Faculty Bibliography

OBJECT/OBJECTIVE:Randomized clinical trials have established that lumbar selective dorsal rhizotomy (SDR) reduces lower-extremity tone and improves functional outcome in children with spastic cerebral palsy. Significant data exist to support a secondary effect on upper-extremity function in patients with upper-extremity spasticity. The effects of SDR on upper-extremity tone, however, are not well characterized. In this report, the authors sought to assess changes in upper-extremity tone in individual muscle groups after SDR and tried to determine if these changes could be predicted preoperatively. METHODS:The authors retrospectively reviewed 42 children who underwent SDR at Columbia University Medical Center/Morgan Stanley Children's Hospital of NewYork-Presbyterian between 2005 and 2011. Twenty-five had upper-extremity spasticity. All underwent pre- and postoperative examination for measuring tone (Modified Ashworth Scale) and assessing functional outcome. Follow-up examinations with therapists were performed at least once at a minimum of 2 months postoperatively (mean 15 months). RESULTS:In the upper extremities, 23 (92%) of 25 patients had improvements of at least 1 Ashworth point in 2 or more independent motor groups on the Modified Ashworth Scale, and 12 (71%) of 17 families surveyed reported increases in motor control or spontaneous movement. The mean Modified Ashworth Scale scores for all upper-extremity muscle groups demonstrated an improvement from 1.34 to 1.22 (p < 0.001). Patients with a mean preoperative upper-extremity tone of 1.25-1.75 were most likely to benefit from reduction in tone (p = 0.0019). Proximal and pronator muscle groups were most likely to demonstrate reduced tone. CONCLUSIONS:In addition to improvements in lower-extremity tone and function, SDR has demonstrable effects on upper extremities. Greater than 90% of our patients with elevated upper-extremity tone demonstrated reduction in tone in at least 2 muscle groups postoperatively. Patients with a mean Modified Ashworth Scale upper-extremity score of 1.25-1.75 may encounter the greatest reduction in upper-extremity tone.

BACKGROUND:Meningiomas often harbor an immune cell infiltrate that can include substantial numbers of T and B cells. However, their phenotype and characteristics remain undefined. To gain a deeper understanding of the T and B cell repertoire in this tumor, we characterized the immune infiltrate of 28 resected meningiomas representing all grades. METHODS:Immunohistochemistry was used to grossly characterize and enumerate infiltrating lymphocytes. A molecular analysis of the immunoglobulin variable region of tumor-infiltrating B cells was used to characterize their antigen experience. Flow cytometry of fresh tissue homogenate and paired peripheral blood lymphocytes was used to identify T cell phenotypes and characterize the T cell repertoire. RESULTS:A conspicuous B and T cell infiltrate, primarily clustered in perivascular spaces, was present in the microenvironment of most tumors examined. Characterization of 294 tumor-infiltrating B cells revealed clear evidence of antigen experience, in that the cardinal features of an antigen-driven B cell response were present. Meningiomas harbored populations of antigen-experienced CD4+ and CD8+ memory/effector T cells, regulatory T cells, and T cells expressing the immune checkpoint molecules PD-1 and Tim-3, indicative of exhaustion. All of these phenotypes were considerably enriched relative to their frequency in the circulation. The T cell repertoire in the tumor microenvironment included populations that were not reflected in paired peripheral blood. CONCLUSION/CONCLUSIONS:The tumor microenvironment of meningiomas often includes postgerminal center B cell populations. These tumors invariably include a selected, antigen-experienced, effector T cell population enriched by those that express markers of an exhausted phenotype.

BACKGROUND:Perioperative surgical site infection (SSI) after pediatric spine fusion is a recognized complication with rates between 0.5% and 1.6% in adolescent idiopathic scoliosis and up to 22% in "high risk" patients. Significant variation in the approach to infection prophylaxis has been well documented. The purpose of this initiative is to develop a consensus-based "Best Practice" Guideline (BPG), informed by both the available evidence in the literature and expert opinion, for high-risk pediatric patients undergoing spine fusion. For the purpose of this effort, high risk was defined as anything other than a primary fusion in a patient with idiopathic scoliosis without significant comorbidities. The ultimate goal of this initiative is to decrease the wide variability in SSI prevention strategies in this area, ultimately leading to improved patient outcomes and reduced health care costs. METHODS:An expert panel composed of 20 pediatric spine surgeons and 3 infectious disease specialists from North America, selected for their extensive experience in the field of pediatric spine surgery, was developed. Using the Delphi process and iterative rounds using a nominal group technique, participants in this panel were as follows: (1) surveyed for current practices; (2) presented with a detailed systematic review of the relevant literature; (3) given the opportunity to voice opinion collectively; and (4) asked to vote regarding preferences privately. Round 1 was conducted using an electronic survey. Initial results were compiled and discussed face-to-face. Round 2 was conducted using the Audience Response System, allowing participants to vote for (strongly support or support) or against inclusion of each intervention. Agreement >80% was considered consensus. Interventions without consensus were discussed and revised, if feasible. Repeat voting for consensus was performed. RESULTS:Consensus was reached to support 14 SSI prevention strategies and all participants agreed to implement the BPG in their practices. All agreed to participate in further studies assessing implementation and effectiveness of the BPG. The final consensus driven BPG for high-risk pediatric spine surgery patients includes: (1) patients should have a chlorhexidine skin wash the night before surgery; (2) patients should have preoperative urine cultures obtained; (3) patients should receive a preoperative Patient Education Sheet; (4) patients should have a preoperative nutritional assessment; (5) if removing hair, clipping is preferred to shaving; (6) patients should receive perioperative intravenous cefazolin; (7) patients should receive perioperative intravenous prophylaxis for gram-negative bacilli; (8) adherence to perioperative antimicrobial regimens should be monitored; (9) operating room access should be limited during scoliosis surgery (whenever practical); (10) UV lights need NOT be used in the operating room; (11) patients should have intraoperative wound irrigation; (12) vancomycin powder should be used in the bone graft and/or the surgical site; (13) impervious dressings are preferred postoperatively; (14) postoperative dressing changes should be minimized before discharge to the extent possible. CONCLUSIONS:In conclusion, we present a consensus-based BPG consisting of 14 recommendations for the prevention of SSIs after spine surgery in high-risk pediatric patients. This can serve as a tool to reduce the variability in practice in this area and help guide research priorities in the future. Pending such data, it is the unsubstantiated opinion of the authors of the current paper that adherence to recommendations in the BPG will not only decrease variability in practice but also result in fewer SSI in high-risk children undergoing spinal fusion. LEVEL OF EVIDENCE/METHODS:Not applicable.

Convection-enhanced delivery (CED) for the treatment of malignant gliomas is a technique that can deliver chemotherapeutic agents directly into the tumor and the surrounding interstitium through sustained, low-grade positive-pressure infusion. This allows for high local concentrations of drug within the tumor while minimizing systemic levels that often lead to dose-limiting toxicity. Diffuse intrinsic pontine gliomas (DIPGs) are universally fatal childhood tumors for which there is currently no effective treatment. In this report the authors describe CED of the topoisomerase inhibitor topotecan for the treatment of DIPG in 2 children. As part of a pilot feasibility study, the authors treated 2 pediatric patients with DIPG. Stereotactic biopsy with frozen section confirmation of glial tumor was followed by placement of bilateral catheters for CED of topotecan during the same procedure. The first patient underwent CED 210 days after initial diagnosis, after radiation therapy and at the time of tumor recurrence, with a total dose of 0.403 mg in 6.04 ml over 100 hours. Her Karnofsky Performance Status (KPS) score was 60 before CED and 50 posttreatment. Serial MRI initially demonstrated a modest reduction in tumor size and edema, but the tumor progressed and the patient died 49 days after treatment. The second patient was treated 24 days after the initial diagnosis prior to radiation with a total dose of 0.284 mg in 5.30 ml over 100 hours. Her KPS score was 70 before CED and 50 posttreatment. Serial MRI similarly demonstrated an initial modest reduction in tumor size. The patient subsequently underwent fractionated radiation therapy, but the tumor progressed and she died 120 days after treatment. Topotecan delivered by prolonged CED into the brainstem in children with DIPG is technically feasible. In both patients, high infusion rates (> 0.12 ml/hr) and high infusion volumes (> 2.8 ml) resulted in new neurological deficits and reduction in the KPS score, but lower infusion rates (< 0.04 ml/hr) were well tolerated. While serial MRI showed moderate treatment effect, CED did not prolong survival in these 2 patients. More studies are needed to improve patient selection and determine the optimal flow rates for CED of chemotherapeutic agents into DIPG to maximize safety and efficacy. Clinical trial registration no.: NCT00324844.

Pediatric patients bridged to heart transplant with LVADs require chronic anticoagulation and are at increased risk of hemorrhagic complications, including intracranial hemorrhage. In this population, intracranial hemorrhage is often fatal. We report a case of successful management of a five-yr-old-boy with DCM on an LVAD who developed a subdural hematoma. We initially chose medical management, weighing the patient's high risk of thromboembolism from anticoagulation reversal against the risk of his chronic subdural hematoma. When head CT showed expansion of the hemorrhage with increasing midline shift, we chose prompt surgical evacuation of the hematoma with partial reversal of anticoagulation, given the increased risk of acute deterioration. The patient ultimately received an orthotopic heart transplant and was discharged with no permanent neurological complications. This represents a case of a pediatric patient on an LVAD who survived a potentially fatal subdural hematoma and was successfully bridged to cardiac transplantation.

OBJECT/OBJECTIVE:Idiopathic intracranial hypertension (IIH) may be refractory to available medical and surgical therapies. Patients with this condition may suffer from intractable headaches, experience visual deterioration, or have other symptoms related to elevated intracranial pressure. Internal cranial expansion (ICE) is a novel surgical procedure that the authors have developed for the treatment of patients with this condition. Here, they describe ICE and present their initial experience in using this surgical procedure for the treatment of patients with refractory IIH. METHODS:The authors conducted a retrospective review of 10 consecutive patients who underwent ICE for the treatment of IIH during a 5-year period. Preoperative and postoperative clinical parameters including patient symptoms, presence of papilledema, and available ICP or CSF opening pressures were compared. Procedural details and complications were noted. Intracranial volume increases were calculated using available pre- and postoperative CT scans. RESULTS:Follow-up for the 10 patients in this series ranged from 1 to 39.6 months (mean 15.5 months). Technically successful ICE was performed in all patients within the cohort. Surgical complications included a single postoperative seizure in one patient and a sagittal sinus tear with no clinical sequelae in another patient. At the time of last follow-up, 7 (70%) of 10 patients were either symptomatically improved or asymptomatic. Six (67%) of 9 patients with preoperative headaches had reduction or resolution of this symptom, and all patients (4 of 4) with preoperative papilledema had a reduction in or complete resolution of this sign. Postoperative ICP or CSF opening pressures were normal in all patients (4 of 4) tested. Postoperative intracranial volume expansion ranged between 3.8% and 12%. CONCLUSIONS:Internal cranial expansion is a safe and effective surgery for the treatment of patients with refractory IIH. This surgery expands the intracranial volume and thus promotes ICP normalization, which may lead to the reduction or complete resolution of the signs and symptoms of IIH. Internal cranial expansion may be used as part of a multidisciplinary management approach in the treatment of refractory IIH.