The two-hit hypothesis of neural injury in the wake of open neural tube defects suggests an opportunity for preservation of function and potential reversibility of early morphological changes in the fetus diagnosed with myelomeningocele. The Management of Myelomeningocele Study (MOMS) demonstrated reduced need for shunting and improved neurological function in patients treated in utero relative to postnatally, thereby offering level 1 evidence supporting fetal repair. Subsequent studies have offered additional information about urological, orthopedic, radiological, and maternal factors surrounding fetal repair. The quest for robust long-term neurocognitive and motor function data is underway and poised to shape the future of fetal repair. In addition, technical innovations such as fetoscopic surgery aim to minimize maternal morbidity while conferring the beneficial effects observed with open intrauterine intervention.
JNSPG 75th Anniversary Invited Review Article
Michael C. Dewan and John C. Wellons III
Krishnan Ravindran, John C. Wellons and Michael C. Dewan
The optimal revascularization for pediatric moyamoya for reducing the incidence of future stroke events remains to be determined.
The authors conducted a search of PubMed, MEDLINE, Embase, and Web of Science electronic databases from inception until January 2019. The primary endpoint was the presence of a future ischemic stroke event. Secondary endpoints were angiographic outcomes as measured by postoperative Matsushima grade and clinical symptom persistence. Patients who underwent either direct or combined direct/indirect revascularization were classified into the direct cohort. Data from each study on presence of postoperative stroke events were used to generate standardized mean differences and 95% confidence intervals, which were combined using inverse variance-weighted averages of standardized mean differences in a random effects model.
Twenty-nine studies met the inclusion criteria for analysis, comprising 2258 patients (1011 males, mean age 8.3 ± 1.8 years) who were followed up clinically for an average of 71.4 ± 51.3 months. One hundred fifty-four patients underwent direct bypass alone, 680 patients underwent either direct or combined direct/indirect revascularization procedures, while 1424 patients underwent indirect bypass alone. The frequencies of future stroke events in patients undergoing direct bypass alone, combined bypass, or indirect bypass alone were 1 per 190.3 patient-years, 1 per 108.9 patient-years, and 1 per 61.1 patient-years, respectively, in each cohort. The estimated stroke rates were 9.0% with indirect revascularization, 4.5% with direct revascularization alone, and 6.0% with combined revascularization. A forest plot did not reveal any significant differences in the incidence of future stroke events or angiographic outcomes following direct-only, combined, or indirect-only revascularization.
Direct, indirect, and combined indirect/direct bypass techniques are all effective revascularization options for pediatric moyamoya disease. A relative paucity of granular studies—and inherent surgical selection bias—limits direct comparison between interventions. Suitably designed prospective cohort studies may be useful in identifying patients likely to receive benefit from specific procedures.
Benjamin C. Warf, Michael Dewan and John Mugamba
Dandy-Walker complex (DWC) is a continuum of congenital anomalies comprising Dandy-Walker malformation (DWM), Dandy-Walker variant (DWV), Blake pouch cyst, and mega cisterna magna (MCM). Hydrocephalus is variably associated with each of these, and DWC-associated hydrocephalus has mostly been treated by shunting, often with 2-compartment shunting. There are few reports of management by endoscopic third ventriculostomy (ETV). This study is the largest series of DWC or DWM-associated hydrocephalus treated by ETV, and the first report of treatment by combined ETV and choroid plexus cauterization (ETV/CPC) in young infants with this association.
A retrospective review of the CURE Children's Hospital of Uganda clinical database between 2004 and 2010 identified 45 patients with DWC confirmed by CT scanning (25 with DWM, 17 with DWV, and 3 with MCM) who were treated for hydrocephalus by ETV/CPC. Three were excluded because of other potential causes of hydrocephalus (2 postinfectious and 1 posthemorrhagic).
The median age at treatment was 5 months (88% of patients were younger than 12 months). There was a 2.4:1 male predominance among patients with DWV. An ETV/CPC (ETV only in one) was successful with no further operations in 74% (mean and median follow-up 24.2 and 20 months, respectively [range 6–65 months]). The rate of success was 74% for DWM, 73% for DWV, and 100% for MCM; 95% had an open aqueduct, and none required posterior fossa shunting.
Endoscopic treatment of DWC-associated hydrocephalus should be strongly considered as the primary management in place of the historical standard of creating shunt dependence.
Michael C. Dewan, Jaims Lim, Chevis N. Shannon and John C. Wellons III
Up to one-third of patients with a posterior fossa brain tumor (PFBT) will experience persistent hydrocephalus mandating permanent CSF diversion. The optimal hydrocephalus treatment modality is unknown; the authors sought to compare the durability between endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) therapy in the pediatric population.
The authors conducted a systematic review of articles indexed in PubMed between 1986 and 2016 describing ETV and/or VPS treatment success/failure and time-to-failure rate in patients < 19 years of age with hydrocephalus related to a PFBT. Additionally, the authors conducted a retrospective review of their institutional series of PFBT patients requiring CSF diversion. Patient data from the systematic review and from the institutional series were aggregated and a time-to-failure analysis was performed comparing ETV and VPS using the Kaplan-Meier method.
A total of 408 patients were included from 12 studies and the authors' institutional series: 284 who underwent ETV and 124 who underwent VPS placement. The analysis included uncontrolled studies with variable method and timing of CSF diversion and were subject to surgeon bias. No significant differences between cohorts were observed with regard to age, sex, tumor grade or histology, metastatic status, or extent of resection. The cumulative failure rate of ETV was 21%, whereas that of VPS surgery was 29% (p = 0.105). The median time to failure was earlier for ETV than for VPS surgery (0.82 [IQR 0.2–1.8] vs 4.7 months [IQR 0.3–5.7], p = 0.03). Initially the ETV survival curve dropped sharply and then stabilized around 2 months. The VPS curve fell gradually but eventually crossed below the ETV curve at 5.7 months. Overall, a significant survival advantage was not demonstrated for one procedure over the other (p = 0.21, log-rank). However, postoperative complications were higher following VPS (31%) than ETV (17%) (p = 0.012).
ETV failure occurred sooner than VPS failure, but long-term treatment durability may be higher for ETV. Complications occurred more commonly with VPS than with ETV. Limited clinical conclusions are drawn using this methodology; the optimal treatment for PFBT-related hydrocephalus warrants investigation through prospective studies.
Nishit Mummareddy, Michael C. Dewan, Michael R. Mercier, Robert P. Naftel, John C. Wellons III and Christopher M. Bonfield
The authors aimed to provide an updated and consolidated report on the epidemiology, management, and functional outcome of cases of myelomeningocele (MMC) in patients with scoliosis.
A comprehensive literature search was performed using MEDLINE, Embase, Google Scholar, and the Cochrane Database of Systematic Reviews on cases of MMC in patients with scoliosis between 1980 and 2016. The initial search yielded 670 reports. After removing duplicates and applying inclusion criteria, we included 32 full-text original articles in this study.
Pooled statistical analysis of the included articles revealed the prevalence of scoliosis in MMC patients to be 53% (95% CI 0.42–0.64). Slightly more females (56%) are affected with both MMC and scoliosis than males. Motor level appears to be a significant predictor of prevalence, but not severity, of scoliosis in MMC patients. Treatment options for these patients include tethered cord release (TCR) and fusion surgeries. Curvature improvement and stabilization after TCR may be limited to patients with milder (< 50°) curves. Meanwhile, more aggressive fusion procedures such as a combined anterior-posterior approach may result in more favorable long-term scoliosis correction, albeit with greater complication rates. Quality of life metrics including ambulatory status and sitting stability are influenced by motor level of the lesion as well as the degree of the scoliosis curvature.
Scoliosis is among the most common and challenging comorbidities from which patients with MMC suffer. Although important epidemiological and management trends are evident, larger, prospective studies are needed to discover ways to more accurately counsel and more optimally treat these patients.
Michael C. Dewan, Reid C. Thompson, Steven N. Kalkanis, Fred G. Barker II and Constantinos G. Hadjipanayis
Antiepileptic drugs (AEDs) are often administered prophylactically following brain tumor resection. With conflicting evidence and unestablished guidelines, however, the nature of this practice among tumor surgeons is unknown.
On November 24, 2015, a REDCap (Research Electronic Database Capture) survey was sent to members of the AANS/CNS Section on Tumors to query practice patterns.
Responses were received from 144 individuals, including 18.8% of board-certified neurosurgeons surveyed (across 86 institutions, 16 countries, and 5 continents). The majority reported practicing in an academic setting (85%) as a tumor specialist (71%). Sixty-three percent reported always or almost always prescribing AED prophylaxis postoperatively in patients with a supratentorial brain tumor without a prior seizure history. Meanwhile, 9% prescribed occasionally and 28% rarely prescribed AED prophylaxis. The most common agent was levetiracetam (85%). The duration of seizure prophylaxis varied widely: 25% of surgeons administered prophylaxis for 7 days, 16% for 2 weeks, 21% for 2 to 6 weeks, and 13% for longer than 6 weeks. Most surgeons (61%) believed that tumor pathology influences epileptogenicity, with high-grade glioma (39%), low-grade glioma (31%), and metastases (24%) carrying the greatest seizure risk. While the majority used prophylaxis, 62% did not believe or were unsure if prophylactic AEDs reduced seizures postoperatively. The vast majority (82%) stated that a well-designed randomized trial would help guide their future clinical decision making.
Wide knowledge and practice gaps exist regarding the frequency, duration, and setting of AED prophylaxis for seizure-naive patients undergoing brain tumor resection. Acceptance of universal practice guidelines on this topic is unlikely until higher-level evidence supporting or refuting the value of modern seizure prophylaxis is demonstrated.
Michael C. Dewan, Gabrielle A. White-Dzuro, Philip R. Brinson, Reid C. Thompson and Lola B. Chambless
Seizures are among the most common perioperative complications in patients undergoing craniotomy for brain tumor resection and have been associated with increased disease progression and decreased survival. Little evidence exists regarding the relationship between postoperative seizures and hospital quality measures, including length of stay (LOS), disposition, and readmission. The authors sought to address these questions by analyzing a glioma population over 15 years.
A retrospective cohort study was used to evaluate the outcomes of patients who experienced a postoperative seizure. Patients with glioma who underwent craniotomy for resection between 1998 and 2013 were enrolled in the institutional tumor registry. Basic data, including demographics and comorbidities, were recorded in addition to hospitalization details and complications. Seizures were diagnosed by clinical examination, observation, and electroencephalography. The Student t-test and chi-square test were used to analyze differences in the means between continuous and categorical variables, respectively. Multivariate logistic and linear regression was used to compare multiple clinical variables against hospital quality metrics and survival figures, respectively.
In total, 342 patients with glioma underwent craniotomy for first-time resection. The mean age was 51.0 ± 17.3 years, 192 (56.1%) patients were male, and the median survival time for all grades was 15.4 months (range 6.2–24.0 months). High-grade glioma (Grade III or IV) was seen in 71.9% of patients. Perioperative antiepileptic drugs were administered to 88% of patients. Eighteen (5.3%) patients experienced a seizure within 14 days postoperatively, and 9 (50%) of these patients experienced first-time seizures. The mean time to the first postoperative seizure was 4.3 days (range 0–13 days). There was no significant association between tumor grade and the rate of perioperative seizure (Grade I, 0%; II, 7.0%; III, 6.1%; IV, 5.2%; p = 0.665). A single ictal episode occurred in 11 patients, while 3 patients experienced 2 seizures and 4 patients developed 3 or more seizures. Compared with their seizure-free counterparts, patients who experienced a perioperative seizure had an increased average hospital (6.8 vs 3.6 days, p = 0.032) and ICU LOS (5.4 vs 2.3 days; p < 0.041). Seventy-five percent of seizure-free patients were discharged home in comparison with 55.6% of seizure patients (p = 0.068). Patients with a postoperative seizure were significantly more likely to visit the emergency department within 90 days (44.4% vs 19.0%; OR 3.41 [95% CI 1.29–9.02], p = 0.009) and more likely to be readmitted within 90 days (50.0% vs 18.4%; OR 4.45 [95% CI 1.69–11.70], p = 0.001). In addition, seizure-free patients had a longer median overall survival (15.6 months [interquartile range 6.6–24.4 months] vs 3.0 months [interquartile range 1.0–25.0 months]; p = 0.013).
Patients with perioperative seizures following glioma resection required longer hospital and ICU LOS, were readmitted at higher rates than seizure-free patients, and experienced shorter overall survival. Biological and clinical factors that predispose to the development of seizures after glioma surgery portend a worse outcome. Efforts to identify these factors and reduce the risk of postoperative seizure should remain a priority among neurosurgical oncologists.