Citations

Introduction Moyamoya disease was first described in the 1950’s. After over six decades, however, the underlying etiology of Moyamoya still remains unknown. It has been postulated that underlying inflammatory or autoimmune (AI) processes may play a role in the development of this condition. In order to further investigate this hypothesis, we studied the clinical and epidemiological attributes of patients with concurrent Moyamoya disease and AI condition(s). Methods A systematic review was performed including studies reporting patient level data of Moyamoya disease and concomitant autoimmune disease. Relevant studies were identified using Preferred reporting Items for Systematic Reviews and Meta‐Analysis criteria. Results There were 739 results of which 149 were included in this study. The first reports of concurrent Moyamoya and AI occurred in 1991 and involved 2 cases of Moyamoya and associated Graves’ disease. These patients were treated with antithyroid medication alone and showed improvement. Altogether, our search yielded a total of 257 patients (192 females, 48 males, 17 unspecified). A total of 158 cases were reported as “Moyamoya Disease” and 99 were reported as “Moyamoya Syndrome/Vasculopathy.” Most cases were ischemic (175 ischemic, 15 hemorrhagic) in nature. Bilaterality of the disease was reported in 130 cases, unilaterality in 34 cases. The most commonly reported ethnicity was Chinese (26 cases), followed by Japanese (17 cases), and Korean (17 cases). The most common co‐presenting AI conditions were Graves’ disease (150 cases, 58.4%), Lupus (26 cases, 10.1%), antiphospholipid syndrome (19 cases, 7.4%), Type 1 Diabetes (19 cases, 7.4%), and Multiple Sclerosis (7 cases, 2.7%). Conclusions There are numerous reports describing patients diagnosed with Moyamoya in addition to coexisting AI conditions. Our study shows that the demographic characteristics of co‐presentation align with the common autoimmune (female predominance) and Moyamoya (high east Asian prevalence) attributes. These results warrant further investigation into a possible causal or synergistic relationship between Moyamoya and AI disease.

Introduction Arteriovenous fistulas at the craniocervical junction (CCAVFs) are challenging to treat due to variation in angioarchitecture and shunting sites. No consensus exists as to whether open surgery or endovascular approaches are better in regards to outcomes, complications, and need for reintervention. As such, weexplore the efficacy, outcomes, and complications of endovascular versus open surgery for dural arteriovenous fistulas at the craniocervical junction. Methods A systematic review was performed using the EMBASE, PubMed,and Cochrane databases in April 2022. MeSH search terms included (craniocervical) AND (arteriovenous OR fistula OR AVF). Inclusion criteria were defined as patients with CCAVFs who were treated with open surgery or endovascular therapy with reported clinical outcomes at 6 months or later. Results A total of 357 studies were screened; of which 75 were included. A total of 416 patients (309 males, 91 females) were included with an average age of 61.9 years. A total of 236 patients underwent surgery (mean age: 61.5), 71 patients underwent embolization (mean age: 62.6), and 25 patients underwent a combination (mean age: 54.7). Outcomes were reported in 39 surgery cases (mean follow up time: 31.4 months), and 54 endovascular cases (mean follow up time: 24.2 months). Within the open surgery group 47 (57.3%) had complete symptom resolution, 23 (28%) had symptom improvement or stabilization, 11 (13.4%) permanent deficit, and 1 (1.2%) resulted in death. Within the endovascular group 26 (56.5%) had complete symptom resolution, 5 (10.9%) had symptom improvement or stabilization, 15 (32.6%) permanent deficit, and 0 (0%) resulted in death. Conclusions Open surgery and embolization yield comparable symptomatic improvement and stabilization. However, the rate of permanent deficits is higher withembolization, while mortality is higher with open surgery. Further studies are required to better associate these outcomes to baseline parameters including treatment decision making, size of the lesion, patient age, and co‐morbidities.

Introduction While neurovascular surgeries have largely been performed by neurosurgeons, the advent of endovascular procedures has produced increasing involvement of other specialists in this arena (i.e. neurologists and radiologists).This study aims to analyzethe involvement of different specialties within theneuroendovascular workforce by characterizingthem by their primary specialty. Methods The Medicare Provider Utilization Database was queried from 2013 to 2019 for all primary Current Procedural Terminology (CPT) codes identified by the American Medical Association as pertaining to endovascular procedures of the nervous system (61623, 61624, 61630, 61635, 61626, 61645, and 61650). We counted the number of unique providers in respective fields (neurology, neurosurgery, and radiology) who performed these procedures. Statistical analyses, including data aggregation, exploratory analysis, and propensity adjustment, were performed using R, version 4.0.1 (The R Foundation, Vienna, Austria). The two‐sided Mann‐Kendall trend test, a non‐parametric statistical test that assesses for monotonic trends in either an upward or downward trend, was utilized to assess for trends over time. Within each year analyzed, a Chi‐squared test for trend in proportions was used. A significance level of 0.05 was used. Results In 2013, neurosurgeons comprised 45% of the workforce performing these procedures, neurologists were 9%, and radiologists were 47%. By 2019, neurosurgeons decreased to 34.5% of the workforce, while neurologists increased to 21.5%, and radiologists decreased slightly to 44%. Neurologists were the only field in which the proportional shift in providers was noted to have a significant change in trajectory (p:0.04), an upward trajectory. Overall proportional differences between respective specialists were statistically significant each year (p< 0.01). Conclusions Neurologists are increasingly performing endovascular procedures. Increased communication and coordination between specialties can improve disparities in care to ensure adequate access to neurovascular care across the US.

Introduction Endovascular procedures have become increasingly popular in recent years due to preference of minimally invasive approaches and technological advancement.This study aims to characterize the trends in procedural rates of common neuro‐endovascular procedures performed by neurologists, neurosurgeons, and radiologists. Methods The Medicare Provider Utilization Database was queried from 2013 to 2019 for all primary Current Procedural Terminology codes identified by the American Medical Association as pertaining to endovascular procedures of the nervous system (61623, 61624, 61630, 61635, 61626, 61645, and 61650). Statistical analyses, including data aggregation, exploratory analysis, and propensity adjustment, were performed using R, version 4.0.1 (The R Foundation, Vienna, Austria). The two‐sided Mann‐Kendall trend test, a non‐parametric statistical test that assesses for monotonic trends in either an upward or downward trend, was utilized to assess for trends over time. A significance level of 0.05 was used. Results Between 2013 to 2019 a total of 40,730 endovascular procedures were performed by neurosurgeons, neurologists and radiologists treating Medicare patients. When all codes were combined, there was a significant increase in the number of procedures done by all specialists: Radiology (2013:1080; 2019:4938; p:0.02), Neurosurgery (2013:1230; 2019:4508; p< 0.01), and Neurology (2013:205; 2019:2397; p:0.04). Significant increases in mechanical thrombectomy (CPT61645) were observed in all fields: Radiology (2016:1287, 2019:3542; p< 0.01), Neurosurgery (2016:610; 2019:2326; p< 0.01), Neurology (2016:569; 2019:1951; p< 0.01). Increases in transcatheter permanent occlusion (CPT61624) were observed in neurosurgery (2013:1230; 2019:2049; p:0.04). Increases in temporary balloon artery occlusion (CPT61623) were noted in neurology (2013:21; 2019:27; p:0.04). Conclusions Endovascular procedures have seen a dramatic rise in utilization over a short amount of time, particularly mechanical thrombectomy. Future investigation should include more inclusive datasets beyond the Medicare population.

Introduction Poor‐grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality. Overall, 20–30% of aSAH are described as poor grade. Despite recent advances in management strategies, prognosis of poor‐grade aSAH remains dismal. As such, we review the most current literature regarding management strategies that can be used to decrease the risk of the four most common causes of secondary brain injury: 1) aneurysm re‐rupture, 2) hydrocephalus, 3) cerebral salt wasting, and 4) delayed cerebral ischemia/vasospasm. Methods We present a 46‐year‐old female patient with poor‐grade aSAH after a loss of consciousness following thunderclap headache. Examination showed a dilated left pupil and Glasgow Coma Scale (GCS) of 4. Imaging revealed a ruptured anterior communicating artery aneurysm, and she was subsequently taken to the neuro‐interventional radiology suite for EVD placement. On POD 7 Transcranial Doppler (TCD) suggested moderate vasospam of left MCA. Two successful balloon angioplasties of the basilar, ACA‐A1, and MCA‐M1 were successfully performed on separate consecutive days. By POD 10, intermittent severe ICP spikes required targeted temperature management (TTM) with hypothermia. On POD 24, her ICP normalized, she was no longer comatose, and her EVD was clamped and removed. She was rapidly weaned off ventilator and transitioned to rehabilitation. 3‐months postoperatively, Modified Rankin Scale score was 0. Results Based upon the result of our literature review, we propose maintaining blood pressure below 160 mmHg prior to intervention, after which it can be increased to 160–240 mmHg to prevent vasospasm. Transcranial Doppler is essential to detect vasospasm as the aSAH symptoms subtle; once identified, vasospasm can be successfully treated with balloon angioplasty. Finally, targeted temperature management, mannitol, hypertonic saline, and neuromuscular paralysis are essential for postoperative management of ICP levels. Conclusions The multimodal approach should be considered when managing poor grade aSAH. Further research in aSAH management would benefit the patients who present with poor prognosis, thereby improving patient care and leading to a standard, effective approach for aSAH management.

Based on seminal research from the 1970s and 1980s, the myth that the knees should only move as far anterior during the barbell squat until they vertically align with the tips of the feet in the sagittal plane still exists today. However, the role of both the hip joint and the lumbar spine, which are exposed to high peak torques during this deliberate restriction in range of motion, has remained largely unnoticed in the traditional literature. More recent anthropometric and biomechanical studies have found disparate results regarding anterior knee displacement during barbell squatting. For a large number of athletes, it may be favorable or even necessary to allow a certain degree of anterior knee displacement in order to achieve optimal training outcomes and minimize the biomechanical stress imparted on the lumbar spine and hip. Overall, restricting this natural movement is likely not an effective strategy for healthy trained individuals. With the exception of knee rehabilitation patients, the contemporary literature suggests it should not be practiced on a general basis.

AbstractBackgroundProstate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression‐based subtyping model based on prostate‐specific biological processes was sought.MethodsUnsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts.ResultsClustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01–0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09–0.51).ConclusionsWith the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features.Plain language summary Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors—the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management.

Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these entities, EZH2 and POU2F3, and compared them with conventional immunostains. Whole slide sections of 37 thymic carcinomas, 23 type A thymomas, 13 type B3 thymomas, and 8 micronodular thymomas with lymphoid stroma (MNTLS) were immunostained for EZH2, POU2F3, CD117, CD5, TdT, BAP1, and MTAP. POU2F3 (≥10% hotspot staining), CD117, and CD5 showed 100% specificity for thymic carcinoma versus thymoma with 51%, 86%, and 35% sensitivity, respectively, for thymic carcinoma. All POU2F3 positive cases were also positive for CD117. All thymic carcinomas showed >10% EZH2 staining. EZH2 (≥80% staining) had a sensitivity of 81% for thymic carcinoma and a specificity of 100% for thymic carcinoma versus type A thymoma and MNTLS but had poor specificity (46%) for thymic carcinoma versus B3 thymoma. Adding EZH2 to a panel of CD117, TdT, BAP1, and MTAP increased cases with informative results from 67/81 (83%) to 77/81 (95%). Overall, absent EZH2 staining may be useful for excluding thymic carcinoma, diffuse EZH2 staining may help to exclude type A thymoma and MNTLS, and ≥10% POU2F3 staining has excellent specificity for thymic carcinoma versus thymoma.

Abstract Background H3K27-altered diffuse midline glioma (DMG) is the deadliest pediatric brain tumor; despite intensive research efforts, every clinical trial to date has failed. Is this because we are choosing the wrong drugs? Or are drug delivery and other pharmacokinetic variables at play? We hypothesize that the answer is likely a combination, where optimization may result in a much needed novel therapeutic approach. Methods We used in vitro drug screening, patient samples, and shRNA knockdown models to identify an upregulated target in DMG. A single small molecule protein kinase inhibitor with translational potential was selected for systemic and direct, loco-regional delivery to patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM). Pharmacokinetic studies were conducted in non-tumor bearing rats. Results Aurora kinase (AK) inhibitors demonstrated strong antitumor effects in DMG drug screens. Additional in vitro studies corroborated the importance of AK to DMG survival. Systemic delivery of alisertib showed promise in subcutaneous PDX but not intracranial GEMM and PDX models. Repeated loco-regional drug administration into the tumor through convection-enhanced delivery (CED) was equally inefficacious, and pharmacokinetic studies revealed rapid clearance of alisertib from the brain. In an effort to increase the drug to tumor residence time, continuous CED over 7 days improved drug retention in the rodent brainstem and significantly extended survival in both orthotopic PDXs and GEMMs. Conclusions These studies provide evidence for increasing drug-tumor residence time of promising targeted therapies via extended CED as a valuable treatment strategy for DMG.