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Oliver Flouty, Kazuaki Yamamoto, Jurgen Germann, Irene E. Harmsen, Hyun Ho Jung, Cletus Cheyuo, Ajmal Zemmar, Vanessa Milano, Can Sarica, and Andres M. Lozano

OBJECTIVE

Pain is the most common nonmotor symptom of Parkinson’s disease (PD) and is often undertreated. Deep brain stimulation (DBS) effectively mitigates the motor symptoms of this multisystem neurodegenerative disease; however, its therapeutic effect on nonmotor symptoms, especially pain, remains inconclusive. While there is a critical need to help this large PD patient population, guidelines for managing this significant disease burden are absent. Herein, the authors systematically reviewed the literature and conducted a meta-analysis to study the influence of traditional (subthalamic nucleus [STN] and globus pallidus internus [GPi]) DBS on chronic pain in patients with PD.

METHODS

The authors performed a systematic review of the literature and a meta-analysis following PRISMA guidelines. Risk of bias was assessed using the levels of evidence established by the Oxford Centre for Evidence-Based Medicine. Inclusion criteria were articles written in English, published in a peer-reviewed scholarly journal, and about studies conducting an intervention for PD-related pain in no fewer than 5 subjects.

RESULTS

Twenty-six studies were identified and included in this meta-analysis. Significant interstudy heterogeneity was detected (Cochran’s Q test p < 0.05), supporting the use of the random-effects model. The random-effects model estimated the effect size of DBS for the treatment of idiopathic pain as 1.31 (95% CI 0.84–1.79). The DBS-on intervention improved pain scores by 40% as compared to the control state (preoperative baseline or DBS off).

CONCLUSIONS

The results indicated that traditional STN and GPi DBS can have a favorable impact on pain control and improve pain scores by 40% from baseline in PD patients experiencing chronic pain. Further trials are needed to identify the subtype of PD patients whose pain benefits from DBS and to identify the mechanisms by which DBS improves pain in PD patients.

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Mihir Khunte, Xiao Wu, Emily W. Avery, Dheeraj Gandhi, Seyedmehdi Payabvash, Charles Matouk, Jeremy J. Heit, Max Wintermark, Gregory W. Albers, Pina Sanelli, and Ajay Malhotra

OBJECTIVE

Acute ischemic stroke patients with large-vessel occlusion and good collateral blood flow have significantly better outcomes than patients with poor collateral circulation. The purpose of this study was to evaluate the cost-effectiveness of endovascular thrombectomy (EVT) based on collateral status and, in particular, to analyze its effectiveness in ischemic stroke patients with poor collaterals.

METHODS

A decision analysis study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT based on collateral status. The study was performed over a lifetime horizon with a societal perspective in the US setting. Base-case analysis was done for good, intermediate, and poor collateral status. One-way, two-way, and probabilistic sensitivity analyses were performed.

RESULTS

EVT resulted in greater effectiveness of treatment compared to no EVT/medical therapy (2.56 QALYs in patients with good collaterals, 1.88 QALYs in those with intermediate collaterals, and 1.79 QALYs in patients with poor collaterals), which was equivalent to 1050, 771, and 734 days, respectively, in a health state characterized by a modified Rankin Scale (mRS) score of 0–2. EVT also resulted in lower costs in patients with good and intermediate collaterals. For patients with poor collateral status, the EVT strategy had higher effectiveness and higher costs, with an incremental cost-effectiveness ratio (ICER) of $44,326/QALY. EVT was more cost-effective as long as it had better outcomes in absolute numbers in at least 4%–8% more patients than medical management.

CONCLUSIONS

EVT treatment in the early time window for good outcome after ischemic stroke is cost-effective irrespective of the quality of collateral circulation, and patients should not be excluded from thrombectomy solely on the basis of collateral status. Despite relatively lower benefits of EVT in patients with poor collaterals, even smaller differences in better outcomes have significant long-term financial implications that make EVT cost-effective.

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Collin J. Larkin, Ketan Yerneni, Constantine L. Karras, Zachary A. Abecassis, Guangyu Zhou, Christina Zelano, Ashley N. Selner, Jessica W. Templer, and Matthew C. Tate

OBJECTIVE

Intraoperative stimulation is used as a crucial adjunct in neurosurgical oncology, allowing for greater extent of resection while minimizing morbidity. However, limited data exist regarding the impact of cortical stimulation on the frequency of perioperative seizures in these patients.

METHODS

A retrospective chart review of patients undergoing awake craniotomy with electrocorticography data by a single surgeon at the authors’ institution between 2013 and 2020 was conducted. Eighty-three patients were identified, and electrocorticography, stimulation, and afterdischarge (AD)/seizure data were collected and analyzed. Stimulation characteristics (number, amplitude, density [stimulations per minute], composite score [amplitude × density], total and average stimulation duration, and number of positive stimulation sites) were analyzed for association with intraoperative seizures (ISs), ADs, and postoperative clinical seizures.

RESULTS

Total stimulation duration (p = 0.005), average stimulation duration (p = 0.010), and number of stimulations (p = 0.020) were found to significantly impact AD incidence. A total stimulation duration of more than 145 seconds (p = 0.04) and more than 60 total stimulations (p = 0.03) resulted in significantly higher rates of ADs. The total number of positive stimulation sites was associated with increased IS (p = 0.048). Lesions located within the insula (p = 0.027) were associated with increased incidence of ADs. Patients undergoing repeat awake craniotomy were more likely to experience IS (p = 0.013). Preoperative antiepileptic drug use, seizure history, and number of prior resections of any type showed no impact on the outcomes considered.

The charge transferred to the cortex per second during mapping was significantly higher in the 10 seconds leading to AD than at any other time point examined in patients experiencing ADs, and was significantly higher than any time point in patients not experiencing ADs or ISs. Although the rate of transfer for patients experiencing ISs was highest in the 10 seconds prior to the seizure, it was not significantly different from those who did not experience an AD or IS.

CONCLUSIONS

The data suggest that intraoperative cortical stimulation is a safe and effective technique in maximizing extent of resection while minimizing neurological morbidity in patients undergoing awake craniotomies, and that surgeons may avoid ADs and ISs by minimizing duration and total number of stimulations and by decreasing the overall charge transferred to the cortex during mapping procedures.

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Keisuke Takai, Toshiki Endo, Toshitaka Seki, Tomoo Inoue, Izumi Koyanagi, Takafumi Mitsuhara, and

OBJECTIVE

A recent comparative analysis between neurosurgical and endovascular treatments for craniocervical junction (CCJ) arteriovenous fistulas (AVFs) revealed better treatment outcomes in the neurosurgery group than in the endovascular group. This finding was attributed to the higher than expected rate of ischemic complications in the endovascular group than in the neurosurgery group (26% vs 7.7%, p = 0.037). The aim of the present study was to describe ischemic complications associated with treatments for CCJ AVFs.

METHODS

This descriptive study was authorized by the Neurospinal Society of Japan. Data from 97 consecutive patients with CCJ AVFs who underwent neurosurgical (n = 78) or endovascular (n = 19) treatment between 2009 and 2019 were collected from 29 centers. The primary endpoints were details on ischemic complications and their risk factors. Secondary endpoints were details on other complications.

RESULTS

Among all major complications, ischemic complications were the most common (11% of 97 patients), followed by hemorrhagic complications (7.2%), hydrocephalus (2.1%), and CSF leakage (2.1%). Ischemic complications included 8 spinal, 2 brainstem, and 1 cerebellar infarctions. Iatrogenic occlusion of the anterior or posterior spinal artery from the radiculomedullary or radiculopial arteries caused these complications. Ischemic complications resulted in neurological deficits, including motor paresis, sensory disturbances, and brainstem dysfunction. The modified Rankin Scale score was 3 or higher in 36% of patients with ischemic complications at the final follow-up of 23 months. Risk factors associated with ischemic complications were endovascular treatment (OR 4.3, 95% CI 1.1–16) and spinal feeding arteries (OR 3.8, 95% CI 1.03–14). Most of the other complications were addressed by additional treatment without permanent neurological deficits.

CONCLUSIONS

Among ischemic complications associated with treatments for CCJ AVFs, spinal infarctions were the most common and were mostly attributed to endovascular procedures for CCJ AVFs fed by spinal arteries. These results support the use of neurosurgery as the first-line treatment for CCJ AVFs.

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Nolan J. Brown, Rohin Singh, Seung Jin Lee, Paola Suarez-Meade, and Alfredo Quiñones-Hinojosa

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Martin N. Stienen, Menno R. Germans, Olivia Zindel-Geisseler, Noemi Dannecker, Yannick Rothacher, Ladina Schlosser, Julia Velz, Martina Sebök, Noemi Eggenberger, Adrien May, Julien Haemmerli, Philippe Bijlenga, Karl Schaller, Ursula Guerra-Lopez, Rodolfo Maduri, Valérie Beaud, Khalid Al-Taha, Roy Thomas Daniel, Alessio Chiappini, Stefania Rossi, Thomas Robert, Sara Bonasia, Johannes Goldberg, Christian Fung, David Bervini, Marie Elise Maradan-Gachet, Klemens Gutbrod, Nicolai Maldaner, Marian C. Neidert, Severin Früh, Marc Schwind, Oliver Bozinov, Peter Brugger, Emanuela Keller, Angelina Marr, Sébastien Roux, Luca Regli, and

OBJECTIVE

While prior retrospective studies have suggested that delayed cerebral ischemia (DCI) is a predictor of neuropsychological deficits after aneurysmal subarachnoid hemorrhage (aSAH), all studies to date have shown a high risk of bias. This study was designed to determine the impact of DCI on the longitudinal neuropsychological outcome after aSAH, and importantly, it includes a baseline examination after aSAH but before DCI onset to reduce the risk of bias.

METHODS

In a prospective, multicenter study (8 Swiss centers), 112 consecutive alert patients underwent serial neuropsychological assessments (Montreal Cognitive Assessment [MoCA]) before and after the DCI period (first assessment, < 72 hours after aSAH; second, 14 days after aSAH; third, 3 months after aSAH). The authors compared standardized MoCA scores and determined the likelihood for a clinically meaningful decline of ≥ 2 points from baseline in patients with DCI versus those without.

RESULTS

The authors screened 519 patients, enrolled 128, and obtained complete data in 112 (87.5%; mean [± SD] age 53.9 ± 13.9 years; 66.1% female; 73% World Federation of Neurosurgical Societies [WFNS] grade I, 17% WFNS grade II, 10% WFNS grades III–V), of whom 30 (26.8%) developed DCI. MoCA z-scores were worse in the DCI group at baseline (−2.6 vs −1.4, p = 0.013) and 14 days (−3.4 vs −0.9, p < 0.001), and 3 months (−0.8 vs 0.0, p = 0.037) after aSAH. Patients with DCI were more likely to experience a decline of ≥ 2 points in MoCA score at 14 days after aSAH (adjusted OR [aOR] 3.02, 95% CI 1.07–8.54; p = 0.037), but the likelihood was similar to that in patients without DCI at 3 months after aSAH (aOR 1.58, 95% CI 0.28–8.89; p = 0.606).

CONCLUSIONS

Aneurysmal SAH patients experiencing DCI have worse neuropsychological function before and until 3 months after the DCI period. DCI itself is responsible for a temporary and clinically meaningful decline in neuropsychological function, but its effect on the MoCA score could not be measured at the time of the 3-month follow-up in patients with low-grade aSAH with little or no impairment of consciousness. Whether these findings can be extrapolated to patients with high-grade aSAH remains unclear.

Clinical trial registration no.: NCT03032471 (ClinicalTrials.gov)

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Pascal Thomann, Levin Häni, Sonja Vulcu, Alessa Schütz, Maximilian Frosch, Christopher Marvin Jesse, Marwan El-Koussy, Nicole Söll, Arsany Hakim, Andreas Raabe, and Philippe Schucht

OBJECTIVE

The management of asymptomatic intracranial meningiomas is controversial. Through the assessment of growth predictors, the authors aimed to create the basis for practicable clinical pathways for the management of these tumors.

METHODS

The authors volumetrically analyzed meningiomas radiologically diagnosed at their institution between 2003 and 2015. The primary endpoint was growth of tumor volume. The authors used significant variables from the multivariable regression model to construct a decision tree based on the exhaustive Chi-Square Automatic Interaction Detection (CHAID) algorithm.

RESULTS

Of 240 meningiomas, 159 (66.3%) demonstrated growth during a mean observation period of 46.9 months. On multivariable logistic regression analysis, older age (OR 0.979 [95% CI 0.958–1.000], p = 0.048) and presence of calcification (OR 0.442 [95% CI 0.224–0.872], p = 0.019) had a negative predictive value for tumor growth, while T2-signal iso-/hyperintensity (OR 4.415 [95% CI 2.056–9.479], p < 0.001) had a positive predictive value. A decision tree model yielded three growth risk groups based on T2 signal intensity and presence of calcifications. The median tumor volume doubling time (Td) was 185.7 months in the low-risk, 100.1 months in the intermediate-risk, and 51.7 months in the high-risk group (p < 0.001). Whereas 0% of meningiomas in the low- and intermediate-risk groups had a Td of ≤ 12 months, the percentage was 8.9% in the high-risk group (p = 0.021).

CONCLUSIONS

Most meningiomas demonstrated growth during follow-up. The absence of calcifications and iso-/hyperintensity on T2-weighted imaging offer a practical way of stratifying meningiomas as low, intermediate, or high risk. Small tumors in the low- or intermediate-risk categories can be monitored with longer follow-up intervals.

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Elias Elias, Shay Bess, Breton Line, Virginie Lafage, Renaud Lafage, Eric Klineberg, Han Jo Kim, Peter G. Passias, Zeina Nasser, Jeffrey L. Gum, Khal Kebaish, Robert Eastlack, Alan H. Daniels, Gregory Mundis Jr., Richard Hostin, Themistocles S. Protopsaltis, Alex Soroceanu, D. Kojo Hamilton, Michael P. Kelly, Munish Gupta, Robert Hart, Frank J. Schwab, Douglas Burton, Christopher P. Ames, Christopher I. Shaffrey, Justin S. Smith, and

OBJECTIVE

The current literature has primarily focused on the 2-year outcomes of operative adult spinal deformity (ASD) treatment. Longer term durability is important given the invasiveness, complications, and costs of these procedures. The aim of this study was to assess minimum 3-year outcomes and complications of ASD surgery.

METHODS

Operatively treated ASD patients were assessed at baseline, follow-up, and through mailings. Patient-reported outcome measures (PROMs) included scores on the Oswestry Disability Index (ODI), Scoliosis Research Society–22r (SRS-22r) questionnaire, mental component summary (MCS) and physical component summary (PCS) of the SF-36, and numeric rating scale (NRS) for back and leg pain. Complications were classified as perioperative (≤ 90 days), delayed (90 days to 2 years), and long term (≥ 2 years). Analyses focused on patients with minimum 3-year follow-up.

RESULTS

Of 569 patients, 427 (75%) with minimum 3-year follow-up (mean ± SD [range] 4.1 ± 1.1 [3.0–9.6] years) had a mean age of 60.8 years and 75% were women. Operative treatment included a posterior approach for 426 patients (99%), with a mean ± SD 12 ± 4 fusion levels. Anterior lumbar interbody fusion was performed in 35 (8%) patients, and 89 (21%) underwent 3-column osteotomy. All PROMs improved significantly from baseline to last follow-up, including scores on ODI (45.4 to 30.5), PCS (31.0 to 38.5), MCS (45.3 to 50.6), SRS-22r total (2.7 to 3.6), SRS-22r activity (2.8 to 3.5), SRS-22r pain (2.3 to 3.4), SRS-22r appearance (2.4 to 3.5), SRS-22r mental (3.4 to 3.7), SRS-22r satisfaction (2.7 to 4.1), NRS for back pain (7.1 to 3.8), and NRS for leg pain (4.8 to 3.0) (all p < 0.001). Degradations in some outcome measures were observed between the 2-year and last follow-up evaluations, but the magnitudes of these degradations were modest and arguably not clinically significant. Overall, 277 (65%) patients had at least 1 complication, including 185 (43%) perioperative, 118 (27%) delayed, and 56 (13%) long term. Notably, the 142 patients who did not achieve 3-year follow-up were similar to the study patients in terms of demographic characteristics, deformities, and baseline PROMs and had similar rates and types of complications.

CONCLUSIONS

This prospective multicenter analysis demonstrated that operative ASD treatment provided significant improvement of health-related quality of life at minimum 3-year follow-up (mean 4.1 years), suggesting that the benefits of surgery for ASD remain durable at longer follow-up. These findings should prove useful for counseling, cost-effectiveness assessments, and efforts to improve the safety of care.

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Eric J. Chalif, Ramin A. Morshed, Jacob S. Young, Alexander F. Haddad, Saket Jain, and Manish K. Aghi

OBJECTIVE

Decision-making in how to manage pituitary adenomas (PAs) in the elderly (age ≥ 65 years) can be challenging given the benign nature of these tumors and concerns about surgical morbidity in these patients. In this study involving a large multicenter national registry, the authors examined treatment trends and surgical outcomes in elderly compared to nonelderly patients.

METHODS

The National Cancer Data Base (NCDB) was queried for adults aged ≥ 18 years with PA diagnosed by MRI (in observed cases) or pathology (in surgical cases) from 2004 to 2016. Univariate and multivariate logistic regressions were used to evaluate the prognostic impact of age and other covariates on 30- and 90-day postsurgical mortality (30M/90M), prolonged (≥ 5 days) length of inpatient hospital stay (LOS), and extent of resection.

RESULTS

A total of 96,399 cases met the study inclusion criteria, 27% of which were microadenomas and 73% of which were macroadenomas. Among these cases were 25,464 elderly patients with PA. Fifty-three percent of these elderly patients were treated with surgery, 1.9% underwent upfront radiotherapy, and 44.9% were observed without treatment. Factors associated with surgical treatment compared to observation included younger age, higher income, private insurance, higher Charlson-Deyo comorbidity (CD) score, larger tumor size, and receiving treatment at an academic hospital (each p ≤ 0.01). Elderly patients undergoing surgery had increased rates of 30M (1.4% vs 0.6%), 90M (2.8% vs 0.9%), prolonged LOS (26.1% vs 23.0%), and subtotal resection (27.2% vs 24.5%; each p ≤ 0.01) compared to those in nonelderly PA patients. On multivariate analysis, age, tumor size, and CD score were independently associated with worse postsurgical mortality. High-volume facilities (HVFs) had significantly better outcomes than low-volume facilities: 30M (0.9% vs 1.8%, p < 0.001), 90M (2.0% vs 3.5%, p < 0.001), and prolonged LOS (21.8% vs 30.3%, p < 0.001). A systematic literature review composed of 22 studies demonstrated an elderly PA patient mortality rate of 0.7%, which is dramatically lower than real-world NCDB outcomes and speaks to substantial selection bias in the previously published literature.

CONCLUSIONS

The study findings confirm that elderly patients with PA are at higher risk for postoperative mortality than younger patients. Surgical risk in this age group may have been previously underreported in the literature. Resection at HVFs better reflects these historical rates, which has important implications in elderly patients for whom surgery is being considered.

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Huy Gia Vuong, Hieu Trong Le, Andrew Jea, Rene McNall-Knapp, and Ian F. Dunn

OBJECTIVE

The prognostic significance and genetic characteristics of H3 K27M–mutant diffuse midline gliomas (DMGs) in different anatomical locations requires further clarification. In this study, the authors integrated published data to investigate the differences between brainstem, thalamic, and spinal cord tumors.

METHODS

PubMed and Web of Science databases were used to search for eligible articles. Studies were included if they provided individual patient data of H3 K27M–mutant DMGs with available tumor locations. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to investigate the survival of each subgroup.

RESULTS

Eight hundred four tumors were identified, including 467, 228, and 109 in the brainstem, thalamus, and spine, respectively. Brainstem tumors were primarily observed in young children, while patients with thalamic and spinal cord tumors afflicted older patients. The Ki-67 labeling index was highest in brainstem tumors. Compared to patients with brainstem tumors, those with thalamic (HR 0.573, 95% CI 0.463–0.709; p < 0.001) and spinal cord lesions (HR 0.460, 95% CI 0.341–0.621; p < 0.001) had a significantly better survival. When patients were stratified by age groups, superior overall survival (OS) of thalamic tumors was observed in comparison to brainstem tumors in young children and adolescents, whereas adult tumors had uniform OS regardless of anatomical sites. Genetically, mutations in HIST1H3B/C (H3.1) and ACVR1 genes were mostly detected in brainstem tumors, whereas spinal cord tumors were characterized by a higher incidence of mutations in the TERT promoter.

CONCLUSIONS

This study demonstrated that H3 K27M–mutant DMGs have distinct clinical characteristics, prognoses, and molecular profiles in different anatomical locations.