Gordon McComb

Recurrence Patterns and Anaplastic Change in a Long-Term Study of Pilocytic Astrocytomas

Thirty-six cases of pilocytic astrocytomas treated at the Childrens Hospital of Los Angeles from 1984 through 1995 were reviewed. The mean age at initial presentation was 8 years (range 15 months to 14 years). These patients were followed for an average of 5.5 years. No patient was given chemotherapy or radiation therapy after the initial surgery for pilocytic astrocytoma. Twenty-three patients (64%) had a gross total resection with no residual tumor on immediate postoperative imaging studies. Three of these children had tumor recurrences 2-5 years after their initial surgery, requiring re-excision of their tumors. All 3 patients are subsequently tumor-free, with follow-up ranging from 4 to 10 years. In 4 patients with residual tumor involving the brainstem, there has been neither imaging evidence of tumor enlargement nor progression of clinical findings at 2.5, 4, 6 and 6 years, respectively. Nine of the 13 patients with residual tumor underwent re-excision, either for progression of symptoms or documented tumor growth on imaging studies. The second operation was undertaken an average of 1 year (range 1 month to 6 years) after the first. In 4 of these children (11% of our whole series), the recurrent tumor was classified as anaplastic astrocytoma. Three of these 4 children received radiation and/or chemotherapy, with only 1 patient showing disease progression in the follow-up period. Repeat blinded histopathological examination of these tumors confirmed both diagnoses. However, it was noted that 3 of the 4 pilocytic astrocytomas which subsequently showed anaplastic change initially displayed increased perivascular cellularity, while only 2 of the remaining 32 tumors exhibited this feature. These results encourage continued vigilance in the follow-up of pilocytic astrocytomas, and describe a histological feature which might indicate a more aggressive disease course.

Surgical Management of Sagittal Synostosis: A Comparative Analysis of Strip Craniectomy and Calvarial Vault Remodeling

Although surgical treatment of sagittal synostosis has become normative, the procedure of choice is still debated. This retrospective analysis, during a 10-year period (1986-1995) at Children’s HospitAlthough surgical treatment of sagittal synostosis has become normative, the procedure of choice is still debated. This retrospective analysis, during a 10-year period (1986-1995) at Childrens Hospital Los Angeles, compares the more conservative strip craniectomy (SC) procedure with a more extensive occipital reduction-biparietal widening calvarial vault remodeling (CVR) technique for the management of sagittal synostosis. SC was performed in 72 patients (61%) and CVR in 46 (39%). Patients undergoing CVR were older (mean 5.3 vs. 3.0 months, p < 0.01), the procedure time longer (mean 126 min vs. 72 min, p < 0.01), intraoperative blood loss greater (mean 243 vs. 54 cm3, p < 0.01), and the frequency of intraoperative blood transfusion increased (100 vs. 38%, p < 0.01; mean volume 357 vs. 51 cm3, p < 0.01) compared to patients undergoing SC. No significant intraoperative complications occurred in either group. The total time of hospitalization was similar (mean 4.4 vs. 3.8 days, p = 0.02). No neurological, hematological, or transfusion-related complications or deaths were encountered in either group. Cosmetic outcomes were significantly better in the CVR group with 79% rated as excellent compared to 41% in the SC group (p < 0.01). Fifty-nine percent of the SC patients manifested bony defects at last follow-up visit. Two SC patients required reoperation for poor cosmetic outcomes; CVR was successfully employed in both cases. These findings demonstrate that CVR is superior to SC in providing immediate and lasting correction of calvarial deformities secondary to sagittal synostosis. The optimal age at time of surgery is <6 months; however, CVR can be utilized throughout infancy, while SC becomes progressively less effective after 6 months of age. No significant complications were observed in either group, despite the increased operative manipulation and greater incidence of blood transfusion in the CVR patients.

Pediatric Traumatic Intracranial Aneurysms

During the past 17 years, 7 children have been treated at Childrens Hospital Los Angeles (CHLA) for traumatic intracranial aneurysms. These patients presented with subarachnoid or intraparenchymal hemorrhage (5 cases), growing fracture (1 case), and behavioral change (1 case). All patients were managed with surgery, and no patient died or was made neurologically worse as a result of such management. The existence of a traumatic aneurysm should be considered when new neurological symptoms develop in a patient with a history of head injury.

The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid

BackgroundCerebrospinal fluid (CSF) contacts many brain regions and may mediate humoral signaling distinct from synaptic neurotransmission. However, synthesis and transport mechanisms for such signaling are not defined. The purpose of this study was to investigate whether human CSF contains discrete structures that may enable the regulation of humoral transmission.MethodsLumbar CSF was collected prospectively from 17 participants: with no neurological or psychiatric disease, with Alzheimers disease, multiple sclerosis, or migraine; and ventricular CSF from two cognitively healthy participants with long-standing shunts for congenital hydrocephalus. Cell-free CSF was subjected to ultracentrifugation to yield supernatants and pellets that were examined by transmission electron microscopy, shotgun protein sequencing, electrophoresis, western blotting, lipid analysis, enzymatic activity assay, and immuno-electron microscopy.ResultsOver 3,600 CSF proteins were identified from repeated shotgun sequencing of cell-free CSF from two individuals with Alzheimers disease: 25% of these proteins are normally present in membranes. Abundant nanometer-scaled structures were observed in ultracentrifuged pellets of CSF from all 16 participants examined. The most common structures included synaptic vesicle and exosome components in 30-200 nm spheres and irregular blobs. Much less abundant nanostructures were present that derived from cellular debris. Nanostructure fractions had a unique composition compared to CSF supernatant, richer in omega-3 and phosphoinositide lipids, active prostanoid enzymes, and fibronectin.ConclusionUnique morphology and biochemistry features of abundant and discrete membrane-bound CSF nanostructures are described. Prostaglandin H synthase activity, essential for prostanoid production and previously unknown in CSF, is localized to nanospheres. Considering CSF bulk flow and its circulatory dynamics, we propose that these nanostructures provide signaling mechanisms via volume transmission within the nervous system that are for slower, more diffuse, and of longer duration than synaptic transmission.

A new, pluronic-based, bone hemostatic agent that does not impair osteogenesis.

OBJECTIVEIntraoperative bone hemostasis can be accomplished using surgical beeswax (bone wax). However, bone wax locally interferes with osteogenesis, and its use is avoided when bone fusion is critical. We describe the use of a Pluronic copolymer blend as a biocompatible, absorbable, hemostatic agent. METHODSA rat femur defect model and a femur gap nonunion model were used. For each surgical model, 24 rats were divided into three treatment groups, i.e., those receiving bone wax implants, Pluronic (90% Pluronic P85/10% Pluronic F88) implants, or no implants (control group). After 10, 21, or 42 days, animals were killed and femora were removed for radiographic analysis and hematoxylin and eosin staining. RESULTSIn the femur defect model, no differences were observed between the Pluronic-treated and control groups; hematoxylin and eosin staining demonstrated bone formation and osteocytes within the defect. In the femur gap nonunion model, no fusions occurred in any group. Development of an osseous callus at the gap site was observed for the control and Pluronic-treated groups. In both models, rats that received bone wax implants exhibited no osseous growth. CONCLUSIONThe Pluronic blend exhibits handling properties similar to those of bone wax, readily achieves hemostasis, and does not inhibit bone regrowth. Pluronic compounds may serve as effective absorbable hemostatic agents for the treatment of bone bleeding in sites where fusion is critical. In addition, this copolymer blend may find use as a vehicle for the short-term release of pharmacological agents, which may further reduce the incidence of infections, reduce inflammation, and improve fusion rates.

Complications of Halo Use in Children

Study Design. Retrospective review. Objective. To evaluate complications of halo use in children. Summary of Background Data. Halos have been used in children for correction of spinal deformity and immobilization of the spine. Complications of halo use in children have been reported, including pin-site complications and neurologic injury from halo traction. The purpose of this report is to report on complications of halo use in children. Methods. The medical records of 68 patients treated with a halo for correction of spinal deformity or immobilization from 1996 to 2005 were reviewed. Mean age of children was 10 (1–20) years. The halo device was used to apply traction for correction of spinal deformity in 31 patients, and immobilization alone with halo vest in 37 patients. Results. The overall rates of complications are significant at 53% (36/68). Pin-site complications included 13 infections successfully treated with oral antibiotics and 4 pins that needed to be removed. Two pins were replaced due to skull penetration, and 1 scar site was surgically revised. There were a total of 9 neurologic complications that occurred in 7 of 31 patients undergoing halo traction (31% incidence), including 3 cranial nerve injuries, 1 Horner syndrome, 4 extremity weaknesses, and 1 bradycardia. All traction-related neurologic problems resolved with removal or decrease of the magnitude of traction, with 4 cases improving immediately, 3 cases within 2 days, and the 2 other cases resolving in 1 and 5 months. Lastly, there were 7 vest-related complications including 5 pressure sores, 1 cracking of the vest, and 1 halo-vest readjustment. Conclusion. This is the largest reported series of halo use in children. The overall rate of complications is 53% (36/68), and 10% (7/68) of children required unanticipated surgery for treatment of these complications. The most common complication was pin-site infections, with 76% (13/17) of these resolving with oral antibiotics alone. Traction-related neurologic injuries that occurred were common, 31% (9/31) but all resolved with a decrease or removal of traction weight, with complete resolution occurring immediately in 4 of 9 events. We recommend serial neurologic examinations of children in halo traction, with immediate removal or decrease in weights at the first sign of injury.

Supratentorial ependymoma in children: To observe or to treat following gross total resection?†

The standard treatment for ependymoma is surgical resection followed by postoperative irradiation to the local site. The role of radiation therapy in completely resected supratentorial ependymoma has been questioned over the past two decades.

Subcutaneous palisading granuloma of the scalp in childhood

Subcutaneous palisading granulomas, lesions characterized by collagen necrosis and chronic inflammatory changes, may present as ill-defined, immobile, nontender masses of the scalp. They are frequently multiple and may vary in size over time. Imaging studies rarely show involvement of the calvarium. The histological pattern of palisading histiocytes around necrobiotic granulomas is seen in association with a variety of systemic illnesses but more commonly occurs as an isolated entity in childhood. They are unlikely to herald rheumatological disease unless the erythrocyte sedimentation rate is elevated. In the presence of juvenile rheumatoid arthritis, histological confirmation is usually not indicated. If the lesions are not associated with any other clinical symptoms excisional biopsy may be indicated to establish a diagnosis. The nodules need not be removed as they will spontaneously regress.

Central nervous system (CNS) tumors in the first six months of life: the Children's Hospital Los Angeles experience, 1979-2005.

Background: The authors report the experience at the Childrens Hospital Los Angeles with brain tumors diagnosed before 6 months of age, describing the characteristics of the patients, their tumors, treatment strategies, and prognostic factors. Methods: Thirty-three children who were identified between 1979 and 2005 were included. Twelve were female (36%). There were 11 gliomas, 9 choroid plexus tumors, 8 medulloblastomas and supratentorial primitive neuroectodermal tumors (PNET), 2 atypical teratoid/rhabdoid tumors (ATRT), and 1 each of ependymoma, craniopharyngioma, and immature teratoma. Locations of primary tumors included 21 supratentorial (64%) and 7 posterior fossa, and 5 tumors involved both compartments. The treatment strategies included 5 patients with biopsy only, 18 less than gross total resections (<GTRx), and 9 GTRx. Fourteen children (42%) received chemotherapy. Three patients (9%) received irradiation, 1 at initial diagnosis and 2 at relapse. Nine patients (27%) demonstrated metastases, 6 at diagnosis and 3 at relapse. Results: The Kaplan Meier analysis of event-free survival (EFS) and overall survival (OS) for all patients is 21 ± 9% and 35 ± 9% at 5 years. For the glioma patients, the 4-year OS is 48 ± 17%, while the 5-year OS for the medulloblastoma/PNET/ATRT patients is 12 ± 11% (p = .39). The 5-year OS for children achieving a GTRx is 64 ± 21% and for those with <GTRx is 27 ± 10% (p = .08).

A retrospective analysis of recurrent intracranial ependymoma

Recurrence occurs in almost 50% of patients with intracranial ependymoma, and their outcome following recurrence is poor.