Stephanie Greene

Meningiomas in children and adolescents: a meta-analysis of individual patient data

BACKGROUND The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma. METHODS Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models. FINDINGS From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0·16, 95% CI 0·10-0·25; p<0·0001) and overall survival (0·21, 0·11-0·39; p<0·0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0·59, 0·30-1·16; p=0·128) or overall survival (1·10, 0·53-2·28; p=0·791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2·36, 1·23-4·51; p=0·010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1·45, 1·09-1·92; p=0·011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3·90, 2·10-7·26; p<0·0001) and grade II tumours (2·49, 1·11-5·56; p=0·027). INTERPRETATION Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow-up. FUNDING None.

Meningiomas in Children

Objective: Pediatric meningioma is a rare diagnosis. This retrospective review seeks to elucidate pertinent characteristics of pediatric patients presenting with meningioma. Methods: The Seattle Children’s Hospital and Regional Medical Center brain tumor database was surveyed from 1940 through 2004. Twenty patients were identified. Results: The median age of the 20 patients was 13 years. Five patients had radiation-induced meningiomas. Five patients had neurofibromatosis type 2. Ten patients had spontaneously arising meningiomas, 2 of which were malignant. Conclusion: Patients with spontaneously arising meningiomas were younger than those with identified risk factors. There was no recurrence in patients with radiation-induced meningiomas. The only death occurred in a patient with a malignant meningioma.

The impact of attention deficit hyperactivity disorder on recovery from mild traumatic brain injury

OBJECT Attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) are significant independent public health concerns in the pediatric population. This study explores the impact of a premorbid diagnosis of ADHD on outcome following mild TBI. METHODS The charts of all patients with a diagnosis of mild closed head injury (CHI) and ADHD who were admitted to Childrens Hospital of Pittsburgh between January 2003 and December 2010 were retrospectively reviewed after institutional review board approval was granted. Patient demographics, initial Glasgow Coma Scale (GCS) score, hospital course, and Kings Outcome Scale for Childhood Head Injury (KOSCHI) score were recorded. The results were compared with a sample of age-matched controls admitted with a diagnosis of CHI without ADHD. RESULTS Forty-eight patients with mild CHI and ADHD, and 45 patients with mild CHI without ADHD were included in the statistical analysis. Mild TBI due to CHI was defined as an initial GCS score of 13-15. The ADHD group had a mean age of 12.2 years (range 6-17 years), and the control group had a mean age of 11.14 years (range 5-16 years). For patients with mild TBI who had ADHD, 25% were moderately disabled (KOSCHI Score 4b), and 56% had completely recovered (KOSCHI Score 5b) at follow-up. For patients with mild TBI without ADHD, 2% were moderately disabled and 84% had completely recovered at follow-up (p < 0.01). Patients with ADHD were statistically significantly more disabled after mild TBI than were control patients without ADHD, even when controlling for age, sex, initial GCS score, hospital length of stay, length of follow-up, mechanism of injury, and presence of other (extracranial) injury. CONCLUSIONS Patients who sustain mild TBIs in the setting of a premorbid diagnosis of ADHD are more likely to be moderately disabled by the injury than are patients without ADHD.

The development of Moyamoya syndrome after proton beam therapy.

The development of Moyamoya syndrome (MMS) after cranial irradiation for pediatric tumors has been well established. However, information on the development of MMS after proton beam radiotherapy is sparse. We present the case of a 2‐year‐old child who developed radiation‐induced MMS after treatment with proton beam therapy. Pediatr Blood Cancer 2014; 61:1490–1492.

Fetal Therapy for Isolated Aqueductal Stenosis.

Aqueductal stenosis (AS) is a form of noncommunicating hydrocephalus, which causes increased intracranial pressure secondary to obstruction of the aqueduct of Sylvius. Relief of intracranial pressure in the fetus by ventriculoamniotic shunting may diminish or even prevent permanent neurologic injury. Shunting was attempted in the 1980s but was abandoned due to technical difficulties. Given the advances in prenatal diagnosis and fetal intervention over the last 3 decades, we believe that an evidence-based reevaluation of the option is timely and appropriate. The aim of this review article is to discuss the clinical significance of the diagnosis of AS, current management strategies, current diagnostic capabilities, new shunt technology, and barriers to progress. Finally, we will advance a research agenda that will provide evidence-based management recommendations.

Is Postoperative CT Scanning Predictive of Subdural Electrode Placement Complications in Pediatric Epileptic Patients

Aims: To understand the reliability of postoperative CT scans to predict the development of intracranial hemorrhagic complications associated with subdural electrode implants for monitoring intractable seizure, we reviewed the data of a consecutive series of children treated at our institution. Methods: Forty children (mean age: 11.4 years) with subdural electrode implants were reviewed. The immediate postoperative CT scans were evaluated for the presence of hemorrhagic complications and/or brain swelling resulting in a midline shift. Results: Twenty-six patients (65%) presented a postoperative midline shift (range = 2–10 mm; mean shift = 4.0 mm). Two children had a midline shift of >5 mm. Two patients with a shift of <5 mm at the first CT scan required a repeat craniotomy. These patients experienced worsening neurologic symptoms in a delayed fashion on postoperative days 1 and 4, respectively. This was correlated to an increase in midline shift of >5 mm. Conclusions: Subdural electrode implants in children are safe. The presence of a midline shift of <5 mm is common postoperatively. The presence and extension of the midline shift at the first CT scan does not seem to be predictive of the development of symptomatic complications with a mass effect. Complications happened in a delayed fashion.

The impact of mode of delivery on infant neurologic outcomes in myelomeningocele

BACKGROUND Controversy exists regarding the optimal route of delivery for fetuses who are diagnosed prenatally with myelomeningocele. Current recommendations are based partly on antiquated studies with questionable methods. All studies that have been published to date suffer from nonstandardized outcome measures, selection bias, and small sample size. The larger studies are >15 years old. OBJECTIVE The purpose of this study was to provide information for evidence-based decision-making regarding the impact of route of delivery on motor outcomes for pediatric patients with prenatally were diagnosed myelomeningocele in a well-defined retrospective cohort. STUDY DESIGN Medical records were reviewed retrospectively for all neonates who had been diagnosed with a myelomeningocele at birth from 1995-2015 within the University of Pittsburgh Medical Center system, as identified through the Childrens Hospital of Pittsburgh Neurosurgery Department operative database. Records were matched with maternal records with the use of the Center for Assistance in Research that used eRecord. Data from 72 maternal-neonatal pairs were analyzed for multiple variables. The primary outcome measure was the difference between the functional and anatomic motor levels in the child at the age of 2 years, stratified by mode of delivery and presence or absence of labor. The sample size necessary to detect a difference between the groups with power of 0.8 and significance of .05 was calculated to be 52 subjects total (26 per group). RESULTS Functional levels were slightly better than predicted by anatomic levels for all pediatric patient groups, regardless of mode of delivery or presence of labor. Anatomic levels were slightly lower (better), and defects were smaller for those infants who underwent vaginal delivery or a trial of labor, likely attributable to selection bias. Attempts to correct for this selection bias did not change the results. No other outcomes that were analyzed were associated significantly with mode of delivery or presence of labor. CONCLUSION No benefit to motor function from delivery by cesarean section or avoidance of labor was demonstrated statistically in this mother-infant cohort.

Neurocutaneous melanosis is associated with tethered spinal cord.

PurposeNeurocutaneous melanosis (NCM) is a rare congenital disorder occurring in children born with multiple or large congenital melanocytic nevi (CMN) in association with melanocytic deposits in the leptomeninges. Multiple associations between NCM and other syndromes or neurologic abnormalities have been reported. Of note, there exists a possible association between NCM and tethered cord (TC).MethodsWe retrospectively reviewed charts and films of all patients with the diagnosis of NCM at the Children’s Hospital of Pittsburgh (CHP) from August 2002 to present.ResultsFive children met the criteria for NCM at our institution over a 12-year period. Apart from the melanocytic deposits, one or more additional spinal abnormalities were identified in all children. Three children had radiographic evidence of a low-lying conus medullaris, two of which also demonstrated lipomatous infiltration of the filum terminale, consistent with a tethered cord (TC).ConclusionsClinical features of NCM include dermatologic and neurologic manifestations. To date, this is the first series to note an association between NCM and TC. While nearly all recent series of NCM patients advocate early MRI of the neuroaxis, we recommend screening imaging of the spine on children with possible NCM regardless of the locations of CMN.

PHACE syndrome is associated with intracranial cavernous malformations

IntroductionPHACE syndrome is a neurocutaneous disorder involving large facial hemangiomas in association with posterior fossa abnormalities, cerebral arterial anomalies, cardiac defects, and eye abnormalities. A recent consensus statement has delineated criteria necessary for the diagnosis of PHACE syndrome. Extracutaneous manifestations of PHACE syndrome predominately affect the cerebrovascular system. To date, there are no reports of cerebral cavernous malformations (CCMs) in children with PHACE syndrome.MethodsWe reviewed the charts of children admitted to the Children’s Hospital of Pittsburgh who met criteria for PHACE syndrome, and evaluated neuroimaging for cerebrovascular abnormalities, including the finding of CCMs.ResultsSix children met criteria for PHACE syndrome at our institution over a 10-year period. All children were female. All children had cerebrovascular abnormalities sufficient to meet major criteria for diagnosis. Four children (66.7 %) were found incidentally to have CCMs; all lesions measured less than 5 mm at the time of diagnosis and were asymptomatic.ConclusionAt present, CCMs are not listed among the diagnostic criteria for PHACE syndrome, and they have not previously been reported in association with PHACE syndrome. Hypoxic injury in utero may be the common denominator in the pathogenesis of many of the abnormalities already accepted in the criteria for PHACE syndrome and the formation of CCMs. In the setting of PHACE syndrome, we encourage clinicians to evaluate children for CCMs, which are readily apparent on the already-recommended screening MRIs.

Coexistence of dermal sinus tract, dermoid cyst, and encephalocele in a patient presenting with nasal cellulitis.

Dermoid cysts, encephaloceles, and dermal sinus tracts represent abnormalities that develop during the process of embryogenesis. The elucidation of the precise timing of formation for these malformations has remained elusive at the molecular level of study. Yet, clinical experience has demonstrated that these malformations do not all occur in the same patient, suggesting a shared pathway that goes awry at distinct points for different patients, resulting in 1 of the 3 malformations. Herein the authors describe a case in which all 3 malformations were present in a single patient. This is the first description in the English literature of a sincipital encephalocele occurring with a dermoid cyst and a dermal sinus tract.