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Michael L. Martini, Sean N. Neifert, William H. Shuman, Emily K. Chapman, Alexander J. Schüpper, Eric K. Oermann, J Mocco, Michael Todd, James C. Torner, Andrew Molyneux, Stephan Mayer, Peter Le Roux, Mervyn D. I. Vergouwen, Gabriel J. E. Rinkel, George K. C. Wong, Peter Kirkpatrick, Audrey Quinn, Daniel Hänggi, Nima Etminan, Walter M. van den Bergh, Blessing N. R. Jaja, Michael Cusimano, Tom A. Schweizer, Jose I. Suarez, Hitoshi Fukuda, Sen Yamagata, Benjamin Lo, Airton Leonardo de Oliveira Manoel, Hieronymus D. Boogaarts, R. Loch Macdonald, and on behalf of the SAHIT Collaboration

OBJECTIVE

Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory–based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy.

METHODS

Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SHAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high SHAP importance in predicting rescue therapy administration were used in a propensity score–matched analysis of rescue therapy and 3-month GOS scores.

RESULTS

The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score–matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4–5 (OR 1.63, 95% CI 1.22–2.17).

CONCLUSIONS

Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design.

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Elise C. Bixby, Kira Skaggs, Gerard F. Marciano, Matthew E. Simhon, Richard P. Menger, Richard C. E. Anderson, and Michael G. Vitale

OBJECTIVE

Institutions investigating value and quality emphasize utilization of two attending surgeons with different areas of technical expertise to treat complex surgical cases and to minimize complications. Here, the authors chronicle the 12-year experience of using a two–attending surgeon, two-specialty model to perform hemivertebra resection in the pediatric population.

METHODS

Retrospective cohort data from 2008 to 2019 were obtained from the NewYork-Presbyterian Morgan Stanley Children’s Hospital operative database. This database included all consecutive pediatric patients < 21 years old who underwent hemivertebra resection performed with the two–attending surgeon (neurosurgeon and orthopedic surgeon) model. Demographic information was extracted. Intraoperative complications, including durotomy and direct neurological injury, were queried from the clinical records. Intraoperative neuromonitoring data were evaluated. Postoperative complications were queried, and length of follow-up was determined from the clinical records.

RESULTS

From 2008 to 2019, 22 patients with a median (range) age of 9.1 (2.0–19.3) years underwent hemivertebra resection with the two–attending surgeon, two-specialty model. The median (range) number of levels fused was 2 (0–16). The mean (range) operative time was 5 hours and 14 minutes (2 hours and 59 minutes to 8 hours and 30 minutes), and the median (range) estimated blood loss was 325 (80–2700) ml. Navigation was used in 14% (n = 3) of patients. Neither Gardner-Wells tongs nor halo traction was used in any operation. Neuromonitoring signals significantly decreased or were lost in 14% (n = 3) of patients. At a mean ± SD (range) follow-up of 4.6 ± 3.4 (1.0–11.6) years, 31% (n = 7) of patients had a postoperative complication, including 2 instances of proximal junctional kyphosis, 2 instances of distal junctional kyphosis, 2 wound complications, 1 instance of pseudoarthrosis with hardware failure, and 1 instance of screw pullout. The return to the operating room (OR) rate was 27% (n = 6), which included patients with the abovementioned wound complications, distal junctional kyphosis, pseudoarthrosis, and screw pullout, as well as a patient who required spinal fusion after loss of motor evoked potentials during index surgery.

CONCLUSIONS

Twenty-two patients underwent hemivertebra resection with a two–attending surgeon, two-specialty model over a 12-year period at a specialized children’s hospital, with a 14% rate of change in neuromonitoring, 32% rate of nonneurological complications, and a 27% rate of unplanned return to the OR.

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Sen Gao, Jeffrey Nelson, Shantel Weinsheimer, Ethan A. Winkler, Caleb Rutledge, Adib A. Abla, Nalin Gupta, Joseph T. Shieh, Daniel L. Cooke, Steven W. Hetts, Tarik Tihan, Christopher P. Hess, Nerissa Ko, Brian P. Walcott, Charles E. McCulloch, Michael T. Lawton, Hua Su, Ludmila Pawlikowska, and Helen Kim

OBJECTIVE

Sporadic brain arteriovenous malformation (BAVM) is a tangled vascular lesion characterized by direct artery-to-vein connections that can cause life-threatening intracerebral hemorrhage (ICH). Recently, somatic mutations in KRAS have been reported in sporadic BAVM, and mutations in other mitogen-activated protein kinase (MAPK) signaling pathway genes have been identified in other vascular malformations. The objectives of this study were to systematically evaluate somatic mutations in MAPK pathway genes in patients with sporadic BAVM lesions and to evaluate the association of somatic mutations with phenotypes of sporadic BAVM severity.

METHODS

The authors performed whole-exome sequencing on paired lesion and blood DNA samples from 14 patients with sporadic BAVM, and 295 genes in the MAPK signaling pathway were evaluated to identify genes with somatic mutations in multiple patients with BAVM. Digital droplet polymerase chain reaction was used to validate KRAS G12V and G12D mutations and to assay an additional 56 BAVM samples.

RESULTS

The authors identified a total of 24 candidate BAVM-associated somatic variants in 11 MAPK pathway genes. The previously identified KRAS G12V and G12D mutations were the only recurrent mutations. Overall, somatic KRAS G12V was present in 14.5% of BAVM lesions and G12D was present in 31.9%. The authors did not detect a significant association between the presence or allelic burden of KRAS mutation and three BAVM phenotypes: lesion size (maximum diameter), age at diagnosis, and age at ICH.

CONCLUSIONS

The authors confirmed the high prevalence of somatic KRAS mutations in sporadic BAVM lesions and identified several candidate somatic variants in other MAPK pathway genes. These somatic variants may contribute to understanding of the etiology of sporadic BAVM and the clinical characteristics of patients with this condition.

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Puneet Jain, Ayako Ochi, Carter McInnis, Hiroshi Otsubo, O. Carter Snead III, George M. Ibrahim, Elizabeth Donner, and Elysa Widjaja

OBJECTIVE

Bottom-of-sulcus dysplasia (BOSD) is challenging to identify radiologically. The aim of this study was to explore seizure outcomes after resective surgery or MR-guided laser interstitial thermal therapy (MRgLITT) in children with BOSD.

METHODS

Children with radiologically defined BOSD who underwent resective surgery or MRgLITT, with at least 1 year of follow-up were included. Clinical, radiological, neurophysiological, and histological data were extracted from medical records. Invasive video EEG (IVEEG) was used to evaluate the ictal onset zone or motor/language mapping, wherever appropriate. Histology of MRI-visible BOSD, including the overlying and adjacent cortex, was also evaluated.

RESULTS

Forty-one children with BOSD underwent surgical treatment. The lesion was initially overlooked on MRI in 20 patients (48.8%). Of 34 patients who underwent IVEEG and who had available ictal data, the ictal onset zone extended beyond the MRI-visible BOSD in 23 patients (67.6%). Surgical treatment included lesionectomy (24 patients), extended lesionectomy (12 patients), lobectomy (1 patient), and ablation of BOSD (4 patients). The pathology in 37 patients who underwent resection showed focal cortical dysplasia type IIB and type IIA in 21 (53.8%) and 16 patients (41%), respectively. Seizure freedom was achieved in 32 patients (78.1%) after a mean follow-up of 4.3 years.

CONCLUSIONS

Seizure outcomes after resective surgery or MRgLITT in children with BOSD were generally favorable. The authors found that the neurophysiological abnormality and pathology often extended beyond the MRI-visible BOSD.

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Ana M. Castaño-Leon, Marta Cicuendez, Blanca Navarro-Main, Igor Paredes, Pablo M. Munarriz, Amaya Hilario, Ana Ramos, Pedro A. Gomez, and Alfonso Lagares

OBJECTIVE

A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model.

METHODS

The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients.

RESULTS

Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, characterization of TAI lesions in the CC, and the presence of thalamic/basal ganglia lesions were independent prognostic factors. The performance of the proposed model was higher than that of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) model in the validation cohort.

CONCLUSIONS

Very limited colocalization of hyperintensities (none for microbleeds) with FA values was discovered. DTI and conventional MRI provide complementary prognostic information, and their combination can improve the performance of traditional prognostic models.

Free access

Connor T. A. Brenna, Jerry C. Ku, Christopher R. Pasarikovski, Stefano M. Priola, Erin E. Dyer, Peter Howard, Ashish Kumar, Leodante da Costa, and Victor X. D. Yang

OBJECTIVE

Mechanical endovascular thrombectomy (EVT) is an increasingly relied-on treatment for clot retrieval in the context of ischemic strokes, which otherwise are associated with significant morbidity and mortality. Despite several known risks associated with this procedure, there is a high degree of technical heterogeneity across both centers and operators. The most common procedural complications occur at the point of transfemoral access (the common femoral artery), and include access-site hematomas, dissections, and pseudoaneurysms. Other interventional fields have previously popularized the use of ultrasound to enhance the anatomical localization of structures relevant to vascular access and thereby reducing access-site complications. In this study, the authors aimed to describe the ultrasound-guided EVT technique performed at a large, quaternary neurovascular referral center, and to characterize the effects of ultrasound guidance on access-site complications.

METHODS

A retrospective chart review of all patients treated with EVT at a single center between January 2013 and August 2020 was performed. Patients in this cohort were treated using a universal, unique, ultrasound-guided, single-wall puncture technique, which bears several theoretical advantages over the standard technique of arterial puncture via palpation.

RESULTS

There were 479 patients treated with EVT within the study period. Twenty patients in the cohort were identified as having experienced some form of access-site complication. Eight (1.67%) of these patients experienced minor access-site complications, all of which were groin hematomas and none of which were clinically significant, as defined by requiring surgical or interventional management or transfusion. The remaining 12 patients experienced arterial dissection (n = 5), arterial pseudoaneurysm (n = 4), retroperitoneal hematoma (n = 2), or arterial occlusion (n = 1), with only 1.04% (5/479) requiring surgical or interventional management or transfusion.

CONCLUSIONS

The authors found an overall reduction in total access-site complications as well as minor access-site complications in the study cohort compared with previously published randomized controlled trials and observational studies in the recent literature. The findings suggested that there may be a role for routine use of ultrasound-guided puncture techniques in EVT to decrease rates of complications.

Free access

Martina Sebök, Christiaan Hendrik Bas van Niftrik, Susanne Wegener, Andreas Luft, Luca Regli, and Jorn Fierstra

OBJECTIVE

In symptomatic patients with cerebrovascular steno-occlusive disease, impaired blood oxygenation level–dependent cerebrovascular reactivity (BOLD-CVR) and increased flow velocity of the P2 segment of the posterior cerebral artery (PCA-P2) on transcranial Doppler (TCD) ultrasonography have been introduced as emerging clinical imaging parameters to identify patients at high risk for recurrent ischemic events. Since hemodynamic physiology differs between the acute and chronic stages of ischemic stroke, the authors sought to investigate whether those parameters have merit for both the acute and chronic stages of ischemic stroke.

METHODS

From a prospective database, patients who underwent BOLD-CVR and TCD examinations in the acute stroke stage (< 10 days) were matched to patients in the chronic stroke stage (> 3 months). A linear regression analysis for both groups was performed between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR of the ipsilateral (affected) hemisphere, the ipsilateral middle cerebral artery (MCA) territory, and the ipsilateral steal volume (i.e., paradoxical BOLD-CVR response). The resulting slopes and intercepts were statistically compared to evaluate differences between groups.

RESULTS

Forty matched patient pairs were included. Regression analysis showed no significant difference for either the intercept (p = 0.84) or the slope (p = 0.85) between PCA-P2 flow velocity and BOLD-CVR as measured for the ipsilateral (affected) hemisphere. Similarly, no significant difference was seen between PCA-P2 flow velocity and BOLD-CVR of the ipsilateral MCA territory (intercept, p = 0.72; slope, p = 0.36) or between PCA-P2 flow velocity and steal volume (intercept, p = 0.59; slope, p = 0.34).

CONCLUSIONS

The study results indicated that the relationship between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR remains the same during the acute and chronic stages of ischemic stroke. This provides further support that these novel hemodynamic imaging parameters may have merit to assess the risk for recurrent ischemic events for a wide ischemic stroke population. PCA-P2 systolic flow velocity, in particular, may be a highly practical screening tool, independent of ischemic stroke stage.

Open access

Jiuhong Li, Jiaojiang He, Lunxin Liu, and Liangxue Zhou

A 57-year-old female presented with headache and dizziness for 3 months. Preoperative MRI revealed a lesion located at the pineal region and back side of the third ventricle, accompanied by hydrocephalus. The infratentorial supracerebellar approach may cause visuomotor, acousticomotor, and hearing disturbances. With the patient in a supine position, the authors used a frontal linear incision that was 3 cm anterior to the coronal suture and 2 cm away from the midline and an anterior endoscopic transcortical approach, which could achieve endoscopic third ventriculostomy, alleviating and preventing hydrocephalus due to postoperative adhesion and resection of the lesion at the same time. The pathological diagnosis was cavernous hemangioma.

The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID215.

Free access

Rania Abdelkhaleq, Youngran Kim, Swapnil Khose, Peter Kan, Sergio Salazar-Marioni, Luca Giancardo, and Sunil A. Sheth

OBJECTIVE

In patients with large-vessel occlusion (LVO) acute ischemic stroke (AIS), determinations of infarct size play a key role in the identification of candidates for endovascular stroke therapy (EVT). An accurate, automated method to quantify infarct at the time of presentation using widely available imaging modalities would improve screening for EVT. Here, the authors aimed to compare the performance of three measures of infarct core at presentation, including an automated method using machine learning.

METHODS

Patients with LVO AIS who underwent successful EVT at four comprehensive stroke centers were identified. Patients were included if they underwent concurrent noncontrast head CT (NCHCT), CT angiography (CTA), and CT perfusion (CTP) with Rapid imaging at the time of presentation, and MRI 24 to 48 hours after reperfusion. NCHCT scans were analyzed using the Alberta Stroke Program Early CT Score (ASPECTS) graded by neuroradiology or neurology expert readers. CTA source images were analyzed using a previously described machine learning model named DeepSymNet (DSN). Final infarct volume (FIV) was determined from diffusion-weighted MRI sequences using manual segmentation. The primary outcome was the performance of the three infarct core measurements (NCHCT-ASPECTS, CTA with DSN, and CTP-Rapid) to predict FIV, which was measured using area under the receiver operating characteristic (ROC) curve (AUC) analysis.

RESULTS

Among 76 patients with LVO AIS who underwent EVT and met inclusion criteria, the median age was 67 years (IQR 54–76 years), 45% were female, and 37% were White. The median National Institutes of Health Stroke Scale score was 16 (IQR 12–22), and the median NCHCT-ASPECTS on presentation was 8 (IQR 7–8). The median time between when the patient was last known to be well and arrival was 156 minutes (IQR 73–303 minutes), and between NCHCT/CTA/CTP to groin puncture was 73 minutes (IQR 54–81 minutes). The AUC was obtained at three different cutoff points: 10 ml, 30 ml, and 50 ml FIV. At the 50-ml FIV cutoff, the AUC of ASPECTS was 0.74; of CTP core volume, 0.72; and of DSN, 0.82. Differences in AUCs for the three predictors were not significant for the three FIV cutoffs.

CONCLUSIONS

In a cohort of patients with LVO AIS in whom reperfusion was achieved, determinations of infarct core at presentation by NCHCT-ASPECTS and a machine learning model analyzing CTA source images were equivalent to CTP in predicting FIV. These findings have suggested that the information to accurately predict infarct core in patients with LVO AIS was present in conventional imaging modalities (NCHCT and CTA) and accessible by machine learning methods.

Open access

Juan M. Revuelta Barbero, Roberto M. Soriano, Rima S. Rindler, David P. Bray, Oswaldo Henriquez, C. Arturo Solares, and Gustavo Pradilla

The authors present the case of a 20-year-old male with a history of headaches and blurred vision found to have a pineal mass and chronic hydrocephalus. The patient initially underwent an endoscopic third ventriculostomy and pineal mass biopsy that revealed a low-grade neuroepithelial neoplasm. A microsurgery-endoscope–assisted paramedian supracerebellar-infratentorial approach was chosen and a gross-total resection was achieved. The patient’s postoperative and follow-up course has been unremarkable, with early postoperative imaging demonstrating no residual tumoral mass. The operative video highlights the advantages of endoscopic visualization for deep lesions in the pineal region and posterior third ventricle.

The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2119.