Ablation of apparent diffusion coefficient hyperintensity clusters in mesial temporal lobe epilepsy improves seizure outcomes after laser interstitial thermal therapy.

OBJECTIVE: Laser interstitial thermal therapy (LiTT) is a minimally invasive surgical procedure for intractable mesial temporal epilepsy (mTLE). LiTT is safe and effective, but seizure outcomes are highly variable due to patient variability, suboptimal targeting, and incomplete ablation of the epileptogenic zone. Apparent diffusion coefficient (ADC) is a magnetic resonance imaging (MRI) sequence that can identify potential epileptogenic foci in the mesial temporal lobe to improve ablation and seizure outcomes. The objective of this study was to investigate whether ablation of tissue clusters with high ADC values in the mesial temporal structures is associated with seizure outcome in mTLE after LiTT. METHODS: Twenty-seven patients with mTLE who underwent LiTT at our institution were analyzed. One-year seizure outcome was categorized as complete seizure freedom (International League Against Epilepsy [ILAE] Class I) and residual seizures (ILAE Class II-VI). Volumes of hippocampus and amygdala were segmented from the preoperative T1 MRI sequence. Spatially distinct hyperintensity clusters were identified in the preoperative ADC map. Proportion of cluster volume and number ablated were associated with seizure outcomes. RESULTS: The mean age at surgery was 37.5 years and the mean follow-up duration was 1.9 years. Proportions of hippocampal cluster volume (p = .013) and number (p = .03) ablated were significantly higher in patients with seizure freedom. For amygdala clusters, the proportion of cluster number ablated was significantly associated with seizure outcome (p = .026). In the combined amygdalohippocampal complex, ablation of amygdalohippocampal clusters reliably predicted seizure outcome by their volume ablated (area under the curve [AUC] = 0.7670, p = .02). SIGNIFICANCE: Seizure outcome after LiTT in patients with mTLE was associated significantly with the extent of cluster ablation in the amygdalohippocampal complex. The results suggest that preoperative ADC analysis may help identify high-yield pathological tissue clusters that represent epileptogenic foci. ADC-based cluster analysis can potentially assist ablation targeting and improve seizure outcome after LiTT in mTLE.

Non-staged bilateral Globus Pallidus Internus deep brain stimulation lead revision using intraoperative MRI: a case report and literature review.

BACKGROUND: Deep brain stimulation (DBS) lead revision due to suboptimal therapy is common but there is no standardised protocol. We describe a novel technique using iMRI to perform concurrent new Globus Pallidus Internus (GPi) DBS lead implantation and old lead removal in a dystonia patient.Case-description: A 60-year-old woman with medication and neurotoxin-refractory isolated cervical dystonia underwent awake bilateral GPi DBS surgery with MER-guided lead implantation. She initially had a favourable response but later reported suboptimal benefit despite reprogramming. MRI demonstrated suboptimal lead placement and MRI-guided revision surgery under general anesthesia was planned. The goal was to place new leads superior and medial to the existing leads. Using a 1.5 T iMRI and the ClearPoint® NeuroNavigation system, new leads were placed through the existing burr holes, into the new targets with radial errors < 0.08mm bilaterally without crossing the old leads. The old leads were then removed and the new leads connected to the existing pulse generator. The patient tolerated the procedure well and had improved side-effect profile at all contacts at 1-month follow-up. CONCLUSIONS: Non-staged iMRI-guided DBS revision surgery under general anesthesia is technically feasible and is an alternative strategy to a staged iMRI-guided revision surgery or an awake MER-guided revision surgery in select patients.

Odor identification predicts postoperative seizure control following magnetic resonance-guided laser interstitial thermal therapy.

OBJECTIVE: Olfactory dysfunction has been well documented in individuals with temporal lobe epilepsy, but its use in presurgical planning has yet to be examined. We assessed the role of preoperative odor identification in mesial onset seizure localization utilizing stereoelectroencephalography (S-EEG) and magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) outcome. METHODS: We identified 30 patients who had typical seizures captured during S-EEG monitoring or MRgLiTT of mesial temporal structures (n = 17 S-EEG, n = 13 MRgLiTT); seizure onset zone was classified as unilateral mesial seizure onset, or multifocal with unilateral mesial onset and nonmesial onset. Odor identification ability was assessed using the Sniffin' Sticks Odor Identification Test (SSOIT). Patients also completed measures of confrontation naming and auditory-verbal learning/memory using the Boston Naming Test and Hopkins Verbal Learning Test-Revised, respectively. RESULTS: Overall, patients with intractable focal epilepsy exhibited poor olfactory performance (median [M] = 10.4, interquartile range [IQR] = 9.4-11.8). Of 19 patients who underwent MRgLiTT, 10 patients (52.6%) were seizure-free at last follow-up (M = 13 months, IQR =10-18). Patients who were seizure-free after MRgLiTT (n = 10) had poorer odor identification scores (M = 9, IQR = 7-13) compared to patients with seizure reoccurrence (M = 13, IQR = 12.5-15). Odor identification score was inversely associated with seizure freedom, with odds ratio = 0.60 (95% confidence interval [CI] = 0.38-0.95, P = .03). Receiver operating characteristic analysis revealed that an SSOIT score of 12 was the ideal cutoff for predicting favorable seizure outcome (area under the curve = 0.84, 95% CI = 0.64-1.0). Sensitivity was 88.9% and specificity was 78.9%, with a likelihood ratio of 2.9 of seizure failure in patients who had an odor identification score ≥ 12. SIGNIFICANCE: Interictal olfactory dysfunction is commonly seen in patients with intractable focal epilepsy. Odor identification is a novel, noninvasive presurgical biomarker to distinguish who may or may not benefit from MRgLiTT of mesial temporal structures.

Trends in glioblastoma: outcomes over time and type of intervention: a systematic evidence based analysis.

INTRODUCTION: Despite 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: Coadministration 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.

Olfactory Testing in Temporal Lobe Epilepsy: a Systematic Review.

PURPOSE OF REVIEW: Olfactory 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 FINDINGS: Olfactory 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. Rigorous 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.

Propensity for different vascular distributions and cerebral edema of intraparenchymal brain metastases from different primary cancers.

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%]; χ2 = 6.10, p = 0.01). BMs from melanoma were less likely to be located in cerebellar territory (n = 11 [9%]; χ2 = 14.1, p < 0.001), and more likely to be located in lateral (n = 5 [4%]; χ2 = 4.56, p = 0.03) and medial lenticulostriate territories (n = 2 [2%]; χ2 = 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.

Intravenous Thrombolysis for Stroke and Presumed Stroke in Human Immunodeficiency Virus-Infected Adults: A Retrospective, Multicenter US Study.

BACKGROUND AND PURPOSE: Human immunodeficiency virus (HIV) infection has been shown to increase both ischemic and hemorrhagic stroke risks, but there are limited data on the safety and outcomes of intravenous thrombolysis with tPA (tissue-type plasminogen activator) for acute ischemic stroke in HIV-infected patients. METHODS: A retrospective chart review of intravenous tPA-treated HIV patients who presented with acute stroke symptoms was performed in 7 large inner-city US academic centers (various search years between 2000 and 2017). We collected data on HIV, National Institutes of Health Stroke Scale score, ischemic stroke risk factors, opportunistic infections, intravenous drug abuse, neuroimaging findings, and modified Rankin Scale score at last follow-up. RESULTS: We identified 33 HIV-infected patients treated with intravenous tPA (mean age, 51 years; 24 men), 10 of whom were stroke mimics. Sixteen of 33 (48%) patients had an HIV viral load less than the limit of detection while 10 of 33 (30%) had a CD4 count <200/mm3. The median National Institutes of Health Stroke Scale score at presentation was 9, and mean time from symptom onset to tPA was 144 minutes (median, 159). The median modified Rankin Scale score for the 33-patient cohort was 1 and for the 23-patient actual stroke cohort was 2, measured at a median of 90 days poststroke symptom onset. Two patients had nonfatal hemorrhagic transformation (6%; 95% confidence interval, 1%-20%), both in the actual stroke group. Two patients had varicella zoster virus vasculitis of the central nervous system, 1 had meningovascular syphilis, and 7 other patients were actively using intravenous drugs (3 cocaine, 1 heroin, and 3 unspecified), none of whom had hemorrhagic transformation. CONCLUSIONS: Most HIV-infected patients treated with intravenous tPA for presumed and actual acute ischemic stroke had no complications, and we observed no fatalities. Stroke mimics were common, and thrombolysis seems safe in this group. We found no data to suggest an increased risk of intravenous tPA-related complications because of concomitant opportunistic infections or intravenous drug abuse.

Volumetric tumor growth rates of meningiomas involving the intracranial venous sinuses.

OBJECT: There 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. METHODS: Adult 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. RESULTS: Of 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). CONCLUSIONS: This 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.

Minority Patients are Less Likely to Undergo Withdrawal of Care After Spontaneous Intracerebral Hemorrhage.

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.

Extending the resection beyond the contrast-enhancement for glioblastoma: feasibility, efficacy, and outcomes.

OBJECT: It is becoming well-established that increasing extent of resection with decreasing residual volume is associated with delayed recurrence and prolonged survival for patients with glioblastoma (GBM). These prior studies are based on evaluating the contrast-enhancing (CE) tumour and not the surrounding fluid attenuated inversion recovery (FLAIR) volume. It therefore remains unclear if the resection beyond the CE portion of the tumour if it translates into improved outcomes for patients with GBM. METHODS: Adult patients who underwent resection of a primary glioblastoma at a tertiary care institution between January 1, 2007 and December 31, 2012 and underwent radiation and temozolomide chemotherapy were retrospectively reviewed. Pre and postoperative MRI images were measured for CE tumour and FLAIR volumes. Multivariate proportional hazards were used to assess associations with both time to recurrence and death. Values with p < 0.05 were considered statistically significant. RESULTS: 245 patients met the inclusion criteria. The median [IQR] preoperative CE and FLAIR tumour volumes were 31.9 [13.9-56.1] cm3 and 78.3 [44.7-115.6] cm3, respectively. Following surgery, the median [IQR] postoperative CE and FLAIR tumour volumes were 1.9 [0-7.1] cm3 and 59.7 [29.7-94.2] cm3, respectively. In multivariate analyses, the postoperative FLAIR volume was not associated with recurrence and/or survival (p > 0.05). However, the postoperative CE tumour volume was significantly associated with both recurrence [HR (95%CI); 1.026 (1.005-1.048), p = 0.01] and survival [HR (95%CI); 1.027 (1.007-1.032), p = 0.001]. The postoperative FLAIR volume was also not associated with recurrence and/or survival among patients who underwent gross total resection of the CE portion of the tumour as well as those who underwent supratotal resection. CONCLUSIONS: In this study, the volume of CE tumour remaining after resection is more important than FLAIR volume in regards to recurrence and survival for patients with GBM.

Risk factors for postoperative urinary retention after deep brain stimulation surgery: the role of the subthalamic nucleus.

OBJECTIVE: Deep brain stimulation (DBS) is a common procedure in neurosurgery used for the treatment of Parkinson's disease (PD) and essential tremor (ET) among other disorders. Lower urinary tract dysfunction is a common complication in PD, and this study aimed to evaluate the risk factors of postoperative urinary retention (POUR) after DBS surgery in patients with PD compared with patients with ET. Understanding the risk factors associated with this complication may help in the development of strategies to minimize its occurrence and improve patient outcomes. METHODS: The study was a retrospective analysis of patients who underwent DBS surgery for PD and ET at the University of Florida between 2010 and 2021. The surgical technique used has been described in previous articles and included a two-stage procedure, with stage 1 involving burr hole placement, microelectrode recording, and electrode implantation and stage 2 involving the placement of an implantable pulse generator (IPG). Data were collected on patient characteristics and surgical details and analyzed using univariate and mixed-linear models. Post hoc propensity score matching was used to confirm the association between subthalamic nucleus (STN)-DBS and POUR. RESULTS: The study included 350 patients (153 with PD and 197 with ET) who underwent 1086 DBS surgeries (lead implantations, IPG placement, and IPG replacements). The POUR rates were 16.6% (79/477), 5.2% (19/363), and 0.4% (1/246) for stage 1, stage 2, and IPG replacement procedures, respectively. Optimal mixed-effects logistic modeling revealed history of urinary retention (OR 9.3, p = 0.004), male sex (OR 2.7, p = 0.011), having an electrode placed or connected for the first time (OR 2.2, p = 0.014), anesthesia time (OR 1.5 for each 30-minute increase, p < 0.0001), preoperative opioid use (OR 1.4 for each additional 10 morphine milligram equivalents, p = 0.032), and Charlson Comorbidity Index (OR 1.4 per comorbidity, p = 0.017) to be significant risk factors for POUR. Having an electrode in the STN was found to be protective of POUR (propensity score-matched analysis: OR 0.2, p = 0.010). CONCLUSIONS: Most risk factors found to increase the risk of POUR in DBS are not modifiable but are still important to consider in preoperative planning. Opioid use reduction and shorter anesthesia time may be modifiable risk factors to weigh against their alternative. Targeting the STN during DBS may result in decreased rates of POUR. This highlights the potential for STN-targeted DBS in reducing POUR risk in PD and ET patients.

Active recharge biphasic stimulation for the intraoperative monopolar review in deep brain stimulation.

Introduction: 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. Methods: 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. Results: 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 t-test (p = 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 r = 0.5281, p < 0.001) than intraoperative active recharge (Pearson r = 0.340, p = 0.018), however the difference between these correlations was not statistically significant on Fisher Z correlation test (p = 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 t-test (p = 0.134). Conclusions: 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.

Neuronal tissue collection from intra-cranial instruments used in deep brain stimulation surgery for Parkinson's disease with implications for study of alpha-synuclein.

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.

Analysis of alpha-synuclein harvested from intracranial instruments used in deep brain stimulation surgery for Parkinson's disease.

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 purified from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is robustly detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg protein (n=15) is able to be purified, with immunoblot assays specific for αSyn reactive in all tested samples. Light microscopy revealed axons and capillaries as the primary components of purified tissue (n=3). Further analysis was conducted using western blot, demonstrating that 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 pathologic αSyn can be reliably purified from living PD patients with this method.

Neural Bypasses: Literature Review and Future Directions in Developing Artificial Neural Connections.

Reported neuro-modulation schemes in the literature are typically classified as closed-loop or open-loop. A novel group of recently developed neuro-modulation devices may be better described as a neural bypass, which attempts to transmit neural data from one location of the nervous system to another. The most common form of neural bypasses in the literature utilize EEG recordings of cortical information paired with functional electrical stimulation for effector muscle output, most commonly for assistive applications and rehabilitation in spinal cord injury or stroke. Other neural bypass locations that have also been described, or may soon be in development, include cortical-spinal bypasses, cortical-cortical bypasses, autonomic bypasses, peripheral-central bypasses, and inter-subject bypasses. The most common recording devices include EEG, ECoG, and microelectrode arrays, while stimulation devices include both invasive and noninvasive electrodes. Several devices are in development to improve the temporal and spatial resolution and biocompatibility for neuronal recording and stimulation. A major barrier to entry includes neuroplasticity and current decoding mechanisms that regularly require retraining. Neural bypasses are a unique class of neuro-modulation. Continued advancement of neural recording and stimulating devices with high spatial and temporal resolution, combined with decoding mechanisms uninhibited by neuroplasticity, can expand the therapeutic capability of neural bypassing. Overall, neural bypasses are a promising modality to improve the treatment of common neurologic disorders, including stroke, spinal cord injury, peripheral nerve injury, brain injury and more.

Treatment of breast cancer brain metastases: radiotherapy and emerging preclinical approaches.

The breast is one of the common primary sites of brain metastases (BM). Radiotherapy for BM from breast cancer may include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and stereotactic radiotherapy (SRT), but a consensus is difficult to reach because of the wide and varied protocols, indications, and outcomes of these interventions. Overall, dissemination of disease, patient functional status, and tumor size are all important factors in the decision of treatment with WBRT or SRS. Thus far, previous studies indicate that WBRT can improve tumor control compared to SRS, but increase side effects, however no randomized trials have compared the efficacy of these therapies in BM from breast cancer. Therapies targeting long non-coding RNAs and transcription factors, such as MALAT1, HOTAIR, lnc-BM, TGL1, and ATF3, have the potential to both prevent metastatic spread and treat BM with improved radiosensitivity. Given the propensity for HER2+ breast cancer to develop BM, the above-mentioned cell lines may represent an important target for future investigations, and the development of everolimus and pyrotinib are equally important.

Focused ultrasound: Innovation in use for neurologic conditions.

Focused ultrasound has emerged as a key tool for neurologic disorders. In this focused review, we discuss the utility in disrupting the blood brain barrier to maximize treatment. This can facilitate creating direct coagulative lesions and aid in the administration of chemotherapy. Furthermore, it can facilitate neuromodulation when used in pulse sequencing. The current literature regarding brain tumors, essential tremor, and obsessive-compulsive disorder is reviewed. Additionally, concepts and experimental outcomes for neurodegenerative disease such as Alzheimer's is presented. Focused ultrasound as a tool is still in its infancy but the potential for adjuvant and direct therapy is promising. More clinical uses will become apparent in coming decades.

Apparent diffusion coefficient of piriform cortex and seizure outcome in mesial temporal lobe epilepsy after MR-guided laser interstitial thermal therapy: a single-institution experience.

OBJECTIVE: Piriform cortex (PC) is one of the critical structures in the epileptogenesis of mesial temporal lobe epilepsy (mTLE), but its role is poorly understood. The authors examined the utility of apparent diffusion coefficient (ADC; an MR-based marker of tissue pathology) of the PC as a predictor of seizure outcome in patients with mTLE undergoing MR-guided laser interstitial thermal therapy (MRgLITT). METHODS: A total of 33 patients diagnosed with mTLE who underwent MRgLITT at the authors' institution were included in the study. The 6-month postoperative seizure outcomes were classified using the International League Against Epilepsy (ILAE) system as good (complete seizure freedom, ILAE class I) and poor (seizure present, ILAE classes II-VI). The PC and ablation volumes were manually segmented from both the preoperative and intraoperative MRI sequences, respectively. The mean ADC intensities of 1) preablation PC; 2) total ablation volume; 3) ablated portion of PC; and 4) postablation residual PC were calculated and compared between good and poor outcome groups. Additionally, the preoperative PC volumes and proportion of PC volume ablated were examined and compared between the subjects in the two outcome groups. RESULTS: The mean age at surgery was 36.5 ± 3.0 years, and the mean follow-up duration was 1.9 ± 0.2 years. Thirteen patients (39.4%) had a good outcome. The proportion of PC ablated was significantly associated with seizure outcome (10.16 vs 3.30, p < 0.05). After accounting for the variability in diffusion tensor imaging acquisition parameters, patients with good outcome had a significantly higher mean ADC of the preablation PC (0.3770 vs -0.0108, p < 0.05) and the postoperative residual PC (0.4197 vs 0.0309, p < 0.05) regions compared to those with poor outcomes. No significant differences in ADC of the ablated portion of PC were observed (0.2758 vs -0.4628, p = 0.12) after performing multivariate analysis. CONCLUSIONS: A higher proportion of PC ablated was associated with complete seizure freedom. Preoperative and postoperative residual ADC measures of PC were significantly higher in the good seizure outcome group in patients with mTLE who underwent MRgLITT, suggesting that ADC analysis can assist with postablation outcome prediction and patient stratification.

Piriform Cortex Ablation Volume Is Associated With Seizure Outcome in Mesial Temporal Lobe Epilepsy.

BACKGROUND: Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear. OBJECTIVE: To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT. METHODS: We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019. RESULTS: Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not ( P > .05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 ( P > .05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085, 95% CI [1.012-1.193], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041). CONCLUSION: Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.

Total Fasting and Dehydration in the Operating Room: How Can Surgeons Survive and Thrive?

OBJECTIVES: Hydration and nutrition are critical to achieving optimal performance. This study aimed to assess the impact of limited oral intake in the operating room environment on surgical resident health, well-being, and performance. DESIGN: Electronic survey was sent to 94 surgical trainees at our institution in 2020. Chi-square analyses were performed to assess for differences in survey responses by sex. SETTING: A single tertiary-care institution. PARTICIPANTS: Surveys were sent to surgical residents and fellows in general surgery, neurosurgery, and orthopedic surgery. Seventy-nine (80%) of the 94 residents and fellows responded. RESULTS: Of the 79 responses, most trainees (79%) experienced dehydration within 6 hours of operating. Forty-four (56%) reported no fluid intake for greater than 6 hours on average, and 39 (49%) reported that they frequently had difficulty rehydrating in between cases. Most of the respondents (70%) frequently experienced symptoms of dehydration, including orthostasis, headache, and constipation. Fifty-six (71%) believed that dehydration frequently affected their performance. Compared to men, women were more likely to feel dehydrated within 4 hours of operating (58% vs. 25%, p = 0.005). Women were also more likely to have difficulty rehydrating in between cases (75% vs. 38%, p = 0.0026), experience symptoms of dehydration (92% vs. 60%, p = 0.0049), and report that dehydration affects surgical performance (88% vs. 64%, p = 0.0318). CONCLUSIONS: Prolonged fasting and dehydration are common issues that may negatively impact performance and wellbeing of surgical trainees. Also, dehydration may affect men and women differently.