Cell division cycle 42 binding protein beta as a plasma-based biomarker for cerebral cavernous malformations

Journal of Neurosurgery Pediatrics · 2026-01-30

OBJECTIVE: Cerebral cavernous malformations (CCMs) are groups of blood vessels that develop abnormally in both the brain and/or spinal cord. Currently, MRI and/or CT are the primary methods for assessing CCMs. Plasma-based biomarkers could serve as a complement to standard imaging techniques by providing a quantitative and molecular-based technique to detect disease at lower cost. Therefore, the authors evaluated cell division cycle 42 binding protein beta (CDC42BPB) as a potential novel plasma biomarker for CCMs. METHODS: Plasma samples were obtained from patients with pathological analysis-confirmed CCM (n = 10, age 1-16 years) and compared to controls (n = 24, age 1-19 years). The protein levels were measured using the Olink Proximity Extension Assay. Findings were confirmed with ELISA. CDC42BPB expression was further analyzed with Western blot and immunohistochemistry analysis in patient-derived primary cells and CCM tissues, respectively. RESULTS: CCM patients exhibited significantly higher CDC42BPB plasma levels compared to controls (approximately 6-fold greater expression, p = 0.004). Furthermore, the high CDC42BPB plasma expression was concordant with the protein levels in CCM tissues and patient-derived primary cells. CONCLUSIONS: The authors present data supporting the measurement of CDC42BPB plasma level as a putative biomarker for CCMs. These findings have implications relevant to improving diagnosis, follow-up, and molecular pathophysiological analysis.

Medical management of cerebellar mutism syndrome at a quaternary children’s hospital

Child s Nervous System · 2025-02-03

PURPOSE: We aimed to evaluate the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating cerebellar mutism syndrome (CMS). METHODS: We retrospectively reviewed all pediatric patients who underwent a posterior fossa tumor resection between May 2007 to September 2022 at a single quaternary pediatric hospital. We evaluated clinical presentation and hospital course, including imaging findings, pathology, and surgical approaches. Propensity score matching was used to compare the symptom duration of patients who received SSRIs versus those who did not. RESULTS: A total of 292 patients met the criteria with 25% (n = 73) being diagnosed with CMS. Several factors were significantly associated with a CMS diagnosis, such as pre-operative hydrocephalus (p = 0.002), a vermis-splitting approach (p = 0.007), tumor in the fourth ventricle (p = 0.010), medulloblastoma diagnosis (p = 0.009), and postoperative complication (p < 0.001). Of the patients diagnosed with CMS, 32.9% (n = 24) received SSRI treatment, specifically fluoxetine (n = 18) and sertraline (n = 6). Overall, treatment did not decrease the duration of CMS symptoms or shorten the inpatient rehab course compared to matched controls. However, within the cohort of fluoxetine-treated patients, earlier initiation of medication was significantly correlated with a shorter duration of mutism (p = 0.007). CONCLUSIONS: We report the largest cohort of CMS patients treated with SSRIs. The lack of overall clinical benefit when compared to untreated patients in our study may be due to the length of delay in starting an SSRI, since early initiation of fluoxetine correlated with shorter CMS symptoms. These results support the importance of early clinical detection of CMS and potentially treating CMS early in the patient's postoperative course.

462 Burr Hole Hemispherotomy: A Retrospective Series of Seven Cases of Hemispheric Disconnection Performed Via a Single Eighteen-millimeter Burr Hole

Neurosurgery · 2025-03-14

INTRODUCTION: Hemispherotomy represents definitive treatment for drug-resistant epilepsy with unilateral hemispheric onset. Traditional approaches involve a large incision and open craniotomy, with associated risks of blood loss, infection, poor wound healing, pain, cosmetic concerns, and long hospital stays. The authors describe a minimally invasive technique for performing a hemispherotomy through a single burr hole overlying the Sylvian fissure. METHODS: A retrospective analysis was performed on the first seven patients to have undergone burr hole hemispherotomy. Data on demographics, hospital stay, complications, completeness of disconnection, and post-operative seizure control were collected. RESULTS: Hemispherotomy was performed through a 15–18 mm burr hole on seven patients–four with epilepsy due to perinatal stroke, one with hemispheric malformation including schizencephaly, and two with a history of traumatic brain injury. Patient ages ranged from 18 months to 21 years at surgery. Complete hemispheric disconnection was achieved in all cases. Estimated blood loss was minimal (mean 25.7 cc, median 20, range 20–50) with no perioperative blood transfusions, intraoperative complications, or deaths. One patient returned to the operating room for closure of a wound dehiscence secondary to a fall. Opioid usage was minimal, with an average total postoperative opioid usage through post-operative day 5 of 468.9 morphine μg/kg equivalents (median 372.6 μg/kg, range 0.0 to 1751.7 μg/kg). One patient experienced a delayed ipsilateral basal ganglia hemorrhage with self-limited symptoms. All patients experienced substantial reduction in seizure burden, with 71% (5/7) achieving Engel Class IA outcome. No patients developed hydrocephalus or shunt malfunction. CONCLUSIONS: The burr hole hemispherotomy approach consistently achieved complete hemispheric disconnection and therefore represents a viable surgical approach. Preliminary results suggest a favorable risk profile.

Burr Hole Hemispherotomy: Case Series

Operative Neurosurgery · 2025-03-05 · 1 citations

BACKGROUND AND OBJECTIVES: Hemispherotomy represents definitive treatment for drug-resistant epilepsy with unilateral hemispheric onset. Traditional approaches involve a large incision and open craniotomy, with associated risks of blood loss, infection, poor wound healing, pain, cosmetic concerns, and long hospital stays. The authors describe a minimally invasive hemispherotomy technique through a single burr hole overlying the Sylvian fissure. A case series of the first cohort of patients to undergo this procedure is detailed to provide an initial evaluation of the safety and efficacy of this approach. METHODS: A retrospective analysis was performed on the first 7 patients to have undergone burr hole hemispherotomy at the Children's Hospital of Philadelphia. Data on demographics, hospital stay, complications, completeness of disconnection, and postoperative seizure control were collected. RESULTS: Hemispherotomy was performed through a 15 to 18 mm burr hole on 7 patients-4 with epilepsy due to perinatal stroke, 1 with hemispheric malformation including schizencephaly, and 2 with a history of traumatic brain injury. Patient ages ranged from 18 months to 21 years at surgery. Complete hemispheric disconnection was achieved in all cases. Estimated blood loss was minimal (mean 25.7 cc, median 20, range 20-50) with no perioperative blood transfusions, intraoperative complications, or deaths. One patient returned to the operating room for closure of a wound dehiscence secondary to a fall. Opioid usage was minimal, with an average total postoperative opioid usage through postoperative day 5 of 468.9 morphine µg/kg equivalents (median 372.6 µg/kg, range 0.0-1751.7 µg/kg). One patient experienced a delayed ipsilateral basal ganglia hemorrhage with self-limited symptoms. All patients experienced substantial reduction in seizure burden, with 71% (5/7) achieving Engel Class IA outcome. No patients developed hydrocephalus or shunt malfunction. CONCLUSION: The burr hole hemispherotomy approach consistently achieved complete hemispheric disconnection and represents a viable surgical approach. Preliminary results suggest a favorable risk profile.

Use of a machine learning algorithm with a focus on spinopelvic parameters to predict development of symptomatic tethered cord after initial untethering surgery

Journal of Neurosurgery Pediatrics · 2024-03-02 · 2 citations

OBJECTIVE: Among patients with a history of prior lipomyelomeningocele repair, an association between increased lumbosacral angle (LSA) and cord retethering has been described. The authors sought to build a predictive algorithm to determine which complex tethered cord patients will develop the symptoms of spinal cord retethering after initial surgical repair with a focus on spinopelvic parameters. METHODS: An electronic medical record database was reviewed to identify patients with complex tethered cord (e.g., lipomyelomeningocele, lipomyeloschisis, myelocystocele) who underwent detethering before 12 months of age between January 1, 2008, and June 30, 2022. Descriptive statistics were used to characterize the patient population. The Caret package in R was used to develop a machine learning model that predicted symptom development by using spinopelvic parameters. RESULTS: A total of 72 patients were identified (28/72 [38.9%] were male). The most commonly observed dysraphism was lipomyelomeningocele (41/72 [56.9%]). The mean ± SD age at index MRI was 2.1 ± 2.2 months, at which time 87.5% of patients (63/72) were asymptomatic. The mean ± SD lumbar lordosis at the time of index MRI was 23.8° ± 11.1°, LSA was 36.5° ± 12.3°, sacral inclination was 30.4° ± 11.3°, and sacral slope was 23.0° ± 10.5°. Overall, 39.6% (25/63) of previously asymptomatic patients developed new symptoms during the mean ± SD follow-up period of 44.9 ± 47.2 months. In the recursive partitioning model, patients whose LSA increased at a rate ≥ 5.84°/year remained asymptomatic, whereas those with slower rates of LSA change experienced neurological decline (sensitivity 77.5%, specificity 84.9%, positive predictive value 88.9%, and negative predictive value 70.9%). CONCLUSIONS: This is the first study to build a machine learning algorithm to predict symptom development of spinal cord retethering after initial surgical repair. The authors found that, after initial surgery, patients who demonstrate a slower rate of LSA change per year may be at risk of developing neurological symptoms.

Technical note: Traumatic atlanto-occipital dislocation and severe subaxial cervical distraction injury in an infant

Spinal Cord Series and Cases · 2024-01-04

Intracranial complications secondary to acute bacterial sinusitis requiring neurosurgical intervention before and after the onset of the COVID-19 pandemic

Journal of Neurosurgery Pediatrics · 2024-08-03 · 7 citations

OBJECTIVE: Intracranial complications of acute bacterial sinusitis are rare pathologies that occur in children, and are associated with significant neurological morbidity and mortality. There is a subjective concern among neurosurgeons that the incidence of this rare disease has increased since the onset of the novel COVID-19 pandemic. The primary objective of this study was to review the presentation and management of patients admitted at the authors' institution with intracranial extension of sinusitis, to better understand the local disease burden relative to the COVID-19 pandemic. METHODS: This is a single-center retrospective observational cohort study. The patients underwent neurosurgical intervention for intracranial extension of sinusitis between January 1, 2007, and March 1, 2023. The historical cohort was defined as those patients who presented prior to March 2020. Clinical covariates such as surgical and microbiological data were collected and analyzed. RESULTS: A total of 78 patients (55 historical, 23 new) were included; they had a median age of 11.7 years and a male predominance of 69.2%. There was a significant increase in the annual rate of neurosurgical intervention for suppurative intracranial extension of acute bacterial sinusitis after the onset of the COVID-19 pandemic, with an average of 4.2 cases per year prior to March 2020 compared to 7.7 cases per year after that date (p = 0.013). This increase was largely driven by the unprecedented case volume of 13 cases in 2022. Patients in the new cohort were older (p = 0.009) and more likely to have Pott's puffy tumor/frontal bone osteomyelitis (p = 0.003) at the time of presentation than patients in the historical cohort. Patients in the new cohort had lower rates of readmission within 30 days of discharge than those in the historical cohort (p = 0.047). In both cohorts, patients with seizure on presentation were more likely to have neurological sequelae at last follow-up (p = 0.004), which occurred at a median of 2.9 months after discharge. CONCLUSIONS: Clinicians encountering pediatric patients presenting with persistent symptoms of acute bacterial sinusitis must have a high index of suspicion for suppurative intracranial extension. Prompt neuroimaging and subsequent neurosurgical intervention are critical to ensure timely diagnosis and treatment. The results in this study show a significant increase in the number of neurosurgical interventions for suppurative intracranial extension of sinusitis per year after the onset of the COVID-19 pandemic. Further research is needed to understand the underlying pathophysiology of this clinical phenomenon.

SURG-06. FRAMELESS STEREOTACTIC INTRACRANIAL CATHETER PLACEMENT FOR DELIVERY OF INTRATUMORAL CELLULAR THERAPIES

Neuro-Oncology · 2024-06-18

Abstract BACKGROUND As the leading disease-related cause of death in children, pediatric brain tumors, and in particular diffuse midline glioma, require novel treatment approaches. Cellular-based therapies offer promise, but challenges still exist in defining their optimal delivery route. Emerging data from our group suggest there may be a role for intratumoral injection in treatment algorithms. We here describe a surgical workflow for intratumoral injection of cellular therapies that utilizes existing and widely used neurosurgical technologies that can be incorporated into future clinical trials. METHODS Infusion target and catheter trajectory was planned using standard pre-operative MRI. Components from an FDA-approved frameless stereotactic intracranial biopsy system were chosen such that they would accept and guide an FDA-approved rigid intracranial catheter system intended for MR-guided procedures. Following catheter insertion, an intraoperative CT was used to determine accuracy of catheter placement by merging the image with the pre-operative MRI. RESULTS The proposed system was tested in a simulated fashion using a phantom cranial model registered to an accompanying brain MRI. The stereotactic biopsy mount was affixed to the skull at the planned entry site for a posterior fossa approach to the pons. Catheter insertion depth was determined using the stereotactic system and the catheter was inserted to this depth through the biopsy mount. Intraoperative CT confirmed the catheter tip location which correlated with the planned infusion target with sub-millimetric accuracy. CONCLUSION Our proposed intratumoral delivery method using frameless stereotaxy shows promise for use in future clinical trials that require intratumoral delivery of cellular therapies. Utilizing FDA-approved devices allows for quick integration into protocols and their wide-spread use makes the approach generalizable. This approach also eliminates the need for MR-guided procedures which can increase cost and require significant hospital resources to perform. Future work will be aimed at streamlining the intraoperative workflow.

Isolated unilateral alar ligamentous injury: illustrative cases

Journal of Neurosurgery Case Lessons · 2024-04-01 · 1 citations

BACKGROUND: Isolated unilateral alar ligament injury (IUALI) is a rare and likely underreported occurrence after upper cervical trauma, with only 16 cases documented in the literature to date. Patients generally present with neck pain, and definitive diagnosis is typically made by magnetic resonance imaging (MRI). Unfortunately, likely due in part to its rarity, there are no formal guidelines for the treatment of an IUALI. Furthermore, there is a limited understanding of the long-term consequences associated with its inadequate treatment. OBSERVATIONS: Here, the authors report on three pediatric patients, each found to have an IUALI after significant trauma. All patients presented with neck tenderness, and two of the three had associated pain-limited range of neck motion. Imaging revealed either a laterally deviated odontoid process on cervical radiographs and/or MRI evidence of ligamentous strain or discontinuity. Each patient was placed in a hard cervical collar for 1 to 2 months with excellent resolution of symptoms. A comprehensive review of the literature showed that all patients with IUALI who had undergone external immobilization with either rigid cervical collar or halo fixation had favorable outcomes at follow-up. LESSONS: For patients with IUALI, a moderate course of nonsurgical management with rigid external immobilization appears to be an adequate first-line treatment.

Burr Hole Hemispherotomy—Modification of Trans-Sylvian Peri-Insular Technique: 2-Dimensional Operative Video

Operative Neurosurgery · 2024-01-30 · 3 citations

Trans-sylvian peri-insular hemispherotomy represents a functional hemispherectomy with minimal brain removal used for treatment of refractory hemispheric epilepsy. 1 Exposure for this procedure is achieved by craniotomy. Refinement in the hemispherotomy technique, including trends toward minimizing cortical resection, has contributed to a substantial drop in complication rates. 2 We present a refinement of this technique, allowing for complete hemispheric disconnection through a single burr hole. In this instance, this technique was applied in the case of a 4-year-old girl who presented with medically refractory epilepsy, which had developed on the first day of life due to a perinatal incomplete left middle cerebral artery stroke. Postoperatively, the patient experienced no worsening of her preexisting right-sided hemiparesis and remains seizure-free 18 months postoperatively, now off medication. While the trans-sylvian peri-insular hemispherotomy represents an established surgical technique, this is the first report of this procedure performed in a minimally invasive fashion through a single burr hole. Beyond the minimal incision and small aperture in the skull, seldom appreciated nuances of hemispheric disconnection are described and demonstrated, including amygdala disconnection, hippocampal tail disconnection directly into splenium disconnection, concomitant intermediate disconnection and callosotomy, and frontobasal disconnection landmarks. Consent was obtained from the patient's parents for the surgical procedure, use of outcome videos, and for publication of this video and associated materials. The participants and patient's parents consented to publication of their images and that of the patient.