Benjamin C. Kennedy, Michael B. Cloney, Richard C. E. Anderson and Neil A. Feldstein
Choroid plexus papillomas (CPPs) are rare neoplasms, often found in the atrium of the lateral ventricle of infants, and cause overproduction hydrocephalus. The extensive vascularity and medially located blood supply of these tumors, coupled with the young age of the patients, can make prevention of blood loss challenging. Preoperative embolization has been advocated to reduce blood loss and prevent the need for transfusion, but this mandates radiation exposure and the additional risks of vessel injury and stroke. For these reasons, the authors present their experience using the superior parietal lobule approach to CPPs of the atrium without adjunct therapy.
A retrospective review was conducted of all children who presented to Columbia University/Morgan Stanley Children's Hospital of New York with a CPP in the atrium of the lateral ventricle and who underwent surgery using a superior parietal lobule approach without preoperative embolization.
Nine children were included, with a median age of 7 months. There were no perioperative complications or new neurological deficits. All patients had intraoperative blood loss of less than 100 ml, with a mean minimum hematocrit of 26.9% (range 19.6%–36.2%). No patients required a blood transfusion. The median follow-up was 39 months, during which time no patient demonstrated residual or recurrent tumor on MRI, nor did any have an increase in ventricular size or require CSF diversion.
The superior parietal lobule approach is safe and effective for very young children with CPPs in the atrium of the lateral ventricle. The results suggest that preoperative embolization is not essential to avoid transfusion or achieve overall good outcomes in these patients. This management strategy avoids radiation exposure and the additional risks associated with embolization.
Benjamin C. Kennedy, Kathleen M. Kelly, Michelle Q. Phan, Samuel S. Bruce, Michael M. McDowell, Richard C. E. Anderson and Neil A. Feldstein
Symptomatic pediatric Chiari malformation Type I (CM-I) is most often treated with posterior fossa decompression (PFD), but controversy exists over whether the dura needs to be opened during PFD. While dural opening as a part of PFD has been suggested to result in a higher rate of resolution of CM symptoms, it has also been shown to lead to more frequent complications. In this paper, the authors present the largest reported series of outcomes after PFD without dural opening surgery, as well as identify risk factors for recurrence.
The authors performed a retrospective review of 156 consecutive pediatric patients in whom the senior authors performed PFD without dural opening from 2003 to 2013. Patient demographics, clinical symptoms and signs, radiographic findings, intraoperative ultrasound results, and neuromonitoring findings were reviewed. Univariate and multivariate regression analyses were performed to determine risk factors for recurrence of symptoms and the need for reoperation.
Over 90% of patients had a good clinical outcome, with improvement or resolution of their symptoms at last follow-up (mean 32 months). There were no major complications. The mean length of hospital stay was 2.0 days. In a multivariate regression model, partial C-2 laminectomy was an independent risk factor associated with reoperation (p = 0.037). Motor weakness on presentation was also associated with reoperation but only with trend-level significance (p = 0.075). No patient with < 8 mm of tonsillar herniation required reoperation.
The vast majority (> 90%) of children with symptomatic CM-I will have improvement or resolution of symptoms after a PFD without dural opening. A non–dural opening approach avoids major complications. While no patient with tonsillar herniation < 8 mm required reoperation, children with tonsillar herniation at or below C-2 have a higher risk for failure when this approach is used.
Benjamin C. Kennedy, Michael M. McDowell, Peter H. Yang, Caroline M. Wilson, Sida Li, Todd C. Hankinson, Neil A. Feldstein and Richard C. E. Anderson
Pediatric patients with sickle cell anemia (SCA) carry a significant risk of developing moyamoya syndrome (MMS) and brain ischemia. The authors sought to review the safety and efficacy of pial synangiosis in the treatment of MMS in children with SCA by performing a comprehensive review of all previously reported cases in the literature.
The authors retrospectively reviewed the clinical and radiographic records in 17 pediatric patients with SCA treated at the Morgan Stanley Children's Hospital of New York (MSCHONY) who developed radiological evidence of MMS and underwent pial synangiosis between 1996 and 2012. The authors then added any additional reported cases of pial synangiosis for this population in the literature for a combined analysis of clinical and radiographic outcomes.
The combined data consisted of 48 pial synangiosis procedures performed in 30 patients. Of these, 27 patients (90%) presented with seizure, stroke, or transient ischemic attack, whereas 3 (10%) were referred after transcranial Doppler screening. At the time of surgery, the median age was 12 years. Thirteen patients (43%) suffered an ischemic stroke while on chronic transfusion therapy. Long-term follow-up imaging (MR angiography or catheter angiography) at a mean of 25 months postoperatively was available in 39 (81%) treated hemispheres. In 34 (87%) of those hemispheres there were demonstrable collateral vessels on imaging. There were 4 neurological events in 1590 cumulative months of follow-up, or 1 event per 33 patient-years. In the patients in whom complete data were available (MSCHONY series, n = 17), the postoperative stroke rate was reduced more than 6-fold from the preoperative rate (p = 0.0003).
Pial synangiosis in patients with SCA, MMS, and brain ischemia appears to be a safe and effective treatment option. Transcranial Doppler and/or MRI screening in asymptomatic patients with SCA is recommended for the diagnosis of MMS.
Benjamin C. Kennedy, Taylor B. Nelp, Kathleen M. Kelly, Michelle Q. Phan, Samuel S. Bruce, Michael M. McDowell, Neil A. Feldstein and Richard C. E. Anderson
Chiari malformation Type I (CM-I) is associated with a syrinx in 25%–85% of patients. Although posterior fossa decompression (PFD) without dural opening is an accepted treatment option for children with symptomatic CM-I, many surgeons prefer to open the dura if a syrinx exists. The purpose of this study was to investigate the frequency and timing of syrinx resolution in children undergoing PFD without dural opening for CM-I.
A retrospective review of 68 consecutive pediatric patients with CM-I and syringomyelia who underwent PFD without dural opening was conducted. Patient demographics, presenting symptoms and signs, radiographic findings, and intraoperative ultrasound and neuromonitoring findings were studied as well as the patients’ clinical and radiographic follow-up.
During the mean radiographic follow-up period of 32 months, 70% of the syringes improved. Syrinx improvement occurred at a mean of 31 months postoperatively. All patients experienced symptom improvement within the 1st year, despite only 26% of patients showing radiographic improvement during that period. Patients presenting with sensory symptoms or motor weakness had a higher likelihood of having radiographic syrinx improvement postoperatively.
In children with CM-I and a syrinx undergoing PFD without dural opening, syrinx resolution occurs in approximately 70% of patients. Radiographic improvement of the syrinx is delayed, but this does not correlate temporally with symptom improvement. Sensory symptoms or motor weakness on presentation are associated with syrinx resolution after surgery.
Richard C. E. Anderson, Benjamin Kennedy, Candix L. Yanes, James Garvin, Michael Needle, Peter Canoll, Neil A. Feldstein and Jeffrey N. Bruce
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.
Benjamin C. Kennedy, Randy S. D’Amico, Brett E. Youngerman, Michael M. McDowell, Kristopher G. Hooten, Daniel Couture, Andrew Jea, Jeffrey Leonard, Sean M. Lew, David W. Pincus, Luis Rodriguez, Gerald F. Tuite, Michael L. Diluna, Douglas L. Brockmeyer, Richard C. E. Anderson and Pediatric Craniocervical Society
The long-term consequences of atlantoaxial (AA) and occipitocervical (OC) fusion and instrumentation in young children are unknown. Anecdotal reports have raised concerns regarding altered growth and alignment of the cervical spine after surgical intervention. The purpose of this study was to determine the long-term effects of these surgeries on the growth and alignment of the maturing spine.
A multiinstitutional retrospective chart review was conducted for patients less than or equal to 6 years of age who underwent OC or AA fusion with rigid instrumentation at 9 participating centers. All patients had at least 3 years of clinical and radiographic follow-up data and radiographically confirmed fusion. Preoperative, immediate postoperative, and most recent follow-up radiographs and/or CT scans were evaluated to assess changes in spinal growth and alignment.
Forty children (9 who underwent AA fusion and 31 who underwent OC fusion) were included in the study (mean follow-up duration 56 months). The mean vertical growth over the fused levels in the AA fusion patients represented 30% of the growth of the cervical spine (range 10%–50%). Three different vertical growth patterns of the fusion construct developed among the 31 OC fusion patients during the follow-up period: 1) 16 patients had substantial growth (13%–46% of the total growth of the cervical spine); 2) 9 patients had no meaningful growth; and 3) 6 patients, most of whom presented with a distracted atlantooccipital dislocation, had a decrease in the height of the fused levels (range 7–23 mm). Regarding spinal alignment, 85% (34/40) of the patients had good alignment at follow-up, with straight or mildly lordotic cervical curvatures. In 1 AA fusion patient (11%) and 5 OC fusion patients (16%), we observed new hyperlordosis (range 43°–62°). There were no cases of new kyphosis or swan-neck deformity, evidence of subaxial instability, or unintended subaxial fusion. No preoperative predictors of these growth patterns or alignment were evident.
These results demonstrate that most young children undergoing AA and OC fusion with rigid internal fixation continue to have good cervical alignment and continued growth within the fused levels during a prolonged follow-up period. However, some variability in vertical growth and alignment exists, highlighting the need to continue close long-term follow-up.
Randy S. D’Amico, Justin A. Neira, Jonathan Yun, Nikita G. Alexiades, Matei Banu, Zachary K. Englander, Benjamin C. Kennedy, Timothy H. Ung, Robert J. Rothrock, Alexander Romanov, Xiaotao Guo, Binsheng Zhao, Adam M. Sonabend, Peter Canoll and Jeffrey N. Bruce
Intracerebral convection-enhanced delivery (CED) has been limited to short durations due to a reliance on externalized catheters. Preclinical studies investigating topotecan (TPT) CED for glioma have suggested that prolonged infusion improves survival. Internalized pump-catheter systems may facilitate chronic infusion. The authors describe the safety and utility of long-term TPT CED in a porcine model and correlation of drug distribution through coinfusion of gadolinium.
Fully internalized CED pump-catheter systems were implanted in 12 pigs. Infusion algorithms featuring variable infusion schedules, flow rates, and concentrations of a mixture of TPT and gadolinium were characterized over increasing intervals from 4 to 32 days. Therapy distribution was measured using gadolinium signal on MRI as a surrogate. A 9-point neurobehavioral scale (NBS) was used to identify side effects.
All animals tolerated infusion without serious adverse events. The average NBS score was 8.99. The average maximum volume of distribution (Vdmax) in chronically infused animals was 11.30 mL and represented 32.73% of the ipsilateral cerebral hemispheric volume. Vdmax was achieved early during infusions and remained relatively stable despite a slight decline as the infusion reached steady state. Novel tissue TPT concentrations measured by liquid chromatography mass spectroscopy correlated with gadolinium signal intensity on MRI (p = 0.0078).
Prolonged TPT-gadolinium CED via an internalized system is safe and well tolerated and can achieve a large Vdmax, as well as maintain a stable Vd for up to 32 days. Gadolinium provides an identifiable surrogate for measuring drug distribution. Extended CED is potentially a broadly applicable and safe therapeutic option in select patients.
Peter J. Madsen, Vivek P. Buch, Jennifer E. Douglas, Arjun K. Parasher, David K. Lerner, Erin Alexander, Alan D. Workman, James N. Palmer, Shih-Shan Lang, Benjamin C. Kennedy, Arastoo Vossough, Nithin D. Adappa and Phillip B. Storm
Craniopharyngioma represents up to 10% of pediatric brain tumors. Although these lesions are benign, attempts at gross-total resection (GTR) can lead to serious complications. More conservative approaches have emerged but require adjuvant radiation. Endoscopic endonasal surgery (EES) aimed at GTR has the potential to result in fewer complications, but there has been limited comparison to open surgery. The authors performed a review of these two approaches within their institution to elucidate potential benefits and complication differences.
The authors performed a retrospective review of pediatric patients undergoing resection of craniopharyngioma at their institution between 2001 and 2017. Volumetric analysis of tumor size and postoperative ischemic injury was performed. Charts were reviewed for a number of outcome measures.
A total of 43 patients with an average age of 8.2 years were identified. Open surgery was the initial intervention in 15 and EES in 28. EES was performed in patients 3–17 years of age. EES has been the only approach used since 2011. In the entire cohort, GTR was more common in the EES group (85.7% vs 53.3%, p = 0.03). Recurrence rate (40% vs 14.2%, p = 0.13) and need for adjuvant radiation (20.0% vs 10.7%, p = 0.71) were higher in the open surgical group, although not statistically significant. Pseudoaneurysm development was only observed in the open surgical group. Volumetric imaging analysis showed a trend toward larger preoperative tumor volumes in the open surgical group, so a matched cohort analysis was performed with the largest tumors from the EES group. This revealed no difference in residual tumor volume (p = 0.28), but the volume of postoperative ischemia was still significantly larger in the open group (p = 0.004). Postoperative weight gain was more common in the open surgical group, a statistically significant finding in the complete patient group that trended toward significance in the matched cohort groups. Body mass index at follow-up correlated with volume of ischemic injury in regression analysis of the complete patient cohort (p = 0.05).
EES was associated with similar, if not better, extent of resection and significantly less ischemic injury than open surgery. Pseudoaneurysms were only seen in the open surgical group. Weight gain was also less prevalent in the EES cohort and appears be correlated with extent of ischemic injury at time of surgery.