Neuromodulation with Ultrasound: Hypotheses on the Directionality of Effects and a Community Resource.

Low-intensity Transcranial Ultrasound Stimulation (TUS) is a promising non-invasive technique for deep-brain stimulation and focal neuromodulation. Research with animal models and computational modelling has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first conduct a systematic review of human TUS studies for perturbing neural function and alleviating brain disorders. We then collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on the human TUS study reported outcomes to date ( n = 32 studies, 37 experiments). We find that parameters such as the duty cycle show some predictability regarding whether the targeted area's function is likely to be enhanced or suppressed. Given that human TUS sample sizes are exponentially increasing, we recognize that results can stabilize or change as further studies are reported. Therefore, we conclude by establishing an Iowa-Newcastle (inTUS) resource for the systematic reporting of TUS parameters and outcomes to support further hypothesis testing for greater precision in brain stimulation and neuromodulation with TUS. Highlights: Systematic review of human TUS studies for enhancing or suppressing neural functionCollated set of hypotheses on using TUS to bias towards enhancement or suppressionMeta-analysis results identify parameters that may bias the directionality of effectsTUS resource established for systematic reporting of TUS parameters and outcomes.

Primary Embolization of Cerebral Arteriovenous Malformations With Intention to Cure: A Systematic Review of Literature and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear. METHODS: We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis. RESULTS: We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%). CONCLUSION: Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.

Contemporary Methods for Detection and Intervention of Distal Medium and Small Vessel Occlusions.

The efficacy of using mechanical thrombectomy for proximal large vessel occlusions has been demonstrated in multiple large-scale trials and has further raised the question of its potential utility for distal medium and small vessel occlusions (DMSVOs). Their longer, more tortuous course and smaller corresponding vascular territories render a significant challenge for detection and intervention. The aim of this study is to provide a comprehensive overview of the current imaging and endovascular intervention options for DMSVOs and review the current works in the literature. Compared with traditional computed tomography angiography (CTA) and CT perfusion, recent advances such as multiphase CTA and maps derived from the time-to-maximum parameter coupled with artificial intelligence have demonstrated increased sensitivity for the detection of DMSVOs. Furthermore, newer generations of mini stent retrievers and thromboaspiration devices have allowed for the access and navigation of smaller and more fragile distal arteries. Preliminary studies have suggested that mechanical thrombectomy using this newer generation of devices is both safe and feasible in distal medium-sized vessels, such as M2. However, endovascular intervention utilizing such contemporary methods and devices must be balanced at the discretion of operator experience and favorable vascular anatomy. Further large-scale multicenter clinical trials are warranted to elucidate the indications for as well as to strengthen the safety and efficacy of this approach.

Deep brain stimulation for substance use disorder: a systematic review and meta-analysis.

Objective: Substance use disorder (SUD) is a significant public health issue with a high mortality rate. Deep brain stimulation (DBS) has shown promising results in treating SUD in certain cases. In this study, we conducted a meta-analysis to evaluate the efficacy of DBS in the treatment of SUD and reduction of relapse rates. Methods: We performed a thorough and methodical search of the existing scientific literature, adhering to the PRISMA guidelines, to identify 16 original studies that fulfilled our inclusion criteria. We used the evidence levels recommended by the Oxford Centre for Evidence-Based Medicine to assess bias. The R version 4.2.3 software was utilized to calculate the mean effect size. We estimated study heterogeneity by employing tau2 and I2 indices and conducting Cochran's Q test. Results: The results showed that DBS treatment resulted in a significant improvement in the clinical SUD scales of patients, with an average improvement of 59.6%. The observed relapse rate was 8%. The meta-analysis estimated a mean effect size of 55.9 [40.4; 71.4]. Heterogeneity analysis showed a large degree of heterogeneity among the included studies. Subgroup and meta-regression analysis based on age and SUD type suggested that DBS may be more effective for patients above 45 years of age, and for alcohol and opioid addiction compared to nicotine addiction. Conclusion: The current literature suggests that DBS has a moderate effect on SUD symptoms. However, the limited number of studies and small sample size indicate that more research is needed to better understand the factors that influence its effectiveness.

Novel Use of Robotically Harvested Internal Thoracic Artery in High-Flow Cerebral Bypass.

Mesenchymal tumors of the head and neck can lead to tumor-induced osteopeni, necessitating a biochemical cure to alleviate associated symptoms. We present a case of a 40-year-old man who presented with diffuse pain and wheelchair dependency secondary to a skull base mesenchymal tumor producing tumor-induced osteopeni. The tumor involved the cavernous sinus, infratemporal fossa, and middle cranial fossa. The patient failed the balloon occlusion test. Additionally, the patient consented to the procedure. Cerebral revascularization was performed using a robotically harvested internal thoracic artery because of the patient's short radial arteries and history of chronic superficial and deep vein thrombosis. After the common carotid artery-internal thoracic artery-M2 bypass, the patient underwent endovascular embolization of the external carotid artery feeders and occlusion of the cavernous external carotid artery. Several days later, the patient underwent a gross total resection via endoscopic assisted microsurgery. The residual biochemical disease was then addressed via supplemental radiosurgery. The patient's clinical outcome was favorable, with regained ambulatory function and resolution of initial symptoms. Unfortunately, he developed left optic neuropathy due to the embolization of the external carotid artery feeders.

Microsurgical Resection of Spinal Arteriovenous Malformation with Clipping of Anterior Spinal Artery Aneurysm.

Spinal cord arteriovenous malformations (AVMs) are rare and usually present in younger patients. We present the case of a 76-year-old woman with a 2-year history of unsteady gait. She presented to us with sudden-onset thoracic pain, numbness, and weakness in both legs. She was found to have urinary retention, dissociative pain loss in the left leg, and weakness involving the right leg. Magnetic resonance imaging demonstrated an intramedullary spinal AVM with subarachnoid hemorrhage and cord edema. The spinal angiogram detailed the architecture of the AVM and revealed a flow-related aneurysm in the anterior spinal artery. The patient underwent T8-T11 laminoplasty with a T10 transpedicular approach to allow for ventral exposure of the cord. Initially, a microsurgical clipping of the aneurysm was performed, followed by a pial resection of the AVM. Postoperatively, the patient recovered her bladder control and motor function. She is now able to walk with a walker due to impaired proprioception. Videos 1-4 detail the key steps and techniques for safe clipping and resection.

Long-Term Follow-Up of Cerebral Aneurysms Completely Occluded at 6 Months After Intervention with the Woven EndoBridge (WEB) Device: a Retrospective Multicenter Observational Study.

The Woven EndoBridge (WEB) device has been widely used to treat intracranial wide neck bifurcation aneurysms. Initial studies have demonstrated that approximately 90% of patients have same or improved long-term aneurysm occlusion after the initial 6-month follow up. The aim of this study is to assess the long-term follow-up in aneurysms that have achieved complete occlusion at 6 months. We also compared the predictive value of different imaging modalities used. This is an analysis of a prospectively maintained database across 13 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB device who achieved complete occlusion at first follow-up and had available long-term follow-up. A total of 95 patients with a mean age of 61.6 ± 11.9 years were studied. The mean neck diameter and height were 3.9 ± 1.3 mm and 6.0 ± 1.8 mm, respectively. The mean time to first and last follow-up was 5.4 ± 1.8 and 14.1 ± 12.9 months, respectively. Out of all the aneurysms that were completely occluded at 6 months, 84 (90.3%) showed complete occlusion at the final follow-up, and 11(11.5%) patients did not achieve complete occlusion. The positive predictive value (PPV) of complete occlusion at first follow was 88.4%. Importantly, this did not differ between digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA). This study underlines the importance of repeat imaging in patients treated with the WEB device even if complete occlusion is achieved short term. Follow-up can be performed using DSA, MRA or CTA with no difference in positive predictive value.

The Adjustable Cranial Plate: A Novel Implant Designed to Eliminate the Need for Cranioplasty Surgery Following a Hemicraniectomy Operation.

BACKGROUND: Decompressive hemicraniectomy (DHC) is performed to relieve life-threatening intracranial pressure elevations. After swelling abates, a cranioplasty is performed for mechanical integrity and cosmesis. Cranioplasty is costly with high complication rates. Prior attempts to obviate second-stage cranioplasty have been unsuccessful. The Adjustable Cranial Plate (ACP) is designed for implantation during DHC to afford maximal volumetric expansion with later repositioning without requiring a second major operation. METHODS: The ACP has a mobile section held by a tripod fixation mechanism. Centrally located gears adjust the implant between the up and down positions. Cadaveric ACP implantation was performed. Virtual DHC and ACP placement were done using imaging data from 94 patients who had previously undergone DHC to corroborate our cadaveric results. Imaging analysis methods were used to calculate volumes of cranial expansion. RESULTS: The ACP implantation and adjustment procedures are feasible in cadaveric testing without wound closure difficulties. Results of the cadaveric study showed total volumetric expansion achieved was 222 cm3. Results of the virtual DHC procedure showed the volume of cranial expansion achieved by removing a standardized bone flap was 132 cm3 (range, 89-171 cm3). Applied to virtual craniectomy patients, the total volume of expansion achieved with the ACP implantation operation was 222 cm3 (range, 181-263 cm3). CONCLUSIONS: ACP implantation during DHC is technically feasible. It achieves a volume of cranial expansion that will accommodate that observed following survivable hemicraniectomy operations. Moving the implant from the up to the down position can easily be performed as a simple outpatient or inpatient bedside procedure, thus potentially eliminating second-stage cranioplasty procedures.

Microsurgery of Meningiomas Involving the Superior Sagittal Sinus.

Meningiomas involving major dural sinuses can be difficult to resect without proper handling of the sinus. In young patients, a gross total resection should be attempted when feasible. A 24-year-old man presented with headaches, progressive left-sided weakness, and partial motor seizures. He was found to have a parasagittal meningioma in front of the motor cortex that invaded the superior sagittal sinus (SSS). The sinus was still patent, and the walls were preserved. Thus a gross total resection was achieved with primary suturing of the sinus, followed by reinforcement with an AnastoClip GC. Videos 1-3 details the separation of the tumor from the convexity veins and the cortex, removal of the tumor from the SSS, and reconstruction of the SSS. Gross total resection of meningiomas involving the SSS is achievable without sacrificing the sinus when planned correctly and methodically. The patient consented for the procedure and to the publication of these images.

Minimally Invasive Double-Barrel Superficial Temporal Artery-Middle Cerebral Artery Bypass.

Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is used to augment flow in various cases. We present a patient with a refractory right MCA transient ischemic attack and a minor stroke. He was perfusion dependent. A computed tomography perfusion with acetazolamide challenge showed hypoperfusion in the superior and inferior trunk of the MCA on the right side. We thus used the frontal and parietal branches of the STA to revascularize both territories. This was done via a small single incision and craniotomy. We present here the details of the techniques and surgical nuances (Video 1). The patient consented to the procedure and to the publication of his or her own images.

Increased Concentrations of Atherogenic Proteins in Aneurysm Sac Are Associated with Wall Enhancement of Unruptured Intracranial Aneurysm.

Current MR-vessel wall imaging (VWI) of unruptured intracranial aneurysms (UIAs) permits the visualization of wall structures. Aneurysm wall enhancement (AWE) was associated with atherosclerotic remodeling of the aneurysm wall accompanied by infiltration of inflammatory cells, potentially contributing to rupture. This study sought to investigate whether the luminal concentrations of atherosclerotic proteins in the aneurysm sac were associated with increased wall enhancement of UIAs in VWI. Subjects undergoing endovascular treatment for UIAs were prospectively recruited. All subjects underwent evaluation using 3 T-MRI including pre/post contrast VWI of the UIAs. Blood samples were collected from the aneurysm sac and the parent artery during endovascular procedures. The presence of AWE was correlated with the delta difference in concentration between the aneurysm sac and the parent artery for each atherosclerotic protein. A total of consecutive 45 patients with 50 UIAs were enrolled. The delta differences of anti-oxidized low-density lipoprotein (LDL) antibody, small dense LDL, and lipoprotein(a) [Lp(a)] were significantly higher in UIAs with AWE compared with those without AWE (767.6 ± 1957.1 versus - 442.4 ± 1676.3 mIU/mL, p = 0.02, 114.8 ± 397.7 versus - 518.5 ± 1344.4 µg/mL, p = 0.04, and - 5.6 ± 11.3 versus - 28.7 ± 38.5 µg/mL, p = 0.01, respectively). In multivariate logistic regression analysis, the delta Lp(a) was significantly associated with AWE (p = 0.04). Increased concentrations of atherogenic proteins in the aneurysm sac were significantly associated with wall enhancement of UIAs. Future studies examining the effect of medications for atherosclerosis on the atherogenic proteins within the aneurysm sac and hence the wall enhancement are warranted.

The Woven EndoBridge (WEB) device: feasibility, techniques, and outcomes after FDA approval.

OBJECTIVE: Wide-neck bifurcation cerebral aneurysms have historically required either clip ligation or stent- or balloon-assisted coil embolization. This predicament led to the development of the Woven EndoBridge (WEB) aneurysm embolization system, a self-expanding mesh device that achieves intrasaccular flow disruption and does not require antithrombotic medications. The authors report their operative experience and 6-month follow-up occlusion outcomes with the first 115 aneurysms they treated via WEB embolization. METHODS: The authors reviewed the first 115 cerebral aneurysms they treated by WEB embolization after FDA approval of the WEB embolization device (from February 2019 to January 2021). Data were collected on patient demographics and clinical presentation, aneurysm characteristics, procedural details, postembolization angiographic contrast stasis, and functional outcomes. RESULTS: A total of 110 patients and 115 aneurysms were included in our study (34 ruptured and 81 unruptured aneurysms). WEB embolization was successful in 106 (92.2%) aneurysms, with a complication occurring in 6 (5.5%) patients. Contrast clearance was seen in the arterial phase in 14 (12.2%) aneurysms, in the capillary phase in 16 (13.9%), in the venous phase in 63 (54.8%), and no contrast was seen in 13 (11.3%) of the aneurysms studied. Follow-up angiography was performed on 60 (52.6%) of the aneurysms, with complete occlusion in 38 (63.3%), neck remnant in 14 (23.3%), and aneurysmal remnant in 8 (13.3%). Six (5.5%) patients required re-treatment for persistent aneurysmal residual on follow-up angiography. CONCLUSIONS: The WEB device has been successfully used for the treatment of both unruptured and ruptured wide-neck bifurcation aneurysms by achieving intrasaccular flow diversion. Here, the authors have shared their experience with its unique technical considerations and device size selection, as well as critically reviewed complications and aneurysm occlusion rates.

Postoperative cognitive dysfunction after endovascular treatments for unruptured intracranial aneurysms: A pilot study.

OBJECTIVE: Post operative cognitive dysfunction (POCD) has been widely observed after major surgery, particularly in elderly patients with general anesthesia (GA). However, a specific unanswered question is whether different approaches to anesthetic managements are associated with different cognitive outcomes after endovascular treatments for unruptured intracranial aneurysms (UIAs). The purpose of this study is to assess the correlation of POCD with GA versus monitored anesthesia care (MAC). METHODS: We performed a pragmatic, prospective study to assess the association between different anesthetic approaches and POCD. We compared the pre- and post-procedural Montreal Cognitive Assessment (MoCA) scores in patients with normal cognition who underwent treatments of UIAs with various endovascular methods, using either GA or MAC. RESULTS: A total of 23 patients with UIAs were enrolled in the study. Seven (30.4%) and sixteen (69.6%) UIAs were treated without perioperative complications under GA or MAC, respectively. There was a significant decline in the post-procedural MoCA score under GA (mean difference = 1.14; 95% confidence interval = [0.42-1.87], P < 0.01). By contrast, there was no significant difference of MoCA score between pre- and post-procedure under MAC (mean difference = 0.19; 95% confidence interval = [-0.29-0.67], P = 0.59). CONCLUSIONS: Treating UIAs using MAC was associated with a decrease in POCD as compared to GA in patients undergoing endovascular treatments for UIAs with normal cognition. Larger randomized studies are needed to confirm these findings.

Melatonin and risk of mortality in subjects with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a cause of morbidity associated with aneurysmal subarachnoid hemorrhage (aSAH). Neuroinflammation contributes to the development of DCI. Melatonin is a sleep-promoting hormone known to have cerebral anti-inflammatory properties. We hypothesized that synthetic melatonin (or the selective melatonin receptor agonist ramelteon) incidentally prescribed to improve sleep may lower the incidence of DCI among hospitalized aSAH patients. METHODS: Subjects with a Hunt and Hess Grade I-III were identified from a data registry involving all aSAH patients admitted to our hospital between January 2015 and September 1, 2018. A cohort of patients who received either melatonin or ramelteon during their hospitalization was compared to a matched cohort that did not receive these drugs. The primary endpoint was incidence of DCI. Secondary outcomes included modified Rankin score (mRS) at discharge, discharge destination, and mortality at 6 weeks from discharge. The two groups were compared using univariate analysis. P < 0.05 was considered significant. RESULTS: There was no significant difference in the incidence of DCI (15.8% vs. 16.9%, p = 1), discharge mRS (mRS 0-3: 51.3% vs. 45.1%, p = 0.59), discharge disposition (Home: 43.6% vs. 44.4, p = 0.47), or mortality (0% vs. 9.2%; p = 0.074) between the melatonin/ramelteon and non-melatonin groups. CONCLUSION: The use melatonin had no effect on DCI but may improve mortality in aSAH subjects. Prospective studies using a larger cohort are warranted to validate these findings.

Phase 1/2a Trial of ISPASM.

BACKGROUND AND PURPOSE: Microthrombosis could play a role in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Tirofiban has shown promising results in reducing delayed cerebral ischemia in retrospective studies. However, the safety of using tirofiban in aneurysmal subarachnoid hemorrhage is not rigorously established. METHODS: A phase 1/2a double-blinded randomized controlled trial (2:1 randomization) to assess the safety of a 7-day intravenous infusion of tirofiban compared with placebo, in patients with aneurysmal subarachnoid hemorrhage treated with ventriculostomy placed in the operative room and coiling was conducted. The primary end point was any intracranial hemorrhage during the hospital stay. The secondary end points were: incidence of radiographic and clinical vasospasm, incidence of delayed cerebral ischemia, and incidence of cerebral ischemic changes noted on magnetic resonance imaging or computed tomography. RESULTS: Eighteen patients received intravenous tirofiban and 12 received placebo. There was no difference in baseline characteristics except for higher male proportions in the tirofiban group. There was no difference in death, in development of new or change in existing intracranial hemorrhages, in thrombocytopenia, and need for shunts in the two arms. However, the tirofiban arm had a lower incidence of delayed cerebral ischemia compared with placebo (6% [1/18] versus 33% [4/12]; P=0.04), and less radiographic vasospasm as detected by catheter angiogram or computed tomography angiography (P=0.01) and computed tomography perfusion (P=0.01). CONCLUSIONS: The above preliminary results support proceeding with further testing of the safety and efficacy of 7-day intravenous infusion of tirofiban in a pragmatic (placing external ventricular drain by the bedside), multicenter setting, and using a larger population. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03691727.

Aneurysm Wall Enhancement Is Associated With Decreased Intrasaccular IL-10 and Morphological Features of Instability.

BACKGROUND: High-resolution vessel wall imaging plays an increasingly important role in assessing the risk of aneurysm rupture. OBJECTIVE: To introduce an approach toward the validation of the wall enhancement as a direct surrogate parameter for aneurysm stability. METHODS: A total of 19 patients harboring 22 incidental intracranial aneurysms were enrolled in this study. The aneurysms were dichotomized according to their aneurysm-to-pituitary stalk contrast ratio using a cutoff value of 0.5 (nonenhancing < 0.5; enhancing ≥ 0.5). We evaluated the association of aneurysm wall enhancement with morphological characteristics, hemodynamic features, and inflammatory chemokines directly measured inside the aneurysm. RESULTS: Differences in plasma concentration of chemokines and inflammatory molecules, morphological, and hemodynamic parameters were analyzed using the Welch test or Mann-Whitney U test. The concentration ΔIL-10 in the lumen of intracranial aneurysms with low wall enhancement was significantly increased compared to aneurysms with strong aneurysm wall enhancement (P = .014). The analysis of morphological and hemodynamic parameters showed significantly increased values for aneurysm volume (P = .03), aneurysm area (P = .044), maximal diameter (P = .049), and nonsphericity index (P = .021) for intracranial aneurysms with strong aneurysm wall enhancement. None of the hemodynamic parameters reached statistical significance; however, the total viscous shear force computed over the region of low wall shear stress showed a strong tendency toward significance (P = .053). CONCLUSION: Aneurysmal wall enhancement shows strong associations with decreased intrasaccular IL-10 and established morphological indicators of aneurysm instability.

Case series of sphenoid wing meningioma - What is a maximal safe resection?

BACKGROUND: Sphenoid wing meningiomas are a challenging surgical disease with relatively high perioperative morbidity. Most studies to date have focused on resection strategies as it relates to disease recurrence. Few have examined the optimal strategy as it relates to overall patient survival. We retrospectively reviewed our case series and evaluated extent of resection and perioperative stroke as it relates to all cause and disease-specific survival. PATIENTS/METHODS: Ninety-four patients were included in the study. Demographics, clinical features, operative features and clinical course, and time to mortality evaluation were collected. Extent of resection (EOR) was defined as gross total (GTR, 100%), near total (NTR, ≥ 95%), and subtotal (STR,<95%). RESULTS: The overall mean EOR was 94.5% with 70.2% of cases achieving GTR, 12.8% achieved NTR, and 17% achieved STR. Postoperative stroke only occurred with GTR or NTR (p=0.041). Age alone was significant on Cox regression analysis for all cause mortality (p=0.042, HR 1.054 [95% CI 1.002 - 1.109]). Postoperative stroke was associated with worse disease-specific mortality (p=0.046, HR 23.337 [95% CI 1.052 - 517.782) with no impact from extent of resection (p=0.258). CONCLUSIONS: Although maximizing resection and minimizing recurrence is ideal, GTR or NTR confer a significantly higher stroke risk. Most patients do not die from their meningioma, as all cause mortality was associated only with age. However, perioperative stroke conferred decreased survival throughout follow up. This series demonstrates that an overly aggressive surgical philosophy negatively impacted disease specific survival.

Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy.

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2-4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45-0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32-0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.