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Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson’s disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1–125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P  = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method.

Charge balancing is used in deep brain stimulation (DBS) to avoid net charge accumulation at the tissue-electrode interface that can result in neural damage. Charge balancing paradigms include passive recharge and active recharge. In passive recharge, each cathodic pulse is accompanied by a waiting period before the next stimulation, whereas active recharge uses energy to deliver symmetric anodic and cathodic stimulation pulses sequentially, producing a net zero charge. We sought to determine differences in stimulation induced side effect thresholds between active vs. passive recharge during the intraoperative monopolar review. Sixty-five consecutive patients undergoing DBS from 2021 to 2022 were retrospectively reviewed. Intraoperative monopolar review was performed with both active recharge and passive recharge for all included patients to determine side effect stimulation thresholds. Sixteen patients with 64 total DBS contacts met inclusion criteria for further analysis. Intraoperative monopolar review results were compared with the monopolar review from the first DBS programming visit. The mean intraoperative active recharge stimulation threshold was 4.1 mA, while the mean intraoperative passive recharge stimulation threshold was 3.9 mA, though this difference was not statistically significant on -test ( = 0.442). Mean stimulation threshold at clinic follow-up was 3.2 mA. In Pearson correlation, intraoperative passive recharge thresholds had stronger correlation with follow-up stimulation thresholds (Pearson = 0.5281, < 0.001) than intraoperative active recharge (Pearson = 0.340, = 0.018), however the difference between these correlations was not statistically significant on Fisher correlation test ( = 0.294). The mean difference between intraoperative passive recharge stimulation threshold and follow-up stimulation threshold was 0.8 mA, while the mean difference between intraoperative active recharge threshold and follow-up threshold was 1.2 mA. This difference was not statistically significant on a -test ( = 0.134). Both intraoperative active recharge and passive recharge stimulation were well-correlated with the monopolar review at the first programming visit. No statistically significant differences were observed suggesting that either passive or active recharge may be utilized intraoperatively.

Purpose of ReviewOlfactory testing is a potentially safe, cost-effective, bedside evaluation tool for diagnosis, monitoring, and risk assessment for surgery in temporal lobe epilepsy (TLE) patients, but testing methods and relevant olfactory domains are not standardized. We conducted a systematic review to evaluate olfactory tests in TLE and summarize the results of the literature.Recent FindingsOlfactory tests varied significantly in odorant administration tools and devices, target odorants, evaluation timing, and grading scales. The Smell Threshold Test and University of Pennsylvania Smell Identification Test were the most validated single-domain tests for odor detection and odor identification, respectively. For multi-domain tests, Odor Memory/Discrimination Test and the Sniffin’ Sticks test were the most validated. Results of olfactory tests in TLE are presented by domain.SummaryRigorous validation, standardization, and comparative analysis of existing olfactory tests by domain is urgently needed to establish the utility and efficacy of olfactory testing in TLE.

Background Prior studies of patients in the intensive care unit have suggested racial/ethnic variation in end-of-life decision making. We sought to evaluate whether race/ethnicity modifies the implementation of comfort measures only status (CMOs) in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Methods We analyzed data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a prospective cohort study specifically designed to enroll equal numbers of white, black, and Hispanic subjects. ICH patients aged ≥ 18 years were enrolled in ERICH at 42 hospitals in the USA from 2010 to 2015. Univariate and multivariate logistic regression analyses were implemented to evaluate the association between race/ethnicity and CMOs after adjustment for potential confounders. Results A total of 2705 ICH cases (912 black, 893 Hispanic, 900 white) were included in this study (mean age 62 [SD 14], female sex 1119 [41%]). CMOs patients comprised 276 (10%) of the entire cohort; of these, 64 (7%) were black, 79 (9%) Hispanic, and 133 (15%) white (univariate p  < 0.001). In multivariate analysis, compared to whites, blacks were half as likely to be made CMOs (OR 0.50, 95% CI 0.34–0.75; p  = 0.001), and no statistically significant difference was observed for Hispanics. All three racial/ethnic groups had similar mortality rates at discharge (whites 12%, blacks 9%, and Hispanics 10%; p  = 0.108). Other factors independently associated with CMOs included age ( p  < 0.001), premorbid modified Rankin Scale ( p  < 0.001), dementia ( p  = 0.008), admission Glasgow Coma Scale ( p  = 0.009), hematoma volume ( p  < 0.001), intraventricular hematoma volume ( p  < 0.001), lobar ( p  = 0.032) and brainstem ( p  < 0.001) location and endotracheal intubation ( p  < 0.001). Conclusions In ICH, black patients are less likely than white patients to have CMOs. However, in-hospital mortality is similar across all racial/ethnic groups. Further investigation is warranted to better understand the causes and implications of racial disparities in CMO decisions.

IntroductionDespite aggressive treatment with chemoradiotherapy and maximum surgical resection, survival in patients with glioblastoma (GBM) remains poor. Ongoing efforts are aiming to prolong the lifespan of these patients; however, disparities exist in reported survival values with lack of clear evidence that objectively examines GBM survival trends. We aim to describe the current status and advances in the survival of patients with GBM, by analyzing median overall survival through time and between treatment modalities.MethodsA systematic review was conducted according to PRISMA guidelines to identify articles of newly diagnosed glioblastoma from 1978 to 2018. Full-text glioblastoma papers with human subjects, ≥ 18 years old, and n ≥ 25, were included for evaluation.ResultsThe central tendency of median overall survival (MOS) was 13.5 months (2.3–29.6) and cumulative 5-year survival was 5.8% (0.01%–29.1%), with a significant difference in survival between studies that predate versus postdate the implementation of temozolomide and radiation, [12.5 (2.3–28) vs 15.6 (3.8–29.6) months, P < 0.001]. In clinical trials, bevacizumab [18.2 (10.6–23.0) months], tumor treating fields (TTF) [20.7 (20.5–20.9) months], and vaccines [19.2 (15.3–26.0) months] reported the highest central measure of median survival.ConclusionCoadministration with radiotherapy and temozolomide provided a statistically significant increase in survival for patients suffering from glioblastoma. However, the natural history for GBM remains poor. Therapies including TTF pooled values of MOS and provide means of prolonging the survival of GBM patients.

Abstract Traumatic spinal cord injury (SCI) is a common and devastating condition. In the absence of effective validated therapies, there is an urgent need for novel methods to achieve injury stabilization, regeneration, and functional restoration in SCI patients. Ultrasound is a versatile platform technology that can provide a foundation for viable diagnostic and therapeutic interventions in SCI. In particular, real-time perfusion and inflammatory biomarker monitoring, focal pharmaceutical delivery, and neuromodulation are capabilities that can be harnessed to advance our knowledge of SCI pathophysiology and to develop novel management and treatment options. Our review suggests that studies that evaluate the benefits and risks of ultrasound in SCI are severely lacking and our understanding of the technology's potential impact remains poorly understood. Although the complex anatomy and physiology of the spine and the spinal cord remain significant challenges, continued technological advances will help the field overcome the current barriers and bring ultrasound to the forefront of SCI research and development.

Purpose This study seeks to ascertain whether different primary tumor types have a propensity for brain metastases (BMs) in different cerebral vascular territories and cerebral edema. Methods Consecutive adult patients who underwent surgical resection of a BM at a tertiary care institution between 2001 and 2011 were retrospectively reviewed. Only patients with the most common primary cancers (lung, breast, skin-melanoma, colon, and kidney) were included. Preoperative MRIs were reviewed to classify all tumors by cerebral vascular territory (anterior cerebral artery-ACA, lenticulostriate, middle cerebral artery-MCA, posterior cerebral artery-PCA, posterior fossa, and watershed), and T2-weighted FLAIR widths were measured. Chi square analyses were performed to determine differences in cerebral vascular distribution by primary tumor type, and one-way ANOVA analyses were performed to determine FLAIR signal differences. Results 669 tumors from 388 patients were classified from lung (n = 316 BMs), breast (n = 144), melanoma (n = 119), renal (n = 47), and colon (n = 43). BMs from breast cancer were less likely to be located in PCA territory (n = 18 [13%]; χ 2  = 6.10, p = 0.01). BMs from melanoma were less likely to be located in cerebellar territory (n = 11 [9%]; χ 2  = 14.1, p < 0.001), and more likely to be located in lateral (n = 5 [4%]; χ 2  = 4.56, p = 0.03) and medial lenticulostriate territories (n = 2 [2%]; χ 2  = 6.93, p = 0.009). BMs from breast and melanoma had shorter T2-FLAIR widths, with an average [IQR] of 47.2 [19.6–69.2] mm (p = 0.01) and 41.2 [14.4–62.7] mm (p = 0.002) respectively. Conversely, BMs from renal cancer had longer T2-FLAIR widths (64.2 [43.6–80.8] mm, p = 0.002). Conclusions These findings suggest that different primary tumor types could have propensities for different cerebral vascular territories and cerebral edema.

Abstract INTRODUCTION Due to impaired cerebral autoregulation, blood pressure management during acute ischemic stroke is critical for avoiding secondary neurological injury and poor outcomes. However, questions concerning optimal management of blood pressure (BP) levels during endovascular therapy (EVT) remain unanswered. This study sought to examine the effect of reductions in BP and sustained hypotension during EVT on functional outcome. METHODS We prospectively enrolled patients with acute large-vessel occlusion ischemic stroke undergoing EVT at Yale-New Haven Hospital. Intraprocedural SBP was monitored using a noninvasive BP cuff or an intra-arterial catheter. ? SBP was calculated as the difference between admission SBP and lowest SBP during EVT. Sustained relative hypotension was measured as the area between admission SBP and continuous measurements of intraprocedural SBP (aSBP). Associations with functional outcome assessed using the modified Rankin Scale (mRS) at discharge and 90 d (unfavorable outcome = 3) were assessed using ordinal and binary logistic regression. RESULTS One hundred-twenty patients (mean age 72 ± 14, 69 F, mean NIHSS 18) were included in the study, 79 of which had 90-d outcomes. Mean admission SBP was 153 mm Hg. 92% of patients experienced ? SBP reductions during EVT (mean 46 ± 30 mm Hg). Median ? SBP among patients with favorable outcomes was 28 mm Hg (IQR 5-53) compared to 49 mm Hg (IQR 18-71) among patients with poor outcome. ? SBP was independently associated with higher (worse) mRS scores at discharge (P = .004) and at 90 d (P = .014) after adjusting for age, gender, and admission NIHSS. Every 10 mm Hg reduction in SBP from admission during EVT was associated with a 1.22-fold increase in the odds of having an unfavorable functional outcome at 90 d. The association between aSBP and outcome was also significant at discharge (P = .008) and 90 d (P = .014). CONCLUSION Blood pressure reductions during EVT are common and lead to worse functional outcomes for patients affected by large-vessel acute ischemic stroke.

ObjectThere is currently no consensus as to whether meningiomas located inside the venous sinuses should be aggressively or conservatively treated. The goals of this study were to identify how sinus-invading meningiomas grow, report and compare growth rates of tumor components inside and outside the different venous sinuses, identify risk factors associated with increased tumor growth, and determine the effects of the extent of tumor resection on recurrence for meningiomas that invade the dural venous sinuses.MethodsAdult patients who underwent primary, non-biopsy resection of a WHO grade 1 meningioma invading the dural venous sinuses at a tertiary care institution between 2007 and 2015 were retrospectively reviewed. Rates of tumor growth were fit to several growth models to evaluate the most accurate model. Cohen’s d analysis was used to identify associations with increased growth of tumor in the venous sinuses. Logistic regression was used to compare extent of resection with recurrence.ResultsOf the 68 patients included in the study, 34 patients had postoperative residual tumors in the venous sinuses that were measured over time. The growth model that best fit the growth of intrasinus meningiomas was the Gompertzian growth model (r2 = 0.93). The annual growth rate of meningiomas inside the sinuses was 7.3%, compared to extrasinus tumors with 13.6% growth per year. The only factor significantly associated with increased tumor growth in sinuses was preoperative embolization (effect sizes (ES) [95% CI], 1.874 [7.633–46.735], p = 0.008).ConclusionsThis study shows that meningiomas involving the venous sinuses have a Gompertzian-type growth with early exponential growth followed by a slower growth rate that plateaus when they reach a certain size. Overall, the growth rate of the intrasinus portion is low (7.3%), which is half of the reported growth rates for other studies involving primarily extrasinus tumors.