A multi-stem cell basis for craniosynostosis and calvarial mineralization.

Craniosynostosis is a group of disorders of premature calvarial suture fusion. The identity of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts in craniosynostosis remains poorly understood. Here we show that both physiologic calvarial mineralization and pathologic calvarial fusion in craniosynostosis reflect the interaction of two separate stem cell lineages; a previously identified cathepsin K (CTSK) lineage CSC1 (CTSK+ CSC) and a separate discoidin domain-containing receptor 2 (DDR2) lineage stem cell (DDR2+ CSC) that we identified in this study. Deletion of Twist1, a gene associated with craniosynostosis in humans2,3, solely in CTSK+ CSCs is sufficient to drive craniosynostosis in mice, but the sites that are destined to fuse exhibit an unexpected depletion of CTSK+ CSCs and a corresponding expansion of DDR2+ CSCs, with DDR2+ CSC expansion being a direct maladaptive response to CTSK+ CSC depletion. DDR2+ CSCs display full stemness features, and our results establish the presence of two distinct stem cell lineages in the sutures, with both populations contributing to physiologic calvarial mineralization. DDR2+ CSCs mediate a distinct form of endochondral ossification without the typical haematopoietic marrow formation. Implantation of DDR2+ CSCs into suture sites is sufficient to induce fusion, and this phenotype was prevented by co-transplantation of CTSK+ CSCs. Finally, the human counterparts of DDR2+ CSCs and CTSK+ CSCs display conserved functional properties in xenograft assays. The interaction between these two stem cell populations provides a new biologic interface for the modulation of calvarial mineralization and suture patency.

Posterior cranial vault distraction in children with syndromic craniosynostosis: the era of biodegradable materials-a comprehensive review of the literature and proposed novel global application.

Distraction osteogenesis is utilized to increase intracranial volume in the treatment of restrictive pathologies, most commonly syndromic synostosis. Children too young for open calvarial vault expansion or other systemic or local contraindications to a direct reconstructive approach benefit greatly from distraction osteogenesis, typically addressing posterior vault expansion. Wound infection, cerebrospinal fluid (CSF) leak, device failure, need for a second surgery for removal, and cost, are issues that can limit the use of this approach. These challenges are more pronounced in low- and middle-income countries (LMICs) due to lack of access to the device, the financial burden of the need for a second surgery, and the severity of the implications of infection and CSF leak. Over the last five decades, there has been an increased acceptance of bioresorbable instrumentation in craniofacial surgery. Poly L-lactic acid, polyglycolic acid, and polydioxanone are the most commonly used polymers. New resorbable fixation tools such as ultrasound-activated pins and heat-activated pins are superior to conventional bioresorbable screws in allowing attachment to thinner bone plates. In this paper, we present a review of the literature on cranial vault distraction and the use of bioresorbable materials and propose a novel design of a fully absorbable cranial distractor system using external magnetic distraction control, eliminating the need for external activation ports and a second surgery to remove the hardware. The application of this technology in LMIC settings could advance access to care and treatment options for patients with syndromic synostosis.

The Lost and Variable Cause: A Systematic Review of Shunt-Related Craniosynostosis Occurrence.

OBJECTIVE: Shunt-related craniosynostosis (SRC) is the premature fusion of cranial sutures possibly due to a loss of tension across dura and suture lines after placement of a shunt for hydrocephalus. As modifications in approaches toward shunting represent a modifiable risk factor, prior literature has investigated the determinants and outcomes. However, the data remain highly variable and are limited by single-institution studies. METHODS: A systematic search of PubMed, Embase, and Web of Science from inception to February 2022 was conducted. Studies were screened by 2 reviewers for eligibility based on predefined inclusion/exclusion criteria. RESULTS: In the 9 included articles, the average follow-up time for the entire cohort ranged from 1.5 to 4.2 years. The pooled incidence of SRC across all 9 studies was 6.5% (140/2142), with an individual range of 0.53% (1/188) to 48.8% (61/125). The average time from shunt placement to SRC diagnosis ranged from 0.25 years to 4.6 years. 61% (65/110) of cases included only one suture, 88% (25/28) of these involved the sagittal suture, and those cases with multiple fusions also had 98% involvement of the sagittal suture (45/46). Overall, 94% (1783/1888) of patients had a fixed shunt placed. CONCLUSIONS: Shunt-related craniosynostosis is likely an underreported complication in the treatment of hydrocephalus. Older age at shunt placement, increased number of shunt revision procedures, and lower valve pressure settings may be risk factors for SRC development. Results also indicate that craniosynostosis can develop months to years after shunting. Future quality studies with standardization of data reporting processes are warranted to investigate this clinical problem.

Management of Total Frontal Bone Loss After Surgery for Craniosynostosis: The Modified Visor Bone Flap With Brain Cage.

Complications after craniosynostosis surgery occur in 11% to 36% of cases and may be precipitated by poor soft tissue coverage and concomitant exposure of non-sterile regions; sequelae may result in infection, osteomyelitis, and bone loss requiring complex reconstruction. In the pediatric population, autologous cranioplasty remains the gold standard due to growth potential and a more favorable complication profile than synthetic cranioplasty. Virtual surgery planning (VSP) and computer-assisted design (CAD)/computer-assisted manufacturing (CAM) technology can be utilized to create innovative, patient-specific autologous solutions, similar to the approach with synthetic cranioplasty. A novel surgical approach using VSP was used for an 18-month-old female with near total bifrontal bone loss. Surface area measurements were used to determine the amount of bone available to replace the infected frontal bone. VSP was utilized to determine the most efficient construct configuration possible to achieve maximal coverage via calculation of cranial bone surface area measurements. Surgical reconstruction of the defect was planned as a Modified Visor Bone Flap with Posterior Brain Cage. A construct was fashioned from available cranial bone struts to obtain widespread coverage. 3D Recon images from before and after surgery demonstrate almost complete re-ossification of the cranial vault with significant resulting clinical improvement. Reconstruction of total frontal bone loss is possible by utilizing this technique. VSP can improve the safety and efficiency of complex autologous cranial bone reconstructions. We propose a treatment algorithm to address the problem of near total frontal bone loss in young children for whom alloplastic implants are not suitable.

Comparative Analysis of 2D and 3D Metrics for Evaluation of Postoperative Outcomes Following Endoscopic Suturectomy for Sagittal Craniosynostosis.

To assess whether 3-dimensional (3D) volumetrics can be used to track and evaluate postoperative course of patients treated with endoscopic suturectomy for nonsyndromic sagittal synostosis, we compared changes in 2-dimensional (2D) measurements along with 3D volumetric correlates throughout the period of helmet therapy. Forty-six patients treated at our institution with endoscopic suturectomy for sagittal synostosis were retrospectively reviewed. Head circumference (HC), cephalic index (CI), and total cranial volumes (TCVs) were measured at 3 timepoints following surgery using optical surface scans obtained for helmet orthotics. All measurements showed significant differences between timepoints on the analysis of variance ( P <0.001). There was a significant correlation between CI and TCV (r=0.35, P =0.004) and between HC and TCV (r=0.81, P <0.001). The normalized rate of change over the course of treatment was significantly higher for TCV (36.7%) than for CI (8.8%) and HC (8.4%, P <0.001), with no difference between HC and CI. The authors conclude that 3D metrics were able to reliably follow the course of postoperative 2D metrics. There was a direct and linear correlation between HC and CI with TCV. Total cranial volumes showed the highest rate of sustained change at every timepoint. Although CI and HC plateau after the first measurement, TCV continues to adapt over the course of treatment. These results demonstrate the feasibility and value of volumetrics from 3D imaging to provide a more comprehensive evaluation of postoperative surgical outcomes than traditional 2D metrics without the ionizing radiation traditionally utilized for CT to obtain 3D metrics.

Examining the Role of Early Diagnostic Imaging for Craniosynostosis in the Era of Endoscopic Suturectomy: A Single Institution Experience.

ABSTRACT: Endoscopic suturectomy is a minimally invasive surgical treatment for single-suture craniosynostosis in children between 1 and 4 months of age. This study sought to characterize the role played by diagnostic imaging in facilitating early surgical management with endoscopic suturectomy. The authors also characterized the overall diagnostic utility of imaging in patients assessed for abnormal head shape at their institution, regardless of surgical status. A retrospective cohort of children diagnosed with singlesuture synostosis undergoing either primary endoscopic suturectomy or open calvarial reconstruction at the authors' institution from 1998 to 2018 was first reviewed. Of 132 surgical patients, 53 underwent endoscopic suturectomy and 79 underwent open repair. There was no difference in the proportion of endoscopic and open surgery patients imaged preoperatively before (24.5% versus 35.4%; P = 0.24) or after (28.3% versus 25.3%; P = 0.84) craniofacial assessment. Stratifying by historical epoch (1998-2010 versus 2011-2018), there was also no difference found between preoperative imaging rates (63.6% versus 56.4%; P = 0.35). In another cohort of 175 patients assessed for abnormal head shape, 26.9% were imaged to rule out craniosynostosis. Positive diagnostic imaging rates were recorded for suspected unicoronal (100%), metopic (87.5%), lambdoidal (75.0%), sagittal (63.5%), multisuture (50%), and bicoronal (0%) synostosis. The authors conclude that the use of diagnostic imaging at their institution has not increased despite higher utilization of endoscopic suturectomy and need for expedient identification of surgical candidates.However, their results suggest that imaging may play a greater diagnostic role for suspected bicoronal, sagittal, and multi-sutural synostosis among sutural subtypes of synostosis.

A Retrospective Analysis of the Impact of Health Disparities on Treatment for Single Suture Craniosynostosis Before and During the Pandemic.

Candidates for endoscopic treatment for craniosynostosis must be less than 6 months old. Given the narrow window of eligibility, there is potential for barriers to access to impact the type of surgery a patient receives. We hypothesized that COVID may worsen these potential disparities.Charts were reviewed for children with single suture craniosynostosis from January 2014 to March 2020 (pre-COVID cohort) and March 2020 to September 2021 (COVID cohort) from 2 academic centers.110 children were in the pre-COVID group; 56 were treated open and 54 endoscopically. Of the 44 patients in the COVID cohort, 20 were treated endoscopically and 24 were treated open. There was no significant difference in age of presentation or age of surgery across cohorts when considering type of surgery performed. Rate of endoscopy in the pre-COVID versus COVID cohorts was not significantly different. In both the pre-COVID and COVID cohorts there were significant differences between age of presentation, age of surgery, and type of surgery received based on race-black and Hispanic patients presented later, had surgery later, and underwent open surgery more frequently than their white/Asian counterparts (P = .0095, P = .0067).The pandemic did not alter age of presentation/age of surgery or rates of patients receiving endoscopic surgery in patients with single suture craniosynostosis. There was no relationship between insurance status and type of surgery received during the pandemic, however Hispanic and black patients presented later and underwent surgery at an older age compared to white/Asian patients as they did pre-pandemic.

Impact of health disparities on treatment for single-suture craniosynostosis in an era of multimodal care.

Craniosynostosis is the premature fusion of the skull. There are two forms of treatment: open surgery and minimally invasive endoscope-assisted suturectomy. Candidates for endoscopic treatment are less than 6 months of age. The techniques are equally effective; however, endoscopic surgery is associated with less blood loss, minimal tissue disruption, shorter operative time, and shorter hospitalization. In this study, the authors aimed to evaluate the impact of race/ethnicity and insurance status on age of presentation/surgery in children with craniosynostosis to highlight potential disparities in healthcare access. Charts were reviewed for children with craniosynostosis at two tertiary care hospitals in New York City from January 1, 2014, to August 31, 2020. Clinical and demographic data were collected, including variables pertaining to family socioeconomic status, home address/zip code, insurance status (no insurance, Medicaid, or private), race/ethnicity, age and date of presentation for initial consultation, type of surgery performed, and details of hospitalization. Children with unknown race/ethnicity and those with syndromic craniosynostosis were excluded. The data were analyzed via t-tests and chi-square tests for statistical significance (p < 0.05). A total of 121 children were identified; 62 surgeries were performed open and 59 endoscopically. The mean age at initial presentation of the cohort was 6.68 months, and on the day of surgery it was 8.45 months. Age at presentation for the open surgery cohort compared with the endoscopic cohort achieved statistical significance at 11.33 months (SD 12.41) for the open cohort and 1.86 months (SD 1.1473) for the endoscopic cohort (p < 0.0001). Age on the day of surgery for the open cohort versus the endoscopic cohort demonstrated statistical significance at 14.19 months (SD 15.05) and 2.58 months (SD 1.030), respectively. A statistically significant difference between the two groups was noted with regard to insurance status (p = 0.0044); the open surgical group comprised more patients without insurance and with Medicaid compared with the endoscopic group. The racial composition of the two groups reached statistical significance when comparing proportions of White, Black, Hispanic, Asian, and other (p = 0.000815), with significantly more Black and Hispanic patients treated in the open surgical group. The results demonstrate a relationship between race and lack of insurance or Medicaid status, and type of surgery received; Black and Hispanic children and children with Medicaid were more likely to present later and undergo open surgery.

Increases in female academic productivity and female mentorship highlight sustained progress in previously identified neurosurgical gender disparities.

OBJECTIVE: A meta-analysis was performed to understand disparities in the representation of female authorship within the neurosurgical literature and implications for career advancement of women in neurosurgery. METHODS: Author names for articles published in 16 of the top neurosurgical journals from 2002 to 2019 were obtained from MEDLINE. The gender of each author was determined using automated prediction methods. Publication trends were compared over time and across subdisciplines. Female authorship was also compared to the proportionate composition of women in the field over time. RESULTS: The metadata obtained from 16 major neurosurgical journals yielded 66,546 research articles. Gender was successfully determined for 96% (127,809/133,578) of first and senior authors, while the remainder (3.9%) were unable to be determined through prediction methods. Across all years, 13.3% (8826) of articles had female first authorship and 9.1% (6073) had female senior authorship. Female first authorship increased significantly over time from 5.8% in 2002 to 17.2% in 2019 (p < 0.001). Female senior authorship also increased significantly over time, from 5.5% in 2002 to 12.0% in 2019 (p < 0.001). The journals with the highest proportions of female first authors and senior authors were the Journal of Neurosurgery: Pediatrics (33.5%) and the Asian Journal of Neurosurgery (23.8%), respectively. Operative Neurosurgery had the lowest fraction of female first (12.4%) and senior (4.7%) authors. There was a significant difference between the year-by-year proportion of female neurosurgical trainees and the year-by-year proportion of female neurosurgical first (p < 0.001) and senior (p < 0.001) authors. Articles were also more likely to have a female first author if the senior author of the article was female (OR 2.69, CI 2.52-2.86; p < 0.001). From 1944 to 2019, the Journal of Neurosurgery showed a steady increase in female first and senior authorship, with a plateau beginning in the 1990s. CONCLUSIONS: Large meta-analysis techniques have the potential to effectively leverage large amounts of bibliometric data to quantify the representation of female authorship in the neurosurgical literature. The proportion of female authors in major neurosurgical journals has steadily increased. However, the rate of increase in female senior authorship has lagged behind the rate of increase in first authorship, indicating a disparity in academic advancement in women in neurosurgery.

Analysis of the Sonopet Ultrasonic Bone Aspirator to Traditional Instrumentation for Endoscopic Suturectomy for Craniosynostosis.

OBJECTIVE: The goal of endoscopic treatment for craniosynostosis is to remove the fused suture and achieve calvarial remodeling with external orthosis. To reduce the need for secondary surgery and to minimize blood loss, instruments that maximize bone removal while minimizing blood loss and risk of dural injury are evolving. The authors therefore assess the safety and efficacy of the Sonopet Ultrasonic Bone Aspirator (UBA) (Stryker, Kalamazoo, MI) for endoscopic suturectomy compared to traditional instrumentation at our institution. METHODS: Retrospective chart review of consecutive endoscopic suturectomies performed from 2011 to 2019 at Weill Cornell Medical Center was conducted, including demographics, cephalic index, surgical indications, operative time, cosmetic and functional results, complications, estimated blood loss (EBL), re-operation rate, length of stay, and length of helmet therapy. These variables were then compared between the Sonopet and non-Sonopet cohorts. RESULTS: Of the 60 patients who underwent endoscopic suturectomy, 16 cases (26.7%) utilized the Sonopet. Mean operative time was 2.8 ±â€Š0.4 hours in the Sonopet group, compared to 3.2 ±â€Š1.2 hours (P = 0.05) without the Sonopet. EBL was 17.8 ±â€Š23.9 cc versus 34.7 ±â€Š75.5 cc (P = 0.20) with versus without the Sonopet respectively. Length of stay and duration of helmet therapy were similar in both groups, ranging from 1 to 3 days (P = 0.68) and 7.25 to 12 months (P = 0.30) respectively. There were no reoperations in the Sonopet group with a mean follow up of 9.18 months. There were 3 reoperations in the non-Sonopet group with a mean follow up of 11.3 months. Among the cases utilizing the Sonopet, 13 (81%) were metopic and three (19%) were coronal synostoses. Of the non-Sonopet cases, 27 (61%) were sagittal, 8 (18%) were metopic, 7 (16%) were coronal, and 2 (5%) were lambdoid synostoses. CONCLUSIONS: The use of the Sonopet resulted in a mean decrease in operative time at our institution (P = 0.18). Lower EBL and reoperation rates with comparable LOS and helmet therapy duration were also seen. This modality should be considered a safe and effective adjunct in appropriate endoscopic craniosynostosis cases.

Cavernous malformation hemorrhage due to trans-mural pressure alterations after cerebrospinal fluid diversion: a case report.

BACKGROUND: Cavernous malformations are rare cerebral pseudo-vascular lesions with annualized bleeding rates of 0.5-3% in most studies. Of the various explored risk factors for bleeding to date, only prior hemorrhage has shown significant correlation. CASE PRESENTATION: In this case, we describe a 65-year old man with a peri-ventricular atrial cavernous malformation that hemorrhaged after CSF diversion via ventriculoperitoneal shunting. Serial imaging showed that bleeding continued until the shunt was revised with a programmable valve set at maximum resistance with the addition of a gravitational unit, thereby lowering the trans-mural pressure differential across the cavernous malformation. CONCLUSIONS: Given that other vascular lesions are subject to hemorrhage from alterations in trans-mural pressure dynamics, we hypothesize that cavernous malformations are similarly affected by trans-mural pressure gradients as they are composed of primitive vascular elements. This hypothesis is corroborated by the temporal correlation of interventions, imaging, and exam findings in the present case, and suggests a potentially important risk factor for hemorrhage in CM patients that affects prognostication and management.

Surgical Management of Complex Syndromic Craniosynostosis: Experience With a Rare Genetic Variant.

Patients with syndromic craniosynostosis (CS) can present with both intracranial and extracranial manifestations. Extracranial features include proptosis, exorbitism, and midface hypoplasia. Intracranial manifestations can include elevated intracranial pressure (ICP), brainstem compression, foramen magnum stenosis or jugular foramen hypoplasia with resultant venous hypertension and anomalous drainage. While fronto-orbital advancement, cranial vault remodeling, and posterior fossa decompression are standard surgical approaches to normalizing orbito-cranial volume and morphology, associated hydrocephalus, anomalous venous drainage, and tonsillar herniation often affect the timing, safety, and selection of corrective interventions. The surgical decision-making to circumvent venous emissaries, effectively time treatment of hydrocephalus, and address posterior versus anterior pathology primarily has not been widely described in the literature, and is important in the development of guidelines in these complex cases. In this report, we describe the surgical management of a patient with Jackson-Weiss syndrome presenting with delayed, but rapidly progressive bilateral lambdoid CS, severe proptosis, midface hypoplasia, elevated ICP, hydrocephalus, tonsillar ectopia, and severe venous hypertension with anomalous drainage. We review the literature related to management of complex synostosis and present our surgical decision-making in the setting of complex syndromic synostosis to aid in the formation of guidelines toward approaching these cases.

Impact of a Multidisciplinary Craniofacial Clinic for Patients With Craniofacial Syndromes on Patient Satisfaction and Outcome.

OBJECTIVE: Multidisciplinary clinics are becoming widely utilized. Given the number of patients with craniofacial syndromes evaluated at our institution, and the burden of assessment by multiple subspecialists, we created an American Cleft Palate-Craniofacial Association-certified Craniofacial Multidisciplinary Clinic (CMC) composed of a nurse practitioner, neurosurgeon, plastic surgeon, otolaryngologist, oromaxillofacial surgeon, geneticist, pulmonologist, occupational therapist, dentist, and child life specialist to improve patient experience, lessen the burden of assessment, decrease time to surgery, and improve patients' understanding of the diagnosis and treatment plan specifically for patients with complex craniofacial syndromes. We reviewed the impact of this clinic after 1 year of implementation. DESIGN: Retrospective review was performed to identify patients with craniofacial syndromic diagnoses seen by the neurosurgery department before and after implementation of the CMC from February 2017 to present. SETTING: The CMC is an outpatient clinic based in a tertiary care academic institution. PATIENTS: Chart review was performed to identify demographic, diagnostic, clinical, and treatment data. We assessed clinic experience, and the impact on quality of clinical and surgical care was assessed via survey. We compared this cohort to patients with similar craniofacial syndromes treated prior to the CMC. Thirty patients seen at the CMC were identified, and data from a comparable cohort of 30 patients seen prior to the clinic's inception was reviewed. RESULTS: Our CMC survey response rate was 67% (n = 20/30) for the CMC patients. Second opinions sought by parents prior to CMC was higher (mean = 0.85, range: 0-3) than for patients seen at the CMC (mean = 0.16, range: 0-1). Mean time to surgery before the CMC was 10.1 months (range: 1-15) compared to 4 months (range: 3-5) after implementation. Parents agreed that they felt well-informed about their diagnosis (n = 18/20, 90%), and that the presence of a plastic surgeon (19/20, 95%) and a nurse practitioner (17/20, 85%) were valuable in coordination of their care. Following surgery, 76% (n = 13/17) of patients who received surgery were happy with the outcome, 76% (n = 13/17) were happy with the appearance of the scar, and 95% (n = 19/20) would recommend the CMC to others. CONCLUSION: Multidisciplinary evaluation of patients with complex craniofacial conditions provides comprehensive, efficient, and effective care, as well as improved parent satisfaction and knowledge base.

Rapidly Progressive Multisutural Craniosynostosis in a Patient With Jackson-Weiss Syndrome and a De Novo FGFR2 Pathogenic Variant.

Little is currently known about the mechanisms by which pathogenic variants of FGFR2 produce changes in the FGFR protein and influence the clinical presentation of affected individuals. We report on a patient with a de novo pathogenic variant of FGFR2 and a phenotype consistent with Jackson-Weiss syndrome who presented with delayed, rapidly progressive multisutural craniosynostosis and associated medical complications. Using 3-dimensional modeling of the FGFR protein, we provide evidence that this variant resulted in abnormal dimerization and constitutive activation of FGFR, leading to the Jackson-Weiss phenotype. Knowledge regarding the correlation between genotype and phenotype of persons with FGFR2-related craniosynostosis has the potential to allow for anticipation of medical complications, institution of early treatment, and improved clinical outcomes.

Pre-operative embolization of a choroid plexus carcinoma: review of the vascular anatomy.

AIM: The purpose of this case is to highlight the benefits of preoperative embolization as well as to review the vascular anatomy that needs to be recognized in order to perform pre-operative embolization of choroid plexus tumors. METHOD: We achieve this by presenting the case of a 12-month-old female who had symptoms of raised intracranial pressure. MRI demonstrated a large vividly enhancing mass centered within the atria of the right lateral ventricle associated with hydrocephalus in keeping with a choroid plexus tumor. RESULT: Enlarged anterior and posterior choroidal arteries supplying the tumor were noted on the MRI scan. Pre-operative embolization was performed with NBCA glue via the anterior and posterior choroidal arteries. Subsequently, total surgical resection was achieved with only 200 cc of blood loss. Pathology confirmed a choroid plexus carcinoma. CONCLUSION: Pre-operative embolization can be useful in minimizing blood loss during excision of choroid plexus tumors. It is important to understand the anatomy of the anterior and posterior choroidal arteries to perform embolization of these tumors safely.

Rasmussen's encephalitis: advances in management and patient outcomes.

PURPOSE: Rasmussen's encephalitis (RE) is a hemispheric inflammatory disorder resulting in progressive epilepsy, hemiparesis, and cognitive decline. Controversy surrounds the most effective timing of surgery with respect to language dominance, functional status, and seizure outcome. We describe our experience with RE to inform treatment decisions. METHODS: A retrospective chart review was performed in children diagnosed with RE from 1983 to 2012. RESULTS: Thirteen consecutive cases were identified: six males and seven females with a mean age of 10.6 years (range 5-18). Nine patients received immunotherapy, with transient benefit in three, treatment-associated complications in two, and no difference in their mean time to treatment (5.38 vs 6.37 years p = 0.74) or long-term outcome. Mean follow-up was 5.6 years (range 0.58-12.25). There was no difference in outcome based on pre-operative duration of seizures. At last follow-up, 63 % of surgically treated patients achieved seizure freedom, 100 % had improved seizure control, 90 % had improved cognitive function, 36 % stopped medication, and 63 % tapered medication. Language improved in 83 % of patients with dominant disease. These findings were not associated with age at treatment. All surgical patients were ambulatory at last follow-up. CONCLUSIONS: Hemispherotomy achieves good seizure control with cognitive improvement and ambulatory status post-operatively. Time to surgery and dominant disease were not associated with outcome, suggesting that hemispherotomy can be offered early or late, with expectations of good seizure control and functional outcome, even with dominant disease.

Medulloblastoma subgroups remain stable across primary and metastatic compartments.

Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.

The Role of Virtual Surgical Planning in Surgery for Complex Craniosynostosis.

Background: Virtual surgical planning (VSP) decreases reliance on intraoperative subjective assessment of aesthetic and functional outcomes in craniofacial surgery. Here, we describe our experience of using VSP for complex craniosynostosis surgery to inform preoperative decision making and optimize postoperative outcomes. Methods: Chart review was performed for children treated with craniosynostosis at our institution from 2015 to 2021. Eight VSP maneuvers were defined and assigned to each patient when applicable: (1) complex cranioplasty: combined autologous and synthetic; (2) autologous cranioplasty; (3) synthetic cranioplasty; (4) vector analysis and distractor placement; (5) complex osteotomies; (6) multilayered intraoperative plans; (7) volume analysis; and (8) communication with parents. Outcomes between VSP and non-VSP cohorts were compared. Results: Of 166 total cases, 32 were considered complex, defined by multisutural craniosynostosis, syndromic craniosynostosis, or revision status. Of these complex cases, 20 underwent VSP and 12 did not. There was no difference in mean operative time between the VSP and non-VSP groups (541 versus 532 min, P = 0.82) or in unexpected return to operating room (10.5% versus 8.3%, P = 0.84). VSP was most often used to communicate the surgical plan with parents (90%) and plan complex osteotomies (85%). Conclusions: In this cohort, VSP was most often used to communicate the surgical plan with families and plan complex osteotomies. Our results indicate that VSP may improve intraoperative efficiency and safety for complex craniosynostosis surgery. This tool can be considered a useful adjunct to plan and guide intraoperative decisions in complex cases, reducing variability and guiding parental expectations.