanical failure, the authors created a benchtop mechanical model to mimic mechanical stressors on a shunt system. To test shunt fracture, cyclical loading on the catheter-valve connection site was tested with the shunt catheter held perpendicular to the valve. Standard methods were used to secure the catheter and valves with Nurolon. These commercial systems were compared to integrated catheters and valves (manufactured as one unit). To test complete separation/disconnection of the shunt catheter and valve, a parallel displacement test was conducted using both Nurolon and silk sutures. Finally, the stiffness of the catheters was assessed. All mechanical investigations were conducted on shunts from two major shunt companies, assigned as either company A or company B. RESULTS: Cyclical loading experiments found that shunts from company B fractured after a mean of 4936 ± 1725 cycles (95% CI 2990-6890 cycles), while those of company A had not failed after 8000 cycles. The study of parallel displacement indicated complete disconnection of company B's shunt catheter-valve combination using Nurolon sutures after being stretched an average 32 ± 5.68 mm (95% CI 25.6-38.4 mm), whereas company A's did not separate using either silk or Nurolon sutures. During the stiffness experiments, the catheters of company B had statistically significantly higher stiffness of 13.23 ± 0.15 N compared to those of company A, with 6.16 ± 0.29 N (p < 0.001). CONCLUSIONS: Mechanical shunt failure from shunt catheter-valve disconnection or fracture is a significant cause of shunt failure. This study demonstrates, for the first time, a correlation between shunt catheters that are less mechanically stiff and those that are less likely to disconnect from the valve when outstretched and are also less likely to tear when held at an angle from the valve outlet. The authors propose an intervention to the standard of care wherein less stiff catheters are trialed to reduce disconnection.

Pneumocephalus in a Pediatric Patient with Glioma Receiving Trametinib.

The mitogen-activated protein kinase (MAPK) pathway consists of the Ras/Raf/MEK/ERK signaling cascade, and its upregulation plays a major role in the pathogenesis of pediatric astrocytomas and molecular inhibitors of this pathway including trametinib and dabrafenib have been tested in early-phase clinical trials and used by pediatric oncologists in children with BRAF-mutated gliomas. We report a clinical case where a child with progressive BRAF-mutated glioma developed an uncommon and difficult to manage complication - pneumocephalus from intracranial air entry and trapping through dehisced surgical wounds and preexisting skull burr holes. The patient's wound breakdown coincided with skin toxicity from MEK inhibitor therapy. With increasing use of targeted molecular inhibitors in pediatric neuro-oncology, this case illustrates the potentially complicated course of MEK inhibitor therapy in patients with scalp surgical wounds and burr holes that were placed within few weeks from initiation of drug therapy, especially if patients have additional factors that can contribute to poor wound healing such as use of steroids and malnutrition.

Anatomical hemispherectomy revisited-outcome, blood loss, hydrocephalus, and absence of chronic hemosiderosis.

PURPOSE: To evaluate microsurgical trans-sylvian trans-ventricular anatomical hemispherectomy with regard to seizure outcome, risk of hydrocephalus, blood loss, and risk of chronic hemosiderosis in patients with intractable seizures selected for surgery using current preoperative assessment techniques. METHODS: Out of 86 patients who underwent hemispherectomy between February 2000 and April 2019, by a single surgeon, at a tertiary care referral center, 77 patients (ages 0.2-20 years; 40 females) who had an anatomical hemispherectomy were analyzed. Five of these were 'palliative' surgeries. One-stage anatomical hemispherectomy was performed in 55 children, two-stage anatomical hemispherectomy after extraoperative intracranial monitoring in 16, and six hemispherectomies were done following failed previous resection. Mean follow-up duration was 5.7 years (range 1-16.84 years). Forty-six patients had postoperative MRI scans. RESULTS: Ninety percent of children with non-palliative hemispherectomy achieved ILAE Class-1 outcome. Twenty-seven patients were no longer taking anticonvulsant medications. Surgical failures (n = 4) included one patient with previous meningoencephalitis, one with anti-GAD antibody encephalitis, one with idiopathic neonatal thalamic hemorrhage, and one with extensive tuberous sclerosis. There were no failures among patients with malformations of cortical development. Estimated average blood loss during surgery was 387 ml. Ten (21%) children developed hydrocephalus and required a shunt following one-stage hemispherectomy, whereas 10 (50%) patients developed hydrocephalus among those who had extraoperative intracranial monitoring. Only 20% of the shunts malfunctioned in the first year. Early malfunctions were related to the valve and later to fracture disconnection of the shunt. One patent had a traumatic subdural hematoma. None of the patients developed clinical signs of chronic 'superficial cerebral hemosiderosis' nor was there evidence of radiologically persistent chronic hemosiderosis in patients who had postoperative MRI imaging. CONCLUSION: Surgical results of anatomical hemispherectomy are excellent in carefully selected cases. Post-operative complications of hydrocephalus and intraoperative blood loss are comparable to those reported for hemispheric disconnective surgery (hemispherotomy). The rate of shunt malfunction was less than that reported for patients with hydrocephalus of other etiologies Absence of chronic 'superficial hemosiderosis', even on long-term follow-up, suggests that anatomical hemispherectomy should be revisited as a viable option in patients with intractable seizures and altered anatomy such as in malformations of cortical development, a group that has a reported high rate of seizure recurrence related to incomplete disconnection following hemispheric disconnective surgery.