Evaluating the potential role of determinants of health on encephalocele patient outcomes - a combined retrospective study and systematic review.

INTRODUCTION: To evaluate the outcomes and demographics of encephalocele patients who were born and received treatment in our neonatal ICU and conduct a PRISMA literature review. METHODS: An Institutional Review Board (IRB)-approved retrospective cohort study was undertaken to investigate the results of treating encephalocele patients at Jackson Memorial Hospital (JMH) from 1998 to 2022. The study focused on assessing outcomes and the impact of maternal socioeconomic factors, such as religion, age, and education, along with the timing of diagnosis, in connection with a systematic review. RESULTS: A total of 20 encephalocele patients were identified (13 females and 7 males), with 15 having available medical records for review. Most of these cases involved occipital encephaloceles (73.3%). Maternal ages at the time of delivery ranged from 15 to 42 years, with a mean age of 27.3 years. The average gestational age at birth was 37 weeks. Ten cases had a prenatal diagnosis documented, occurring between 12 and 24.5 weeks of gestation. Three of the surviving patients had records of prenatal counseling that included discussions about termination. No infections were reported. Among the 15 cases, 11 patients (73.3%) were alive at the last follow-up, with a mean age at follow-up of 4.12 years, ranging from 6 weeks to 15 years post-birth. Hydrocephalus was noted in 26.7%. Only 1 mother had completed high school. Most mothers were either on Medicaid (9 patients) or uninsured (3 patients), with only 3 having commercial insurance. Religious affiliations varied among the mothers, with 14 out of 15 identifying with a particular religion. The systematic review identified 22 articles from various countries, with 11 articles meeting the inclusion criteria for qualitative analysis. These articles revealed potential maternal risk factors for encephaloceles, including low-nutrient diets, inadequate folic acid intake, young maternal age, advanced maternal age, low socioeconomic status, and limited educational attainment. CONCLUSIONS: In the twenty-first century, there is a positive trend in the survival rates of children born with encephalocele. However, maternal factors such as low socioeconomic status and limited educational attainment remain prominent, affecting their ability to access timely prenatal care and impacting follow-up medical care for these children.

Myc and Loss of p53 Cooperate to Drive Formation of Choroid Plexus Carcinoma.

Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the Myc oncogene and deleting the Trp53 tumor suppressor gene in murine neural stem cells or progenitors. Murine CPC resembled their human counterparts at a histologic level, and like the hypodiploid subset of human CPC, exhibited multiple whole-chromosome losses, particularly of chromosomes 8, 12, and 19. Analysis of murine and human CPC gene expression profiles and copy number changes revealed altered expression of genes involved in cell cycle, DNA damage response, and cilium function. High-throughput drug screening identified small molecule inhibitors that decreased the viability of CPC. These models will be valuable tools for understanding the biology of choroid plexus tumors and for testing novel approaches to therapy. SIGNIFICANCE: This study describes new mouse models of choroid plexus carcinoma and uses them to investigate the biology and therapeutic responsiveness of this highly malignant pediatric brain tumor.

Presentation and outcomes in surgically and conservatively managed pediatric Rathke cleft cysts.

OBJECTIVE Rathke cleft cysts (RCCs) are sellar lesions that are commonly encountered in adults but infrequently diagnosed in the pediatric population. As a result, the optimal management of pediatric RCCs remains a subject of controversy. Only 2 prior surgical series have been published on pediatric RCCs and no study has compared the presentation and outcomes of surgically versus conservatively managed cases. The authors therefore performed a comparative analysis of pediatric cases of RCC in which patients were treated with surgery or managed in a conservative manner. METHODS All cases involving pediatric patients diagnosed with an RCC at the University of Virginia between 2000 and 2016 were included in this study. Patient medical records, operative notes, and neuroimaging findings were reviewed. Patients who developed visual field deficits, radiographic evidence of chiasmal compression, or medically refractory headaches were considered candidates for surgical intervention. All patients who were selected for surgery underwent an endoscopic endonasal approach with cyst fenestration. RESULTS A total of 24 pediatric patients were diagnosed with an RCC over a 16-year period. Seven patients ultimately underwent transsphenoidal cyst fenestration, and 17 were managed conservatively. The patients' age at diagnosis, cyst size, and pituitary function at the time of RCC diagnosis were similar in the conservatively and surgically managed cohorts. At diagnosis, 19 of 24 patients endorsed headaches that led to neuroimaging. All patients in the surgical cohort endorsed severe headaches at diagnosis compared with 71% in the conservative group. For the 7 patients treated with surgery, complete cyst evacuation was achieved in 86% of cases. Transient postoperative endocrinopathy occurred in 4 (57%) of 7 surgically treated individuals and resolved in all cases. In the conservative cohort, 1 patient developed a delayed pituitary-related endocrinopathy. Headache resolution occurred in 5 (71%) of the 7 patients who underwent surgery and 7 (58%) of the 12 who were treated without surgery. Cyst recurrence was documented in 1 individual in the surgical cohort who underwent a subtotal cyst fenestration that ultimately required re-intervention. In the conservative cohort, spontaneous cyst shrinkage occurred in 35% of patients with a median time to regression of 23.5 months. CONCLUSIONS Pediatric RCCs are benign sellar lesions that often present with headaches. While cyst fenestration mitigates headaches in most patients, the majority of conservatively managed pediatric patients with RCCs will have spontaneous headache resolution. Furthermore, spontaneous RCC regression occurs in a substantial number of individuals. Thus, in the absence of optic compression, visual field deficit, or diagnostic uncertainty, many pediatric cases of RCC can be managed conservatively.

Novel GOPC(FIG)-ROS1 fusion in a pediatric high-grade glioma survivor.

Pediatric high-grade glioma is a rare tumor characterized by high mortality. The authors report the first case of a high-grade glioma associated with a GOPC(FIG)-ROS1 fusion in a pediatric patient. The patient underwent gross-total resection at the age of 4 years, followed by adjuvant high-dose chemotherapy and autologous hematopoietic stem cell rescue. At 30 months after transplantation, she remains disease free.

Spatial heterogeneity in medulloblastoma.

Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.

A quantitative analysis of craniopharyngioma cyst expansion during and after radiation therapy and surgical implications.

OBJECTIVE When complete resection of craniopharyngioma is not achievable or the sequelae are prohibitive, limited surgery and radiation therapy have demonstrated excellent local disease control while minimizing treatment-related sequelae. When residual tissue exists, there is a propensity for further cyst development and expansion during and after radiation therapy. This can result in obstructive hydrocephalus, visual changes, and/or clinical decline. The authors present a quantitative analysis of cyst expansion during and after radiotherapy and examine how it affected subsequent management. METHODS The authors performed an institutional review board-approved retrospective study of patients with histologically confirmed craniopharyngioma treated between 2000 and 2015 with surgery and intensity-modulated radiation therapy (IMRT) at a single institution. Volumetric measurements of cyst contours were generated by radiation oncology treatment planning software postoperatively, during IMRT, and up to 12 months after IMRT. Patient, tumor, and treatment-related variables were collected until the last known follow-up and were analyzed. RESULTS Twenty-seven patients underwent surgery and IMRT. The median total radiation dose was 54 Gy. Of the 27 patients, 11 patients (40.7%) demonstrated cyst expansions within 1 year of IMRT. Of note, all tumors with cyst expansion were radiographically Puget Grade 2. Maximal cyst expansion peaked at 4.27 months following radiation therapy, with a median volume growth of 4.1 cm3 (mean 9.61 cm3) above the postoperative cyst volume. Eight patients experienced spontaneous cyst regression without therapeutic intervention. Three patients experienced MRI-confirmed cyst enlargement during IMRT, all of whom required adaptive planning to ensure adequate coverage of the entire tumor volume. Two of these 3 patients required ventriculoperitoneal shunt placement and additional intervention. One underwent additional resection, and the other had placement of an intracystic catheter for aspiration and delivery of intracystic interferon within 12 months of completing IMRT. All 3 patients now have stable disease. CONCLUSIONS Craniopharyngioma cyst expansion occurred in approximately 40% of the patients during or after radiotherapy. In the majority of patients, cyst expansion was a self-limiting process and did not confer a worse outcome. During radiotherapy, cyst expansion may be apparent on image-guided radiation therapy. Adaptive IMRT planning may be required to ensure that the intended IMRT dose covers the entire tumor and cyst volume. The sequelae of cyst expansion include progressive hydrocephalus, which may be treated with a shunt. For patients with solitary cyst expansion, cyst aspiration and/or intracystic interferon may result in disease control.

Reevaluating the weekend effect on patients with hydrocephalus undergoing operative shunt intervention.

OBJECT Recently published data have suggested an increase in adverse outcomes in pediatric patients after insertion or revision of a ventricular CSF diversion shunt after a same-day weekend procedure. The authors undertook an evaluation of the impact of weekend admission and time to shunting on surgery-related quality outcomes in pediatric patients who underwent ventricular shunt insertion or revision. METHODS Pediatric patients with hydrocephalus who underwent ventriculoperitoneal, ventriculoatrial, or ventriculopleural shunt placement were selected from the 2000-2010 Nationwide Inpatient Sample and Kids' Inpatient Database. Multivariate regression analyses (adjusted for patient, hospital, case severity, and time to shunting) were used to determine the differences in inpatient mortality and routine discharge rates among patients admitted on a weekday versus those among patients admitted on a weekend. RESULTS There were 99,472 pediatric patients with shunted hydrocephalus, 16% of whom were admitted on a weekend. After adjustment for disease severity, time to procedure, and admission acuity, weekend admission was not associated with an increase in the inpatient mortality rate (p = 0.46) or a change in the percentage of routine discharges (p = 0.98) after ventricular shunt procedures. In addition, associations were unchanged after an evaluation of patients who underwent shunt revision surgery. High-volume centers were incidentally noted in multivariate analysis to have increased rates of routine discharge (OR 1.04 [95% CI 1.01-1.07]; p = 0.02). CONCLUSIONS Contrary to those of previous studies, the authors' data suggest that weekend admission is not associated with poorer outcomes for ventricular shunt insertion or revision. Increased rates of routine discharge were noted at high-volume centers.

Utility of diffusion tensor imaging studies linked to neuronavigation and other modalities in repeat hemispherotomy for intractable epilepsy.

OBJECT Hemispherectomy for unilateral, medically refractory epilepsy is associated with excellent long-term seizure control. However, for patients with recurrent seizures following disconnection, workup and investigation can be challenging, and surgical options may be limited. Few studies have examined the role of repeat hemispherotomy in these patients. The authors hypothesized that residual fiber connections between the hemispheres could be the underlying cause of recurrent epilepsy in these patients. Diffusion tensor imaging (DTI) was used to test this hypothesis, and to target residual connections at reoperation using neuronavigation. METHODS The authors identified 8 patients with recurrent seizures following hemispherectomy who underwent surgery between 1995 and 2012. Prolonged video electroencephalography recordings documented persistent seizures arising from the affected hemisphere. In all patients, DTI demonstrated residual white matter association fibers connecting the hemispheres. A repeat craniotomy and neuronavigation-guided targeted disconnection of these residual fibers was performed. Engel class was used to determine outcome after surgery at a minimum of 2 years of follow-up. RESULTS Two patients underwent initial hemidecortication and 6 had periinsular hemispherotomy as their first procedures at a median age of 9.7 months. Initial pathologies included hemimegalencephaly (n = 4), multilobar cortical dysplasia (n = 3), and Rasmussen's encephalitis (n = 1). The mean duration of seizure freedom for the group after the initial procedure was 32.5 months (range 6-77 months). In all patients, DTI showed limited but definite residual connections between the 2 hemispheres, primarily across the rostrum/genu of the corpus callosum. The median age at reoperation was 6.8 years (range 1.3-14 years). The average time taken for reoperation was 3 hours (range 1.8-4.3 hours), with a mean blood loss of 150 ml (range 50-250 ml). One patient required a blood transfusion. Five patients are seizure free, and the remaining 3 patients are Engel Class II, with a minimum follow-up of 24 months for the group. CONCLUSIONS Repeat hemispherotomy is an option for consideration in patients with recurrent intractable epilepsy following failed surgery for catastrophic epilepsy. In conjunction with other modalities to establish seizure onset zones, advanced MRI and DTI sequences may be of value in identifying patients with residual connectivity between the affected and unaffected hemispheres. Targeted disconnection of these residual areas of connectivity using neuronavigation may result in improved seizure outcomes, with minimal and acceptable morbidity.

Surgical management of large scalp infantile hemangiomas.

BACKGROUND: Infantile Hemangiomas (IH) are the most common benign tumor of infancy, occurring in over 10% of newborns. While most IHs involute and never require intervention, some scalp IHs may cause severe cosmetic deformity and threaten tissue integrity that requires surgical excision. CASE DESCRIPTION: We present our experience with two infants who presented with large scalp IH. After vascular imaging, the patients underwent surgical resection of the IH and primary wound closure with excellent cosmetic outcome. We detail the surgical management of these cases and review the relevant literature. CONCLUSION: In some cases the IHs leave behind fibro-fatty residuum causing contour deformity. Surgery is often required for very large lesions causing extensive anatomical and/or functional disruption. The goal of surgical intervention is to restore normal anatomic contour and shape while minimizing the size of the permanent scar.

Use of the intrathoracic pressure regulator to lower intracranial pressure in patients with altered intracranial elastance: a pilot study.

OBJECT: The intrathoracic pressure regulator (ITPR) is a novel noninvasive device designed to increase circulation and blood pressure. By applying negative pressure during the expiratory phase of ventilation it decreases intrathoracic pressure and enhances venous return, which increases cardiac output. It is possible that the ITPR may both decrease intracranial pressure (ICP) and increase cerebral perfusion pressure (CPP) in brain-injured patients by decreasing cerebral venous blood volume and increasing cardiac output. The authors conducted an open-label, "first-in-humans" study of the ITPR in patients with an ICP monitor or external ventricular drain and altered intracranial elastance. METHODS: This prospective randomized trial commenced July 2009. Baseline hemodynamic variables and ICP were recorded prior to inserting one of the two ITPRs into the ventilator circuit based on a randomization scheme. Depending on the device selected, activation provided either -5 or -9 mm Hg endotracheal tube pressure. Hemodynamic and ICP data were recorded sequentially every 2 minutes for 10 minutes. The first device was turned off for 10 minutes, then it was removed and the second device was applied, and then the procedure was repeated for the second device. RESULTS: Ten patients with elevated ICP secondary to intracranial hemorrhage (n = 4), trauma (n = 2), obstructive hydrocephalus (n = 2), or diffuse cerebral processes (n = 2) were enrolled. Baseline ICP ranged from 12 to 38 mm Hg. With device application, a decrease in ICP was observed in 16 of 20 applications. During treatment with the -5 mm Hg device, there was a mean maximal decrease of 3.3 mm Hg in ICP (21.7 vs 18.4 mm Hg, p = 0.003), which was associated with an increase in CPP of 6.5 mm Hg (58.2 vs 64.7 mm Hg, p = 0.019). During treatment with the -9 mm Hg device, there was a mean maximal decrease of 2.4 mm Hg in ICP (21.1 vs 18.7 mm Hg, p = 0.044), which was associated with an increase in CPP of 6.5 mm Hg (59.2 vs 65.7 mm Hg, p = 0.001). CONCLUSIONS: This pilot study demonstrates that use of the ITPR in patients with altered intracranial elastance is feasible. Although this study was not powered to demonstrate efficacy, these data strongly suggest that the ITPR may be used to rapidly lower ICP and increase CPP without apparent adverse effects. Additional studies will be needed to assess longitudinal changes in ICP when the device is in use and to delineate treatment parameters.

Visual outcomes in pediatric optic pathway glioma after conformal radiation therapy.

PURPOSE: To assess visual outcome prospectively after conformal radiation therapy (CRT) in children with optic pathway glioma. METHODS AND MATERIALS: We used CRT to treat optic pathway glioma in 20 children (median age 9.3 years) between July 1997 and January 2002. We assessed changes in visual acuity using the logarithm of the minimal angle of resolution after CRT (54 Gy) with a median follow-up of 24 months. We included in the study children who underwent chemotherapy (8 patients) or resection (9 patients) before CRT. RESULTS: Surgery played a major role in determining baseline (pre-CRT) visual acuity (better eye: P=.0431; worse eye: P=.0032). The visual acuity in the worse eye was diminished at baseline (borderline significant) with administration of chemotherapy before CRT (P=.0726) and progression of disease prior to receiving CRT (P=.0220). In the worse eye, improvement in visual acuity was observed in patients who did not receive chemotherapy before CRT (P=.0289). CONCLUSIONS: Children with optic pathway glioma initially treated with chemotherapy prior to receiving radiation therapy have decreased visual acuity compared with those who receive primary radiation therapy. Limited surgery before radiation therapy may have a role in preserving visual acuity.

Standards for reporting randomized controlled trials in neurosurgery.

OBJECT: The Consolidated Standards for Reporting of Trials (CONSORT) criteria were published in 1996 to standardize the reporting and improve the quality of clinical trials. Despite having been endorsed by major medical journals and shown to improve the quality of reported trials, neurosurgical journals have yet to formally adopt these reporting criteria. The purpose of this study is to evaluate the quality and reporting of randomized controlled trials (RCTs) in neurosurgery and the factors that may affect the quality of reported trials. METHODS: The authors evaluated all neurosurgical RCTs published in 2006 and 2007 in the principal neurosurgical journals (Journal of Neurosurgery; Neurosurgery; Surgical Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; and Acta Neurochirurgica) and in 3 leading general medical journals (Journal of the American Medical Association, Lancet, and the New England Journal of Medicine). Randomized controlled trials that addressed operative decision making or the treatment of neurosurgical patients were included in this analysis. The RCT quality was evaluated using the Jadad score and the CONSORT checklist. RESULTS: In 2006 and 2007, 27 RCTs relevant to intracranial neurosurgery were reported. Of these trials, only 59% had a Jadad score ≥ 3. The 3 major medical journals all endorsed the CONSORT guidelines, while none of the neurosurgical journals have adopted these guidelines. Randomized controlled trials published in the 3 major medical journals had a significantly higher mean CONSORT score (mean 41, range 39-44) compared with those published in neurosurgical journals (mean 26.4, range 17-38; p < 0.0001). Jadad scores were also significantly higher for the major medical journals (mean 3.42, range 2-5) than neurosurgical journals (mean 2.45, range 1-5; p = 0.05). CONCLUSIONS: Despite the growing volume of RCTs in neurosurgery, the quality of reporting of these trials remains suboptimal, especially in the neurosurgical journals. Improved awareness of the CONSORT guidelines by journal editors, reviewers, and authors of these papers could improve the methodology and reporting of RCTs in neurosurgery.

Conservative management of an acute spontaneous holocord epidural hemorrhage in a hemophiliac infant.

Central nervous system hemorrhages are an uncommon but severe complication of hemophilia, occurring in only 2-8% of children with hemophilia. Less than 10% of these CNS hemorrhages are intraspinal. The authors report on their care of an infant with hemophilia A who presented with irritability, meningismus, and decreased spontaneous movement. These symptoms prompted imaging studies, which revealed a spinal epidural hematoma (SEH) extending from C-1 through the cauda equina. The boy was treated with factor replacement and close monitoring. Repeat radiographic imaging 14 days later demonstrated complete resolution, and the patient had returned to his normal baseline status. A literature review in the modern treatment era revealed 24 cases of SEH in children with hemophilia. Of these 24 cases, 11 underwent laminectomy and 13 received conservative treatment. All conservatively treated patients, 5 of whom had presented with weakness, experienced a full recovery. Of the 11 laminectomy patients, 10 presented with weakness and all but 3 experienced full neurological improvement. These 3 patients were notable for having previously undiagnosed hemophilia. An increased index of suspicion facilitates the essential management features of prompt diagnosis and correction of coagulopathies in children who present with SEHs. The authors apply a multidisciplinary approach involving a pediatric hematologist, neurosurgeon, and pediatric intensive care unit to ensure timely correction of the coagulation disorder, maintenance of adequate factor levels, and close hemodynamic and neurological monitoring. Observation with aggressive correction of coagulopathy is a reasonable treatment choice for hemophilic patients presenting with SEH and a stable neurological examination.

Radiation therapy for pediatric craniopharyngioma.

OBJECT: The treatment of craniopharyngioma is highly controversial. Continued advances in limited surgery and radiation therapy have maintained excellent local disease control while minimizing treatment-related sequelae. Further analyses of outcomes are necessary to characterize the long-term effects of radiation therapy. METHODS: An extensive literature review was performed for all studies including radiation therapy, with or without surgery, for pediatric craniopharyngioma. RESULTS: The authors identified 32 papers describing radiation therapy for treatment of pediatric craniopharyngioma, with disease control ranging from 44 to 100%. Modern studies report at least 90% disease control with 5-year follow-up. Fifteen studies reported outcomes, demonstrating that more than two-thirds of patients treated with surgery and radiation therapy have favorable outcomes, and this rate is more than 85% in the modern era. CONCLUSIONS: Conservative surgery and radiation therapy results in long-term disease control in pediatric patients with craniopharyngioma that is comparable to results obtained with radical surgery alone. However, children with craniopharyngioma remain vulnerable to late treatment failures and side effects from radiation therapy, including endocrinopathies, vasculopathies, and secondary tumors, which may be detrimental to the quality of life. Long-term follow-up beyond 5-10 years is necessary to assess tumor control relative to functional outcomes.

Pseudotumor cerebri after surgical remission of Cushing's disease.

CONTEXT: Pseudotumor cerebri has only been described after successful surgery for Cushing's disease (CD) in case reports. We sought to establish the incidence and timing of its occurrence, identify predisposing factors, characterize the clinical presentations and their severity, and examine the effects of treatment in patients who underwent surgery for CD. SETTING: This study was conducted at two tertiary care centers: The University of Virginia and the National Institutes of Health. PATIENTS: We conducted a retrospective review of 941 surgeries for CD (723 adults, 218 children) to identify patients who developed pseudotumor cerebri after surgery for CD and examine the associated clinical features. RESULTS: Seven children (four males, three females; 3%), but no adults, developed pseudotumor cerebri postoperatively. All underwent resection of an ACTH-secreting adenoma, and postoperative serum cortisol reached a nadir of less than 2 microg/dl. After surgery, all were placed on tapering hydrocortisone replacement therapy. Within 3-52 wk, all seven patients experienced symptoms of pseudotumor cerebri and had ophthalmological examination demonstrating papilledema. One patient had diplopia from a unilateral VIth nerve palsy. Six patients were still on steroid replacement at onset of symptoms. In three patients, a lumbar puncture demonstrated elevated opening pressure. Four patients were treated successfully with a lumbar puncture, steroids, and/or Diamox. Three patients did not receive treatment, and their symptoms resolved over several months. There was no correlation between the degree of hypercortisolism (24-h urinary free cortisol) before surgery and the likelihood of developing pseudotumor cerebri after surgery (P < 0.23). CONCLUSIONS: This series demonstrates a 3% occurrence of pseudotumor cerebri in children after successful surgery for CD, but the absence of the syndrome in adults. Pseudotumor cerebri manifests itself within 1 yr of surgery, often while patients are still undergoing replacement steroid therapy. A patient exhibiting signs of intracranial hypertension after surgery for CD should undergo an evaluation for pseudotumor cerebri. Recognition of the symptoms and treatment should correct and/or prevent ophthalmological sequelae.