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Yong-Chan Kim, Keun-Ho Lee, Gab-Lae Kim, Ki-Tack Kim, Kee-Yong Ha, Seung Nam Ko, Qiang Luo, Tae Won Eom, and Hyun Gon Gwak

OBJECTIVE

Recently, new patient-reported outcome measures (PROMs) of the spine were designed to overcome the limitations of previous spinal PROMs and to consider the whole spine as a single kinetic functional unit. Owing to the significance of spine-hip-knee and global body balance, the spine and lower extremities cannot be considered separately. However, no reports have evaluated lower-extremity functional outcome using PROMs after lumbar spine surgery. The authors aimed to elucidate changes in hip and knee PROMs after lumbar interbody fusion and to evaluate the sagittal spinopelvic radiographic parameters that were most strongly correlated with lower-extremity PROMs.

METHODS

In 2018, the authors consecutively evaluated patients who underwent lumbar interbody fusion surgery with at most three levels. Preoperative and 1-year postoperative clinical and radiographic data were assessed. Spinal functional outcomes were measured with the Oswestry Disability Index (ODI), visual analog scale (VAS) for pain, and Scoliosis Research Society–22r (SRS-22r) questionnaire. Lower-extremity functional outcomes were evaluated with the Harris Hip Score (HHS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression was used to evaluate the relationship between spinal and lower-extremity PROMs and spinopelvic radiographic parameters.

RESULTS

The authors enrolled 67 patients, with a mean age of 66.4 years. The average number of surgical levels was 1.7. All assessed PROMs improved significantly after surgery (p < 0.001 for ODI, p < 0.001 for VAS, p = 0.017 for SRS-22r, p = 0.042 for HHS, and p = 0.033 for WOMAC). Spinopelvic parameters, including lumbar lordosis (LL), pelvic tilt (PT), C7 sagittal vertical axis, and sagittal radiographic parameters of hip and knee, significantly improved after surgery. On linear regression analysis, HHS and WOMAC correlated with LL and PT, respectively (β = 0.554 and p = 0.043 for correlation of HHS with LL; β = 1.573 and p = 0.021 for correlation of WOMAC with PT).

CONCLUSIONS

The current study demonstrated that lumbar fusion surgery may induce postoperative improvements in lower-extremity functional and radiological outcomes. However, among radiographic parameters, changes in LL and PT were the most strongly associated with lower-extremity PROMs.

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Konstantina Svokos, Lígia Batista-Silverman, Sarah J. Graber, Brent R. O’Neill, and Michael H. Handler

OBJECTIVE

Occult spinal dysraphism (OSD) is a common pediatric neurosurgical diagnosis rife with controversy surrounding both the screening of asymptomatic infants and the threshold to offer a prophylactic detethering operation. The authors sought to clarify international practice patterns with a survey of pediatric neurosurgeons.

METHODS

A survey asked pediatric neurosurgeons whether they would perform imaging in patients with a variety of cutaneous stigmata associated with OSD and whether they would offer prophylactic detethering surgery for asymptomatic patients with a variety of imaging findings on the OSD spectrum.

RESULTS

Completed surveys were received from 141 pediatric neurosurgeons. Broad consensus was demonstrated on the need for obtaining images in sample patients with more severe stigmata ranging from large lipoma with a skin appendage to focal dysplastic skin in the lumbar midline. Ninety percent of respondents would perform MRI for these patients. In contrast, for patients with a low-sacral dimple, flat hemangioma, and symmetric (Y-shaped) splaying of the intergluteal cleft, opinion on the need for imaging varied considerably (between 57% and 89% recommended imaging). Respondents differed on the type of imaging that they would perform, with 31% to 38% recommending ultrasound screening. The responses reflected less consensus on when to offer surgery to patients with simple spinal tethering (low-lying conus medullaris and fatty filum terminale). Both a lower level of the conus and increased thickness of the filum terminale affected decision-making.

CONCLUSIONS

The results of this survey showed significant consensus on the recommendation for screening imaging in patients with more dramatic cutaneous stigmata, although these stigmata are the rarest. A significant variance in opinions was reflected in the recommendation for imaging of the most common cutaneous stigmata. Consensus was also lacking on which lesions deserve prophylactic detethering surgery. Significant equipoise exists for future study of screening imaging and of surgical decision-making in patients with asymptomatic OSD and associated cutaneous stigmata.

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Miao Hu, Aining Lai, Zheng Zhang, Jingjing Chen, Tao Lin, Jun Ma, Ce Wang, Yichen Meng, and Xuhui Zhou

OBJECTIVE

Surgical management of scoliosis curves between 70° and 100° remains controversial. The authors designed this randomized controlled trial to validate the efficacy of intraoperative halo-femoral traction (IOHFT) in patients with adolescent idiopathic scoliosis (AIS), Cobb angles between 70° and 100°, and flexibility < 35%.

METHODS

The authors prospectively recruited and randomized 29 patients with severe AIS scheduled for posterior surgery into a traction group or control (nontraction) group. The primary outcome measures were operative time, blood loss, and length of hospital stay. Secondary outcomes included degree of spine deformity correction, traction-related complications, and health-related quality of life.

RESULTS

In the traction group, the average preoperative Cobb angle was 83.2°, with an average 20.6% flexibility. The average postoperative Cobb angle was 16.1° and the major curve was 18.3° at the final follow-up. In the control group, the average preoperative major curve was 80.3° with 22.8% flexibility. The average postoperative Cobb angle was 16.1° and the major curve was 18.1° at the final follow-up. The operative duration was 325.7 minutes for the traction group and 385.4 minutes for the control group (p = 0.018). Compared with the control group, the traction group had a 29.5% reduction in intraoperative blood loss and a significantly lower rate of blood transfusion (13.3% vs 50.0%, p = 0.033). There were no neurological complications in either group. One patient in the traction group had a superficial infection at the traction site.

CONCLUSIONS

Use of IOHFT contributed to significant reductions in operative time and blood transfusion requirements, with no added morbidity. It is an effective and safe method to assist correction of AIS curves between 70° and 100° and flexibility < 35%.

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Robert N. Holdefer, Christoph N. Seubert, Stanley A. Skinner, and Andrew T. Humbert

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Silky Chotai, Jeffrey L. Nadel, Katherine G. Holste, James M. Mossner, Brandon W. Smith, Joseph R. Kapurch, Karin M. Muraszko, Hugh J. L. Garton, Cormac O. Maher, and Jennifer M. Strahle

OBJECTIVE

The objective of this study was to understand the natural history of scoliosis in patients with Chiari malformation type I (CM-I) with and without syringomyelia.

METHODS

A retrospective review of data was conducted. Patients with CM-I were identified from a cohort of 14,118 individuals age 18 years or younger who had undergone MRI over an 11-year period at the University of Michigan. Patients eligible for study inclusion had a coronal curve ≥ 10° on radiography, associated CM-I with or without syringomyelia, and at least 1 year of clinical follow-up prior to any surgery. Curve magnitude at initial diagnosis, prior to posterior fossa decompression (PFD; if applicable), and at the last follow-up (prior to any surgical correction of scoliosis) was recorded, and clinical and radiographic characteristics were noted. The change in curve magnitude by 10° was defined as curve progression (increase by 10°) or regression (decrease by 10°).

RESULTS

Forty-three patients met the study inclusion criteria and were analyzed. About one-third (35%) of the patients presented with symptoms attributed to their CM-I. The mean degree of scoliosis at presentation was 32.6° ± 17.7°. Twenty-one patients (49%) had an associated syrinx. The mean tonsil position below the level of the foramen magnum was 9.8 ± 5.8 mm. Patients with a syrinx were more likely to have a curve > 20° (86% vs 41%, p = 0.002). Curve magnitude remained stable (≤ ±10°) in 77% of patients (33/43), progressed in 16% (7/43), and regressed in 7% (3/43). Mean age was higher (14.8 ± 0.59 years) among patients with regressed curves (p = 0.026). All regressed curves initially measured ≤ 20° (mean 14° ± 5.3°), and none of the patients with regressed curves had a syrinx. The change in curve magnitude was statistically similar in patients with (7.32° ± 17.7°) and without (5.32° ± 15.8°) a syrinx (p = 0.67). After a mean follow-up of 3.13 ± 2.04 years prior to surgery, 27 patients (63%) ultimately underwent posterior fossa or scoliosis correction surgery. For those who eventually underwent PFD only, the rate of change in curve magnitude prior to surgery was 0.054° ± 0.79°. The rate of change in curve magnitude was statistically similar before (0.054° ± 0.79°) and after (0.042° ± 0.33°) surgery (p = 0.45) for patients who underwent PFD surgery only.

CONCLUSIONS

The natural history of scoliosis in the presence of CM-I is variable, though most curves remained stable. All curves that regressed were ≤ 20° at initial diagnosis, and most patients in such cases were older at scoliosis diagnosis. Patients who underwent no surgery or PFD only had similar profiles for the change in curve magnitude, which remained relatively stable overall, as compared to patients who underwent PFD and subsequent fusion, who demonstrated curve progression. Among the patients with a syrinx, no curves regressed, most remained stable, and some progressed. Understanding this variability is a first step toward building a prediction model for outcomes for these patients.

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Minjae Cho, So Young Ji, Kyeong-O Go, Kyung Seok Park, Jong-Min Kim, Young-Tae Jeon, Jung-Hee Ryu, Sanghon Park, and Jung Ho Han

OBJECTIVE

The lateral spread response (LSR) is an aberrant electrophysiological response in which a stimulus on one branch of the facial nerve spills over to other branches of the nerve, which can be captured by electrodes near each branch. The authors performed this study to evaluate the prognostic value of the follow-up LSR with a sufficient time interval from intraoperative LSR (IO-LSR) after microvascular decompression (MVD) for hemifacial spasm (HFS), excluding the interference of various intraoperative situations.

METHODS

A total of 247 patients treated with MVD for HFS between June 2011 and March 2019 were enrolled in this study. The IO-LSR was routinely evaluated in all patients. The LSR was checked again on postoperative day (POD) 2 after surgery (POD2-LSR). A total of 228 patients (92.3%) were considered cured at the last clinical follow-up.

RESULTS

The IO-LSR disappeared in 189 patients (76.5%), and among them, 181 patients (95.8%) were cured 1 year after surgery. The POD2-LSR disappeared in 193 patients (78.1%), and 185 patients (95.9%) among them were cured. Among the 189 patients in which the IO-LSR disappeared, the POD2-LSR reappeared in 26 patients (13.8%). In contrast, the POD2-LSR disappeared in 30 (51.7%) of 58 patients for whom the IO-LSR continued at the end of surgery. When classified into groups according to the status of the IO-LSR and POD2-LSR, in the group of patients in whom both LSRs disappeared, the cure rate was 98.2%, which was significantly higher than that of the other 3 groups (p < 0.05, Cochran-Armitage trend test). The use of both LSRs was found to be significantly associated with better predictability (p < 0.05, McNemar’s test).

CONCLUSIONS

Postoperative follow-up LSR examination may be beneficial in predicting clinical outcomes after MVD for HFS, especially when considered together with IO-LSR.

Open access

Aisha Khan, Anthony Diaz, Adriana E. Brooks, S. Shelby Burks, Gagani Athauda, Patrick Wood, Yee-Shuan Lee, Risset Silvera, Maxwell Donaldson, Yelena Pressman, Kim D. Anderson, Mary Bartlett Bunge, Damien D. Pearse, W. Dalton Dietrich, James D. Guest, and Allan D. Levi

OBJECTIVE

Schwann cells (SCs) have been shown to play an essential role in axon regeneration in both peripheral nerve injuries (PNIs) and spinal cord injuries (SCIs). The transplantation of SCs as an adjunctive therapy is currently under investigation in human clinical trials due to their regenerative capacity. Therefore, a reliable method for procuring large quantities of SCs from peripheral nerves is necessary. This paper presents a well-developed, validated, and optimized manufacturing protocol for clinical-grade SCs that are compliant with Current Good Manufacturing Practices (CGMPs).

METHODS

The authors evaluated the SC culture manufacturing data from 18 clinical trial participants who were recruited for autologous SC transplantation due to subacute SCI (n = 7), chronic SCI (n = 8), or PNIs (n = 3). To initiate autologous SC cultures, a mean nerve length of 11.8 ± 3.7 cm was harvested either from the sural nerve alone (n = 17) or with the sciatic nerve (n = 1). The nerves were digested with enzymes and SCs were isolated and further expanded in multiple passages to meet the dose requirements for transplantation.

RESULTS

An average yield of 87.2 ± 89.2 million cells at P2 and 150.9 ± 129.9 million cells at P3 with high viability and purity was produced. Cell counts and rates of expansion increased with each subsequent passage from P0 to P3, with the largest rate of expansion between P2 and P3. Larger harvest nerve lengths correlated significantly with greater yields at P0 and P1 (p < 0.05). In addition, a viability and purity above 90% was sustained throughout all passages in nearly all cell products.

CONCLUSIONS

This study presents reliable CGMP-compliant manufacturing methods for autologous SC products that are suitable for regenerative treatment of patients with SCI, PNI, or other conditions.

Open access

David Mathieu, Rupesh Kotecha, Arjun Sahgal, Antonio De Salles, Laura Fariselli, Bruce E. Pollock, Marc Levivier, Lijun Ma, Ian Paddick, Jean Regis, Shoji Yomo, John H. Suh, Muni Rubens, and Jason P. Sheehan

OBJECTIVE

A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations.

METHODS

The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing’s disease, and prolactinomas were selected and included in the analysis.

RESULTS

For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%–98.0%), 44.0% (95% CI 35.0%–53.0%), and 17.0% (95% CI 13.0%–23.0%), respectively. For Cushing’s disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%–95.0%), 48.0% (95% CI 35.0%–61.0%), and 21.0% (95% CI 13.0%–31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%–95.0%), 28.0% (95% CI 19.0%–39.0%), and 12.0% (95% CI 6.0%–24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes.

CONCLUSIONS

SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.

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Andy S. Ding, Sakibul Huq, Joshua Casaos, Divyaansh Raj, Manuel Morales, Tianna Zhao, Timothy Kim, Siddhartha Srivastava, Ayush Pant, Riccardo Serra, Noah L. Gorelick, Henry Brem, and Betty Tyler

OBJECTIVE

Atypical teratoid rhabdoid tumors (ATRTs) are aggressive pediatric brain tumors with no current standard of care and an estimated median patient survival of 12 to 18 months. Previous genetic analyses have implicated cyclin D1 and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase that is implicated in many cancers, as key drivers of tumorigenicity in ATRTs. Since the effects of EZH2 and cyclin D1 are facilitated by a host of cyclin-dependent kinases (CDKs), the authors sought to investigate the potential therapeutic effects of targeting CDKs in ATRTs with the multi–CDK inhibitor, TG02.

METHODS

Human ATRT cell lines BT12, BT37, CHLA05, and CHLA06 were selected for investigation. The effects of TG02 on cell viability, proliferation, clonogenicity, and apoptosis were assessed via Cell Counting Kit-8 assays, cell counting, clonogenic assays, and flow cytometry, respectively. Similar methods were used to determine the effects of TG02 combined with radiation therapy (RT) or cisplatin. Synergism indices for TG02-cisplatin combination therapy were calculated using CompuSyn software.

RESULTS

TG02 was observed to significantly impair ATRT cell growth in vitro by limiting cell proliferation and clonogenicity, and by inducing apoptosis. TG02 inhibited ATRT cell proliferation and decreased cell viability in a dose-dependent manner with nanomolar half maximal effective concentration (EC50) values (BT12, 207.0 nM; BT37, 127.8 nM; CHLA05, 29.7 nM; CHLA06, 18.7 nM). TG02 (150 nM) dramatically increased the proportion of apoptotic ATRT cells 72 hours posttreatment (TG02 8.50% vs control 1.52% apoptotic cells in BT12, p < 0.0001; TG02 70.07% vs control 15.36%, p < 0.0001). Combination therapy studies revealed that TG02 acted as a potent radiosensitizer in ATRT cells (BT12 surviving fraction, RT 51.2% vs RT + TG02 21.7%). Finally, CompuSyn analysis demonstrated that TG02 acted synergistically with cisplatin against ATRT cells at virtually all therapeutic doses. These findings were consistent in cell lines that cover all three molecular subgroups of ATRTs.

CONCLUSIONS

The results of this investigation have established that TG02 is an effective therapeutic against ATRTs in vitro. Given the lack of standard therapy for ATRTs, these findings help fill an unmet need and support further study of TG02 as a potential therapeutic option for patients with this deadly disease.

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Raymund L. Yong, William Cheung, Raj K. Shrivastava, and Joshua B. Bederson

OBJECTIVE

High-quality neurosurgery resident training is essential to developing competent neurosurgeons. Validated formative tools to assess faculty teaching performance exist, but are not used widely among Accreditation Council for Graduate Medical Education (ACGME) residency programs in the United States. Furthermore, their longer-term impact on teaching performance improvement and educational outcomes remains unclear. The goal of this study was to assess the impact of implementing an evaluation system to provide faculty with feedback on teaching performance in a neurosurgery residency training program over a 4-year period.

METHODS

The authors performed a prospective cohort study in which a modified version of the System for Evaluation of Teaching Qualities (SETQ) instrument was administered to neurosurgical trainees in their department regularly every 6 months. The authors analyzed subscale score dynamics to identify the strongest correlates of faculty teaching performance improvement. ACGME program survey results and trainee performance on written board examinations were compared for the 3 years before and after SETQ implementation.

RESULTS

The overall response rate among trainees was 91.8%, with 1044 surveys completed for 41 faculty. Performance scores improved progressively from cycle 1 to cycle 6. The strongest correlate of overall performance was providing positive feedback to trainees. Compared to the 3 years prior, the 3 years following SETQ implementation saw significant increases in written board examination and ACGME resident survey scores compared to the national mean.

CONCLUSIONS

Implementation of SETQ was associated with significant improvements in faculty teaching performance as judged by trainees over a 4-year period, and guided curricular changes in the authors’ training program that resulted in improved educational outcomes.