A clinical primer for the glymphatic system.

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.

Presentation, imaging, patterns of care, growth, and outcome in sporadic and von Hippel-Lindau-associated central nervous system hemangioblastomas.

OBJECT: Hemangioblastoma is a relatively rare neoplasm occurring mostly in the cerebellum that may arise sporadically or in the context of von Hippel-Lindau (VHL) syndrome. Presentation, imaging, natural history, surgical patterns of care, and outcomes are incompletely defined for this uncommon lesion. We reviewed our large institutional series to help clarify these issues. METHODS: Retrospective analysis of consecutive, neurosurgically managed CNS hemangioblastomas at Mayo Clinic, 1988-2018. RESULTS: Two hundred and eighty five hemangioblastomas were treated in 184 unique patients (115 sporadic, 69 VHL). Compared to sporadic patients, VHL patients were younger (36.7 vs 51.7 years; p < 0.0001), were treated while asymptomatic more commonly (47.3 vs 4.2%; p < 0.0001), had smaller lesions (6.6 vs 13.9 mL; p < 0.0001), and harbored lesions with associated cysts less frequently (51.0 vs 75.0%; p = 0.0002). Macrocystic tumor architecture was associated with larger lesion size and greater symptom severity. Solid lesions later formed cysts at a median 130 months. Growth in both total volume and solid component accelerated after cyst formation (10.6 and 6.0 times median rate prior to cyst emergence). VHL patients died at a younger age (47.9 vs 74.5, p = 0.0017) and were more likely to die of direct disease sequelae. Though treatment-free survival time was significantly longer in sporadic cases, a substantial fraction (> 40%) developed tumor recurrence/progression requiring additional treatment. CONCLUSIONS: Hemangioblastoma presentation varies with etiology and clinical course is more complicated in VHL cases. Nodular lesions often develop cysts over time which is associated with accelerated tumor growth. Sporadic cases have a previously unappreciated but substantial risk of late recurrence/progression requiring treatment.

Impact of tumor-associated syrinx on outcomes following resection of primary ependymomas of the spinal cord.

PURPOSE: To interrogate the association of tumor-associated syrinxes with postoperative neurological and oncological outcomes in patients surgically treated for WHO grade 2 spinal ependymomas. METHODS: Adults treated for primary spinal intramedullary ependymomas between 2000 and 2020 were identified and data were gathered on preoperative neurological exam, radiographic characteristics, operative details, and postoperative neurological outcome. Neurological status was graded on the modified McCormick Scale (MMS). Neurological worsening immediately postoperatively and at last follow-up were defined by ≥ 1 MMS grade deterioration. Decision-tree analyses were also performed to identify independent predictors of new neurological deficits. RESULTS: Seventy patients were identified; mean age 45.4 ± 12.7; 60% male. Forty-eight patients (68.6%) had tumor-associated syrinxes, were more common among males (68.8%) and cervical lesions (68.8 vs. 31.8%; P = 0.005). Postoperatively patients with syrinxes had better MMS (P = 0.035) and were less likely to require a gait aid (39.6 vs. 81.8; P = 0.002). This latter difference persisted to last follow-up (22.9 vs. 59.1%; P = 0.006). On decision-tree analysis the strongest predictors of long-term neurological worsening were advanced age (≥ 63 years) and worse baseline neurological function. Worsened neurological status in the immediate postoperative period was best predicted by thoracic localization, the presence of a hemosiderin cap, and longer craniocaudal extension. CONCLUSION: For spinal ependymomas, tumor-associated syrinxes may portend decreased risk for immediate postoperative neurologic deficits but do not predict long-term neurological outcomes (MMS) or odds of successful gross total resection. Thoracic localization appears to best predict new immediate postoperative deficits, and worse baseline neurological function and advanced age best predict long-term deficits.

Positive impact of the pandemic: the effect of post-COVID-19 virtual visit implementation on departmental efficiency and patient satisfaction in a quaternary care center.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has significantly changed clinical practice across US healthcare. Increased adoption of telemedicine has emerged as an alternative to in-person contact for patient-physician interactions. The aim of this study was to analyze the impact of telemedicine on workflow and care delivery from January 2019 to December 2021 in a neurosurgical department at a quaternary care center. METHODS: Prospectively captured data on clinic appointment utilization, duration, and outcomes were queried. Visits were divided into in-person visits and telemedicine appointments, categorized as follow-up visits of previously surgically treated patients, internal consultations, new patient visits, and early postoperative returns after surgery. Appointment volume was compared pre- and postpandemic using March 2020 as the pandemic onset. Clinical efficiency was measured by time to appointment, rate of on-time appointments, proportion of appointments resulting in surgical intervention (surgical yield), and patient-reported satisfaction, the latter measured as the proportion of patients indicating "high likelihood to recommend practice." RESULTS: A total of 54,562 visits occurred, most commonly for follow-up for previously operated patients (51.8%), internal new patient referrals (24.5%), and external new patient referrals (19.8%). Total visit volume was stable pre- to postpandemic (1521.3 vs 1512, p = 0.917). However, in-person visits significantly decreased (1517/month vs 1220/month, p < 0.001), with a nadir in April 2020, while telemedicine appointment utilization increased significantly (0.3% vs 19.1% of all visits). Telemedicine utilization remained stable throughout the 1st calendar year following the pandemic. Telemedicine appointments were associated with shorter time to appointment than in-person visits both before and after the pandemic onset (0-5 days from appointment request: 60% vs 33% vs 29.8%, p < 0.001). Patients had on-time appointments in 87% of telemedicine encounters. Notably, telemedicine appointments resulted in surgery in 31.8% of internal consultations or new patient visits, a significantly lower rate than that for in-person visits (51.8%). After the widespread integration of telemedicine, patient satisfaction for all visits was higher than before the pandemic onset (85.9% vs 88.5%, p = 0.027). CONCLUSIONS: Telemedicine use significantly increased following the pandemic onset, compensating for observed decreases in face-to-face visits. Utilization rates have remained stable, suggesting effective integration, and delays between referrals and appointments were lower than for in-person visits. Importantly, telemedicine integration was not associated with a decrease in overall patient satisfaction, although telemedicine appointments had a lower surgical yield. These data suggest that telemedicine smoothened the impact of the pandemic on clinical workflow and helped to maintain continuity and quality of outpatient care.

A mentorship model for neurosurgical training: the Mayo Clinic experience.

Neurosurgical education is a continually developing field with an aim of training competent and compassionate surgeons who can care for the needs of their patients. The Mayo Clinic utilizes a unique mentorship model for neurosurgical training. In this paper, the authors detail the historical roots as well as the logistical and experiential characteristics of this teaching model. This model was first established in the late 1890s by the Mayo brothers and then adopted by the Mayo Clinic Department of Neurological Surgery at its inception in 1919. It has since been implemented enterprise-wide at the Minnesota, Florida, and Arizona residency programs. The mentorship model is focused on honing resident skills through individualized attention and guidance from an attending physician. Each resident is closely mentored by a consultant during a 2- or 3-month rotation, which allows for exposure to more complex cases early in their training. In this model, residents take ownership of their patients' care, following them longitudinally during their hospital course with guided oversight from their mentors. During the chief year, residents have their own clinic, operating room (OR) schedule, and OR team and service nurse. In this model, chief residents conduct themselves more in the manner of an attending physician than a trainee but continue to have oversight from staff to provide a "safety net." The longitudinal care of patients provided by the residents under the mentorship model is not only beneficial for the trainee and the hospital, but also has a positive impact on patient satisfaction and safety. The Mayo Clinic Mentorship Model is one of many educational models that has demonstrated itself to be an excellent approach for resident education.

NIH funding trends for neurosurgeon-scientists from 1993-2017: Biomedical workforce implications for neurooncology.

INTRODUCTION: Neurosurgeons represent 0.5% of all physicians and currently face a high burden of disease. Physician-scientists are essential to advance the mission of National Academies of Science (NAS) and National Institutes of Health (NIH) through discovery and bench to bedside translation. We investigated trends in NIH neurosurgeon-scientist funding over time as an indicator of physician-scientist workforce training. METHODS: We used NIH Research Portfolio Online Reporting Tools (RePORTER) to extract grants to neurosurgery departments and neurosurgeons from 1993 to 2017. Manual extraction of each individual grant awardee was conducted. RESULTS: After adjusting for U.S. inflation (base year: 1993), NIH funding to neurosurgery departments increased yearly (P < 0.00001). However, neurosurgeon-scientists received significantly less NIH funding compared to scientists (including basic scientists and research only neurosurgeons) (P = 0.09). The ratio of neurosurgeon-scientists to scientists receiving grants was significantly reduced (P = 0.002). Interestingly, the percentage of oncology-related neurosurgery grants significantly increased throughout the study period (P = 0.002). The average number of grants per neurosurgeon-scientists showed an upward trend (P < 0.001); however, the average number of grants for early-career neurosurgeon-scientists, showed a significant downward trend (P = 0.05). CONCLUSION: Over the past 23 years, despite the overall increasing trends in the number of NIH grants awarded to neurosurgery departments overall, the proportion of neurosurgeon-scientists that were awarded NIH grants compared to scientists demonstrates a declining trend. This observed shift is disproportionate in the number of NIH grants awarded to senior level compared to early-career neurosurgeon-scientists, with more funding allocated towards neurosurgical-oncology-related grants.

Prognostic significance of subdural hygroma for post-traumatic hydrocephalus after decompressive craniectomy in the traumatic brain injury setting: a systematic review and meta-analysis.

Post-traumatic hydrocephalus (PTH) is a potentially morbid sequela of decompressive craniectomy for traumatic brain injury (TBI). Subdural hygromas are commonly identified following decompressive craniectomy, but the clinical relevance and predictive relationship with PTH in this patient cohort is not completely understood. Survey of seven electronic databases from inception to June 2019 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Multivariate hazard ratios (HRs) for PTH by the presence of subdural hygroma were extracted and pooled by meta-analysis of proportions with random effects modeling. We systematically identified nine pertinent studies describing outcomes of 1010 TBI patients managed by decompressive craniectomy. Of the overall cohort, there were 211 (21%) females and median age was 37.5 years (range 33-53). On presentation, median Glasgow Coma Scale was 7 (range, 5-8). In sum, PTH was reported in 228/840 (27%) cases, and subdural hygroma was reported in 449/1010 (44%) cases across all studies. Pooling multivariate-derived HRs indicated that subdural hygroma was a significant, independent predictor of PTH (HR, 7.1; 95% CI, 3.3-15.1). The certainty of this association was deemed low due to heterogeneity concerns. The presence of subdural hygroma is associated with increased risk of PTH after decompressive craniectomy among TBI patients based on the current literature and may mandate closer clinical surveillance when detected. Prospective studies, including those of intracranial hydrodynamics following decompressive craniectomy in the setting of TBI, will better validate the certainty of these findings.

Building and implementing an institutional registry for a data-driven national neurosurgical practice: experience from a multisite medical center.

In an era when healthcare "value" remains a much-emphasized concept, measuring and reporting the quality of neurosurgical care and costs remains a challenge for large multisite health systems. Ensuring cohesion in outcomes across multiple sites is important to the development of a holistic competitive marketing strategy that seeks to promote "brand" performance characterized by a superior quality of patient care. This requires mechanisms for data collection and development of a single uniform outcomes measurement system site wide. Operationalizing a true multidisciplinary effort in this space requires intersection of a vast array of information technology and administrative resources along with the neurosurgeons who provide subject-matter expertise relevant to patient care. To measure neurosurgical quality and safety as well as improve payor contract negotiations, a practice analytics dashboard was created to allow summary visualization of operational indicators such as case volumes, quality outcomes, and relative value units and financial indicators such as total hospital costs and charges in order to provide a comprehensive overview of the "value" of surgical care. The current version of the dashboard summarizes these metrics by site, surgeon, and procedure for nearly 30,000 neurosurgical procedures that have been logged into the Mayo Clinic Enterprise Neurosurgery Registry since transition to the Epic electronic health record (EHR) system. In this article, the authors sought to review their experience in launching this EHR-linked data-driven neurosurgical practice initiative across a large, national multisite academic medical center.

Semaphorin 3A mediated brain tumor stem cell proliferation and invasion in EGFRviii mutant gliomas.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of approximately 15 months. Semaphorin 3A (Sema3A), known for its axon guidance and antiangiogenic properties, has been implicated in GBM growth. We hypothesized that Sema3A directly inhibits brain tumor stem cell (BTSC) proliferation and drives invasion via Neuropilin 1 (Nrp1) and Plexin A1 (PlxnA1) receptors. METHODS: GBM BTSC cell lines were assayed by immunostaining and PCR for levels of Semaphorin 3A (Sema3A) and its receptors Nrp1 and PlxnA1. Quantitative BrdU, cell cycle and propidium iodide labeling assays were performed following exogenous Sema3A treatment. Quantitative functional 2-D and 3-D invasion assays along with shRNA lentiviral knockdown of Nrp1 and PlxnA1 are also shown. In vivo flank studies comparing tumor growth of knockdown versus control BTSCs were performed. Statistics were performed using GraphPad Prism v7. RESULTS: Immunostaining and PCR analysis revealed that BTSCs highly express Sema3A and its receptors Nrp1 and PlxnA1, with expression of Nrp1 in the CD133 positive BTSCs, and absence in differentiated tumor cells. Treatment with exogenous Sema3A in quantitative BrdU, cell cycle, and propidium iodide labeling assays demonstrated that Sema3A significantly inhibited BTSC proliferation without inducing cell death. Quantitative functional 2-D and 3-D invasion assays showed that treatment with Sema3A resulted in increased invasion. Using shRNA lentiviruses, knockdown of either NRP1 or PlxnA1 receptors abrogated Sema3A antiproliferative and pro-invasive effects. Interestingly, loss of the receptors mimicked Sema3A effects, inhibiting BTSC proliferation and driving invasion. Furthermore, in vivo studies comparing tumor growth of knockdown and control infected BTSCs implanted into the flanks of nude mice confirmed the decrease in proliferation with receptor KD. CONCLUSIONS: These findings demonstrate the importance of Sema3A signaling in GBM BTSC proliferation and invasion, and its potential as a therapeutic target.

Morbidity and mortality in elderly patients undergoing evacuation of acute traumatic subdural hematoma.

OBJECTIVE: Acute traumatic subdural hematoma (atSDH) can be a life-threatening neurosurgical emergency that necessitates immediate evacuation. The elderly population can be particularly vulnerable to tearing bridging veins. The aim of this study was to evaluate inpatient morbidity and mortality, as well as predictors of inpatient mortality, in a national trauma database. METHODS: The authors queried the 2016-2017 National Trauma Data Bank registry for patients aged 65 years and older who had undergone evacuation of atSDH. Patients were categorized into three age groups: 65-74, 75-84, and 85+ years. A multivariable logistic regression model was fitted for inpatient mortality adjusting for age group, sex, race, presenting Glasgow Coma Scale (GCS) category (3-8, 9-12, and 13-15), Injury Severity Score, presence of coagulopathy, presence of additional hemorrhages (epidural hematoma [EDH], intraparenchymal hematoma [IPH], and subarachnoid hemorrhage [SAH]), presence of midline shift > 5 mm, and pupillary reactivity (both, one, or none). RESULTS: A total of 2508 patients (35% females) were analyzed. Age distribution was as follows: 990 patients at 65-74 years, 1096 at 75-84, and 422 at 85+. Midline shift > 5 mm was present in 72% of cases. With regard to additional hemorrhages, SAH was present in 21%, IPH in 10%, and EDH in 2%. Bilaterally reactive pupils were noted in 90% of patients. A major complication was observed in 14.4% of patients, and the overall mortality rate was 18.3%. In the multivariable analysis, the presenting GCS category was found to be the strongest predictor of postoperative inpatient mortality (3-8 vs 13-15: OR 3.63, 95% CI 2.68-4.92, p < 0.001; 9-12 vs 13-15: OR 2.64, 95% CI 1.79-3.90, p < 0.001; 30% of overall variation), followed by the presence of SAH (OR 2.86, 95% CI 2.21-3.70, p < 0.001; 25% of overall variation) and the presence of midline shift > 5 mm (OR 2.40, 95% CI 1.74-3.32, p < 0.001; 11% of overall variation). Model discrimination was excellent (c-index 0.81). Broken down by age decile group, mortality increased from 8.0% to 15.4% for GCS 13-15 to around 36% for GCS 9-12 to almost as high as 60% for GCS 3-8, particularly in those aged 85 years and older. CONCLUSIONS: The present results from a national trauma database will, the authors hope, assist surgeons in preoperative discussions with patients and their families with regard to expected postoperative outcomes following surgical evacuation of an atSDH.

Reactivation of seizure-related changes to interictal spike shape and synchrony during postseizure sleep in patients.

OBJECTIVE: Local field potentials (LFPs) arise from synchronous activation of millions of neurons, producing seemingly consistent waveform shapes and relative synchrony across electrodes. Interictal spikes (IISs) are LFPs associated with epilepsy that are commonly used to guide surgical resection. Recently, changes in neuronal firing patterns observed in the minutes preceding seizure onset were found to be reactivated during postseizure sleep, a process called seizure-related consolidation (SRC), due to similarities with learning-related consolidation. Because IISs arise from summed neural activity, we hypothesized that changes in IIS shape and relative synchrony would be observed in the minutes preceding seizure onset and would be reactivated preferentially during postseizure slow-wave sleep (SWS). METHODS: Scalp and intracranial recordings were obtained continuously across multiple days from clinical macroelectrodes implanted in patients undergoing treatment for intractable epilepsy. Data from scalp electrodes were used to stage sleep. Data from intracranial electrodes were used to detect IISs using a previously established algorithm. Partial correlations were computed for sleep and wake periods before and after seizures as a function of correlations observed in the minutes preceding seizures. Magnetic resonance imaging (MRI) and computed tomography (CT) scans were co-registered with electroencephalography (EEG) to determine the location of the seizure-onset zone (SOZ). RESULTS: Changes in IIS shape and relative synchrony were observed on a subset of macroelectrodes minutes before seizure onset, and these changes were reactivated preferentially during postseizure SWS. Changes in synchrony were greatest for pairs of electrodes where at least one electrode was located in the SOZ. SIGNIFICANCE: These data suggest preseizure changes in neural activity and their subsequent reactivation occur across a broad spatiotemporal scale: from single neurons to LFPs, both within and outside the SOZ. The preferential reactivation of seizure-related changes in IISs during postseizure SWS adds to a growing body of literature suggesting that pathologic neural processes may utilize physiologic mechanisms of synaptic plasticity.

MR Elastography Demonstrates Unique Regional Brain Stiffness Patterns in Dementias.

OBJECTIVE: The purpose of this study was to investigate age-corrected brain MR elastography (MRE) findings in four dementia cohorts (Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia, and normal pressure hydrocephalus) and determine the potential use as a differentiating biomarker in dementia subtypes. SUBJECTS AND METHODS: Institutional review board approval and written informed consent were obtained to perform MRE on 84 subjects: 20 patients with normal pressure hydrocephalus, eight with Alzheimer disease, five with dementia with Lewy bodies, five with frontotemporal dementia, and 46 cognitively normal control subjects. Shear waves of 60-Hz vibration frequency were transmitted into the brain using a pillowlike passive driver, and brain stiffness was determined in eight different regions (cerebrum, frontal, occipital, parietal, temporal, deep gray matter-white matter, sensorimotor cortex, and cerebellum). All stiffness values were age-corrected and compared with control subjects. The Wilcoxon rank sum test and linear regression were used for statistical analysis. RESULTS: Regional stiffness patterns unique to each dementing disorder were observed. Patients with Alzheimer disease and frontotemporal dementia showed decreased cerebral stiffness (p = 0.001 and p = 0.002, respectively) with regional softening of the frontal and temporal lobes. Patients with Alzheimer disease additionally showed parietal lobe and sensorimotor region softening (p = 0.039 and p = 0.018, respectively). Patients with normal pressure hydrocephalus showed stiffening of the parietal, occipital, and sensorimotor regions (p = 0.007, p < 0.001, and p < 0.0001, respectively). Patients with dementia with Lewy bodies did not show significant stiffness changes in any of the regions. CONCLUSION: Quantitative MRE of changes in brain viscoelastic structure shows unique regional brain stiffness patterns between common dementia subtypes.

Evidence for consolidation of neuronal assemblies after seizures in humans.

The establishment of memories involves reactivation of waking neuronal activity patterns and strengthening of associated neural circuits during slow-wave sleep (SWS), a process known as "cellular consolidation" (Dudai and Morris, 2013). Reactivation of neural activity patterns during waking behaviors that occurs on a timescale of seconds to minutes is thought to constitute memory recall (O'Keefe and Nadel, 1978), whereas consolidation of memory traces may be revealed and served by correlated firing (reactivation) that appears during sleep under conditions suitable for synaptic modification (Buhry et al., 2011). Although reactivation has been observed in human neuronal recordings (Gelbard-Sagiv et al., 2008; Miller et al., 2013), reactivation during sleep has not, likely because data are difficult to obtain and the effect is subtle. Seizures, however, provide intense and synchronous, yet sparse activation (Bower et al., 2012) that could produce a stronger consolidation effect if seizures activate learning-related mechanisms similar to those activated by learned tasks. Continuous wide-bandwidth recordings from patients undergoing intracranial monitoring for drug-resistant epilepsy revealed reactivation of seizure-related neuronal activity during subsequent SWS, but not wakefulness. Those neuronal assemblies that were most strongly activated during seizures showed the largest correlation changes, suggesting that consolidation selectively strengthened neuronal circuits activated by seizures. These results suggest that seizures "hijack" physiological learning mechanisms and also suggest a novel epilepsy therapy targeting neuronal dynamics during post-seizure sleep.

Introduction to Microsurgery of the Third Ventricle, Pineal Region, and Tentorial Incisura.

This edition of the Video Supplement entitled "Microsurgery of the Third Ventricle, Pineal Region, and Tentorial Incisura" highlights approaches to accessing the third ventricle for surgical resection of a variety of pathologies. The third ventricle has critical neurovascular anatomy that must always be respected to prevent patient harm. Visualization of critical anatomy in three dimensions from a surgeon' line of sight is important when planning the optimum surgical approach. Some of the keys to safely operating in this region include thoughtful head positioning, limitation of brain retraction, and the use of trajectories which capitalize on CSF cisterns and fissures. Some of the videos included in this volume illustrate standard operations while others depict more unique and innovative approaches that take advantage of these surgical windows. We hope you enjoy the videos included in this supplement.

Surgical and medical management of extracranial carotid artery aneurysms.

OBJECTIVE: Extracranial carotid artery aneurysms (ECCAs) are extremely rare with limited information about management options. Our purpose was to review our institution's experience with ECCAs during 15 years and to discuss the presentation and treatment of these aneurysms. METHODS: A retrospective review of patients diagnosed with ECCAs from 1998 to 2012 was performed. Symptoms, risk factors, etiology, diagnostic methods, treatments, and outcomes were reviewed. RESULTS: During the study period, 141 aneurysms were diagnosed in 132 patients (mean age, 61 years; 69 men). There were 116 (82%) pseudoaneurysms and 25 (18%) true aneurysms; 69 (49%) aneurysms were asymptomatic, whereas 72 (52%) had symptoms (28 painless masses; 10 transient ischemic attacks; 10 vision symptoms; 9 ruptures; 8 strokes; 4 painful mass; 1 dysphagia; 1 tongue weakness; 1 bruit). Causes of true aneurysms included fibromuscular dysplasia in 15 patients, Ehlers-Danlos syndrome in three, Marfan syndrome in one, and uncharacterized connective tissue diseases in two. Of 25 true aneurysms, 11 (44%) were symptomatic; 15 (60%) true aneurysms underwent open surgical treatment, whereas 10 (40%) were managed nonoperatively. Postoperative complications included one stroke during a mean follow-up of 31 months (range, 0-166 months). No aneurysms managed nonoperatively required intervention during a mean follow-up of 77 months (range, 1-115 months). Of 116 pseudoaneurysms, 60 (52%) were symptomatic; 33 (29%) pseudoaneurysms underwent open surgery, 18 (15%) underwent endovascular intervention, and 65 (56%) were managed medically. Pseudoaneurysm after endarterectomy (28 patients; 24%) presented at a mean of 82 months from the surgical procedure. Mean follow-up for all aneurysms was 33.9 months. One (0.7%) aneurysm-related death occurred (rupture treated palliatively). No patient undergoing nonoperative management suffered death or major morbidity related to the aneurysm. Nonoperative management was more common in asymptomatic patients (71%) than in symptomatic patients (31%). CONCLUSIONS: ECCAs are uncommon and may be manifested with varying symptoms. All segments of the carotid artery are susceptible, although the internal is most commonly affected. Open surgical intervention was more common in patients with symptoms and with true aneurysms. Patients with pseudoaneurysms were more likely to undergo endovascular intervention. Nonoperative treatment is safe in selected patients.

Pediatric ischemic stroke from an apoplectic prolactinoma.

INTRODUCTION: Pediatric pituitary neoplasms and associated pituitary apoplexy are uncommon. There are few reports in pediatric patients of pituitary apoplexy causing focal arterial compression or diffuse vasospasm resulting in cerebral infarction, and the acute, focal neurological deficits associated with stroke differ from the typical presentation of an apoplectic pituitary tumor. We report the first case of a teenage female with an apoplectic macroprolactinoma presenting with stuttering cerebral infarction secondary to compression of the internal carotid artery (ICA). CASE: A 14-year-old female was transferred from an outside facility after presenting with right hand paresthesias and word-finding difficulty that eventually progressed to include right upper extremity weakness and mental status changes. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed an apoplectic macroprolactinemia and diffusion-weighted imaging showed acute stroke in the left anterior and middle cerebral artery distributions. Evaluation of the cerebral vasculature with MRA showed focal compression of the left supraclinoid ICA. Despite prompt surgical decompression, the patient developed right lower extremity weakness in addition to her other deficits though her deficits improved after inpatient rehabilitation. CONCLUSIONS: In the pediatric population, there is only one other case of pituitary apoplexy presenting with stroke, which was secondary to vasospasm. We present the first case of pituitary apoplexy presenting with stroke secondary to ICA compression. Though rare, it is important to consider that pituitary apoplexy may present with non-classical symptoms such as ischemic stroke even in pediatric patients.

Factors contributing to the yield of asymmetric bilateral implantation of intracranial electrodes.

OBJECTIVE: To determine the outcome of implanting fewer electrodes over the hemisphere with less supporting presurgical localizing data. METHODS: We retrospectively reviewed our epilepsy surgery database at Mayo Clinic, Rochester, Minnesota, between January 1, 1999, and December 31, 2011, to identify patients who had an asymmetric number of electrode contacts implanted in each hemisphere for seizure localization. We scored each presurgical noninvasive data point (0, 0.5, or 1) to predict the likelihood of identifying seizure onset in the hemisphere with fewer intracranial electrode contacts (HFEC). An aggregate score was obtained for each patient. RESULTS: Thirteen (37%) of 35 patients had HFEC-onset seizures on intracranial electroencephalography (iEEG). The following factors predicted HFEC-onset seizures: (1) temporal lobe epilepsy (p = 0.02); (2) interictal scalp electroencephalographic discharges at the HFEC (p = 0.04); and (3) both interictal and ictal scalp EEG discharges at the HFEC (p = 0.01). The median (range) aggregate score was 2 (1-3) for patients with HFEC-onset seizures recorded on iEEG and 1 (0-3) for patients without HFEC-onset seizures (p = 0.001). Using this scoring model, the odds ratio of identifying HFEC-onset seizures on iEEG was 6.4 for each one-point increment in the aggregate score. The area under the receiver operating characteristic curve for this model was 0.84, suggesting excellent ability of the aggregate score to discriminate between patients with and without HFEC-onset seizures on iEEG. SIGNIFICANCE: Implanting electrodes on the basis of limited supporting presurgical data may be useful in selected patients, especially those with temporal lobe epilepsy, interictal scalp discharges involving the HFEC, or both interictal and ictal scalp discharges involving the HFEC. In addition, our proposed scoring system may be helpful in selecting patients with complicated epilepsy for implantation of an asymmetric number of intracranial electrodes in the hemispheres.

Increased cortical extracellular adenosine correlates with seizure termination.

OBJECTIVE: Seizures are currently defined by their electrographic features. However, neuronal networks are intrinsically dependent on neurotransmitters of which little is known regarding their periictal dynamics. Evidence supports adenosine as having a prominent role in seizure termination, as its administration can terminate and reduce seizures in animal models. Furthermore, microdialysis studies in humans suggest that adenosine is elevated periictally, but the relationship to the seizure is obscured by its temporal measurement limitations. Because electrochemical techniques can provide vastly superior temporal resolution, we test the hypothesis that extracellular adenosine concentrations rise during seizure termination in an animal model and humans using electrochemistry. METHODS: White farm swine (n = 45) were used in an acute cortical model of epilepsy, and 10 human epilepsy patients were studied during intraoperative electrocorticography (ECoG). Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS)-based fast scan cyclic voltammetry (FSCV) and fixed potential amperometry were obtained utilizing an adenosine-specific triangular waveform or biosensors, respectively. RESULTS: Simultaneous ECoG and electrochemistry demonstrated an average adenosine increase of 260% compared to baseline, at 7.5 ± 16.9 s with amperometry (n = 75 events) and 2.6 ± 11.2 s with FSCV (n = 15 events) prior to electrographic seizure termination. In agreement with these animal data, adenosine elevation prior to seizure termination in a human patient utilizing FSCV was also seen. SIGNIFICANCE: Simultaneous ECoG and electrochemical recording supports the hypothesis that adenosine rises prior to seizure termination, suggesting that adenosine itself may be responsible for seizure termination. Future work using intraoperative WINCS-based FSCV recording may help to elucidate the precise relationship between adenosine and seizure termination.

A Novel Preoperative Score to Predict Long-Term Biochemical Remission in Patients with Growth-Hormone Secreting Pituitary Adenomas.

OBJECTIVE: Transsphenoidal surgery (TSS) is considered the treatment of choice in most patients with growth hormone (GH)-secreting pituitary adenomas. Several preoperative factors have been studied to predict postsurgical remission. Our objective was to design a score that could be used in the preoperative setting to identify patients that will achieve long-term biochemical remission after TSS. METHODS: A retrospective analysis of consecutive patients with GH-secreting pituitary adenomas that underwent TSS in our institution from 2000 to 2015 who fulfilled prespecified criteria were included. Logistic regression methods were used to evaluate independent preoperative variables predicting long-term remission. Beta coefficients were used to create a scoring system for clinical practice. RESULTS: Sixty-eight patients were included, with a mean follow-up time of 87 months. Twenty (29%) patients had tumors with a Knosp grade ≥ 3A. Gross-total resection was achieved in 43 (63%) patients. Thirty-three (48%) patients had long-term biochemical remission after TSS. In a multivariate analysis, the following variables were statistically significantly associated with long-term biochemical remission: age, adenoma size (diameter), Knosp grade, GH level, and insulin growth-factor 1index 1 at diagnosis. A score of <3 out of 8 total points was identified as a cutoff associated with long-term remission, with a sensitivity of 91.4% and specificity of 72.7% (AUC 0.867, OR 28.44, 95% CI 6.94-116.47, P = < 0.001). CONCLUSIONS: A novel, simple, easy-to-use scoring system was created to identify patients with the highest chances of long-term biochemical remission following TSS. This scale should be prospectively validated in a multicenter study before widespread adoption.

Traumatic vertebral artery injury: Denver grade, bilaterality, and stroke risk. A systematic review and meta-analysis.

OBJECTIVE: Vertebral artery injury (VAI), a complication of blunt trauma, may cause posterior circulation stroke. An association of disease severity, classified in Denver grades, with stroke risk has not been shown. Using a literature-based analysis, the authors estimated the incidence of VAI following blunt trauma with the aim to investigate the impact of Denver grade and bilateral VAI on stroke occurrence. METHODS: A systematic review of the literature on VAI following blunt trauma was conducted, and data on its incidence, the severity per Denver grade, and stroke occurrence were collected. The incidence of VAI and stroke occurrence were analyzed cumulatively and between Denver grades. A meta-analysis with random-effects models was performed. RESULTS: Fifty-six studies including 2563 patients were identified. The overall incidence of VAI was 0.49% among blunt trauma cases and 14.5% among patients screened via any type of angiography. The incidence rates of bilateral VAI and concurrent carotid injury among all VAIs were 12.3% and 19.2%, respectively. VAI severity by Denver grade was as follows: grade I, 23.4%; grade II, 28.2%; grade III, 5.8%; grade IV, 42.1%; and grade V, 0.5%. The overall stroke risk was 5.32%, differing significantly among lesions of different Denver grades (p = 0.02). Grade III and IV lesions had the highest stroke prevalence (9.8% and 10.9% respectively), while strokes occurred significantly less frequently in patients with grade I and II lesions (1.9% and 3.0%, respectively). Denver grade V cases were too rare for meaningful analysis. Bilateral VAI was associated with a 33.2% stroke prevalence. The association between Denver grade and stroke occurrence persisted in a sensitivity subanalysis including only unilateral cases (p = 0.03). CONCLUSIONS: VAI complicates a small yet nontrivial fraction of blunt trauma cases, with Denver grade IV lesions being the most common. This is the first study to document a significantly higher stroke prevalence among grade III and IV VAIs compared with grade I and II VAIs independently from bilaterality. Bilateral VAIs carry a significantly higher stroke rate.