Risk assessment of early therapeutic anticoagulation following cranial surgery: an institutional case series.

OBJECTIVE: Postoperative thrombotic complications represent a unique challenge in cranial neurosurgery as primary treatment involves therapeutic anticoagulation. The decision to initiate therapy and its timing is nuanced, as surgeons must balance the risk of catastrophic intracranial hemorrhage (ICH). With limited existing evidence to guide management, current practice patterns are subjective and inconsistent. The authors assessed their experience with early therapeutic anticoagulation (≤ 7 days postoperatively) initiation for thrombotic complications in neurosurgical patients undergoing cranial surgery to better understand the risks of catastrophic ICH. METHODS: Adult patients treated with early therapeutic anticoagulation following cranial surgery were considered. Anticoagulation indications were restricted to thrombotic or thromboembolic complications. Records were retrospectively reviewed for demographics, surgical details, and anticoagulation therapy start. The primary outcome was the incidence of catastrophic ICH, defined as ICH resulting in reoperation or death within 30 days of anticoagulation initiation. As a secondary outcome, post-anticoagulation cranial imaging was reviewed for new or worsening acute blood products. Fisher's exact and Wilcoxon rank-sum tests were used to compare cohorts. Cumulative outcome analyses were performed for primary and secondary outcomes according to anticoagulation start time. RESULTS: Seventy-one patients satisfied the inclusion criteria. Anticoagulation commenced on mean postoperative day (POD) 4.3 (SD 2.2). Catastrophic ICH was observed in 7 patients (9.9%) and was associated with earlier anticoagulation initiation (p = 0.02). Of patients with catastrophic ICH, 6 (85.7%) had intra-axial exploration during their index surgery. Patients with intra-axial exploration were more likely to experience a catastrophic ICH postoperatively compared to those with extra-axial exploration alone (OR 8.5, p = 0.04). Of the 58 patients with postoperative imaging, 15 (25.9%) experienced new or worsening blood products. Catastrophic ICH was 9 times more likely with anticoagulation initiation within 48 hours of surgery (OR 8.9, p = 0.01). The cumulative catastrophic ICH risk decreased with delay in initiation of anticoagulation, from 21.1% on POD 2 to 9.9% on POD 7. Concurrent antiplatelet medication was not associated with either outcome measure. CONCLUSIONS: The incidence of catastrophic ICH was significantly increased when anticoagulation was initiated within 48 hours of cranial surgery. Patients undergoing intra-axial exploration during their index surgery were at higher risk of a catastrophic ICH.

Treatment outcomes for ARUBA-eligible brain arteriovenous malformations: a comparison of real-world data from the NVQI-QOD AVM registry with the ARUBA trial.

BACKGROUND: Significant controversy exists about the management of unruptured cerebral arteriovenous malformations (AVMs). Results from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that intervention increases the risk of stroke/death compared with medical management. However, numerous study limitations raised concerns about the trial's generalizability. OBJECTIVE: To assess the rate of stroke/death and functional outcomes in ARUBA-eligible patients from a multicenter database, the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). METHODS: We performed a retrospective analysis of prospectively collected data of ARUBA-eligible patients who underwent intervention at 18 participating centers. The primary endpoint was stroke/death from any cause. Secondary endpoints included neurologic, systemic, radiographic, and functional outcomes. RESULTS: 173 ARUBA-eligible patients underwent intervention with median follow-up of 269 (25-722.5) days. Seventy-five patients received microsurgery±embolization, 37 received radiosurgery, and 61 received embolization. Baseline demographics, risk factors, and general AVM characteristics were similar between groups. A total of 15 (8.7%) patients experienced stroke/death with no significant difference in primary outcome between treatment modalities. Microsurgery±embolization was more likely to achieve AVM obliteration (P<0.001). Kaplan-Meier survival curves demonstrated no difference in overall death/stroke outcomes between the different treatment modalities' 5-year period (P=0.087). Additionally, when compared with the ARUBA interventional arm, our patients were significantly less likely to experience death/stroke (8.7% vs 30.7%; P<0.001) and functional impairment (mRS score ≥2 25.4% vs 46.2%; P<0.01). CONCLUSION: Our results suggest that intervention for unruptured brain AVMs at comprehensive stroke centers across the United States is safe.

Prognosticators of Functional Outcome After Supratentorial Minimally Invasive Intracranial Hemorrhage Evacuation With Tubular Retractor Systems.

BACKGROUND AND OBJECTIVES: Prognosticators of good functional outcome after minimally invasive surgical (MIS) intracranial hemorrhage (ICH) evacuation are poorly defined. This study aims to investigate clinical and radiographic prognosticators of poor functional outcome after MIS evacuation of ICH with tubular retractor systems. METHODS: Single-center retrospective review of adult (age ≥18 years) patients who underwent surgical evacuation of a spontaneous supratentorial ICH evacuation using tubular retractors from 2013 to 2022 was performed. Clinical and radiographic factors, such as antiplatelet/anticoagulant use, initial NIH Stroke Scale, ICH score, premorbid modified Rankin Scale (mRS), intraventricular hemorrhage (IVH) severity according to the modified Graeb scale, and preoperative/postoperative ICH volume, were collected. The main outcome was poor functional outcome, defined as mRS score of 4-6 within 1 year postoperatively. RESULTS: Eighty-eight patients were included. Clinical follow-up data were available for 64 (73%) patients. Of those, 43 (67%) had a poor functional outcome. On multivariate Cox regression, postoperative ICH volume ≥15 mL (hazard ratio [HR] = 2.46 [95% CI: 1.25-4.87]; P = .010) and higher modified Graeb score (HR = 1.04 [95% CI: 1-1.1]; P = .035] significantly increased the risk of poor functional outcome. Elevated postoperative ICH volume was predicted by the presence of lobar ICH (vs nonlobar, OR = 3.32 [95% CI: 1.01-11.55]; P = .043) and higher preoperative ICH volume (OR = 1.05 [1.02-1.08]; P < .001). A minimum of 60% ICH evacuation yielded an improvement in mRS 4-6 rates (HR 0.3 [95% CI: 0.1-0.8], P = .013). In patients without IVH and with a >80% ICH evacuation, the rate of mRS 4-6 was 42% compared with 67% in the whole patient sample ( P = .017). CONCLUSION: Increased IVH volumes and residual postoperative ICH volumes are associated with poor functional outcome after MIS ICH evacuation. Postoperative ICH volume was associated with lobar ICH location as well as preoperative ICH volume. These factors may help to prognosticate patient outcomes and improve selection criteria for MIS ICH evacuation techniques.

Posterior Approach to Meckel's Cave: Retrosigmoid Craniectomy with Endoscopic Assistance.

Background Meckel's cave involvement in tumors pose a challenge due to their surrounding neurovascular structure and deep location. Case Review A 24-year-old male presented with progressive headaches and right sided trigeminal neuralgia with a large epidermoid. The tumor extended from the ambient cistern to the cerebellomedullary cistern and involved Meckel's cave ( Fig. 1 ). Technical Note/Video Description A retrosigmoid craniectomy was performed. Cranial nerves 3, 4, 6, 7, and 10, and auditory brainstem responses were monitored. Once the craniectomy was completed the dura was opened and cerebrospinal fluid (CSF) was released from the cisterna magna to allow for the tumor resection to be done without the use of any retractors ( Fig. 2 ). Care was taken to ensure that cranial nerves in the posterior fossa were detethered to prevent any traction injury. Using ring curettes the pearly white epidermoid tumor was able to be debulked. After all the possible tumor was resected with the microscope, the 30-degree endoscope was used to identify the porus trigeminus. Malleable ring curettes and a malleable suction were used to remove the soft tumor from this location. The patient transiently had loss of hearing but this returned within 2 weeks after surgery. Conclusions The retrosigmoid approach is familiar to all neurosurgeons and with the adjunct of an angled endoscope, the posterior Meckel's cave can be easily reached. This is particularly useful for tumors with soft consistency. The assistance of the endoscope allows Meckel's cave visualization without additional drilling while still allowing safe resection of tumor from around the trigeminal nerve. The link to the video can be found at: https://youtu.be/01aqOyUmSW0 .

Early post-Humanitarian Device Exemption experience with the Neuroform Atlas stent.

INTRODUCTION: The low-profile Neuroform Atlas stent received FDA Humanitarian Device Exemption status (HDE) in January 2018 for stent-assisted coil embolization of wide-necked saccular aneurysms. We review and report our results with the Atlas stent in our institution within the first year after its HDE approval. METHODS: Our retrospective chart review identified patients treated with the Atlas stent. We analyzed the patient demographics, aneurysm characteristics, stent parameters and configuration, complications, angiographic, and clinical outcomes at discharge. RESULTS: From January to December 2018, 76 Atlas stents were deployed in 58 patients (average 1.3 stents/patient). Median patient age was 63.5 (IQR 56-71) years. Fifty-six (96.6%) patients had elective embolization of unruptured aneurysms, while two (3.4%) patients underwent embolization of a ruptured aneurysm within 2 weeks of subarachnoid hemorrhage. Forty (69.0%) patients were treated with a single stent, 15 (25.9%) with a Y-stent, and three (5.2%) with X-stent configuration. All stent deployments were technically successful. Most stents (82.9%) were the smallest 3 mm diameter devices. Procedural complications included transient stent-associated thrombosis in three (5.2%) patients and aneurysm rupture in one (1.7%). None had distal embolization, associated cerebral infarction, or permanent neurological deficits. Immediate Raymond-Roy 1 occlusion was achieved in 41 (70.7%) patients. Median hospital length of stay for elective aneurysm embolization was 1 day. Excellent outcomes with median National Institute of Health Stroke Scale score 0 (IQR 0-0) and modified Rankin Score 0 (IQR 0-1) were seen for elective patients at discharge. CONCLUSION: The Neuroform Atlas stent provided a reliable technical and safety profile for the treatment of intracranial wide-neck aneurysms. Further experience is needed to determine long-term durability and safety of this device.

Early versus Delayed Extracranial-Intracranial Bypass Surgery in Symptomatic Atherosclerotic Occlusion.

BACKGROUND: Clinical trials of extracranial-intracranial (EC-IC) bypass surgery studied patients in subacute and chronic stage after ischemic event. OBJECTIVE: To investigate the short-term outcomes of EC-IC bypass in progressive acute ischemic stroke or recent transient ischemic attacks. METHODS: The study was a retrospective review at a single tertiary referral center from 2008 to 2015. Inclusion criteria consisted of EC-IC bypass within 1 yr of last ischemic symptoms ipsilateral to atherosclerotic occlusion of internal carotid or middle cerebral artery. Early bypass group who underwent surgery within 7 d of last ischemic symptoms were compared to late bypass group who underwent surgery >7 d from last ischemic symptom. The primary endpoint was perioperative ischemic or hemorrhagic stroke or intracranial hemorrhage within 7 d of surgery. RESULTS: Of 126 patients who underwent EC-IC bypass during the period, 81 patients met inclusion criteria, 69 (85%) persons had carotid artery occlusion, 7 (9%) had proximal MCA occlusion, and 5 (6%) had both. Early surgery had a 31% (9/29) perioperative stroke rate compared to 11.5% (6/52) of patients undergoing late bypass (P = .04). Of patients with acute stroke within 7 d of surgery, 41% (7/17) had perioperative stroke within 7 d (P = .07). Six of nine patients (67%) with blood pressure dependent fluctuation of neurologic symptoms had perioperative stroke (P = .049). CONCLUSION: EC-IC bypass in setting of acute symptomatic stroke within 1 wk may confer higher risk of perioperative stroke. Patients undergoing expedited or urgent bypass for unstable or fluctuating stroke symptoms might be at highest risk for perioperative stroke.

BrainPath-Mediated Resection of a Ruptured Subcortical Arteriovenous Malformation.

BACKGROUND: Although tubular retractor systems have gained popularity for other indications, there have been few reports of their use for arteriovenous malformation (AVM) surgery. A patient was diagnosed with a ruptured 1.2-cm subcortical AVM after presenting with intracerebral hemorrhage in the right frontal lobe and anterior basal ganglia. The characteristics of this AVM made it amenable to resection using a tubular retractor. OBJECTIVE: To demonstrate the feasibility and safety of AVM resection using a tubular retractor system. METHODS: Resection of the ruptured 1.2-cm subcortical AVM was performed utilizing the BrainPathTM (NICO corp, Indianapolis, Indiana) tubular retractor system. RESULTS: The BrainPathTM approach provided sufficient visualization and surgical freedom to permit successful AVM resection and hematoma evacuation. Postoperative imaging demonstrated near total hematoma removal and angiographic obliteration of the AVM. There were no complications, and the patient made an excellent recovery. CONCLUSION: Tubular retractors warrant consideration for accessing small, deep, ruptured AVMs. The nuances of such systems and their role in AVM surgery are discussed.

Treatment Outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformation-Eligible Unruptured Brain Arteriovenous Malformation Patients.

BACKGROUND: The guideline for treating unruptured brain arteriovenous malformations (ubAVMs) remains controversial. A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) reported lower risk of stroke or death with conservative management compared to interventional treatment. There were numerous limitations to the study, including short follow-up period and disproportionate number of patients treated with surgery and embolization. OBJECTIVE: To evaluate whether treatment of ARUBA-eligible patients have acceptable outcomes at our institution. METHODS: Retrospective analysis was performed on 673 patients with brain AVMs treated at our institution between 2001 and 2014. One hundred five patients were ARUBA eligible and included in the study. Patients were divided into the microsurgery or Gamma Knife Radiosurgery (GKS; Elekta, Stockholm, Sweden) arm depending on their final treatment. Mean follow-up period was 43 mo (range 4-136 mo). Primary outcome was stroke or death. RESULTS: A total of 8 (7.6%) patients had a stroke or died. The overall risk of stroke or death was 11.4% (5 of 44 patients) for the microsurgery arm and 4.9% (3 of 61 patients) for the GKS arm. The annual rates of stroke or death were 2.1%, 4.0%, and 1.2% for the entire patient cohort, microsurgery arm, and GKS arm, respectively. AVM obliteration rates at the end of the follow-up period were 95.5% and 47.5% for the microsurgery and GKS arms, respectively. CONCLUSION: We report a lower overall risk of stroke or death in our ARUBA-eligible patients following treatment than ARUBA. Our results suggest that microsurgery and GKS may be appropriate treatments for patients with ubAVM.

Neuronavigation using three-dimensional proton magnetic resonance spectroscopy data.

BACKGROUND: Applications in clinical medicine can benefit from fusion of spectroscopy data with anatomical imagery. For example, new 3-dimensional (3D) spectroscopy techniques allow for improved correlation of metabolite profiles with specific regions of interest in anatomical tumor images, which can be useful in characterizing and treating heterogeneous tumors that appear structurally homogeneous. OBJECTIVES: We sought to develop a clinical workflow and uniquely capable custom software tool to integrate advanced 3-tesla 3D proton magnetic resonance spectroscopic imaging ((1)H-MRSI) into industry standard image-guided neuronavigation systems, especially for use in brain tumor surgery. METHODS: (1)H-MRSI spectra from preoperative scanning on 15 patients with recurrent or newly diagnosed meningiomas were processed and analyzed, and specific voxels were selected based on their chemical contents. 3D neuronavigation overlays were then generated and applied to anatomical image data in the operating room. The proposed 3D methods fully account for scanner calibration and comprise tools that we have now made publicly available. RESULTS: The new methods were quantitatively validated through a phantom study and applied successfully to mitigate biopsy uncertainty in a clinical study of meningiomas. CONCLUSIONS: The proposed methods improve upon the current state of the art in neuronavigation through the use of detailed 3D (1)H-MRSI data. Specifically, 3D MRSI-based overlays provide comprehensive, quantitative visual cues and location information during neurosurgery, enabling a progressive new form of online spectroscopy-guided neuronavigation.

Central neuromodulation for refractory pain.

Chronic neuropathic pain affects 8.2% of adults, extrapolated to roughly 18 million people every year in the United States. Patients who have pain that cannot be controlled with pharmacologic management or less invasive techniques can be considered for deep brain stimulation or motor cortex stimulation. These techniques are not currently approved by the Food and Drug Administration for chronic pain and are, thus, considered off-label use of medical devices for this patient population. Conclusive effectiveness studies are still needed to demonstrate the best targets as well as the reliability of the results with these approaches.

Magnetic resonance imaging volumetric assessment of the extent of contrast enhancement and resection in oligodendroglial tumors.

OBJECT: Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q). METHODS: The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors. RESULTS: Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q. CONCLUSIONS: In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.

Accurate state estimation from uncertain data and models: an application of data assimilation to mathematical models of human brain tumors.

BACKGROUND: Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor. RESULTS: We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise. CONCLUSIONS: The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling. REVIEWERS: This article was reviewed by Anthony Almudevar, Tomas Radivoyevitch, and Kristin Swanson (nominated by Georg Luebeck).