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R. Tyler Frizzell, Yves J. Meyer, D. John Borchers, Bradley E. Weprin, Elizabeth C. Allen, W. Rene Pogue, John S. Reisch, Alan D. Cherrington and H. Hunt Batjer

✓ The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on cerebral metabolism and blood flow were studied in 29 dogs during cerebral hypoperfusion. Three groups of animals were studied during a 45-minute normotensive and a 30-minute hypotensive period: 10 control animals without etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals receiving doses of etomidate sufficient to suppress electroencephalographic bursts (high-dose group). The mean arterial pressure fell to similar levels (p < 0.05) during hypotension in all three groups (40 ± 5, 38 ± 3, and 27 ± 6 mm Hg, respectively). The mean cerebral oxygen extraction fraction rose (p < 0.05) from 0.23 ± 0.02 to 0.55 ± 0.08 in the five control animals tested and from 0.33 ± 0.02 to 0.53 ± 0.02 in the seven animals tested in the low-dose group, but did not increase (p > 0.05) in the four animals tested in the high-dose group (0.24 ± 0.03 to 0.23 ± 0.05). Mean cerebral blood flow levels decreased in all groups during hypotension (p < 0.05): 42 ± 3 to 21 ±4 ml/100 gm/min (52% ± 12% decrease) in the five animals tested in the control group, 60 ± 8 to 24 ± 6 ml/100 gm/min (56% ± 13% decrease) in the four animals tested in the low-dose group, and 55 ± 8 to 22 ± 3 ml/100 gm/min (60% ± 4% decrease) in the four animals tested in the high-dose group. In summary, the cerebral oxygen extraction fraction increased in the control animals and low-dose recipients during hypotension, suggesting the presence of threatened cerebral tissue. In contrast, the cerebral oxygen extraction did not change during hypotension when high-dose etomidate was administered. It is concluded that high-dose etomidate may preserve the cerebral metabolic state during hypotension in the present model.

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Bradley E. Weprin, Walter A. Hall, Jesse Goodman and George L. Adams

✓ Mucormycosis refers to a group of rapidly progressive infections caused by fungi belonging to the order Mucorales. Infection most often develops in individuals with immunological or metabolic compromise, although patients without underlying abnormalities have been affected. Specific clinical manifestations are associated with various predisposing factors. Rhinocerebral mucormycosis is the most common form and most frequently develops in individuals with poorly controlled diabetes mellitus. The extent of anatomical involvement and clinical course are unpredictable, depending on the intrinsic factors of the host. Over the past 20 years the prognosis for patients with rhinocerebral mucormycosis, once considered to be a uniformly fatal disease, has improved. Coordinated medical and surgical treatment, including rapid diagnosis, the advent of systemic antifungal agents, aggressive surgical debridement, and control of the underlying disease process, have been credited with its successful management. The range of survival rates recorded with the regimen of combined therapies is wide because the number of patients reported is limited and anatomical involvement is diverse. Survival with intracerebral abscess is rare.

The authors describe the successful management of a patient who developed a bifrontal fungal abscess during treatment for rhinocerebral mucormycosis associated with ketoacidosis and diabetes mellitus. The patient remains without radiographic or clinical evidence of infection more than 2 years after treatment. The authors review the characteristic clinical, radiographic, and pathological features of previously reported infections and emphasize the importance of early detection and aggressive treatment in the management of this frequently fulminant and fatal disease.

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Daniel C. Bowers, Lynn Gargan, Bradley E. Weprin, Arlynn F. Mulne, Roy D. Elterman, Louis Munoz, Cole A. Giller and Naomi J. Winick

Object

The object of this study was to identify prognostic factors for survival among children with recurrent medulloblastoma.

Methods

Postprogression survival and patient, tumor, and treatment factors were examined in 46 cases of recurrent medulloblastoma (mean age of patients at diagnosis 6.5 years, mean age at progression 8.4 years). Differences were calculated by Kaplan–Meier log-rank analysis. Multivariate analysis was performed using the Cox proportional hazard model.

Results

The probability of 5-year survival was 26.3%. Forty-one patients received salvage therapy and five patients received hospice care only. Log-rank analysis showed an association between prolonged patient survival and recurrence limited to the primary site (p = 0.008), initial therapy including the Pediatric Oncology Group (POG) regimen for the treatment of brain tumors in infants (“Baby POG;” p = 0.037), and treatment with radiation therapy (RT) following initial progression (p = 0.015). Cox regression analysis showed a significant association between prolonged survival and only one variable—tumor recurrence restricted to the primary site (p = 0.037). There was no significant association between prolonged survival and any other variables, including patient sex, age at progression, interval from tumor diagnosis to progression, initial tumor stage, and salvage treatment with chemotherapy. Subgroup analysis revealed that site of tumor progression was also prognostic for survival among the subgroup of patients older than 3 years of age at diagnosis who were initially treated with RT and chemotherapy (p = 0.017, log-rank test).

Conclusions

Some children with recurrent medulloblastoma will be long-term survivors, and certain features are associated with likelihood of survival. Patients whose tumors recur at only the primary tumor site have an increased chance of prolonged survival.

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Atif Haque, Angela V. Price, Frederick H. Sklar, Dale M. Swift, Bradley E. Weprin and David J. Sacco

Object

Rigid fixation of the upper cervical spine has become an established method of durable stabilization for a variety of craniocervical pathological entities in children. In children, specifically, the use of C1–2 transarticular screws has been proposed in recent literature to be the gold standard configuration for pathology involving these levels. The authors reviewed the use of rigid fixation techniques alternative to C1–2 transarticular screws in children. Factors evaluated included ease of placement, complications, and postoperative stability.

Methods

Seventeen patients, ranging in age from 3 to 17 years (mean 9.6 years), underwent screw fixation involving the atlas or axis for a multitude of pathologies, including os odontoideum, Down syndrome, congenital instability, iatrogenic instability, or posttraumatic instability. All patients had preoperative instability of the occipitocervical or atlantoaxial spine demonstrated on dynamic lateral cervical spine radiographs. All patients also underwent preoperative CT scanning and MR imaging to evaluate the anatomical feasibility of the selected hardware placement. Thirteen patients underwent C1–2 fusion, and 4 underwent occipitocervical fusion, all incorporating C-1 lateral mass screws, C-2 pars screws, and/or C-2 laminar screws within their constructs. Patients who underwent occipitocervical fusion had no instrumentation placed at C-1. One patient's construct included sublaminar wiring at C-2. All patients received autograft onlay either from from rib (in 15 patients), split-thickness skull (1 patient), or local bone harvested within the operative field (1 patient). Nine patients' constructs were supplemented with recombinant human bone morphogenetic protein at the discretion of the attending physician. Eight patients had surgical sacrifice of 1 or both C-2 nerve roots to better facilitate visualization of the C-1 lateral mass. One patient was placed in halo-vest orthosis postoperatively, while the rest were maintained in rigid collars.

Results

All 17 patients underwent immediate postoperative CT scanning to evaluate hardware placement. Follow-up was achieved in 16 cases, ranging from 2 to 39 months (mean 14 months), and repeated dynamic lateral cervical spine radiography was performed in these patients at the end of their follow-up period. Some, but not all patients, also underwent delayed postoperative CT scans, which were done at the discretion of the treating attending physician. No neurovascular injuries were encountered, no hardware revisions were required, and no infections were seen. No postoperative pain was seen in patients who underwent C-2 nerve root sacrifice. Stability was achieved in all patients postoperatively. In all patients who underwent delayed postoperative CT scanning, the presence of bridging bone was shown spanning the fused levels.

Conclusions

Screw fixation of the atlas using lateral mass screws, in conjunction with C-2 root sacrifice in selected cases, and of the axis using pars or laminar screws is a safe method for achieving rigid fixation of the upper cervical spine in the pediatric population.

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Dongmei He, David G. Genecov, Morley Herbert, Raul Barcelo, Mohammed E. Elsalanty, Bradley E. Weprin and Lynne A. Opperman

Object

This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein–2 (rhBMP-2) delivered in a collagen sponge–collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines.

Methods

Forty immature male beagles were used to create two 2.5 × 4–cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 × 3–cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15% hydroxyapatite [HA]/85% tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed.

Results

Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non–rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05).

Conclusions

The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.

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William W. Scott, Korgun Koral, Linda R. Margraf, Laura Klesse, David J. Sacco and Bradley E. Weprin

Although intracerebral schwannomas are typically regarded as benign intracranial tumors, malignancy and recurrence have been reported among patients harboring such neoplasms. The available literature consists of case reports and small series that present variable characteristics distinguishing these unusual lesions. Little advancement has been made to further the understanding and management of these tumors. The authors present 3 cases from their institution that highlight the difference between typical benign intracerebral schwannomas and histopathological variants that may portend more aggressive behavior. Also provided is a review of the literature in the hope of gaining a better understanding of these rare tumors.

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William W. Scott, Bradley E. Weprin and Dale M. Swift

Object

Osteopetrosis is a rare congenital metabolic bone disease. There are very few reports in the literature associating cerebellar tonsillar herniation (CTH) and hydrocephalus requiring neurosurgical attention. The authors present cases of osteopetrosis requiring neurosurgical intervention from their practice and offer a detailed account of the literature.

Methods

A retrospective review was conducted at the authors' institution, and all children with osteopetrosis requiring neurosurgical attention were identified. Medical charts and radiographic studies were reviewed. Data including age at presentation, sex, symptoms at presentation, age at follow-up, the presence of any neurological comorbidities, and surgical procedures performed were recorded.

Results

Four patients were identified as having osteopetrosis requiring neurosurgical attention at the authors' institution between January 1, 2005, and January 1, 2014. There were 3 females and 1 male with an average age at presentation of 11.1 years; patients were observed for a mean of 4.4 years. All of the patients were identified as harboring jugular foraminal stenosis and CTH. Seventy-five percent of these patients developed hydrocephalus, and in those cases a triventricular pattern of dilation was noted. One patient developed syringomyelia. Three of the 4 patients underwent neurosurgical procedures. Cerebrospinal fluid diversion was performed in 2 patients via a ventriculoperitoneal shunt in one case and an endoscopic third ventriculostomy (ETV) in the other. The former patient required a proximal revision at 2 years for bony overgrowth at the site of the bur hole. Two patients underwent a suboccipital decompression. In patients undergoing CSF diversion, there was improvement in ventricle size.

Conclusions

Variable degrees of hindbrain crowding and/or CTH are mentioned throughout the literature, suggesting that this entity is nearly always present in this patient population. The progressive triventricular hydrocephalus seen in these cases results from a complex combination of both communicating and noncommunicating pathology, which may depend on the type of osteopetrosis, age at presentation, and the presence and degree of venous collateralization, and it appears that the hydrocephalus is more prevalent and more likely to be treated in infants and in the younger, school-aged population. The acquired hindbrain fullness in conjunction with the triventricular pattern of hydrocephalus has kept the authors enthusiastic regarding the use of ETV in these complicated cases.

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Brett A. Whittemore, Dale M. Swift, Bradley E. Weprin and Frederick J. Duffy Jr.

OBJECTIVE

Large myelomeningocele defects and poor surrounding tissue quality make some defects particularly difficult to close primarily. This paper describes the superior gluteal artery perforator (SGAP) flap technique for defect closure and long-term clinical outcomes.

METHODS

The technique for closing a myelomeningocele with an SGAP flap is described. A retrospective chart review was performed on a cohort of 11 patients who underwent closure in this manner.

RESULTS

Between 1999 and 2015, 271 myelomeningoceles were closed, 11 of which were SGAP flap closures. The mean defect size was 5.5 × 7.2 cm. All patients underwent ventriculoperitoneal shunting. There were no cases of CSF infection. Five patients had minor wound issues (small dehiscence or eschar formation) that healed satisfactorily. Two patients had soft-tissue wound infections and required multiple revisions; one patient had multiple severe developmental abnormalities, and the other patient's flap had healed with a thick underlying fat pad 4 months postoperatively. No patients had significant surgical site pain on long-term follow-up.

CONCLUSIONS

The SGAP flap technique achieves tension-free closure with vascularized, fat-bearing full-thickness skin. It is useful for closure of large, complex defects, is not associated with chronic pain, and carries a morbidity risk that is comparable to other complex myelomeningocele closure techniques.

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Tarek Y. El Ahmadieh, Cody B. Wolfe, Joyce Koueik, Bradley E. Weprin, Bermans J. Iskandar and Angela V. Price

Neuroendoscopy has demonstrated safety and efficacy in the treatment of a host of pediatric neurosurgical pathologies. With the increase in its applicability, several associated complications have been described in the literature. A common practice in pediatric neurosurgery is the use of Gelfoam sponge pledget in the burr hole, followed by bone fragments and dust (obtained from the created burr hole), to cover the dural defect. This technique is used to enhance burr hole sealing and potentially prevent CSF leakage from the surgical site. Reports on intracranial bone dust migration associated with this technique are scarce. The authors report 2 cases of intracranial migration of bone fragments after an endoscopic third ventriculostomy and an endoscopic colloid cyst resection. The bone fragment migration was thought to be caused by negative pressure from a lumbar puncture in one case and external trauma to the head in the other. As endoscopy becomes more widely used, it is important to be aware of this potential complication that may in some cases require an intervention. A review of the cases reported in the literature is provided and a technique is suggested to help prevent this complication.

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M. Burhan Janjua, Sumanth Reddy, William C. Welch, Amer F. Samdani, Ali K. Ozturk, Steven W. Hwang, Angela V. Price, Bradley E. Weprin and Dale M. Swift

OBJECTIVE

The risk of readmission after brain tumor resection among pediatric patients has not been defined. The authors’ objective was to evaluate the readmission rates and predictors of readmission after pediatric brain tumor resection.

METHODS

Nationwide Readmissions Database (NRD) data sets from 2010 to 2014 were searched for unplanned readmissions within 30 days of the discharge date after pediatric brain tumor resection. Patient demographic variables included sex, age, expected payment source (Medicaid or private insurance), and median annual household income. Readmission events for chemotherapy, radiation therapy, or further tumor resection were not included.

RESULTS

Of 282 patients (12.7%) readmitted within 30 days of the index event, the median time to readmission was 10 days (IQR 5–19 days). The most common reason for readmission was hydrocephalus, which accounted for 19% of readmission events. Other CNS-related complications (24%), surgical site infections or septicemia (14%), seizures (7%), and hematological disorders (7%) accounted for other major readmission events. The median charge for readmission events was $35,431, and the median length of readmission stay was 4 days. In multivariate regression, factors associated with a significant increase in readmission risk included Medicaid as the primary payor, discharge from the index event with home health services, and fluid and electrolyte disorders during the index event.

CONCLUSIONS

More than 10% of pediatric brain tumor patients have unplanned readmission events within 30 days of discharge after tumor resection. Medicaid patients and those with preoperative or early postoperative fluid and electrolyte disturbances may benefit from early or frequent outpatient visits after tumor resection.