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Clinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas

Joanna K. Tabor, Joseph O’Brien, Sagar Vasandani, Shaurey Vetsa, Haoyi Lei, Muhammad I. Jalal, Neelan J. Marianayagam, Lan Jin, Miguel Millares Chavez, Joseph Haynes, Alper Dincer, Kanat Yalcin, Stephanie M. Aguilera, Sacit Bulent Omay, Ketu Mishra-Gorur, Declan McGuone, Saul F. Morales-Valero, Robert K. Fulbright, Murat Gunel, E. Zeynep Erson-Omay, and Jennifer Moliterno

OBJECTIVE

Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities—however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium.

METHODS

Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed.

RESULTS

A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade—i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival.

CONCLUSIONS

Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.

In Journal of Neurosurgery Publish Before Print

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Defining the minimal clinically important difference in smartphone-based mobility after spine surgery: correlation of survey questionnaire to mobility data

Presented at the 2023 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Daksh Chauhan, Hasan S. Ahmad, Robert Subtirelu, Sai Mannam, Ryan Turlip, Kevin Bryan, Shreya Bathula, Yohannes Ghenbot, Andrew I. Yang, Michael Y. Wang, Gregory Basil, Zarina S. Ali, and Jang W. Yoon

OBJECTIVE

Patient-reported outcome measures (PROMs) are the gold standard for assessing postoperative outcomes in spine surgery. However, PROMs are also limited by the inherent subjectivity of self-reported qualitative data. Recent literature has highlighted the utility of patient mobility data streamed from smartphone accelerometers as an objective measure of functional outcomes and complement to traditional PROMs. Still, for activity-based data to supplement existing PROMs, they must be validated against current metrics. In this study, the authors assessed the relationships and concordance between longitudinal smartphone-based mobility data and PROMs.

METHODS

Patients receiving laminectomy (n = 21) or fusion (n = 10) between 2017 and 2022 were retrospectively included. Activity data (steps-per-day count) recorded in the Apple Health mobile application over a 2-year perioperative window were extracted and subsequently normalized to allow for intersubject comparison. PROMS, including the visual analog scale (VAS), Patient Reported Outcome Measurement Information System Pain Interference (PROMIS-PI), Oswestry Disability Index (ODI), and EQ-5D, collected at the preoperative and 6-week postoperative visits were retrospectively extracted from the electronic medical record. Correlations between PROMs and patient mobility were assessed and compared between patients who did and those who did not achieve the established minimal clinically important difference (MCID) for each measure.

RESULTS

A total of 31 patients receiving laminectomy (n = 21) or fusion (n = 10) were included. Change between preoperative and 6-week postoperative VAS and PROMIS-PI scores demonstrated moderate (r = −0.46) and strong (r = −0.74) inverse correlations, respectively, with changes in normalized steps-per-day count. In cohorts of patients who achieved PROMIS-PI MCID postoperatively, indicating subjective improvement in pain, there was a 0.784 standard deviation increase in normalized steps per day, representing a 56.5% improvement (p = 0.027). Patients who did achieve the MCID of improvement in either PROMIS-PI or VAS after surgery were more likely to experience an earlier sustained improvement in physical activity commensurate to or greater than their preoperative baseline (p = 2.98 × 10−18) than non-MCID patients.

CONCLUSIONS

This study demonstrates a strong correlation between changes in mobility data extracted from patient smartphones and changes in PROMs following spine surgery. Further elucidating this relationship will allow for more robust supplementation of existing spine outcome measure tools with analyzed objective activity data.

In Journal of Neurosurgery: Spine Publish Before Print

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Demographics, referral patterns, and outcome of patients with neural tube defects in southwestern Uganda

Maria Punchak, Josephine Nambi Najjuma, Shahaan S. Razak, Zaina Nakaziba, Amos Mbusa Kasoba, Michael M. Haglund, Anthony T. Fuller, and David Kitya

OBJECTIVE

In Uganda, the burden of neural tube defects (NTDs) poses a serious neurosurgical and public health challenge; however, published data on this patient population are lacking. The authors sought to characterize the population of patients with NTDs, maternal characteristics, and referral patterns of these patients, and to quantify the burden of NTDs in southwestern Uganda.

METHODS

A retrospective neurosurgical database at a referral hospital was reviewed to identify all patients with NTDs treated between August 2016 and May 2022. Descriptive statistics were used to characterize the patient population and maternal risk factors. A Wilcoxon rank-sum test and chi-square test were used to determine the association between demographic variables and patient mortality.

RESULTS

A total of 235 patients were identified (121 male, 52%). The median age at presentation was 2 days (IQR 1–8 days). A total of 87% of patients with NTDs presented with spina bifida (n = 204) and 31 presented with encephalocele (13%). The most common location of dysraphism was lumbosacral (n = 180, 88%). Of all patients, 80% were delivered vaginally (n = 188). Overall, 67% of patients were discharged (n = 156) and 10% died (n = 23). The median length of stay was 12 days (IQR 7–19 days). The median maternal age was 26 years (IQR 22–30 years). The majority of mothers received only primary education (n = 100, 43%). The majority of mothers reported prenatal folate use (n = 158, 67%) and regular antenatal care (n = 220, 94%), although only 23% underwent an antenatal ultrasound (n = 55). Mortality was associated with younger age at presentation (p = 0.01), need for blood transfusion (p = 0.016) and oxygen supplementation (p < 0.001), and maternal education level (p = 0.001).

CONCLUSIONS

To the authors’ knowledge, this is the first study to describe the population of patients with NTDs and their mothers in southwestern Uganda. A prospective case-control study is necessary to identify unique demographic and genetic risk factors associated with NTDs in this region.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Duration of neurological deficit and outcomes in the surgical treatment of spinal coccidioidomycosis

Alexa Semonche, Justin K. Scheer, Vinil N. Shah, Monica Fung, Lee A. Tan, Dean Chou, Praveen V. Mummaneni, Sigurd H. Berven, Christopher P. Ames, Vedat Deviren, Alekos A. Theologis, and Aaron J. Clark

OBJECTIVE

Vertebral osteomyelitis is a rare complication of coccidioidomycosis infection. Surgical intervention is indicated when there is failure of medical management or presence of neurological deficit, epidural abscess, or spinal instability. The relationship between timing of surgical intervention and recovery of neurological function has not been previously described. The purpose of this study was to investigate if the duration of neurological deficits at presentation affects neurological recovery after surgical intervention.

METHODS

This was a retrospective study of all patients diagnosed with coccidioidomycosis involving the spine at a single tertiary care center between 2012 and 2021. Data collected included patient demographics, clinical presentation, radiographic information, and surgical intervention. The primary outcome was change in neurological examination after surgical intervention, quantified according to the American Spinal Injury Association Impairment Scale. The secondary outcome was the complication rate. Logistic regression was used to test if the duration of neurological deficits was associated with improvement in the neurological examination after surgery.

RESULTS

Twenty-seven patients presented with spinal coccidioidomycosis between 2012 and 2021; 20 of these patients had vertebral involvement on spinal imaging with a median follow-up of 8.7 months (IQR 1.7–71.2 months). Of the 20 patients with vertebral involvement, 12 (60.0%) presented with a neurological deficit with a median duration of 20 days (range 1–61 days). Most patients presenting with neurological deficit (11/12, 91.7%) underwent surgical intervention. Nine (81.2%) of these 11 patients had an improved neurological examination after surgery and the other 2 had stable deficits. Seven patients had improved recovery sufficient to improve by 1 grade according to the AIS. The duration of neurological deficits on presentation was not significantly associated with neurological improvement after surgery (p = 0.49, Fisher’s exact test).

CONCLUSIONS

The duration of neurological deficits on presentation should not deter surgeons from operative intervention in cases of spinal coccidioidomycosis.

In Journal of Neurosurgery: Spine Publish Before Print

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Impact of neighborhood deprivation and social vulnerability on long-term outcomes and desire for revision in patients with craniosynostosis

Kaamya Varagur, John Murphy, Esther Ochoa, Gary B. Skolnick, Sybill D. Naidoo, Sean D. McEvoy, Jennifer M. Strahle, and Kamlesh B. Patel

OBJECTIVE

The authors utilized the area deprivation index (ADI), a validated composite measure of socioeconomic disadvantage, and the social vulnerability index (SVI) to examine whether differences in neighborhood deprivation impact interventions and outcomes among patients with craniosynostosis.

METHODS

Patients who underwent craniosynostosis repair between 2012 and 2017 were included. The authors collected data about demographic characteristics, comorbidities, follow-up visits, interventions, complications, desire for revision, and speech, developmental, and behavioral outcomes. National percentiles for ADI and SVI were determined using zip and Federal Information Processing Standard (FIPS) codes. ADI and SVI were analyzed by tertile. Firth logistic regressions and Spearman correlations were used to assess associations between ADI/SVI tertile and outcomes/interventions that differed on univariate analysis. Subgroup analysis was performed to examine these associations in patients with nonsyndromic craniosynostosis. Differences in length of follow-up among the nonsyndromic patients in the different deprivation groups were assessed with multivariate Cox regressions.

RESULTS

In total, 195 patients were included, with 37% of patients in the most disadvantaged ADI tertile and 20% of patients in the most vulnerable SVI tertile. Patients in more disadvantaged ADI tertiles were less likely to have physician-reported desire (OR 0.17, 95% CI 0.04–0.61, p < 0.01) or parent-reported desire (OR 0.16, 95% CI 0.04–0.52, p < 0.01) for revision, independent of sex and insurance status. In the nonsyndromic subgroup, inclusion in a more disadvantaged ADI tertile was associated with increased odds of speech/language concerns (OR 4.42, 95% CI 1.41–22.62, p < 0.01). There were no differences in interventions received or outcomes among SVI tertiles (p ≥ 0.24). Neither ADI nor SVI tertile was associated with risk of loss to follow-up among nonsyndromic patients (p ≥ 0.38).

CONCLUSIONS

Patients from the most disadvantaged neighborhoods may be at risk for poor speech outcomes and different standards of assessment for revision. Neighborhood measures of disadvantage represent a valuable tool to improve patient-centered care by allowing for modification of treatment protocols to meet the unique needs of patients and their families.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Implantation accuracy and operative variables in robot-assisted stereoelectroencephalography

Suk Joon Lee, Philip S. Lee, Amir H. Faraji, R. Mark Richardson, and Vasileios Kokkinos

OBJECTIVE

The stereoelectroencephalography (SEEG) procedure provides a unique 3D overview of the seizure-onset zone. Although the success of SEEG relies on the accuracy of depth electrode implantation, few studies have investigated how different implantation techniques and operative variables affect accuracy. This study examined the effect of two different electrode implantation techniques (external vs internal stylet) on implantation accuracy while controlling for other operative variables.

METHODS

The implantation accuracy of 508 depth electrodes from 39 SEEG cases was measured after coregistration of postimplantation CT or MR images with planned trajectories. Two different implantation techniques were compared: preset length with internal stylet use and measured length with external stylet use. Correlations between implantation accuracy and technique type, entry angle, intended implantation depth, and other operative variables were determined statistically using multiple regression analysis.

RESULTS

Multiple regression analysis showed that the internal stylet technique exhibited a larger target radial error (p = 0.046) and angular deviation (p = 0.039) with a smaller depth error (p < 0.001) than the external stylet technique. Entry angle and implantation depth were positively correlated with target radial error (p = 0.007 and < 0.001, respectively) only for the internal stylet technique.

CONCLUSIONS

Better target radial accuracy was achieved when an external stylet was used to open the intraparenchymal pathway for the depth electrode. In addition, more oblique trajectories were equally accurate to orthogonal ones with the usage of an external stylet, while more oblique trajectories were associated with larger target radial errors with the usage of an internal stylet (without an external stylet).

In Journal of Neurosurgery Publish Before Print

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Letter to the Editor. Hospital Frailty Risk Score and outcome predictions

Michael M. Covell, Georgios P. Skandalakis, Kavelin Rumalla, Meic H. Schmidt, and Christian A. Bowers

In Journal of Neurosurgery Publish Before Print

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Letter to the Editor. Spinal instrumentation strategies

Andrew J. Fabiano

In Journal of Neurosurgery: Spine Publish Before Print

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Letter to the Editor. Tracking neurosurgery resident performance on simulation-based training tasks

David S. Hersh, Jonathan E. Martin, Inam U. Kureshi, and Ketan R. Bulsara

In Journal of Neurosurgery Publish Before Print

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Outcome of stereo-electroencephalography with single-unit recording in drug-refractory epilepsy

Yasunori Nagahama, Sandra Dewar, Eric Behnke, Dawn Eliashiv, John M. Stern, Guldamla Kalender, Tony A. Fields, Charles Wilson, Richard Staba, Jerome Engel Jr., and Itzhak Fried

OBJECTIVE

The aim of this study was to evaluate the utility and safety of "hybrid" stereo-electroencephalography (SEEG) in guiding epilepsy surgery and in providing information at single-neuron levels (i.e., single-unit recording) to further the understanding of the mechanisms of epilepsy and the neurocognitive processes unique to humans.

METHODS

The authors evaluated 218 consecutive patients undergoing SEEG procedures from 1993 through 2018 at a single academic medical center to assess the utility and safety of this technique in both guiding epilepsy surgery and providing single-unit recordings. The hybrid electrodes used in this study contained macrocontacts and microwires to simultaneously record intracranial EEG and single-unit activity (hybrid SEEG). The outcomes of SEEG-guided surgical interventions were examined, as well as the yield and scientific utility of single-unit recordings in 213 patients who participated in the research involving single-unit recordings.

RESULTS

All patients underwent SEEG implantation by a single surgeon and subsequent video-EEG monitoring (mean of 10.2 electrodes per patient and 12.0 monitored days). Epilepsy networks were localized in 191 (87.6%) patients. Two clinically significant procedural complications (one hemorrhage and one infection) were noted. Of 130 patients who underwent subsequent focal epilepsy surgery with a minimum 12-month follow-up, 102 (78.5%) underwent resective surgery and 28 (21.5%) underwent closed-loop responsive neurostimulation (RNS) with or without resection. Seizure freedom was achieved in 65 (63.7%) patients in the resective group. In the RNS group, 21 (75.0%) patients achieved 50% or greater seizure reduction. When the initial period of 1993 through 2013 before responsive neurostimulator implantation in 2014 was compared with the subsequent period of 2014 through 2018, the proportion of SEEG patients undergoing focal epilepsy surgery grew from 57.9% to 79.7% due to the advent of RNS, despite a decline in focal resective surgery from 55.3% to 35.6%. A total of 18,680 microwires were implanted in 213 patients, resulting in numerous significant scientific findings. Recent recordings from 35 patients showed a yield of 1813 neurons, with a mean yield of 51.8 neurons per patient.

CONCLUSIONS

Hybrid SEEG enables safe and effective localization of epileptogenic zones to guide epilepsy surgery and provides unique scientific opportunities to investigate neurons from various brain regions in conscious patients. This technique will be increasingly utilized due to the advent of RNS and may prove a useful approach to probe neuronal networks in other brain disorders.

In Journal of Neurosurgery Publish Before Print