The 50 most-cited articles in Neurosurgery, 2019

Large vessel occlusions (LVOs), variably defined as blockages of the proximal intracranial anterior and posterior circulation, account for approximately 24% to 46% of acute ischemic strokes. Commonly refractory to intravenous tissue plasminogen activator (tPA), LVOs place large cerebral territories at ischemic risk and cause high rates of morbidity and mortality without further treatment. Over the past few years, an abundance of high-quality data has demonstrated the efficacy of endovascular thrombectomy for improving clinical outcomes in patients with LVOs, transforming the treatment algorithm for affected patients. In this review, we discuss the epidemiology, pathophysiology, natural history, and clinical presentation of LVOs as a framework for understanding the recent clinical strides of the endovascular era.

BACKGROUND: Increasing prevalence of metastatic disease has been accompanied by increasing rates of surgical intervention. Current tools have poor to fair predictive performance for intermediate (90-d) and long-term (1-yr) mortality. OBJECTIVE: To develop predictive algorithms for spinal metastatic disease at these time points and to provide patient-specific explanations of the predictions generated by these algorithms. METHODS: Retrospective review was conducted at 2 large academic medical centers to identify patients undergoing initial operative management for spinal metastatic disease between January 2000 and December 2016. Five models (penalized logistic regression, random forest, stochastic gradient boosting, neural network, and support vector machine) were developed to predict 90-d and 1-yr mortality. RESULTS: Overall, 732 patients were identified with 90-d and 1-yr mortality rates of 181 (25.1%) and 385 (54.3%), respectively. The stochastic gradient boosting algorithm had the best performance for 90-d mortality and 1-yr mortality. On global variable importance assessment,…

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, 9 are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, 3 are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The complete guideline document and supplemental…

BACKGROUND: Concussion is a heterogeneous mild traumatic brain injury (mTBI) characterized by a variety of symptoms, clinical presentations, and recovery trajectories. By thematically classifying the most common concussive clinical presentations into concussion subtypes (cognitive, ocular-motor, headache/migraine, vestibular, and anxiety/mood) and associated conditions (cervical strain and sleep disturbance), we derive useful definitions amenable to future targeted treatments. OBJECTIVE: To use evidence-based methodology to characterize the 5 concussion subtypes and 2 associated conditions and report their prevalence in acute concussion patients as compared to baseline or controls within 3 d of injury. METHODS: A multidisciplinary expert workgroup was established to define the most common concussion subtypes and their associated conditions and select clinical questions related to prevalence and recovery. A literature search was conducted from January 1, 1990 to November 1, 2017. Two experts abstracted study characteristics and results independently for each article selected for…

BACKGROUND: Microvascular decompression (MVD) is a potentially curative surgery for drug-resistant trigeminal neuralgia (TN). Predictors of pain freedom after MVD are not fully understood. OBJECTIVE: To describe rates and predictors for pain freedom following MVD. METHODS: Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, PubMed, Cochrane Library, and Scopus were queried for primary studies examining pain outcomes after MVD for TN published between 1988 and March 2018. Potential biases were assessed for included studies. Pain freedom (ie, Barrow Neurological Institute score of 1) at last follow-up was the primary outcome measure. Variables associated with pain freedom on preliminary analysis underwent formal meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for possible predictors. RESULTS: Outcome data were analyzed for 3897 patients from 46 studies (7 prospective, 39 retrospective). Overall, 76.0% of patients achieved pain freedom after MVD with a mean follow-up of 1.7 ± 1.3 (standard deviation) yr.…

Flow diverters have drastically changed the landscape of intracranial aneurysm treatment and are now considered first-line therapy for select lesions. Their mechanism of action relies on intrinsic alteration in hemodynamic parameters, both at the parent artery and within the aneurysm sac. Moreover, the device struts act as a nidus for endothelial cell growth across the aneurysm neck ultimately leading to aneurysm exclusion from the circulation. In silico computational analyses and investigations in preclinical animal models have provided valuable insights into the underlying biological basis for flow diverter therapy. Here, we review the present understanding pertaining to flow diverter biology and mechanisms of action, focusing on stent design, induction of intra-aneurysmal thrombosis, endothelialization, and alterations in hemodynamics.

BACKGROUND: Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). OBJECTIVE: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. METHODS: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. RESULTS: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at…

BACKGROUND: The use of a subdural drain (SDD) after burr-hole drainage of chronic subdural hematoma (cSDH) reduces recurrence at 6 mo. Subperiosteal drains (SPDs) are considered safer, since they are not positioned in direct contact to cortical structures, bridging veins, or hematoma membranes. OBJECTIVE: To investigate whether the recurrence rate after insertion of a SPD is noninferior to the insertion of a more commonly used SDD. METHODS: Multicenter, prospective, randomized, controlled, noninferiority trial analyzing patients undergoing burr-hole drainage for cSDH aged 18 yr and older. After hematoma evacuation, patients were randomly assigned to receive either a SDD (SDD-group) or a SPD (SPD-group). The primary endpoint was recurrence indicating a reoperation within 12 mo, with a noninferiority margin of 3.5%. Secondary outcomes included clinical and radiological outcome, morbidity and mortality rates, and length of stay. RESULTS: Of 220 randomized patients, all were included in the final analysis (120 SPD and 100 SDD). Recurrence rate was lower in the SPD group (8.33%, 95%…

BACKGROUND: Although survival statistics in patients with glioblastoma multiforme (GBM) are well-defined at the group level, predicting individual patient survival remains challenging because of significant variation within strata. OBJECTIVE: To compare statistical and machine learning algorithms in their ability to predict survival in GBM patients and deploy the best performing model as an online survival calculator. METHODS: Patients undergoing an operation for a histopathologically confirmed GBM were extracted from the Surveillance Epidemiology and End Results (SEER) database (2005-2015) and split into a training and hold-out test set in an 80/20 ratio. Fifteen statistical and machine learning algorithms were trained based on 13 demographic, socioeconomic, clinical, and radiographic features to predict overall survival, 1-yr survival status, and compute personalized survival curves. RESULTS: In total, 20 821 patients met our inclusion criteria. The accelerated failure time model demonstrated superior performance in terms of discrimination (concordance index = 0.70), calibration,…

Adult spinal deformity (ASD) has gained significant attention over the past decade with improvements in diagnostic tools, classification schemes, and surgical technique. The demographics of the aging population in the United States are undergoing a fundamental shift as medical care advances and life expectancy increases. The "baby boomers" represent the fastest growing demographic in the United States and by 2050, the number of individuals 65 yr and older is projected to reach 89 million, more than double its current size. Based on current prevalence estimates there are approximately 27.5 million elderly individuals with some form of spinal deformity, which will place a significant burden on our health care systems. Rates of surgery for ASD and case complexity are both increasing, with concomitant increase in the cost of deformity care. At the same time, patients are more medically complex with increasing number of comorbidities that result in increased surgical risk and complication profiles. This review aims to highlight recent trends in the epidemiology and socioeconomic patterns…

Brain-computer interface (BCI) technology is rapidly developing and changing the paradigm of neurorestoration by linking cortical activity with control of an external effector to provide patients with tangible improvements in their ability to interact with the environment. The sensor component of a BCI circuit dictates the resolution of brain pattern recognition and therefore plays an integral role in the technology. Several sensor modalities are currently in use for BCI applications and are broadly either electrode-based or functional neuroimaging-based. Sensors vary in their inherent spatial and temporal resolutions, as well as in practical aspects such as invasiveness, portability, and maintenance. Hybrid BCI systems with multimodal sensory inputs represent a promising development in the field allowing for complimentary function. Artificial intelligence and deep learning algorithms have been applied to BCI systems to achieve faster and more accurate classifications of sensory input and improve user performance in various tasks. Neurofeedback is an important advancement in the…

Artificial intelligence (AI)-facilitated clinical automation is expected to become increasingly prevalent in the near future. AI techniques may permit rapid and detailed analysis of the large quantities of clinical data generated in modern healthcare settings, at a level that is otherwise impossible by humans. Subsequently, AI may enhance clinical practice by pushing the limits of diagnostics, clinical decision making, and prognostication. Moreover, if combined with surgical robotics and other surgical adjuncts such as image guidance, AI may find its way into the operating room and permit more accurate interventions, with fewer errors. Despite the considerable hype surrounding the impending medical AI revolution, little has been written about potential downsides to increasing clinical automation. These may include both direct and indirect consequences. Directly, faulty, inadequately trained, or poorly understood algorithms may produce erroneous results, which may have wide-scale impact. Indirectly, increasing use of automation may exacerbate de-skilling of human physicians due to…

The recently reported superiority of mechanical thrombectomy to intravenous thrombolytics has jettisoned endovascular intervention into the forefront of acute ischemic stroke (AIS) management. These successes have allowed a chance for recanalization for patients not meeting the strict eligibility criteria for intravenous thrombolytics. Stent retrieval and aspiration have emerged as two of the most popular and effective approaches for AIS thrombectomy. Since the beginning of mechanical thrombectomy with the Merci device (Stryker) and first-generation Penumbra aspiration system (Penumbra Inc), contemporary techniques have demonstrated reliable recanalization and improved clinical outcomes. Here, we review the use of stent retrieval and aspiration, as well as their synergy, in the management of AIS.

BACKGROUND: Laser interstitial thermal therapy (LITT) is an adjuvant treatment for intracranial lesions that are treatment refractory or in deep or eloquent brain. Initial studies of LITT in surgical neuro-oncology are limited in size and follow-up. OBJECTIVE: To present our series of LITT in surgical neuro-oncology to better evaluate procedural safety and outcomes. METHODS: An exploratory cohort study of all patients receiving LITT for brain tumors by a single senior neurosurgeon at a single center between 2013 and 2018. Primary outcomes included extent of ablation (EOA), time to recurrence (TTR), local control at 1-yr follow-up, and overall survival (OS). Secondary outcomes included complication rate. Outcomes were compared by tumor subtype. Predictors of outcomes were identified. RESULTS: A total of 91 patients underwent 100 LITT procedures; 61% remain alive with 72% local control at median 7.2 mo follow-up. Median TTR and OS were 31.9 and 16.9 mo, respectively. For lesion subtypes, median TTR (months, not applicable [N/A] if <50% rate observed), local control rates at 1-yr…

BACKGROUND: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types. OBJECTIVE: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma. METHODS: Patients received a single intravenous dose of tozuleristide 3 to 29 h before surgery. Fluorescence images of tumor and cavity in Situ before and after resection and of excised tissue ex Vivo were acquired, along with safety and pharmacokinetic measures. RESULTS: A total of 17 subjects received doses between 3 and 30 mg. No dose-limiting toxicity was observed, and no reported adverse events were considered related to tozuleristide. At doses of 9 mg and above, the terminal serum half-life for tozuleristide was approximately 30 min. Fluorescence signal was detected in both high- and low-grade glial tumors, with…

Flow diverters (FDs) have changed the management of brain aneurysms; not only for complex aneurysms (giant, fusiform and blister) refractory to conventional therapies, but also for unruptured lesions previously managed by traditional surgical or coil-based endovascular methods. Since 2011 when the PipelineTM Embolization Device (Medtronic) was cleared by the Food and Drug Administration for adults with large or giant wide-neck intracranial aneurysms of the internal carotid artery proximal to the posterior communicating segment, the role of flow diversion for aneurysm treatment has expanded-supported by favorably low complication and high cure rates compared with alternative treatments. Here we review the key clinical trials and the long term outcomes that have demonstrated safety and efficacy of minimized porosity endoluminal devices in the treatment of cerebral aneurysms.

BACKGROUND: Patients with severe cubital tunnel syndrome often have poor functional recovery with conventional surgical treatment. Postsurgical electrical stimulation (PES) has been shown to enhance axonal regeneration in animal and human studies. OBJECTIVE: To determine if PES following surgery for severe cubital tunnel syndrome would result in better outcomes compared to surgery alone. METHODS: Patients with severe cubital tunnel syndrome in this randomized, double-blind, placebo-controlled trial were randomized in a 1:2 ratio to the control or stimulation groups. Control patients received cubital tunnel surgery and sham stimulation, whereas patients in the stimulation group received 1-h of 20 Hz PES following surgery. Patients were assessed by a blinded evaluator annually for 3 yr. The primary outcome was motor unit number estimation (MUNE) and secondary outcomes were grip and key pinch strength and McGowan grade and compound muscle action potential. RESULTS: A total of 31 patients were enrolled: 11 received surgery alone and 20 received surgery and PES. Three years following…

BACKGROUND: Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative. OBJECTIVE: To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy. METHODS: A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected. RESULTS: Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were…

Aggressiveness has a high prevalence in psychiatric patients and is a major health problem. Two brain areas involved in the neural network of aggressive behavior are the amygdala and the hypothalamus. While pharmacological treatments are effective in most patients, some do not properly respond to conventional therapies and are considered medically refractory. In this population, surgical procedures (ie, stereotactic lesions and deep brain stimulation) have been performed in an attempt to improve symptomatology and quality of life. Clinical results obtained after surgery are difficult to interpret, and the mechanisms responsible for postoperative reductions in aggressive behavior are unknown. We review the rationale and neurobiological characteristics that may help to explain why functional neurosurgery has been proposed to control aggressive behavior.

BACKGROUND: Despite our inability to accurately predict survival in many cancer patients, a life expectancy of at least 3 mo is historically necessary to be considered for surgical treatment of spinal metastases. OBJECTIVE: To compare health-related quality of life (HRQOL) in patients surviving <3 mo after surgical treatment to patients surviving >3 mo to assess the validity of this inclusion criteria. METHODS: Patients who underwent surgery for spinal metastases between August 2013 and May 2017 were retrospectively identified from an international cohort study. HRQOL was evaluated using generic and disease-specific outcome tools at baseline and at 6 and 12 wk postsurgery. The primary outcome was the HRQOL at 6 wk post-treatment measured by the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ). RESULTS: A total of 253 patients were included: 40 patients died within the first 3 mo after surgery and 213 patients survived more than 3 mo. Patients surviving <3 mo after surgery presented with lower baseline performance status. Adjusted analyses for baseline performance status…

BACKGROUND: For patients with focal drug-resistant epilepsy (DRE), surgical resection of the epileptogenic zone (EZ) may offer seizure freedom and benefits for quality of life. Yet, concerns remain regarding invasiveness, morbidity, and neurocognitive side effects. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a less invasive option for stereotactic ablation rather than resection of the EZ. OBJECTIVE: To provide an introduction to MRgLITT for epilepsy, including historical development, surgical technique, and role in therapy. METHODS: The development of MRgLITT is briefly recounted. A systematic review identified reported techniques and indication-specific outcomes of MRgLITT for DRE in human studies regardless of sample size or follow-up duration. Potential advantages and disadvantages compared to available alternatives for each indication are assessed in an unstructured review. RESULTS: Techniques and outcomes are reported for mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasia, nonlesional epilepsy, tuberous…

INTRODUCTION: Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery. The existing workflow for intraoperative diagnosis based on H&E staining of processed tissue is time-, resource-, and labor-intensive. Moreover, interpretation of intraoperative histologic images is dependent on a pathology workforce that is contracting and unevenly distributed across the centers where cancer surgery is performed worldwide. METHODS: We developed an automated workflow, independent of traditional H&E histology, that combines stimulated Raman histology (SRH), a rapid label-free optical imaging method, and deep convolutional neural networks (CNN) to predict diagnosis at the bedside in near real time. Specifically, our CNN, trained on over 2.5 million SRH images, predicts brain tumor diagnosis in the operating room in under 150 s, which is an order of magnitude faster than conventional techniques (eg, 20-30 min). RESULTS: To validate our workflow in the clinical setting, we designed a multicenter, prospective, noninferiority clinical trial (N = 204) that…

BACKGROUND: Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect on the cerebral perfusion pressure (CPP) and ICP has not been studied rigorously. OBJECTIVE: To determine the difference in effects of HTS and mannitol on the combined burden of high ICP and low CPP in patients with severe TBI. METHODS: We performed a case-control study using prospectively collected data from the New York State TBI-trac® database (Brain Trauma Foundation, New York, New York). Patients who received only 1 hyperosmotic agent, either mannitol or HTS for raised ICP, were included. Patients in the 2 groups were matched (1:1 and 1:2) for factors associated with 2-wk mortality: age, Glasgow Coma Scale score, pupillary reactivity, hypotension, abnormal computed tomography scans, and craniotomy. Primary endpoint was the combined burden of ICPhigh (> 25 mm Hg) and CPPlow (< 60 mm Hg). RESULTS: There were 25 matched pairs for 1:1 comparison and 24 HTS patients matched to 48 mannitol patients in 1:2…

BACKGROUND: Woven EndoBridge (WEB; Sequent Medical) treatment is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms. Initial studies have shown high safety with good efficacy at short term confirmed by trials conducted in United States (WEB-Intrasaccular Therapy) and in Europe (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy [WEBCAST], French Observatory, and WEBCAST-2). OBJECTIVE: To report the 2-yr clinical and anatomical results of WEB treatment in the combined population of 3 European trials. METHODS: In a French Observatory, 2-yr clinical and anatomical data were collected. In WEBCAST and WEBCAST-2, 2-yr follow-up was optional, and data were collected when follow-up was performed. Aneurysm occlusion was evaluated using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. RESULTS: The population for safety was 138/168 patients (82.1%), including 89 females (64.5%), with mean age of 55.5 ± 10.2 yr. The population for efficacy was 121/169 aneurysms (71.6%). Aneurysm locations were middle cerebral artery in 65/121…

BACKGROUND: Therapeutic strategy concerning incidental low-grade glioma (ILGG) is still debated. Early "prophylactic" surgery has been proposed in asymptomatic patients with favorable neurological and oncological outcomes. OBJECTIVE: To assess postoperative ability to resume employment following awake surgery in asymptomatic ILGG patients. To assess extent of resection (EOR), timeline for adjuvant oncological treatment, and survival. METHODS: A total of 74 patients with ILGG who underwent awake surgery with intraoperative mapping were prospectively included, with a minimum follow-up of 12 mo. All clinicoradiological data were collected, and statistical correlations with return to work (RTW) were performed. RESULTS: A total of 66 patients (97.1%) among 68 patients with preoperative professional activities resumed their employment including 62 (91.2%) within 12 mo. Mean time before RTW was 6.8 mo (median: 6 mo, range: 1-36). Two patients experienced seizure-related legal issues impacting their RTW. Clinicoradiological features did not correlate with RTW apart from postoperative…

BACKGROUND: Intractable neck and upper limb pain has historically been challenging to treat with conventional spinal cord stimulation (SCS) being limited by obtaining effective paresthesia coverage. OBJECTIVE: To assess the safety and effectiveness of the 10-kHz SCS system, a paresthesia-independent therapy, in the treatment of neck and upper limb pain. METHODS: Subjects with chronic, intractable neck and/or upper limb pain of ≥5 cm (on a 0-10 cm visual analog scale [VAS]) were enrolled in 6 US centers following an investigational device exemption from the Food and Drug Administration (FDA) and institutional review board approval. Each subject was implanted with 2 epidural leads spanning C2-C6 vertebral bodies. Subjects with successful trial stimulation were implanted with a Senza® system (Nevro Corp) and included in the evaluation of the primary safety and effectiveness endpoints. RESULTS: In the per protocol population, the primary endpoint (≥50% pain relief at 3 mo) was achieved in 86.7% (n = 39/45) subjects. Compared to baseline, subjects reported a significant reduction (P <…

BACKGROUND: Previous reports have suggested an increasing rate of utilization of spinal fusions, but contemporary data have not been analyzed, and there has been little investigation of putative drivers of increased utilization. OBJECTIVE: To investigate whether there is an ongoing trend of increased utilization of spinal fusions in recent data, and if there may be associations with an increasing proportion of elderly in the population, changing patterns of payer-types, and changing reimbursement rates. METHODS: We analyze 7.1 million cases from the National Inpatient Sample between 1998 and 2014. We measure annual utilization per 100 000 persons and conduct trend analyses with subgroup analysis of the senior (65 + ) population. Spine surgery utilization is compared with nonspine surgical procedures (coronary artery bypass grafting, hernia repair, hip, and knee replacement). We assess trends in charges, payer type, Medicare reimbursement rates, and hospital type. RESULTS: There was an 88% increase in the utilization rate of spinal fusion procedures from 1998 to 2014 (from 74 to 139…

Dual antiplatelet therapy is typically employed as a means to mitigate thromboembolic complications after deployment of flow diverters, most commonly consisting of aspirin with either clopidogrel, prasugrel, or ticagrelor. Recent studies have demonstrated at least similar efficacy for ticagrelor as compared to clopidogrel in the form of periprocedural complications and angiographic results. Though controversial, systematic reviews of platelet function assay usage have demonstrated greater rates of thrombotic complications in antiplatelet hyporesponders and greater rates of hemorrhagic complications in hyperresponders. Though in its infancy, the management of antiplatelet therapy for acutely ruptured aneurysms treated with flow diversion is not yet standardized, with approaches including intravenous glycoprotein IIb-IIIa inhibitors and subsequent antiplatelet loading vs antiplatelet loading, response assessment, and subsequent treatment.

BACKGROUND: The safety and efficacy of the first generation of the Pipeline Embolization Device (PED; Medtronic Inc) have been proven in large case series. Ischemic events are one of the most common complications following treatment of aneurysms with flow diverters. The new PED Flex with Shield technology (PED Shield; Medtronic Inc) was introduced to minimize the rate of complications. OBJECTIVE: To evaluate the outcomes of patients harboring aneurysms treated with the PED Shield. METHODS: This was an observational, prospective, single-arm multicenter study of patients treated with the PED Shield. The primary safety endpoint was the absence of major neurological complications and death. The secondary effectiveness endpoint was angiographic occlusion at 6 and 12 mo. Technical complications were also reported. RESULTS: Between November 2017 and December 2018, 151 patients from 7 centers with 182 aneurysms were enrolled. The mean aneurysm size was 7.0 mm; 27 (14.8%) aneurysms were large, and 7 (3.8%) were giant. In 141 of 151 patients (93.4%), the primary endpoint was reached. The…

BACKGROUND: Endoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration. OBJECTIVE: To evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection. METHODS: In this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively. RESULTS: Eighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in…

BACKGROUND: Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes. OBJECTIVE: To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients. METHODS: Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation). RESULTS: Surgical ventricular entry, SVZ-contacting…

BACKGROUND: While consistently recommended, the significance of early ambulation after surgery has not been definitively studied. OBJECTIVE: To identify the relationship between ambulation on the day of surgery (postoperative day (POD)#0) and 90-d adverse events after lumbar surgery. METHODS: The Michigan Spine Surgery Improvement Collaborative (MSSIC) is a prospective multicenter registry of spine surgery patients. As part of routine postoperative care, patients either ambulated on POD#0 or did not. The 90-d adverse events of length of stay (LOS), urinary retention (UR), urinary tract infection (UTI), ileus, readmission, surgical site infection (SSI), pulmonary embolism/deep vein thrombosis (PE/DVT), and disposition to a rehab facility were measured. RESULTS: A total of 23 295 lumbar surgery patients were analyzed. POD#0 ambulation was associated with decreased LOS (relative LOS 0.83, P < .001), rehab discharge (odds ratio [OR] 0.52, P < .001), 30-d (OR 0.85, P = .044) and 90-d (OR 0.86, P = .014) readmission, UR (OR 0.73, P = 10), UTI (OR 73, P = .001), and ileus (OR 0.52, P <…

BACKGROUND: Microvascular decompression (MVD) can be an effective intervention for trigeminal neuralgia (TN); however, an optimal system for patient selection and surgical outcome prediction has not been defined. OBJECTIVE: To develop and validate a preoperative TN grading system for the prediction of long-term pain relief after MVD. METHODS: This retrospective cohort study included consecutive patients suffering unilateral TN who underwent MVD with >18-mo follow-up. A grading system was formulated using 3 previously validated preoperative characteristics. The primary end-point was long-term, pain-free status without use of medication. Ability to predict pain-free status was analyzed by multiple regression and assessed by area under the receiver operating characteristic curve (AUC). Clinical utility to predict MVD success and reduce unnecessary surgeries was assessed by decision-curve analysis. RESULTS: Of 208 patients analyzed, 73% were pain-free without medication at >18-mo follow-up. Pain-free status was predicted by classical TN type, positive response to carbamazepine and/or…

BACKGROUND: Recent randomized control trials (RCTs) established that mechanical thrombectomy is superior to medical therapy for patients with stroke due to a large vessel occlusion. OBJECTIVE: To compare the safety and efficacy profile of the different mechanical thrombectomy strategies. METHODS: A random-effects meta-analysis was performed and the I2 statistic was used to assess heterogeneity according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Nineteen studies with a total of 2449 patients were included. No differences were identified between the stent retrieval and direct aspiration groups in terms of modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 and mTICI 3 recanalization rates, and favorable outcomes (modified Rankin Scale [mRS] ≤ 2). Adverse event rates, including 90-d mortality, symptomatic intracerebral hemorrhage (sICH), and subarachnoid hemorrhage (SAH), were similar between the stent retrieval and direct aspiration groups. The use of the stent retrieval was associated with a higher risk of vasospasm…

Radiotherapy is cytotoxic to tumor cells and is therefore a critical component of therapy for many malignancies, including glioblastoma (GBM). We now appreciate the value of the immunomodulatory effects of radiation that may be important to overall therapeutic success in some patients with this primary brain tumor. Although potentially beneficial immune-stimulating properties of radiotherapy treatment have been the focus of recent study, this modality is actually at the same time associated with the depletion of lymphocytes, which are crucial to the defense against neoplastic development and progression. In this review, we describe the association of systemic lymphopenia with poor tumor outcome, present evidence that radiotherapy is an important contributing cause of lymphodepletion, describe the systemic immune context of tumor and brain injury that contributes to immunosuppression, describe other contributing factors to lymphopenia including concomitant medications and treatments, and speculate about the role of the normal physiologic response to brain injury in the…

BACKGROUND: Various studies suggest that the insular cortex may play an underappreciated role in pediatric frontotemporal/parietal epilepsy. Here, we report on the postsurgical outcomes in 26 pediatric patients with confirmed insular involvement by depth electrode monitoring. OBJECTIVE: To describe one of the largest series of pediatric patients with medically refractory epilepsy undergoing laser interstitial thermal therapy (LITT) or surgical resection of at least some portion of the insular cortex. METHODS: Pediatric patients in whom invasive insular sampling confirmed insular involvement and who subsequently underwent a second stage surgery (LITT or open resection) were included. Complications and Engel Class outcomes at least 1 yr postsurgery were compiled as well as pathology results in the open surgical cases. RESULTS: The average age in our cohort was 10.3 yr, 58% were male, and the average length of follow-up was 2.43 ± 0.20 (SEM) yr. A total of 14 patients underwent LITT, whereas 12 patients underwent open resection. Complications in patients undergoing either LITT or open…

BACKGROUND: Autologous bone removed during craniectomy is often the material of choice in cranioplasty procedures. However, when the patient's own bone is not appropriate (infection and resorption), an alloplastic graft must be utilized. Common options include titanium mesh and polyetheretherketone (PEEK)-based custom flaps. Often, neurosurgeons must decide whether to use a titanium or custom implant, with limited direction from the literature. OBJECTIVE: To compare surgical outcomes of synthetic cranioplasties performed with titanium or vs custom implants. METHODS: Ten-year retrospective comparison of patients undergoing synthetic cranioplasty with titanium or custom implants. RESULTS: A total of 82 patients were identified for review, 61 (74.4%) receiving titanium cranioplasty and 21 (25.6%) receiving custom implants. Baseline demographics and comorbidities of the 2 groups did not differ significantly, although multiple surgical characteristics did (size of defect, indication for craniotomy) and were controlled for via a 2:1 mesh-to-custom propensity matching scheme in which 36…

BACKGROUND: Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET). OBJECTIVE: To determine the predictors of outcomes after FUS-T. METHODS: Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables. RESULTS: A total of 179 patients completed the 12-mo evaluation. The…

BACKGROUND: Stereotactic electroencephalography (SEEG) is a minimally invasive neurosurgical method to localize epileptogenic brain regions in epilepsy but requires days in the hospital with interventions to trigger several seizures. OBJECTIVE: To make initial progress in the development of network analysis methods to identify epileptogenic brain regions using brief, resting-state SEEG data segments, without requiring seizure recordings. METHODS: In a cohort of 15 adult focal epilepsy patients undergoing SEEG, we evaluated functional connectivity (alpha-band imaginary coherence) across sampled regions using brief (2 min) resting-state data segments. Bootstrapped logistic regression was used to generate a model to predict epileptogenicity of individual regions. RESULTS: Compared to nonepileptogenic structures, we found increased functional connectivity within epileptogenic regions (P < .05) and between epileptogenic areas and other structures (P < .01, paired t-tests, corrected). Epileptogenic areas also demonstrated higher clustering coefficient (P < .01) and betweenness centrality…

Flow diverter devices have gained wide acceptance for the treatment of unruptured intracranial aneurysms. Most studies are based on the treatment of large aneurysms harboring on the carotid syphon. However, during the last years the "off-label" use of these stents has widely grown up even if not supported by randomized studies. This review examines the relevant literature concerning "off-label" indications for flow diverter devices, such as for distal aneurysms, bifurcation aneurysms, small aneurysms, recurrent aneurysms, and direct carotid cavernous fistulas.

The introduction of flow diverter technology to the field of neurointervention has revolutionized the treatment of intracranial aneurysms. The therapy approach has shifted from intrasaccular aneurysm treatment to exclusion of the aneurysm from the blood circulation with remodeling of the parent artery. Previously, "difficult"-to-treat aneurysms including fusiform and blister aneurysms, but also aneurysms arising from a diseased vessel segment, can now be safely and permanently treated with flow diverters. A little over a decade ago, after extensive bench testing and refinement of the flow diverter concept, the device was eventually available for clinical use and today it has become a standard treatment for intracranial aneurysms. Currently, United States Food and Drug Administration (FDA)-approved flow diverters are the Pipeline Embolization Device (Medtronic) and the Surpass Streamline Flow Diverter (Stryker). The devices can either be delivered or deployed via a standard femoral artery approach or a radial artery approach. Other considerations for catheter setup and device…

BACKGROUND: Hypothalamic hamartomas (HH) are a challenging pathology that cause gelastic seizures. Magnetic Resonance Imaging-guided Laser Interstitial Thermal Therapy (MRgLITT) offers a safe and effective treatment for HHs via a minimally invasive technique. OBJECTIVE: To determine how clinical outcome correlates to residual tumor volume and surgical strategy by analyzing radiographic data and reconstructing volumetric imaging. METHODS: Clinical and radiographic information of 58 pediatric patients who underwent MRgLITT for HH with at least 6 mo of follow-up were retrospectively reviewed. MR imaging was volumetrically reconstructed to analyze the impact of hamartoma and ablation volumes on outcome. Primary outcome measure was freedom from gelastic seizures. RESULTS: Eighty-one percent of patients were completely free of gelastic seizures at last follow-up; of 22 patients with secondary nongelastic epilepsy, 15 were free of additional seizures. Postoperative complication rate was low. There was no significant difference in gelastic seizure outcome related to pre- or postoperative…

TARGET POPULATION: These recommendations apply to adult patients newly diagnosed with multiple (more than 1) brain metastases. QUESTION 1: In what circumstances should whole brain radiation therapy be recommended to improve tumor control and survival in patients with multiple brain metastases? RECOMMENDATION: Level 2: It is recommended that whole brain radiation therapy can be added to stereotactic radiosurgery to improve local and distant control keeping in mind the potential for worsened neurocognitive outcomes and that there is unlikely to be a significant impact on overall survival. QUESTION 2: In what circumstances should stereotactic radiosurgery be recommended to improve tumor control and survival in patients with multiple brain metastases? RECOMMENDATIONS: Level 1: In patients with 2 to 3 brain metastases not amenable to surgery, the addition of stereotactic radiosurgery to whole brain radiation therapy is not recommended to improve survival beyond that obtained with whole brain radiation therapy alone. Level 3: The use of stereotactic radiosurgery alone is recommended to…

BACKGROUND: The effect of the combined direct/indirect revascularization surgery in Moyamoya disease has not been evaluated sufficiently with regard to cognitive function, brain microstructure, and connectivity. OBJECTIVE: To investigate structural and functional changes following revascularization surgery in patients with moyamoya disease (MMD) through a combined analysis of brain morphology, microstructure, connectivity, and neurobehavioral data. METHODS: Neurobehavioral and neuroimaging examinations were performed in 25 adults with MMD prior to and >12 mo after revascularization surgery. Cognitive function was investigated using the Wechsler Adult Intelligence Scale-III, Trail-Making Test, Wisconsin Card Sorting Test, Continuous Performance Test, Stroop test, and Wechsler Memory Scale. We assessed white matter integrity using diffusion tensor imaging, brain morphometry using magnetization-prepared rapid gradient-echo sequences, and brain connectivity using resting-state functional magnetic resonance imaging (MRI). RESULTS: Cognitive examinations revealed significant changes in…

BACKGROUND: Despite advances in robotic-assisted technology for cardiac and peripheral vascular interventions, a robotic-assisted platform for neurovascular intervention is not yet available. OBJECTIVE: To evaluate the feasibility of the CorPath® GRX robotic-assisted platform (Corindus Inc, Waltham, Massachusetts) for neurovascular interventions through preclinical study. METHODS: The robotic system was tested for its ability to accurately navigate a variety of common neurovascular devices in an in Vitro flow model and in a live, anesthetized pig, under conditions and following procedures appropriate for clinical intervention. An access catheter was introduced manually at the equivalent of the common carotid artery in both models. Endovascular wires and catheters were navigated through the external and internal carotid artery and posterior cerebral vasculature under robotic assistance, using 0.014 in guidewires, 2.4F/1.7F microcatheters, bare-metal stents, and embolic coils. RESULTS: All procedures in both the flow and porcine models, including navigation, wiring, and deployment of…

Flow modification has caused a paradigm shift in the management of intracranial aneurysms. Since the FDA approval of the Pipeline Embolization Device (Medtronic, Dublin, Ireland) in 2011, it has grown to become the modality of choice for a range of carefully selected lesions, previously not amenable to conventional endovascular techniques. While the vast majority of flow-diverting stents operate from within the parent artery (ie, endoluminal stents), providing a scaffold for endothelial cells growth at the aneurysmal neck while inducing intra-aneurysmal thrombosis, a smaller subset of endosaccular flow disruptors act from within the lesions themselves. To date, these devices have been used mostly in Europe, while only utilized on a trial basis in North America. To the best of our knowledge, there has been no dedicated review of these devices. We therefore sought to present a comprehensive review of currently available endosaccular flow disruptors along with high-resolution schematics, presented with up-to-date available literature discussing their technical indications, procedural…

BACKGROUND: A dramatic improvement in obliteration rates of large, wide-necked aneurysms has been observed after the FDA approved the Pipeline Embolization Device (PED) in 2011. OBJECTIVE: To assess the predictors of complications, morbidity, and unfavorable outcomes in a large cohort of patients with aneurysms treated with PED. METHODS: A retrospective chart review of a prospectively maintained database for subjects treated with flow diversion from 2010 to 2019. RESULTS: A total of 598 aneurysms were treated during a period extending from 2010 to 2019 (84.28% females, mean age 55.5 yr, average aneurysm size 8.49 mm). Morbidity occurred at a rate of 5.8% and mortality at a rate of 2.2%. Ischemic stroke occurred at a rate of 3%, delayed aneurysmal rupture (DAR) at 1.2%, and distal intraparenchymal hemorrhage (DIPH) at 1.5%. On multivariate analysis, the predictor of stroke was aneurysm size >15 mm. Predictors of DAR were previous subarachnoid hemorrhage (SAH), increasing aneurysm size, and posterior circulation aneurysm. Predictors of DIPH were using more than 1 PED and baseline…

BACKGROUND: Multimodal analgesia regimens have been suggested to improve pain control and reduce opioid consumption after surgery. OBJECTIVE: To institutionally implement an evidence-based quality improvement initiative to standardize and optimize pain treatment following neurosurgical procedures. Our goal was to objectively evaluate efficacy of this multimodal protocol. METHODS: A retrospective cohort analysis of pain-related outcomes after posterior lumbar fusion procedures was performed. We compared patients treated in the 6 mo preceding (PRE) and 6 mo following (POST) protocol execution. RESULTS: A total of 102 PRE and 118 POST patients were included. The cohorts were well-matched regarding sex, age, surgical duration, number of segments fused, preoperative opioid consumption, and baseline physical status (all P > .05). Average patient-reported numerical rating scale pain scores significantly improved in the first 24 hr postoperatively (5.6 vs 4.5, P < .001) and 24 to 72 hr postoperatively (4.7 vs 3.4, P < .001), PRE vs POST, respectively. Maximum pain scores and time to…

BACKGROUND: Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored. OBJECTIVE: To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas. METHODS: We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression. RESULTS: The study cohort included 227 patients with available follow-up. Following…

BACKGROUND: Five-aminolevulinic acid (5-ALA) is well established for fluorescence-guided resections of malignant gliomas by eliciting the accumulation of fluorescent protoporphyrin IX (PpIX) in tumors. Because of the assumed time point of peak fluorescence, 5-ALA is recommended to be administered 3 h before surgery. However, the actual time dependency of tumor fluorescence has not yet been evaluated in humans and may have important implications. OBJECTIVE: To investigate the time dependency of PpIX by measuring fluorescence intensities in tumors at various time points during surgery. METHODS: Patients received 5-ALA (20 mg/kg b.w.) 3 to 4 h before surgery. Fluorescence intensities (FI) and estimated tumor PpIX concentrations (CPPIX) were measured in the tumors over time with a hyperspectral camera. CPPIX was assessed using hyperspectral imaging and by evaluating fluorescence phantoms with known CPPIX. RESULTS: A total of 201 samples from 68 patients were included in this study. On average, maximum values of calculated FI and CPPIX were observed between 7 and 8 h after 5-ALA…