Faculty Bibliography

OBJECTIVE: To evaluate the safety, efficacy, and utility of a novel surgical strategy consisting of multiple (more than two) operative stages performed during the same hospital admission with subdural grid and strip electrodes in selected pediatric extratemporal epilepsy. METHODS: Subdural grid and strip electrodes were used for multistage chronic electroencephalographic monitoring in 15 pediatric patients (age, <19 yr) with refractory localization-related epilepsy and poor surgical prognostic factors. Initial resective surgery and/or multiple subpial transections were performed, followed by further monitoring and additional resection and/or multiple subpial transections. RESULTS: Mean patient age was 9.7 years. Mean duration of total invasive monitoring was 10.5 days (range, 8-14 d). The first monitoring period averaged 6.5 days, and the second averaged 3.9 days. Additional surgery was performed in 13 of 15 patients. Two patients who did not undergo additional surgery had a Class I outcome. Rationales for reinvestigation included incomplete localization, multifocality, and proximity to eloquent cortex. Complications were minimal, including two transfusions. There were no cases of wound infection, cerebral edema, hemorrhage, or major permanent neurological deficit. Minimum duration of follow-up was 31 months. Outcomes were 60% Engel Class I (9 of 15 patients), 27% Class III (4 of 15 patients), and 13% Class IV (2 of 15 patients). CONCLUSION: In a very select group of pediatric patients with poor surgical prognostic factors, the multistage approach can be beneficial. After failed epilepsy surgery, subsequent reoperation with additional intracranial investigation traditionally is used when a single residual focus is suspected. Our results, however, support the contention that multistage epilepsy surgery is safe, effective, and useful in a challenging and select pediatric population with extratemporal medically refractory epilepsy

Cerebrospinal fluid (CSF) drainage catheters can cause a myriad of complications, in large part because they may migrate from their normal location to almost anywhere in the body. We present the unique case of a female patient who had previously undergone bilateral breast augmentation who experienced sudden painless swelling of her right breast 6 weeks after placement of a ventriculoperitoneal shunt. Radiologic examination demonstrated ensnarement of the distal aspect of the shunt around her implant, with subsequent formation of a CSF pseudocyst. Management of this patient included replacement of the shunt, drainage of the CSF pseudocyst, and preservation of the implant

PURPOSE: To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas. PATIENTS AND METHODS: From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk x three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d x 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue. RESULTS: Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively. CONCLUSION: This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies

Balloon cells (BCs) in focal cortical dysplasia (FCD) and giant cells (GCs) in tubers of the tuberous sclerosis complex (TSC) share phenotypic similarities. TSC1 or TSC2 gene mutations in TSC lead to mTOR pathway activation and p70S6kinase (phospho-S6K) and ribosomal S6 (phospho-S6) protein phosphorylation. Phospho-S6K, phospho-S6, and phospho-S6K-activated proteins phospho-STAT3 and phospho-4EBP1 were detected immunohistochemically in GCs, whereas only phospho-S6 was observed in BCs. Expression of four candidate gene families (cell signaling, cell adhesion, growth factor/receptor, and transcription factor mRNAs) was assayed in single, microdissected phospho-S6-immunolabeled BCs and GCs as a strategy to define whether BCs and GCs exhibit differential transcriptional profiles. Among 60 genes, differential expression of 24 mRNAs distinguished BCs from GCs and only 4 genes showed similar expression profiles between BCs and GCs. Tuberin mRNA levels were reduced in GCs from TSC patients with TSC2 gene mutations but were unchanged in BCs. Phospho-S6K, -S6, -STAT3, and -4EBP1 expression in GCs reflects loss of hamartin-tuberin-mediated mTOR pathway inhibition. Phospho-S6 expression alone in BCs does not support mTOR cascade activation in FCD. Differential gene expression profiles in BCs and GCs supports the hypothesis that these cell types derive by distinct pathogenic mechanisms

Tuberous sclerosis complex is associated with medically refractory seizures and developmental delay in children. These epilepsies are often resistant to antiepileptic drugs, can be quite severe, and usually have a negative impact on the child's neurologic and cognitive development. It is believed that functional outcome is improved if seizures can be controlled at an early age. The surgical treatment of intractable epilepsy in children and adults with tuberous sclerosis complex has gained significant interest in recent years. Previously published studies have shown a potential benefit from resection of single tubers, with most of the results noted in relatively older children. All of these reports support the idea that if a single primary epileptogenic tuber or region can be identified, then a surgical approach is appropriate. However, most children with tuberous sclerosis complex have multiple potentially epileptogenic tubers, rendering localization challenging, and they are therefore rejected as possible surgical candidates. We have used a novel surgical approach using invasive intracranial monitoring, which is typically multistaged and bilateral. This multistage surgical approach has been useful in identifying both primary and secondary epileptogenic zones in patients with tuberous sclerosis complex with multiple tubers. Multiple or bilateral seizure foci are not necessarily a contraindication to surgery in selected patients. Long-term follow-up will determine whether this approach has durable effects. We await better methods for identifying the epileptogenic zone, both noninvasive and invasive

To recognize and make the proper diagnosis of a craniofacial abnormality, it is helpful for the pediatrician to understand the normal embryology, morphologic variations, and the characteristics, types, and timings of defects that can occur. It is important that pediatricians and other caregivers of infants and young children be able to recognize the common cranial abnormalities so that the families maybe properly counseled and referred to an appropriate multidisciplinary craniofacial center. Because the most common causes of distortion or asymmetry are craniosynostosis or deformation, these abnormalities are the primary subjects of this article