Biomarkers that predict neurologic death may allow for personalization of therapy for high-risk brain metastases patients. Patients with NSCLC who underwent comprehensive genomic profiling were identified in an institutional database. Neurologic death was determined by medical record review. Proportional hazards regression models considering non-neurologic death as a competing risk were used to identify mutations statistically associated with the occurrence of neurologic death (p < 0.1) and to create a risk scoring system for neurologic death. A competing risk proportional hazards regression model with non-neurologic death as a competing risk was used to assess the association between the risk score and neurologic death, and to calculate hazard ratios predicting neurologic death between risk groups. 307 patients were included in the primary analysis and 213 in a cohort of patients with brain metastases. Risk scores were constructed in both populations. Patients with higher risk scores had an increased risk of neurologic death when compared to those in the low-risk group, with respective HRs of 3.76 for the entire cohort and 2.87 for the brain metastasis cohort per unit increase in the risk score. When dividing the risk score into three groups, the cumulative incidence of neurologic death in high, moderate, and low risk groups was 49.0

Background:Glioblastomas are characterized by the Warburg effect, driven by upregulation of pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase complex (PDC), leading to lactate accumulation. Dichloroacetate (DCA) is a potent and safe PDK inhibitor that crosses the blood-brain barrier, reverses Warburg metabolism, and reduces lactate levels. Methods:This trial (RO1FD007271) evaluated the pharmacodynamics and pharmacokinetics of oral DCA in recurrent glioblastoma patients requiring surgical debulking. The primary endpoint was decreased PDC phosphorylation (p-PDHA1) in resected tumors. Patients received either 1 week of DCA or no DCA prior to surgery. All patients received DCA postoperatively. Enhancing and non-enhancing tumor tissue, and serial plasma DCA and lactate levels were analyzed. Results:37 patients were enrolled (median age = 60 years). In DCA-treated patients, the contrast-enhancing tumor had lower p-PDHA1, PDK4, HIF1-α, VEGF-α, and PGK1 expression (all P < .05) than non-DCA-treated patients. In non-enhancing tumors, p-PDHA1 and PDK 1-3 expression were not different, but PDK4, PCNA, and PGK1 levels were reduced, and ERK1/2 was increased in DCA-treated patients (all P ≤ .01). At surgery, DCA-treated patients had lower plasma lactate (P = .004) than untreated patients. Postoperatively when all patients received DCA, plasma lactate fell dramatically (P < .001). DCA was well-tolerated but did not delay tumor recurrence. Conclusions:In recurrent glioblastomas, DCA was safe, well-tolerated, and promoted aerobic respiration. It reduced markers of tumor cell proliferation and lowered plasma lactate. Although no clinical benefit was noted, further studies of combination therapy are indicated, given the known association between poor cancer outcomes and elevated PDK expression and lactate levels.

Glioblastoma (GBM) is an extremely aggressive and incurable primary tumor of the brain. GBM is characterized by interpatient and intratumoral heterogeneity, making this cancer particularly resistant to therapy and likely to recur. Mapping the complex dynamics that underpin the development and evolution of gliomas with human-based in vitro models is difficult. This study aimed to generate 3D glioma patient-derived tumor constructs (PTCs) using a clinically relevant, Matrigel-free, hyaluronic acid system, evaluate their suitability in drug screening assays, and determine the stability of their genetic profiles compared to originating tumors. In this study, we utilized a synthetically modified hyaluronic acid and gelatin hydrogel system to generate tumor constructs containing cells from clinical glioma biospecimens. PTCs were characterized phenotypically, after which they were deployed in chemotherapy drug screens using temozolomide (TMZ) and a P53 activator compound. Drug responses of these 3D cultures were compared with 2D cultures, as well as PTCs that were generated after passaging in 2D. RNA sequencing was used to evaluate genetic parity between PTCs or 2D cultures with originating tumor tissues, using The Cancer Genome Atlas (TCGA) GBM subpopulations for subcategorizing. PTCs were created successfully from five World Health Organization (WHO) grade 4, two grade 3, and two grade 2 gliomas. PTCs were maintained with high viability. Chemotherapy drug screens demonstrated that expected TMZ responses were observed for Isocitrate dehydrogenase (IDH) mutant diffuse gliomas while drug response was variable for IDH wildtype GBM PTCs. PTCs demonstrated stable drug response over time, while 2D passaging resulted in significant shifts in drug sensitivity. RNA sequencing revealed maintenance of subpopulation signatures for PTCs which clustered with their originating patient tumor tissue. In contrast, 2D cultures largely clustered together regardless of the patient. Our PTC approach utilizes a defined hydrogel biomaterial system that maintains the genotypic and drug response characteristics of patient tumors making this an ideal ex vivo model for translational applications.

PURPOSE Laser interstitial thermal therapy is a surgical tool used to ablate brain tumors, radiation necrosis, and epileptic foci. Data from the LAANTERN prospective multicenter registry (ClinicalTrials.gov identifier: NCT02392078 ), containing patients with tumor from 25 US centers between 2015 and 2023, were analyzed to determine clinical outcomes. METHODS All patients with primary or metastatic brain tumors treated with LITT using the Monteris NeuroBlate System were included in this analysis. Demographics, intraprocedural data, adverse events, survival data, and data pertaining to functional status over time were prospectively collected and then analyzed. Both univariable and multivariable analyses were performed. RESULTS A total of 787, primary (445) and metastatic brain tumor (342), patients were included. The median age was 59.6 years and the median pediatric age 15 years (n = 18). The median length of hospital stay was 32.4 hours, and 62.6% avoided intensive care unit admission. The adverse event rate was 12.8%, with 65.5% of events considered transient. Mortality rate was 0.25%. Anticonvulsants were stopped in 30%-40% of patients, and 80% of patients stopped steroids after LITT. Quality of life remained stable up to 3 years post-LITT. Greater extent of ablation (EOA) and smaller lesion size were associated with significant improvements in survival outcomes in patients with high-grade glioma and recurrent metastases. CONCLUSION The data from this largest, prospective LITT cohort support the consideration of LITT as a cytoreductive tool for patients with primary and metastatic tumor with short hospital stays, low complication rates, and preserved functional status. The EOA in glioblastoma and lesion volume in metastatic disease emerge as factors that may guide patient selection.

Objective Because brain metastases are biologically heterogeneous, understanding how specific mutation types in conjunction with the cancer’s tissue of origin respond to treatment can help inform patient outcomes and potential treatment strategies. Gastro-intestinal brain metastases are less common, and their outcomes are not well documented in the current literature, which this research article hopes to ameliorate. Methods In this study, we assessed the clinical outcomes of 44 patients with brain metastases from esophageal primaries, either HER2+ or non-HER2+ mutation types, treated between 2001 to 2024. Using a single-institution retrospective database, we assessed the clinical outcomes of local control, regional brain failure, and overall survival. Results We found that non-HER2+ patients had lower brain metastasis velocity (BMV) and distant brain failure rate. HER2+ primaries spread earlier to the brain but had a longer 2 years survival rate. Conclusion Non-HER2+ patients may be a population where a single application of stereotactic radiosurgery (SRS) represents a cost-effective option, whereas the long-term toxicity implications may be higher for HER2+ patients.

Background/Objectives: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. Methods: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample t-testing was used to identify mutations statistically associated with iBMV (p < 0.1). A value of +1 was assigned to each mutation with a positive association (“deleterious genes”), and a value of −1 to each with an inverse association (“protective genes”). The sum of these values was calculated to define iBMV risk scores of −1, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. Results: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. “Deleterious genes” included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; “protective genes” included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and −1, predicted an 88%, 61% and 65% likelihood of developing a BM (p < 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. −1, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and −1 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (p < 0.02). Conclusions: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.

Our patient was a 20-year-old female when diagnosed with a left parietal WHO Grade III anaplastic ganglioglioma (AGG) with BRAFV600E mutation, APC rearrangement exon 16 and CDKN2A/B loss per next generation sequencing after presenting with decreased unilateral visual acuity. Initial treatment included surgical resection, followed by concurrent radiation and temozolomide (TMZ). She initiated anti-BRAFV600E therapy with dabrafenib and trametinib but was intolerant due to intractable flu-like symptoms including fever, rash and fatigue. She declined further therapy after three months. She then completed six months of adjuvant TMZ. Approximately four years after initial diagnosis, she was admitted for progressive symptoms including ocular seizures, cognitive decline, cranial nerve palsies, uncontrolled anxiety and pain. MRI imaging demonstrated a focus of parenchymal enhancement, and adjacent leptomeningeal and cranial nerve enhancement. Following subsequent clinical decline, lumbar puncture confirmed malignant cells and metronomic TMZ was started for two weeks. A supportive care-only approach was considered given her clinical deterioration, including progressive cognitive decline, deafness, and blindness. However, she and her family agreed to initiate treatment with Enc/Bini. Two weeks after starting the BRAF/MEK inhibitor combination, her clinical picture had significantly improved, and the regimen was tolerated with minimal nausea. Ocular and generalized seizures resolved with targeted treatment and transition to lacosamide. Follow up MRI, ten weeks after initiating treatment showed posterior hemisphere cortical and subcortical encephalomalacia, laminar necrosis, increased FLAIR signal, and improving enhancement along the cranial nerves consistent with inflammatory, treatment related changes considering her dramatic clinical improvement. Prior studies in patients with primary CNS tumors and brain metastases have demonstrated encouraging responses and overall tolerability with this regimen. To our knowledge, this represents the first documented case of a rapid and durable (four months to date) clinical and radiographic response to systemic BRAF-targeted therapy in a patient with recurrent-AGG and leptomeningeal spread.

Stereotactic radiosurgery (SRS) has been used to manage patients with intracranial meningioma with contraindications to resection. Limitations to SRS traditionally include tumors > 3 cm due to the risk of posttreatment toxicity. Hypofractionated SRS (hSRS) has been proposed as an alternative for tumors exceeding volume constraints for single-fraction SRS, although how hypofractionation affects the volume versus toxicity relationship has not been reported. Thus, the authors conducted a single-institution retrospective analysis of the medical records of patients receiving single-fraction SRS or multifraction hSRS for large (> 2 cm) meningiomas to assess the effect of hypofractionation on the likelihood of posttreatment toxicity. Patients were identified using the Wake Forest University Department of Radiation Oncology prospectively administered Gamma Knife database. Patients were included if they had single-fraction SRS or multifraction hSRS for a diagnosis of meningioma that was > 2 cm. Analysis was limited to tumor volumes between 2.7 and 49.3 cm3, the overlapping range shared by those undergoing hSRS or SRS. Electronic medical records were used to determine patient and tumor characteristics and clinical outcomes. A total of 121 SRS cases with a median dose of 12 Gy and 51 hSRS cases with a median dose of 20 Gy with tumor volumes between 2.7 and 49.3 cm3 were identified and included in the analysis. The probabilities of freedom from local failure at 1, 3, and 5 years were 87.0%, 79.0%, and 63.6%, respectively, for patients receiving single-fraction SRS and 96.0%, 91.0%, and 91.0%, respectively, for patients receiving multifraction hSRS. The probabilities of overall survival at 1, 3, and 5 years were 97.5%, 79.7%, and 72.6%, respectively, for patients receiving single-fraction SRS and 85.5%, 80.9%, and 76.4%, respectively, for patients receiving multifraction hSRS. Eighteen (14.9%) of 121 patients receiving single-fraction SRS experienced Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 toxicity, and 12 (23.5%) of 51 patients receiving multifraction hSRS experienced CTCAE grade ≥ 2 toxicity. When controlling for tumor volume, despite higher treatment doses in the hSRS group relative to the SRS group, posttreatment toxicity was not significantly different between the groups, and freedom from local failure was improved in the hSRS group. For patients with larger meningiomas, multifraction hSRS may help to limit the risk of posttreatment edema and toxicity, while maintaining acceptable freedom from local failure.

Introduction Clinical success of deep brain stimulation (DBS) depends on accurate electrode placement and stimulation within the brain targets. This study aims to explore the optimal stimulation site in the globus pallidus interna (GPi) to address the existing knowledge gap. Methods A retrospective chart review included Parkinson's disease (PD) patients who underwent GPi DBS between 2020 and 22 at our institution. We used stimulation data at six months post-op to generate a stimulation field model (SFM) for each lead and aggregated to generate volumetric stimulation heatmaps. Primary outcome measure was Clinical Global Impression-Change (CGI-C) scale, determined by response in contralateral tremor, rigidity and bradykinesia, correlated with SFM to generate ideal locations for stimulation in GPi. The secondary outcome measures were difference in pre- and post-DBS Movement Disorders Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS) III scores. Results Twenty-two PD patients with 36 GPi leads were included. Mean age: 64 ± 8.5 years; 67 % were male. For right GPi leads, 11/16 (69 %) had CGI-C of 1 and 5/16 (31 %) had 2. For left GPi leads, 13/20 (65 %) and 7/20 (35 %) had CGI-C of 1 and 2, respectively. MDS-UPDRS improved from 33.5 to 19.7 (41 %) post-op (p = 0.0003) with significant reduction in levodopa equivalent dosage (p = 0.00043). Conclusions We identified the “sweet spot” corresponding with CGI-C of 1 in the postero-lateral and mid region of GPi on axial and coronal sequences, respectively. Our findings support the previously reported limited evidence in the literature and can be helpful in image-guided DBS programming in patients with PD.

Importance:The Implantable Neurostimulator for the Treatment of Parkinson's Disease (INTREPID) trial was a randomized, double-blind, sham-controlled study of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD). Objective:To evaluate the long-term (5-year) outcomes and safety of STN-DBS for PD. Design, Setting, and Participants:This was a prospective, randomized (3:1), 12-week double-blind sham-controlled study at 23 movement disorder centers across the US with an open-label 5-year follow-up. Patients were implanted and followed up with the Vercise DBS system from May 2013 to December 2022. Eligibility required diagnosis of bilateral idiopathic PD with more than 5 years of motor symptoms, more than 6 hours per day of poor motor function, modified Hoehn and Yahr Scale scores higher than 2, Unified Parkinson's Disease Rating Scale (UPDRS-III) score of 30 or higher (medication-off state), and 33% or higher improvement in UPDRS-III medication-on score. Intervention:Bilateral STN-DBS for moderate to advanced PD. Main Outcomes and Measures:Primary outcomes included changes in UPDRS and dyskinesia scores, quality-of-life measures, and safety assessments. Exploratory analyses included medication reduction and DBS association with motor signs. Results:A total of 313 patients were enrolled with 191 receiving the DBS system, and 137 participants (72%) completed the study. The study population had a mean (SD) age of 60 (7.9) years, with 139 (73%) male participants. Motor function without medication as measured by UPDRS-III improved from a mean (SD) of 42.8 (9.4) to 21.1 (10.6) at year 1 (51%; 95% CI, 49%-53%; P < .001) and 27.6 (11.6) at year 5 (36%; 95% CI, 33%-38%; P < .001). Activities of daily living without medication as measured by UPDRS-II improved from a mean (SD) of 20.6 (6.0) to 12.4 (6.1) at year 1 (41%; 95% CI, 38%-42%; P < .001) and 16.4 (6.5) at year 5 (22%; 95% CI, 18%-23%; P < .001). Dyskinesia scores decreased from 4.0 (5.1) to 1.0 (2.1) at year 1 (75%; 95% CI, 73%-75%; P < .001) and to 1.2 (2.1) at year 5 (70%; 95% CI, 63%-75%; P < .001). The levodopa equivalent dose was reduced by 28% at year 1, remaining stable at year 5 (28%; 95% CI, 26%-31%; P < .001). The most common serious adverse event was infection (9 participants). Ten deaths were reported, none related to the study. Conclusions and Relevance:Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant improvement in motor and activities of daily living scores, along with a stable reduction in anti-parkinsonian medication over the 5-year follow-up period.

The neurobiological mechanisms underlying human time perception remain elusive. Evidence has consistently linked striatal dopamine to timing behaviors, but it is still uncertain how rapid changes in dopamine may modulate human time perception. Many tasks designed to measure time perception utilize instrumental conditioning paradigms that reinforce correctly timed intervals. In these tasks, subjects are shown to improve their performance following repeated presentations of temporal cues – a phenomenon known as ‘temporal learning’. We sought to determine the association between rapid changes in human dopamine levels and temporal learning on an interval timing task that tested the reproduction of 1000ms, 3000ms, and 5000ms intervals in the presence and absence of monetary reinforcement. We utilized human voltammetry to measure real-time dopamine concentrations from the striatum of patients with Parkinson’s disease while they performed the interval timing task. We first compared task behavior between patients with Parkinson’s disease and neurologically healthy controls and found significant differences in the reproduction of 1000ms intervals, but not 3000ms or 5000ms intervals of time. Further, we observed that during 1000ms intervals, increases in striatal dopamine concentrations were associated with increases in temporal errors, but only during the expectation of monetary reinforcement. We also demonstrated that as temporal errors decrease overtime during temporal learning, so do striatal dopamine concentrations. These results suggest that dopamine may be driving temporal learning through the generation of temporal errors in response to positive reinforcement. These findings may have significant implications in our understanding of the role that dopamine plays in time perception. Significance Statement Human time perception is a fundamental cognitive ability but the interaction between how the human brain perceives time and dopamine’s role is unclear. This study is the first of its kind to apply human voltammetry to measure rapid changes in dopamine levels associated with temporal learning in the presence and absence of positive reinforcement. We demonstrate that temporal learning may be affected by moment-to-moment changes in dopamine levels, which are also counterintuitively related to the generation of temporal errors in the presence of expectations of rewarding feedback. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, https://ror.org/01cwqze88, KL2TR00142, R01 DA048096, R01 MH121099, R01 NS092701

OBJECTIVE:Gamma Knife radiosurgery (GKRS) is a treatment option for refractory trigeminal neuralgia (TN). However, there is a paucity of data regarding the effectiveness of GKRS for relapsing TN following microvascular decompression (MVD). The aim of this study was to characterize the response rate, complications, pain relief durability, and predictors of pain relapse for salvage GKRS following MVD for TN. METHODS:A retrospective study of all patients who received GKRS for Burchiel type 1 TN (TN1) or type 2 TN (TN2) pain at Wake Forest University School of Medicine was conducted. Pain was measured using the Barrow Neurological Institute (BNI) pain intensity score. After an initial pain response of BNI scores I-III, a BNI score of IV or V constituted relapse. Durability of pain relief was characterized using the Kaplan-Meier estimator. Predictors of relapse were investigated using Cox regression models. Statistical significance was set at p < 0.05. RESULTS:Of 2065 patients with TN1 or TN2, 59 had GKRS post-MVD. Forty-nine (83.1%) of these patients experienced a BNI pain score of I-III at the first follow-up post-GKRS. The median time to relapse was 1.75 years; freedom rates from relapse were 77%, 45.9%, and 30.7% at 1, 2, and 5 years, respectively. Radiofrequency ablation prior to MVD significantly decreased the likelihood of an initial response to salvage GKRS (Fisher's exact test, p = 0.02). After controlling for baseline and clinical characteristics, facial numbness significantly decreased the likelihood of pain relapse (Cox regression, HR 0.15, 95% CI 0.03-0.73; p = 0.01). Conversely, a worse initial pain response significantly increased the likelihood of pain relapse (Cox regression, HR 3.64, 95% CI 1.02-12.95; p = 0.04). Pain relapse within 24 months of the original MVD did not predict durability of pain relief following salvage GKRS (Cox regression, HR 0.94, 95% CI 0.40-2.22; p = 0.89). The overall toxicity rate of salvage GKRS was 35.6%. CONCLUSIONS:Salvage GKRS presents an effective, noninvasive option for recurring TN after MVD, with a comparable response rate to primary GKRS or MVD, and a favorable complications profile relative to salvage MVD. Patients with postoperative facial numbness and a better initial pain response may experience more durable pain relief following salvage GKRS.

Dynamic changes in dopamine, noradrenaline, and serotonin release are believed to causally contribute to the neural computations that support reward-based decision making. Accordingly, changes in signaling by these systems are hypothesized to underwrite multiple cognitive and behavioral symptoms observed in many neurological disorders. Here, we characterize the release of these neurotransmitters measured concurrently in the caudate of patients with Parkinson's disease or essential tremor undergoing deep brain stimulation surgery as they played a social exchange game. We show that violations in the expected value of monetary offers are encoded by opponent patterns of dopamine and serotonin release in essential tremor, but not Parkinson's disease, patients. We also demonstrate that these changes in serotonin signaling comprise a neurochemical boundary that subsegments these two neuromotor diseases. Our combined results point to a neural signature of altered reward processing that can be used to understand the signaling deficiencies that underwrite these diseases.

Purpose/objective(s)Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease.MethodsPatients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Extracranial oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher’s exact tests were used to screen for mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A risk score for the likelihood of oligometastatic disease was generated and correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression. Cox regression was used to determine association between oligometastatic risk score and oligoprogression.Results130 patients met study criteria and were included in the analysis. 51 patients (39%) had extracranial oligometastatic disease. Genetic mutations included in the Guardant panel that were associated (p<0.1) with the presence of oligometastatic disease included ATM, JAK2, MAP2K2, and NTRK1, while ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p=0.2). Oligometastatic risk score was significantly associated with the likelihood of oligoprogression based on the Wald chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p=0.03).ConclusionsElucidation of a genomic signature for extracranial oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients.

Background We sought to determine if using clear masks in the operating room improves communication for patients undergoing awake deep brain stimulation (DBS) surgery. Methods This randomized, controlled study involved patients undergoing awake DBS receiving communication from the neurologist wearing a covered or clear mask for the intraoperative assessment, using a block randomization schedule. Adult patients (>18) undergoing DBS surgery between November 2021 and July 2023 were evaluated for inclusion. The primary outcome was a dichotomized response to the first question of a 10-question survey: “Did this provider explain things in a way that was easy to understand?”, answered using a Likert scale of 1-4. Secondary outcomes included differences in the responses to the remaining questions. Results 104 patients were assessed for eligibility, 72 were enrolled, and 65 completed all questionnaires. More males than females (72.3% versus 27.7%) were enrolled, and most patients (64%) underwent DBS for treatment of Parkinson’s disease. The primary outcome analysis showed 93.5% positive response in the clear mask group compared to 85.3% in the covered mask group (p=0.502). There were no infections within 30 days or study-related adverse events in either population. Discussion This randomized controlled trial demonstrates that the use of clear masks in the setting of awake brain surgery has no difference on patient perception of communication compared to covered masks. There were no infections or mask-related adverse events. This suggests that clear masks are a safe and effective alternative to traditional masks in the operating room.