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Comparative study of preoperative functional imaging combined with tractography for prediction of iatrogenic motor deficits

Matthew Muir, Ron Gadot, Sarah Prinsloo, Hayley Michener, Jeffrey Traylor, Prazwal Athukuri, Sudhakar Tummala, Vinodh A. Kumar, and Sujit S. Prabhu

OBJECTIVE

Robust preoperative imaging can improve the extent of resection in patients with brain tumors while minimizing postoperative neurological morbidity. Both structural and functional imaging techniques can provide helpful preoperative information. A recent study found that transcranial magnetic stimulation (TMS) tractography has significant predictive value for permanent deficits. The present study directly compares the predictive value of TMS tractography and task-based functional MRI (fMRI) tractography in the same cohort of glioma patients.

METHODS

Clinical outcome data were collected from charts of patients with motor eloquent glioma and preoperative fMRI and TMS studies. The primary outcome was a new or worsened motor deficit present at the 3-month postoperative follow-up, which was termed a "permanent deficit." Postoperative MR images were overlaid onto preoperative plans to determine which imaging features were resected. Multiple fractional anisotropic thresholds (FATs) were screened for both TMS and fMRI tractography. The predictive value of the various thresholds was modeled using receiver operating characteristic curve analysis.

RESULTS

Forty patients were included in this study. Six patients (15%) sustained permanent postoperative motor deficits. A significantly greater predictive value was found for TMS tractography than for fMRI tractography regardless of the FAT. Despite 35% of patients showing clinically relevant neuroplasticity captured by TMS, only 2.5% of patients showed a blood oxygen level–dependent signal displaced from the precentral gyrus. Comparing the best-performing FAT for both modalities, TMS seeded tractography showed superior predictive value across all metrics: sensitivity, specificity, positive predictive value, and negative predictive value.

CONCLUSIONS

The results from this study indicate that the prediction of permanent deficits with TMS tractography is superior to that with fMRI tractography, possibly because TMS tractography captures clinically relevant neuroplasticity. However, future large-scale prospective studies are needed to fully illuminate the proper role of each modality in comprehensive presurgical workups for patients with motor-eloquent tumors.

In Journal of Neurosurgery Publish Before Print

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Current state and future direction of quality improvement in pediatric neurosurgery: a survey of pediatric neurosurgeons

Gabriella Pendola, George W. Koutsouras, Joseph Piatt, Bruce A. Kaufman, Carolina Sandoval-Garcia, and Annie I. Drapeau

OBJECTIVE

Quality improvement (QI) is a methodology used to implement sustainable, meaningful change to improve patient outcomes. Given the complex pathologies observed in pediatric neurosurgery, QI projects could potentially improve patient care. Overall, there is a need to characterize the degree of QI opportunities, training, and initiatives within the field of pediatric neurosurgery. Herein the authors aimed to define the current QI landscape in pediatric neurosurgery.

METHODS

A cross-sectional survey was sent to all members of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section on Pediatric Neurological Surgery via email. The responses were anonymized. Questions addressed several relatable QI topics including 1) training and participation in QI; 2) QI infrastructure; 3) QI program incentives; and 4) general opinions on the National Surgical Quality Improvement Program (NSQIP) database, various QI topics, and QI productivity.

RESULTS

Responses were received from 129 participants (20% response rate). Most respondents practiced in an academic setting (59.8%) and at a free-standing pediatric hospital (65.4%). Participation in QI projects was high (81.7%), but only 23.8% of respondents had formal QI training. Only 36.5% of respondents had institutional requirements for QI work; the majority of those were only required to participate as a project team member. Nearly half of the respondents did not receive incentives or institutional support for QI. The majority agreed ("strongly" and "somewhat") that a QI course would be beneficial (75.5%), that QI projects should be considered for publication in neurosurgery journals (88.1%), and that there is a need for national quality metrics (81.4%). Over 88% have an interest in seeing QI project presentations at the annual Pediatric Joint Section meeting. Only 26.3% believed that the NSQIP was a useful QI guide. Respondents suggested further study of the following QI topics: overall rates of infection and their prevention, hydrocephalus, standardized treatment algorithms for common disorders, team communication, pediatric neurosurgery–specific database, access to care, and interprofessional education.

CONCLUSIONS

Areas of opportunity include specialty-specific QI education, tactics for obtaining support to build the QI infrastructure, increased visibility of QI work within pediatric neurosurgery, and a review of available registries to provide readily available data relevant to this specialty.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Intrauterine closure of myelomeningocele defects with primary linear repair versus bipedicle fasciocutaneous flaps: a post-MOMS cohort study with long-term follow-up

Matthew E. Pontell, Aaron M. Yengo-Kahn, Emily Taylor, Morgan Kane, J Michael Newton, Kelly A. Bennett, John C. Wellons III, and Stephane A. Braun

OBJECTIVE

The objective of this study was to determine the effects of in utero bipedicle flaps on maternal-fetal morbidity/mortality, the need for CSF diversion, and long-term functional outcomes.

METHODS

Eighty-six patients who underwent fetal myelomeningocele repair from 2011 to 2021 at a single institution were reviewed. Primary outcomes included intrauterine fetal demise, postnatal death, postnatal myelomeningocele repair dehiscence, and CSF diversion by final follow-up.

RESULTS

The cohorts were no different with regard to race, ethnicity, maternal age at fetal surgery, body mass index, gravidity, parity, gestational age at fetal surgery, estimated fetal weight at fetal surgery, or fetal lesion level. Of the 86 patients, 64 underwent primary linear repair and 22 underwent bipedicle flap repair. There were no significant differences in rates of intrauterine fetal demise, postnatal mortality, midline repair site dehiscence, or the need for CSF diversion by final follow-up. Operative times were longer (32.5 vs 18.7 minutes, p < 0.001) and gestational age at delivery was lower (232 vs 241 days, p = 0.01) in the bipedicle flap cohort, but long-term functional outcomes were not different.

CONCLUSIONS

Analysis of the total cohort affirms the long-term benefits of fetal myelomeningocele repair. In utero bipedicle flaps are safe and can be used for high-tension lesions without increasing perioperative risks to the mother or fetus. In utero flaps preserve the long-term benefits seen with primary linear repair and may expand inclusion criteria for fetal repair, providing life-changing care for more patients.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Letter to the Editor. Interspinous process device clinical practice experience

John W. Gilbert, Brydon Christensen, and Sherri Matheny

In Journal of Neurosurgery: Spine Publish Before Print

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A likely HOXC4 predisposition variant for Chiari malformations

Douglas L. Brockmeyer, Samuel H. Cheshier, Jeff Stevens, Julio C. Facelli, Kerry Rowe, John D. Heiss, Anthony Musolf, David H. Viskochil, Kristina L. Allen-Brady, and Lisa A. Cannon-Albright

OBJECTIVE

Inherited variants predisposing patients to type 1 or 1.5 Chiari malformation (CM) have been hypothesized but have proven difficult to confirm. The authors used a unique high-risk pedigree population resource and approach to identify rare candidate variants that likely predispose individuals to CM and protein structure prediction tools to identify pathogenicity mechanisms.

METHODS

By using the Utah Population Database, the authors identified pedigrees with significantly increased numbers of members with CM diagnosis. From a separate DNA biorepository of 451 samples from CM patients and families, 32 CM patients belonging to 1 or more of 24 high-risk Chiari pedigrees were identified. Two high-risk pedigrees had 3 CM-affected relatives, and 22 pedigrees had 2 CM-affected relatives. To identify rare candidate predisposition gene variants, whole-exome sequence data from these 32 CM patients belonging to 24 CM-affected related pairs from high-risk pedigrees were analyzed. The I-TASSER package for protein structure prediction was used to predict the structures of both the wild-type and mutant proteins found here.

RESULTS

Sequence analysis of the 24 affected relative pairs identified 38 rare candidate Chiari predisposition gene variants that were shared by at least 1 CM-affected pair from a high-risk pedigree. The authors found a candidate variant in HOXC4 that was shared by 2 CM-affected patients in 2 independent pedigrees. All 4 of these CM cases, 2 in each pedigree, exhibited a specific craniocervical bony phenotype defined by a clivoaxial angle less than 125°. The protein structure prediction results suggested that the mutation considered here may reduce the binding affinity of HOXC4 to DNA.

CONCLUSIONS

Analysis of unique and powerful Utah genetic resources allowed identification of 38 strong candidate CM predisposition gene variants. These variants should be pursued in independent populations. One of the candidates, a rare HOXC4 variant, was identified in 2 high-risk CM pedigrees, with this variant possibly predisposing patients to a Chiari phenotype with craniocervical kyphosis.

In Journal of Neurosurgery Publish Before Print

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Long-term follow-up of an overexposure radiation incident in a cohort treated with linear accelerator–based stereotactic radiosurgery for intracranial arteriovenous malformations

Pierre-Yves Borius, Anne Christine Januel, Jean Yves Plas, Pierre Duthil, Jean Albert Lotterie, Igor Latorzeff, and Jean Sabatier

OBJECTIVE

Dosimetric radiosurgery incidents are rare and probably insufficiently reported in scientific publications. After a long follow-up (FU), the authors studied the outcomes of patients treated with overexposure radiation for arteriovenous malformation (AVM) administered via stereotactic radiosurgery (SRS) at their department.

METHODS

Between May 2006 and June 2007, 22 patients were treated for AVM with SRS. The mean (range) patient age was 43.5 (11.8–78) years. Previous treatments were embolization (n = 10), SRS (1), and surgery (1). The average (range) volume was 2.1 (0.2–6.4) cm3. The median prescribed minimal dose was 18.0 Gy. An initial error in the estimation of scatter factors led to overexposure to radiation. Due to this incident, the median delivered minimum dose was 25.0 Gy. All patients were prospectively followed with clinical examination and imaging.

RESULTS

The mean (range) clinical FU was 14.5 (12.0–15.2) years. AVM obliteration after SRS was completed in 90.9% of patients at a mean (range) of 39.4 (24.4–70.4) months. No patient had post-SRS AVM bleeding. Three patients (13.6%) had new permanent deficits due to radiation-induced changes (RICs). Obliteration without new deficits was achieved in 18 patients (81.8%). Two patients had new epilepsy that was probably due to RIC but well controlled. The median (range) MRI FU was 13.8 (2.5–14.9) years. During MRI FU, two RIC periods were observed: one classic period during the first 3 years showed T1-weighted annular irregular enhancement (13%), and the other period between 5 and 15 years after SRS showed the occurrence of cystic and hemorrhagic lesions (22.7%). There were no cases of radiation-induced tumor.

CONCLUSIONS

The present long-term report showed that this overexposure incident probably increased the AVM obliteration rate. This overexposure seems to have induced RIC and in particular a higher rate of cystic and hemorrhagic late lesions with nevertheless moderate clinical consequences. Long-term FU for AVM is mandatory due to the risk of late RIC.

In Journal of Neurosurgery Publish Before Print

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Neuro-oncology authorship trends in gender since 1944: a systematic review of 14,020 articles from five top-tier academic journals

Rosemary T. Behmer Hansen, Ryan A. Behmer Hansen, Justin L. Gold, Sai Batchu, Rebecca D. Lozada, Samantha D. Palma, Stephen J. Susman, William A. Blocher III, and Angela M. Richardson

OBJECTIVE

This study was performed to compare authorship trends, by gender, in the neurosurgical oncology literature.

METHODS

Complete author listings for neurosurgical oncology articles published between 1944 and 2021 in five top neuro-oncology journals were extracted from the PubMed database and journal websites on December 2, 2021. Author gender was characterized with the web application programming interface (API) genderize.io. The statistical significance (p < 0.05) of time-, journal-, and gender-based differences was determined by independent-samples t-test, chi-square test, and/or Fisher’s exact test.

RESULTS

A total of 14,020 articles were written by 67,115 unique authors occupying 97,418 authorship spots. The gender for 80,030 authorship positions (82.2%) was successfully characterized. Male authors were significantly more likely than the female authors to have a first-author publication, have a last-author publication, and have authored multiple articles within the data set. Among authors who published in multiple different years (n = 11,532), women had a shorter time window of publishing (5.46 vs 6.75 years between first and last publication: mean difference [MD] 1.28 [95% CI 1.06–1.50] years, p < 0.001). During this window, however, they were slightly more productive than the men, based on the mean number of publications per year (1.06 vs 1.01 articles: MD 0.05 [95% CI 0.02–0.09] articles, p = 0.002). The percentage of female authors on each neuro-oncology research team has increased by 3.3% (95% CI 2.6%–3.9%) per decade to a mean of 26.5% in the 2020s. Having a female last author was positively associated with having a female first author (OR 2.57 [95% CI 2.29–2.89]) and a higher proportion of women on the research team overall. The percentages of female first and last authors increased at significantly higher rates in medically oriented journals than in surgically oriented journals (first authors: 0.72% [95% CI 0.58%–0.87%] vs 0.36% [95% CI 0.30%–0.42%] per year, p < 0.001; and last authors: 0.50% [95% CI 0.38%–0.62%] vs −0.03% [95% CI −0.10% to 0.05%] per year, p < 0.001).

CONCLUSIONS

Female authorship in top neuro-oncology journals has increased since the 1940s, with female-led teams showing greater gender diversity. However, female researchers lag behind their male counterparts in quantity of published research and are less likely to hold first or last authorship positions. This difference is more pronounced in the three neurosurgical oncology journals than in the two medical neuro-oncology journals, which may reflect the relatively low female representation in neurosurgery relative to medical oncology. Collectively, these trends have meaningful implications for career advancement, which is often dependent on academic productivity.

In Journal of Neurosurgery Publish Before Print

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The neurodevelopmental outcomes of children with encephalocele: a series of 102 patients

Samuel Berchi Kankam, Amin Tavallaii, Esmaeil Mohammadi, Amirhosein Nejat, Zohreh Habibi, and Farideh Nejat

OBJECTIVE

The overall prognosis of encephalocele (EC) is not well described. However, the presence of some risk factors may result in neurodevelopmental delay (NDD) and negatively affect the prognosis of affected patients. The goal of this study was to evaluate neurodevelopmental outcome, as well as the impact of a number of factors on the outcome in patients with ECs.

METHODS

This was an observational, retrospective study including 102 children with EC who were followed at the pediatric neurosurgery department of a tertiary medical center between the years 2010 and 2021. The authors evaluated NDD status according to the Centers for Disease Control and Prevention classification via clinical evaluation and parent interviews in the outpatient setting.

RESULTS

There were 52 boys and 50 girls. The median age at the time of surgery was 4 months (range 1 day–7.5 years). Seventy-one patients (69.6%) had posterior ECs, whereas 31 (30.4%) had anterior ECs. Forty-three (42.2%) of the ECs contained neural tissue. Of the 102 patients, 33 (32.4%) had ventriculomegaly. In terms of NDD, 14 (14.9%) had mild/moderate delay, whereas 17 patients (18.1%) had severe NDD. On univariate analysis, posterior location, size of sac, presence of neural tissue, ventriculomegaly, symptomatic hydrocephalus, and postoperative infection were correlated with NDD. On a multivariate logistic regression model, only neural tissue presence had a statistically significant association with NDD (OR 7.04, 95% CI 1.33–37.2, p = 0.022). Although not statistically significant, children with ventriculomegaly were 2.6 times as likely to have NDD (95% CI 0.59–11.19, p = 0.362).

CONCLUSIONS

This is a single-center study with a large sample size in which the neurodevelopmental status of patients with EC was assessed, and the authors tried to find the risk factors of NDD in these patients. The results showed that the presence of neural tissue within the EC sac was the only risk factor that had independent statistically significant association with NDD.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Recurrent pediatric infratentorial ependymomas: a systematic review and meta-analysis on outcomes and molecular classification

Eric Y. Montgomery, Vineeth Thirunavu, Manasa Pagadala, Nathan A. Shlobin, Ashley S. Plant-Fox, Sandi Lam, and Michael DeCuypere

OBJECTIVE

The aim of this study was to summarize the prognosis of recurrent infratentorial ependymomas based on treatment and molecular characterization.

METHODS

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors searched the PubMed, Scopus, Embase, and Ovid databases for studies on recurrent infratentorial ependymomas in patients younger than 25 years of age. Exclusion criteria included case series of fewer than 5 patients and studies that did not provide time-dependent survival data.

RESULTS

The authors’ database search yielded 482 unique articles, of which 18 were included in the final analysis. There were 479 recurrent infratentorial pediatric ependymomas reported; 53.4% were WHO grade II and 46.6% were WHO grade III tumors. The overall mortality for recurrent infratentorial pediatric ependymomas was 49.1% (226/460). The pooled mean survival was 30.2 months after recurrence (95% CI 22.4–38.0 months). Gross-total resection (GTR) was achieved in 243 (59.0%) patients at initial presentation. The mean survival postrecurrence for those who received initial GTR was 42.3 months (95% CI 35.7–47.6 months) versus 26.0 months (95% CI 9.6–44.6 months) for those who received subtotal resection (STR) (p = 0.032). There was no difference in the mean survival between patients who received GTR (49.3 months, 95% CI 32.3–66.3 months) versus those who received STR (41.4 months, 95% CI 11.6–71.2 months) for their recurrent tumor (p = 0.610). In the studies that included molecular classification data, there were 169 (83.3%) posterior fossa group A (PFA) tumors and 34 (16.7%) posterior fossa group B (PFB) tumors, with 28 tumors harboring a 1q gain. PFA tumors demonstrated worse mean postprogression patient survival (24.7 months, 95% CI 15.3–34.0 months) compared with PFB tumors (48.0 months, 95% CI 32.8–63.2 months) (p = 0.0073). The average postrecurrence survival for patients with 1q+ tumors was 14.7 months.

CONCLUSIONS

The overall mortality rate for recurrent infratentorial ependymomas was found to be 49.1%, with a pooled mean survival of 30.2 months in the included sample population. More than 80% of recurrent infratentorial ependymomas were of the PFA molecular subtype, and both PFA tumors and those with 1q gain demonstrated worse prognosis after recurrence.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Stereotactic radiosurgery and local control of brain metastases from triple-negative breast cancer

Roman O. Kowalchuk, Ajay Niranjan, Judith Hess, Joseph P. Antonios, Michael Y. Zhang, Steve Braunstein, Richard B. Ross, Stylianos Pikis, Christopher P. Deibert, Cheng-chia Lee, Huai-che Yang, Anne-Marie Langlois, David Mathieu, Selcuk Peker, Yavuz Samanci, Chad G. Rusthoven, Veronica Chiang, Zhishuo Wei, L. Dade Lunsford, Daniel M. Trifiletti, and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS.

METHODS

Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy.

RESULTS

Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70–90) and age of 57 years (IQR 48–67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03–0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18–20 Gy) to the median 71% isodose line (IQR 50%–84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis.

CONCLUSIONS

SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.

In Journal of Neurosurgery Publish Before Print