OBJECTIVE The incidence of leptomeningeal disease (LMD) has increased as treatments for brain metastases (BMs) have improved and patients with metastatic disease are living longer. Sample sizes of... Show moreOBJECTIVE The incidence of leptomeningeal disease (LMD) has increased as treatments for brain metastases (BMs) have improved and patients with metastatic disease are living longer. Sample sizes of individual studies investigating LMD after surgery for BMs and its risk factors have been limited, ranging from 200 to 400 patients at risk for LMD, which only allows the use of conventional biostatistics. Here, the authors used machine learning techniques to enhance LMD prediction in a cohort of surgically treated BMs.METHODS A conditional survival forest, a Cox proportional hazards model, an extreme gradient boosting (XGBoost) classifier, an extra trees classifier, and logistic regression were trained. A synthetic minority oversampling technique (SMOTE) was used to train the models and handle the inherent class imbalance. Patients were divided into an 80:20 training and test set. Fivefold cross-validation was used on the training set for hyperparameter optimization. Patients eligible for study inclusion were adults who had consecutively undergone neurosurgical BM treatment, had been admit-ted to Brigham and Women's Hospital from January 2007 through December 2019, and had a minimum of 1 month of follow-up after neurosurgical treatment.RESULTS A total of 1054 surgically treated BM patients were included in this analysis. LMD occurred in 168 patients (15.9%) at a median of 7.05 months after BM diagnosis. The discrimination of LMD occurrence was optimal using an XGboost algorithm (area under the curve = 0.83), and the time to LMD was prognosticated evenly by the random forest algorithm and the Cox proportional hazards model (C-index = 0.76). The most important feature for both LMD clas-sification and regression was the BM proximity to the CSF space, followed by a cerebellar BM location. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest risk factors for both LMD occurrence and time to LMD.CONCLUSIONS The outcomes of LMD patients in the BM population are predictable using SMOTE and machine learn-ing. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest LMD risk factors. Show less
Socolovsky, M.; Barillaro, K.; Bonilla, G.; Masi, G. di; Malessy, M. 2023
OBJECTIVE After brachial plexus injuries (BPIs), nerve transfers are used to restore lost muscle function. Brain plastic-ity underlies the process of regaining volitional control, which encompasses... Show moreOBJECTIVE After brachial plexus injuries (BPIs), nerve transfers are used to restore lost muscle function. Brain plastic-ity underlies the process of regaining volitional control, which encompasses disconnection of the original donor nerve-re-lated programs and reconnection to acceptor nerve programs. To the authors' knowledge, the levels of disconnection and reconnection have never been studied systematically. In this study, the authors developed a novel 4-point plasticity grad-ing scale (PGS) and assessed the degree of volitional control achieved, identifying clinical correlations with this score.METHODS Patients with BPI who underwent a phrenic, spinal accessory, median, and/or ulnar fascicle nerve transfer to restore biceps and deltoid function were asked to maximally contract their target muscle as follows: 1) by using only the donor nerve program, and 2) by activating the target muscle while consciously trying to avoid using the donor nerve, with assessment each time of the Medical Research Council (MRC) scale grade for muscle strength. The authors' PGS was used to rate the level of volitional control achieved. PGS grade 1 represented the lowest independent volitional control, with MRC grade 4 obtained in response to the donor command and MRC grade 0 in response to the acceptor command (minimum brain plasticity), whereas PGS grade 4 was no noticeable contraction in response to the donor com-mand and MRC grade 4 in response to the acceptor command (maximum brain plasticity).RESULTS In total, 153 patients were studied. For biceps restoration, the phrenic nerve was used as a donor in 44 patients, the spinal accessory nerve in 40 patients, and the median and/or ulnar fascicles in 44 patients. A triceps branch was used to restore deltoid function in 25 patients. The level of volitional control achieved was PGS grade 1 in 1 patient (0.6%), grade 2 in 21 patients (13.7%), grade 3 in 103 patients (67.3%), and grade 4 in 28 patients (18.3%). The median PGS grade did not differ significantly between the four donor nerves. No correlations were observed between age, time from BPI to surgery, duration of follow-up, or compliance with rehabilitation and PGS grade.CONCLUSIONS Just around 20% of the authors' patients developed a complete disconnection of the donor program along with complete independent control over the reinnervated muscle. Incomplete disconnection was present in the vast majority of the patients, and the level of disconnection and control was poor in approximately 15% of patients. Brain plasticity underlies patient ability to regain volitional control after a nerve transfer, but this capacity is limited. Show less
OBJECTIVE A major obstacle to improving bedside neurosurgical procedure safety and accuracy with image guidance technologies is the lack of a rapidly deployable, real-time registration and tracking... Show moreOBJECTIVE A major obstacle to improving bedside neurosurgical procedure safety and accuracy with image guidance technologies is the lack of a rapidly deployable, real-time registration and tracking system for a moving patient. This deficiency explains the persistence of freehand placement of external ventricular drains, which has an inherent risk of inaccurate positioning, multiple passes, tract hemorrhage, and injury to adjacent brain parenchyma. Here, the authors introduce and validate a novel image registration and real-time tracking system for frameless stereotactic neuronavigation and catheter placement in the nonimmobilized patient.METHODS Computer vision technology was used to develop an algorithm that performed near- continuous, automatic, and marker-less image registration. The program fuses a subject's preprocedure CT scans to live 3D camera images (Snap-Surface), and patient movement is incorporated by artificial intelligence- driven recalibration (Real-Track). The surface registration error (SRE) and target registration error (TRE) were calculated for 5 cadaveric heads that underwent serial movements (fast and slow velocity roll, pitch, and yaw motions) and several test conditions, such as surgical draping with limited anatomical exposure and differential subject lighting. Six catheters were placed in each cadaveric head (30 total placements) with a simulated sterile technique. Postprocedure CT scans allowed comparison of planned and actual catheter positions for user error calculation.RESULTS Registration was successful for all 5 cadaveric specimens, with an overall mean (+/- standard deviation) SRE of 0.429 +/- 0.108 mm for the catheter placements. Accuracy of TRE was maintained under 1.2 mm throughout specimen movements of low and high velocities of roll, pitch, and yaw, with the slowest recalibration time of 0.23 seconds. There were no statistically significant differences in SRE when the specimens were draped or fully undraped (p = 0.336). Performing registration in a bright versus a dimly lit environment had no statistically significant effect on SRE (p = 0.742 and 0.859, respectively). For the catheter placements, mean TRE was 0.862 +/- 0.322 mm and mean user error (difference between target and actual catheter tip) was 1.674 +/- 1.195 mm.CONCLUSIONS This computer vision-based registration system provided real-time tracking of cadaveric heads with a recalibration time of less than one-quarter of a second with submillimetric accuracy and enabled catheter placements with millimetric accuracy. Using this approach to guide bedside ventriculostomy could reduce complications, improve safety, and be extrapolated to other frameless stereotactic applications in awake, nonimmobilized patients. Show less
Fisher, F.L.; Najafabadi, A.H.Z.; Meer, P.B. van der; Boele, F.W.; Peerdeman, S.M.; Peul, W.C.; ... ; Furth, W.R. van 2022
OBJECTIVE Patients with skull base meningioma (SBM) often require complex surgery around critical neurovascular structures, placing them at high risk of poor health-related quality of life (HRQOL)... Show moreOBJECTIVE Patients with skull base meningioma (SBM) often require complex surgery around critical neurovascular structures, placing them at high risk of poor health-related quality of life (HRQOL) and possibly neurocognitive dysfunction. As the survival of meningioma patients is near normal, long-term neurocognitive and HRQOL outcomes are important to evaluate, including evaluation of the impact of specific tumor location and treatment modalities on these outcomes. METHODS In this multicenter cross-sectional study including patients 5 years or more after their last tumor intervention, Short-Form Health Survey (SF-36) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BN20 questionnaires were used to assess generic and disease-specific HRQOL. Neurocognitive functioning was assessed with standardized neuropsychological assessment. SBM patient assessments were compared with those of 1) informal caregivers of SBM patients who served as controls and 2) convexity meningioma patients. In addition, the authors compared anterior/middle SBM patients with posterior SBM patients and anterior/middle and posterior SBM patients separately with controls. Multivariable and propensity score regression analyses were performed to correct for possible confounders. RESULTS Patients with SBM (n = 89) with a median follow-up of 9 years after the last intervention did not significantly differ from controls (n = 65) or convexity meningioma patients (n = 84) on generic HRQOL assessment. Statistically significantly but not clinically relevantly better disease-specific HRQOL was found for SBM patients compared with convexity meningioma patients. Anterior/middle SBM patients (n = 62) had significantly and clinically relevantly better HRQOL in SF-36 and EORTC QLQ-BN20 scores than posterior SBM patients (n = 27): physical role functioning (corrected difference 17.1, 95% CI 0.2-34.0), motor dysfunction (-10.1, 95% CI -17.5 to -2.7), communication deficit (-14.2, 95% CI -22.7 to -5.6), and weakness in both legs (-10.1, 95% CI -18.8 to -1.5). SBM patients whose primary treatment was radiotherapy had lower HRQOL scores compared with SBM patients who underwent surgery on two domains: bodily pain (-33.0, 95% CI -55.2 to -10.9) and vitality (-18.9. 95% CI -33.7 to -4.1). Tumor location and treatment modality did not result in significant differences in neurocognitive functioning, although 44% of SBM patients had deficits in at least one domain. CONCLUSIONS In the long term, SBM patients do not experience significantly more sequelae in HRQOL and neurocognitive functioning than do controls or patients with convexity meningioma. Patients with posterior SBM had poorer HRQOL than anterior/middle SBM patients, and primary treatment with radiotherapy was associated with worse HRQOL. Neurocognitive functioning was not affected by tumor location or treatment modality. Show less
OBJECTIVE Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and... Show moreOBJECTIVE Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and mortality. Furthermore, they aimed to assess the effectiveness of intravenous alteplase treatment and endovascular treatment (EVT), as well as the best first-line EVT approach in patients with CCE. METHODS The Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry is a prospective, observational multicenter registry of patients treated with EVT for acute ischemic stroke in 16 intervention hospitals in the Netherlands. The association of CCE with functional outcome, reperfusion, and mortality was evaluated using logistic regression models. Univariable comparisons were made to determine the effectiveness of intravenous alteplase treatment and the best first-line EVT approach in CCE patients. RESULTS The study included 3077 patients from the MR CLEAN Registry. Fifty-five patients (1.8%) had CCE. CCE were not significantly associated with worse functional outcome (adjusted common OR 0.71, 95% CI 0.44-1.15), and 29% of CCE patients achieved functional independence. An extended Thrombolysis in Cerebral Infarction score >= 2B was significantly less often achieved in CCE patients compared to non-CCE patients (adjusted OR [aOR] 0.52, 95% CI 0.28- 0.97). Symptomatic intracranial hemorrhage occurred in 8 CCE patients (15%) vs 171 of 3022 non-CCE patients (6%; p = 0.01). The median improvement on the National Institutes of Health Stroke Scale (NIHSS) was 2 in CCE patients versus 4 in non-CCE patients (p = 0.008). CCE were not significantly associated with mortality (aOR 1.16, 95% CI 0.64-2.12). Intravenous alteplase use in CCE patients was not associated with functional outcome or reperfusion. In CCE patients with successful reperfusion, stent retrievers were more often used as the primary treatment device (p = 0.04). CONCLUSIONS While patients with CCE had significantly lower reperfusion rates and less improvement on the NIHSS after EVT, CCE were not significantly associated with worse functional outcome or higher mortality rates. Therefore, EVT should still be considered in this specific group of patients. Show less
OBJECTIVE Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on... Show moreOBJECTIVE Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized num-bers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impair-ment. METHODS The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of >= 10 points. Two prospective registries in Swit- zerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS In the development (2437 patients, 48.2% male; mean age +/- SD: 55 +/- 15 years) and external validation (2427 patients, 42.4% male; mean age +/- SD: 58 +/- 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, al- though machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient. Show less
Dijkland, S.A.; Jaja, B.N.R.; Jagt, M. van der; Roozenbeek, B.; Vergouwen, M.D.I.; Suarez, J.I.; ... ; SAHIT Collaboration 2020
OBJECTIVE Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of... Show moreOBJECTIVE Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of this study was to investigate the presence and magnitude of between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage (aSAH).METHODS The authors analyzed data from 5972 aSAH patients enrolled in randomized clinical trials of 3 different treatments from the Subarachnoid Hemorrhage International Trialists (SAHIT) repository, including data from 179 centers and 20 countries. They used random effects logistic regression adjusted for patient characteristics and timing of aneurysm treatment to estimate between-center and between-country differences in unfavorable outcome, defined as a Glasgow Outcome Scale score of 1-3 (severe disability, vegetative state, or death) or modified Rankin Scale score of 4-6 (moderately severe disability, severe disability, or death) at 3 months. Between-center and between-country differences were quantified with the median odds ratio (MOR), which can be interpreted as the ratio of odds of unfavorable outcome between a typical high-risk and a typical low-risk center or country.RESULTS The proportion of patients with unfavorable outcome was 27% (n = 1599). The authors found substantial between-center differences (MOR 1.26, 95% CI 1.16-1.52), which could not be explained by patient characteristics and timing of aneurysm treatment (adjusted MOR 1.21, 95% CI 1.11-1.44). They observed no between-country differences (adjusted MOR 1.13, 95% CI 1.00-1.40).CONCLUSIONS Clinical outcomes after aSAH differ between centers. These differences could not be explained by patient characteristics or timing of aneurysm treatment. Further research is needed to confirm the presence of differences in outcome after aSAH between hospitals in more recent data and to investigate potential causes. Show less
Object. Accuracy of reinnervation is an important factor that determines outcome after nerve injury and repair. Type grouping-the clustering of muscle fibers of the same type after reinnervation... Show moreObject. Accuracy of reinnervation is an important factor that determines outcome after nerve injury and repair. Type grouping-the clustering of muscle fibers of the same type after reinnervation-can be used to investigate the accuracy of reinnervation. In this study, the degree of type grouping after crush injury in rats was compared with the clustering of muscle fibers after autografting or single-lumen nerve grafting. Methods. Twelve weeks after sciatic nerve crush injury in rats, clustering of Type I muscle fibers was analyzed in the target muscle with adenosine 5'-triphosphatase staining. In addition, the number of regenerated axons was determined in the nerve distal to the crush injury. Results were compared with that of the authors' previous study. Results. Type grouping was more abundant after crush injury than after autograft or single-lumen nerve graft repair. Conclusions. Crush injury leads to more clustered innervation of muscle fibers, probably because the Schwann cell basal lamina tubes are not interrupted as they are in autograft or artificial nerve graft repair. This finding adds to understanding the processes playing a role in nerve regeneration. (DOI: 10.3171/2010.9.JNS091656) Show less
