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Akshitkumar M. Mistry, Nishit Mummareddy, Travis S. CreveCoeur, Jock C. Lillard, Brandy N. Vaughn, Jean-Nicolas Gallant, Andrew T. Hale, Natalie Griffin, John C. Wellons III, David D. Limbrick Jr., Paul Klimo Jr. and Robert P. Naftel

OBJECTIVE

The subventricular zone (SVZ), housed in the lateral walls of the lateral ventricles, is the largest neurogenic niche in the brain. In adults, high-grade gliomas in contact or involved with the SVZ are associated with decreased survival. Whether this association holds true in the pediatric population remains unexplored. To address this gap in knowledge, the authors conducted this retrospective study in a pediatric population with high-grade gliomas treated at three comprehensive centers in the United States.

METHODS

The authors retrospectively identified 63 patients, age ≤ 21 years, with supratentorial WHO grade III–IV gliomas treated at three academic centers. Basic demographic and clinical data regarding presenting signs and symptoms and common treatment variables were obtained. Preoperative MRI studies were evaluated to assess SVZ contact by tumor and to quantify tumor volume.

RESULTS

Sixty-three patients, including 34 males (54%), had a median age of 12.3 years (IQR 6.50–16.2) and a median tumor volume of 39.4 ml (IQR 19.4–65.8). Tumors contacting the SVZ (SVZ+) were noted in 34 patients (54%) and overall were larger than those not in contact with the SVZ (SVZ−; 51.1 vs 27.3, p = 0.002). The SVZ+ tumors were also associated with decreased survival. However, age, tumor volume, tumor grade, and treatment with chemotherapy and/or radiation were not associated with survival in the 63 patients. In the univariable analysis, near-total resection, gross-total resection, and seizure presentation were associated with increased survival (HR = 0.23, 95% CI 0.06–0.88, p = 0.03; HR = 0.26, 95% CI 0.09–0.74, p = 0.01; and HR = 0.46, 95% CI 0.22–0.97, p = 0.04, respectively). In a multivariable stepwise Cox regression analysis, only SVZ+ tumors remained significantly associated with decreased survival (HR = 1.94, 95% CI 1.03–3.64, p = 0.04).

CONCLUSIONS

High-grade glioma contact with the SVZ neural stem cell niche was associated with a significant decrease in survival in the pediatric population, as it is in the adult population. This result suggests that tumor contact with the SVZ is a general negative prognosticator in high-grade glioma independent of age group and invites biological investigations to understand the SVZ’s role in glioma pathobiology.

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Han Yan, Nebras M. Warsi, Abhaya V. Kulkarni, James M. Drake and George M. Ibrahim

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Silky Chotai, Emily W. Chan, Travis R. Ladner, Andrew T. Hale, Stephen R. Gannon, Chevis N. Shannon, Christopher M. Bonfield, Robert P. Naftel and John C. Wellons

OBJECTIVE

The aim of this study was to determine the timeline of syrinx regression and to identify factors mitigating syrinx resolution in pediatric patients with Chiari malformation type I (CM-I) undergoing posterior fossa decompression (PFD).

METHODS

The authors conducted a retrospective review of records from pediatric patients (< 18 years old) undergoing PFD for the treatment of CM-I/syringomyelia (SM) between 1998 and 2015. Patient demographic, clinical, radiological, and surgical variables were collected and analyzed. Radiological information was reviewed at 4 time points: 1) pre-PFD, 2) within 6 months post-PFD, 3) within 12 months post-PFD, and 4) at maximum available follow-up. Syrinx regression was defined as ≥ 50% decrease in the maximal anteroposterior syrinx diameter (MSD). The time to syrinx regression was determined using Kaplan-Meier analysis. Multivariate analysis was conducted using a Cox proportional hazards model to determine the association between preoperative, clinical, and surgery-related factors and syrinx regression.

RESULTS

The authors identified 85 patients with CM-I/SM who underwent PFD. Within 3 months post-PFD, the mean MSD regressed from 8.1 ± 3.4 mm (preoperatively) to 5.6 ± 2.9 mm within 3 months post-PFD. Seventy patients (82.4%) achieved ≥ 50% regression in MSD. The median time to ≥ 50% regression in MSD was 8 months (95% CI 4.2–11.8 months). Using a risk-adjusted multivariable Cox proportional hazards model, the patients who underwent tonsil coagulation (n = 20) had a higher likelihood of achieving ≥ 50% syrinx regression in a shorter time (HR 2.86, 95% CI 1.2–6.9; p = 0.02). Thirty-six (75%) of 45 patients had improvement in headache at 2.9 months (IQR 1.5–4.4 months).

CONCLUSIONS

The maximum reduction in syrinx size can be expected within 3 months after PFD for patients with CM-I and a syrinx; however, the syringes continue to regress over time. Tonsil coagulation was associated with early syrinx regression in this cohort. However, the role of surgical maneuvers such as tonsil coagulation and arachnoid veil identification and sectioning in the overall role of CM-I surgery remains unclear.

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John C. Wellons III, Gerald Grant, Mark D. Krieger, John Ragheb, Shenandoah Robinson, Bradley Weprin and Jeffrey Ojemann

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Andrew T. Hale, P. David Adelson, Gregory W. Albert, Philipp R. Aldana, Tord D. Alden, Richard C. E. Anderson, David F. Bauer, Christopher M. Bonfield, Douglas L. Brockmeyer, Joshua J. Chern, Daniel E. Couture, David J. Daniels, Susan R. Durham, Richard G. Ellenbogen, Ramin Eskandari, Timothy M. George, Gerald A. Grant, Patrick C. Graupman, Stephanie Greene, Jeffrey P. Greenfield, Naina L. Gross, Daniel J. Guillaume, Gregory G. Heuer, Mark Iantosca, Bermans J. Iskandar, Eric M. Jackson, James M. Johnston, Robert F. Keating, Jeffrey R. Leonard, Cormac O. Maher, Francesco T. Mangano, J. Gordon McComb, Thanda Meehan, Arnold H. Menezes, Brent O’Neill, Greg Olavarria, Tae Sung Park, John Ragheb, Nathan R. Selden, Manish N. Shah, Matthew D. Smyth, Scellig S. D. Stone, Jennifer M. Strahle, Scott D. Wait, John C. Wellons, William E. Whitehead, Chevis N. Shannon, David D. Limbrick Jr. and for the Park-Reeves Syringomyelia Research Consortium Investigators

OBJECTIVE

Factors associated with syrinx size in pediatric patients undergoing posterior fossa decompression (PFD) or PFD with duraplasty (PFDD) for Chiari malformation type I (CM-I) with syringomyelia (SM; CM-I+SM) are not well established.

METHODS

Using the Park-Reeves Syringomyelia Research Consortium registry, the authors analyzed variables associated with syrinx radiological outcomes in patients (< 20 years old at the time of surgery) with CM-I+SM undergoing PFD or PFDD. Syrinx resolution was defined as an anteroposterior (AP) diameter of ≤ 2 mm or ≤ 3 mm or a reduction in AP diameter of ≥ 50%. Syrinx regression or progression was defined using 1) change in syrinx AP diameter (≥ 1 mm), or 2) change in syrinx length (craniocaudal, ≥ 1 vertebral level). Syrinx stability was defined as a < 1-mm change in syrinx AP diameter and no change in syrinx length.

RESULTS

The authors identified 380 patients with CM-I+SM who underwent PFD or PFDD. Cox proportional hazards modeling revealed younger age at surgery and PFDD as being independently associated with syrinx resolution, defined as a ≤ 2-mm or ≤ 3-mm AP diameter or ≥ 50% reduction in AP diameter. Radiological syrinx resolution was associated with improvement in headache (p < 0.005) and neck pain (p < 0.011) after PFD or PFDD. Next, PFDD (p = 0.005), scoliosis (p = 0.007), and syrinx location across multiple spinal segments (p = 0.001) were associated with syrinx diameter regression, whereas increased preoperative frontal-occipital horn ratio (FOHR; p = 0.007) and syrinx location spanning multiple spinal segments (p = 0.04) were associated with syrinx length regression. Scoliosis (HR 0.38 [95% CI 0.16–0.91], p = 0.03) and smaller syrinx diameter (5.82 ± 3.38 vs 7.86 ± 3.05 mm; HR 0.60 [95% CI 0.34–1.03], p = 0.002) were associated with syrinx diameter stability, whereas shorter preoperative syrinx length (5.75 ± 4.01 vs 9.65 ± 4.31 levels; HR 0.21 [95% CI 0.12–0.38], p = 0.0001) and smaller pB-C2 distance (6.86 ± 1.27 vs 7.18 ± 1.38 mm; HR 1.44 [95% CI 1.02–2.05], p = 0.04) were associated with syrinx length stability. Finally, younger age at surgery (8.19 ± 5.02 vs 10.29 ± 4.25 years; HR 1.89 [95% CI 1.31–3.04], p = 0.01) was associated with syrinx diameter progression, whereas increased postoperative syrinx diameter (6.73 ± 3.64 vs 3.97 ± 3.07 mm; HR 3.10 [95% CI 1.67–5.76], p = 0.003), was associated with syrinx length progression. PFD versus PFDD was not associated with syrinx progression or reoperation rate.

CONCLUSIONS

These data suggest that PFDD and age are independently associated with radiological syrinx improvement, although forthcoming results from the PFDD versus PFD randomized controlled trial (NCT02669836, clinicaltrials.gov) will best answer this question.

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Jonathan Dallas, Evan Mercer, Rebecca A. Reynolds, John C. Wellons III, Chevis N. Shannon and Christopher M. Bonfield

OBJECTIVE

Isolated, nondisplaced skull fractures (ISFs) are a common result of pediatric head trauma. They rarely require surgical intervention; however, many patients with these injuries are still admitted to the hospital for observation. This retrospective study investigates predictors of vomiting and ondansetron use following pediatric ISFs and the role that these factors play in the need for admission and emergency department (ED) revisits.

METHODS

The authors identified pediatric patients (< 18 years old) with a linear ISF who had presented to the ED of a single tertiary care center between 2008 and 2018. Patients with intracranial hemorrhage, significant fracture displacement, or other traumatic injuries were excluded. Outcomes included vomiting, ondansetron use, admission, and revisit following ED discharge. Both univariable and multivariable analyses were used to determine significant predictors of each outcome (p < 0.05).

RESULTS

Overall, 518 patients were included in this study. The median patient age was 9.98 months, and a majority of the patients (59%) were male. The most common fracture locations were parietal (n = 293 [57%]) and occipital (n = 144 [28%]). Among the entire patient cohort, 124 patients (24%) had documented vomiting, and 64 of these patients (52%) received ondansetron. In a multivariable analysis, one of the most significant predictors of vomiting was occipital fracture location (OR 4.05, p < 0.001). In turn, and as expected, both vomiting (OR 14.42, p < 0.001) and occipital fracture location (OR 2.66, p = 0.017) were associated with increased rates of ondansetron use. A total of 229 patients (44%) were admitted to the hospital, with vomiting as the most common indication for admission (n = 59 [26%]). Moreover, 4.1% of the patients had ED revisits following initial discharge, and the most common reason was vomiting (11/21 [52%]). However, in the multivariable analysis, ondansetron use at initial presentation (and not vomiting) was the sole predictor of revisit following initial ED discharge (OR 5.05, p = 0.009).

CONCLUSIONS

In this study, older patients and those with occipital fractures were more likely to present with vomiting and to be treated with ondansetron. Additionally, ondansetron use at initial presentation was found to be a significant predictor of revisits following ED discharge. Ondansetron could be masking recurrent vomiting in ED patients, and this should be considered when deciding which patients to observe further or discharge.

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Andrew T. Hale, Stephen R. Gannon, Shilin Zhao, Michael C. Dewan, Ritwik Bhatia, Michael Bezzerides, Amanda N. Stanton, Robert P. Naftel, Chevis N. Shannon, Sumit Pruthi and John C. Wellons III

OBJECTIVE

The authors aimed to evaluate clinical, radiological, and surgical factors associated with posterior fossa tumor resection (PFTR)–related outcomes, including postoperative complications related to dural augmentation (CSF leak and wound infection), persistent hydrocephalus ultimately requiring permanent CSF diversion after PFTR, and 90-day readmission rate.

METHODS

Pediatric patients (0–17 years old) undergoing PFTR between 2000 and 2016 at Monroe Carell Jr. Children’s Hospital of Vanderbilt University were retrospectively reviewed. Descriptive statistics included the Wilcoxon signed-rank test to compare means that were nonnormally distributed and the chi-square test for categorical variables. Variables that were nominally associated (p < 0.05) with each outcome by univariate analysis were included as covariates in multivariate linear regression models. Statistical significance was set a priori at p < 0.05.

RESULTS

The cohort consisted of 186 patients with a median age at surgery of 6.62 years (range 3.37–11.78 years), 55% male, 83% Caucasian, and average length of follow-up of 3.87 ± 0.25 years. By multivariate logistic regression, the variables primary dural closure (PDC; odds ratio [OR] 8.33, 95% confidence interval [CI] 1.07–100, p = 0.04), pseudomeningocele (OR 7.43, 95% CI 2.23–23.76, p = 0.0007), and hydrocephalus ultimately requiring permanent CSF diversion within 90 days of PFTR (OR 9.25, 95% CI 2.74–31.2, p = 0.0003) were independently associated with CSF leak. PDC versus graft dural closure (GDC; 35% vs 7%, OR 5.88, 95% CI 2.94–50.0, p = 0.03) and hydrocephalus ultimately requiring permanent CSF diversion (OR 3.30, 95% CI 1.07–10.19, p = 0.0007) were associated with wound infection requiring surgical debridement. By multivariate logistic regression, GDC versus PDC (23% vs 37%, OR 0.13, 95% CI 0.02–0.87, p = 0.04) was associated with persistent hydrocephalus ultimately requiring permanent CSF diversion, whereas pre- or post-PFTR ventricular size, placement of peri- or intraoperative extraventricular drain (EVD), and radiation therapy were not. Furthermore, the addition of perioperative EVD placement and dural closure method to a previously validated predictive model of post-PFTR hydrocephalus improved its performance from area under the receiver operating characteristic curve of 0.69 to 0.74. Lastly, the authors found that autologous (vs synthetic) grafts may be protective against persistent hydrocephalus (p = 0.02), but not CSF leak, pseudomeningocele, or wound infection.

CONCLUSIONS

These results suggest that GDC, independent of potential confounding factors, may be protective against CSF leak, wound infection, and hydrocephalus in patients undergoing PFTR. Additional studies are warranted to further evaluate clinical and surgical factors impacting PFTR-associated complications.

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Brandon G. Rocque, Betsy D. Hopson and Jeffrey P. Blount

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Krishnan Ravindran, John C. Wellons and Michael C. Dewan

OBJECTIVE

The optimal revascularization for pediatric moyamoya for reducing the incidence of future stroke events remains to be determined.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

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Jennifer M. Strahle, Rukayat Taiwo, Christine Averill, James Torner, Chevis N. Shannon, Christopher M. Bonfield, Gerald F. Tuite, Tammy Bethel-Anderson, Jerrel Rutlin, Douglas L. Brockmeyer, John C. Wellons III, Jeffrey R. Leonard, Francesco T. Mangano, James M. Johnston, Manish N. Shah, Bermans J. Iskandar, Elizabeth C. Tyler-Kabara, David J. Daniels, Eric M. Jackson, Gerald A. Grant, Daniel E. Couture, P. David Adelson, Tord D. Alden, Philipp R. Aldana, Richard C. E. Anderson, Nathan R. Selden, Lissa C. Baird, Karin Bierbrauer, Joshua J. Chern, William E. Whitehead, Richard G. Ellenbogen, Herbert E. Fuchs, Daniel J. Guillaume, Todd C. Hankinson, Mark R. Iantosca, W. Jerry Oakes, Robert F. Keating, Nickalus R. Khan, Michael S. Muhlbauer, J. Gordon McComb, Arnold H. Menezes, John Ragheb, Jodi L. Smith, Cormac O. Maher, Stephanie Greene, Michael Kelly, Brent R. O’Neill, Mark D. Krieger, Mandeep Tamber, Susan R. Durham, Greg Olavarria, Scellig S. D. Stone, Bruce A. Kaufman, Gregory G. Heuer, David F. Bauer, Gregory Albert, Jeffrey P. Greenfield, Scott D. Wait, Mark D. Van Poppel, Ramin Eskandari, Timothy Mapstone, Joshua S. Shimony, Ralph G. Dacey Jr., Matthew D. Smyth, Tae Sung Park and David D. Limbrick Jr.

OBJECTIVE

Scoliosis is frequently a presenting sign of Chiari malformation type I (CM-I) with syrinx. The authors’ goal was to define scoliosis in this population and describe how radiological characteristics of CM-I and syrinx relate to the presence and severity of scoliosis.

METHODS

A large multicenter retrospective and prospective registry of pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for clinical and radiological characteristics of CM-I, syrinx, and scoliosis (coronal curve ≥ 10°).

RESULTS

Based on available imaging of patients with CM-I and syrinx, 260 of 825 patients (31%) had a clear diagnosis of scoliosis based on radiographs or coronal MRI. Forty-nine patients (5.9%) did not have scoliosis, and in 516 (63%) patients, a clear determination of the presence or absence of scoliosis could not be made. Comparison of patients with and those without a definite scoliosis diagnosis indicated that scoliosis was associated with wider syrinxes (8.7 vs 6.3 mm, OR 1.25, p < 0.001), longer syrinxes (10.3 vs 6.2 levels, OR 1.18, p < 0.001), syrinxes with their rostral extent located in the cervical spine (94% vs 80%, OR 3.91, p = 0.001), and holocord syrinxes (50% vs 16%, OR 5.61, p < 0.001). Multivariable regression analysis revealed syrinx length and the presence of holocord syrinx to be independent predictors of scoliosis in this patient cohort. Scoliosis was not associated with sex, age at CM-I diagnosis, tonsil position, pB–C2 distance (measured perpendicular distance from the ventral dura to a line drawn from the basion to the posterior-inferior aspect of C2), clivoaxial angle, or frontal-occipital horn ratio. Average curve magnitude was 29.9°, and 37.7% of patients had a left thoracic curve. Older age at CM-I or syrinx diagnosis (p < 0.0001) was associated with greater curve magnitude whereas there was no association between syrinx dimensions and curve magnitude.

CONCLUSIONS

Syrinx characteristics, but not tonsil position, were related to the presence of scoliosis in patients with CM-I, and there was an independent association of syrinx length and holocord syrinx with scoliosis. Further study is needed to evaluate the nature of the relationship between syrinx and scoliosis in patients with CM-I.