Nationwide trends in intensive care unit utilization in the elective endovascular treatment of unruptured intracranial aneurysms.

OBJECTIVE: Multiple studies suggest routine post-operative intensive care unit (ICU) stays after endovascular treatment (EVT) of unruptured intracranial aneurysms (UIAs) is unnecessary, though rates of ICU utilization nationwide are unknown. We aim to evaluate rates and characteristics of ICU utilization in patients undergoing elective endovascular repair of UIAs. METHODS: This is a retrospective cohort study utilizing a nationwide private-payer database in the United States to evaluate the ICU utilization in patients undergoing elective endovascular repair of UIAs between 2005 and 2019. Demographics and pre-operative comorbidities as well as post-procedural complications and discharge status were compared. An analysis of charges and costs was also performed. RESULTS: Among 6218 patients who underwent elective EVT of a UIA, 4890 (78.6%) were admitted to the ICU post-operatively. There were no differences in age, sex, or Charlson comorbidity scores in patients admitted to the ICU post-operatively compared to those admitted elsewhere. ICU utilization was more common in urban locations compared to rural. 12.7% of patients had ICU-specific needs sufficient to be billed by a critical care provider. Total provider costs were significantly higher in patients utilizing the ICU post-operatively, even among uncomplicated patients with routine discharges. CONCLUSION: Most patients undergoing elective endovascular UIA repair in the United States are admitted to the ICU postoperatively. Only 12.7% have ICU needs, and these patients are predictable from pre-operative characteristics or peri-operative complications. Reducing ICU use in this subgroup of patients may be an important target to improve healthcare value in this patient population.

The Prevalence of Seizures in Brain Metastasis Patients on Anticonvulsant Prophylaxis: A Systematic Review and Meta-Analysis.

BACKGROUND: Brain metastasis (BM) prognosis is incredibly poor and is often associated with considerable morbidity. Seizures are commonly present in these patients, and their biopsychosocial impact can be dangerous. The use of antiepileptic drugs (AEDs) as primary prophylaxis remains controversial. This systematic review and meta-analysis aim to evaluate the efficacy of AED prophylaxis in patients with BM. METHODS: MEDLINE via PubMed, Web of Science, EMBASE, and Cochrane were searched for articles pertinent to AED prophylaxis use in patients with BM. Patients with BM previously treated for cancer who were seizure naive at the time of inclusion were included. Data regarding patient characteristics, type of AED, prior treatments, and groups at a high risk of seizure were extracted. Seizure prevalence was obtained. RESULTS: Eight studies were included in this systematic review and meta-analysis; 1902 total patients with BM were included, with 381 receiving antiepileptic prophylaxis, and 1521 receiving no prophylaxis. Although the odds of a seizure in the treatment group was found to be 1.158 times the odds of a seizure in the control group, the odds ratio was not statistically significant (t-statistic = 0.62, P value = 0.5543). CONCLUSIONS: There was no significant difference in the odds of seizure development in control groups compared to patients receiving prophylactic antiepileptic therapy. As patients with BM present with heterogeneity in tumor characteristics and receive various treatment modalities, future research is needed to identify groups that may benefit more significantly from AED prophylaxis.

Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

OBJECTIVE: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

Third Stereotactic Radiosurgery for Residual Arteriovenous Malformations: A Retrospective Multicenter Study.

BACKGROUND AND OBJECTIVES: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual. METHODS: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC. RESULTS: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up. CONCLUSION: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs.

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

Safety and efficacy of endovascular versus microsurgical treatment of unruptured wide-necked middle cerebral artery aneurysms: a propensity score-matched analysis of the NeuroVascular Quality Initiative Quality Outcomes Database Cerebral Aneurysm Registry.

OBJECTIVE: Unruptured, wide-necked middle cerebral artery (WN-MCA) aneurysms have traditionally been considered ideal candidates for microsurgery (MS), although endovascular treatment (EVT) has dramatically increased in popularity with the advent of novel devices such as intrasaccular flow disruptors. The purpose of this study was to evaluate the safety and efficacy of MS versus EVT for unruptured WN-MCA aneurysms. METHODS: The NeuroVascular Quality Initiative Quality Outcomes Database (NVQI-QOD) Cerebral Aneurysm Registry, a multiinstitutional, prospectively collected procedural database, was queried for cases of unruptured WN-MCA aneurysms treated with MS or EVT between 2015 and 2022. A wide neck was defined as an aneurysm neck ≥ 4 mm or a dome/neck ratio ≤ 2. Demographics and aneurysm characteristics were queried. Propensity score matching (PSM) was utilized to match aneurysm size, number of aneurysms treated, patient age, and aneurysm status. Safety outcomes were evaluated including intraoperative and postoperative complication rates. Aneurysm occlusion status and clinical outcomes using the modified Rankin Scale (mRS) score at discharge and the last follow-up were also assessed. RESULTS: Of 671 unruptured MCA aneurysms, 319 were wide necked. Thirty cases were excluded, as the aneurysm had been previously treated. Two hundred eighty-nine operations (203 EVT, 86 MS) in 282 patients satisfied inclusion criteria. After PSM, there were 86 operations in each group for analysis. The mean aneurysm width was 5.0 (EVT) versus 4.9 mm (MS; p = 0.285). Safety data showed similar intraoperative (7.0% EVT vs 3.5% MS, p = 0.496) and postoperative (4.7% vs 7%, p = 0.746) complication rates. The MS patients were more likely to have complete aneurysm occlusion at discharge (90.4% vs 58.8%, p < 0.001). In a limited subset of patients (52.9%) for whom outcome data were available, the EVT patients were more likely to have an mRS score 0 at discharge (50/59 [84.7%] vs 29/54 [53.7%], p < 0.0003] and at the last follow-up (36/55 [65.5%] vs 13/36 [36.1%], p = 0.006). CONCLUSIONS: This study describes a large, modern cohort of propensity score-matched patients who underwent treatment of unruptured WN-MCA aneurysms. Safety data on intraoperative and postoperative complication rates were similar in both treatment groups. MS was more likely to result in complete aneurysm occlusion at discharge. In a subset of patients with available outcome data, EVT was associated with better functional outcomes at discharge and the last follow-up. Given the lack of complete follow-up data and rates of retreatment, these results should be interpreted cautiously.

Rewarded Maze Training Increases Approach Behavior in Rats Through Neurogenesis-Dependent Growth of Ventral Hippocampus-Prelimbic Circuits.

Background: Learning complex navigation routes increases hippocampal volume in humans, but it is not clear whether this growth impacts behaviors outside the learning situation or what cellular mechanisms are involved. Methods: We trained rats with pharmacogenetic suppression of adult neurogenesis and littermate controls in 3 mazes over 3 weeks and tested novelty approach behavior several days after maze exposure. We then measured hippocampus and prelimbic cortex volumes using magnetic resonance imaging and assessed neuronal and astrocyte morphology. Finally, we investigated the activation and behavioral role of the ventral CA1 (vCA1)-to-prelimbic pathway using immediate-early genes and DREADDs (designer receptors exclusively activated by designer drugs). Results: Maze training led to volume increase of both the vCA1 region of the hippocampus and the prelimbic region of the neocortex compared with rats that followed fixed paths. Growth was also apparent in individual neurons and astrocytes in these 2 regions, and behavioral testing showed increased novelty approach in maze-trained rats in 2 different tests. Suppressing adult neurogenesis prevented the effects on structure and approach behavior after maze training without affecting maze learning itself. The vCA1 neurons projecting to the prelimbic area were more activated by novelty in maze-trained animals, and suppression of this pathway decreased approach behavior. Conclusions: Rewarded navigational learning experiences induce volumetric and morphologic growth in the vCA1 and prelimbic cortex and enhance activation of the circuit connecting these 2 regions. Both the structural and behavioral effects of maze training require ongoing adult neurogenesis, suggesting a role for new neurons in experience-driven increases in novelty exploration.

Conscious sedation by sedation-trained interventionalists versus anesthesia providers in patients with acute ischemic stroke undergoing endovascular thrombectomy: A propensity score-matched analysis.

BACKGROUND: The appropriate choice of perioperative sedation during endovascular thrombectomy for ischemic stroke is unknown. Few studies have evaluated the role of nursing-administered conscious sedation supervised by a trained interventionalist. OBJECTIVE: To compare the safety and efficacy of endovascular thrombectomy for ischemic stroke performed with nursing-administered conscious sedation supervised by a trained interventionalist with monitored anesthesia care supervised by an anesthesiologist. METHODS: A retrospective review of a prospectively collected stroke registry was performed. The primary outcome was functional independence at 90 days, defined as a modified Rankin score of 0-2. Propensity score matching was performed to control for known confounders including patient comorbidities, access type, and direct-to-suite transfers. RESULTS: A total of 355 patients underwent endovascular thrombectomy for large vessel occlusion between 2018 and 2022. Thirty five patients were excluded as they arrived at the endovascular suite intubated. Three hundred and twenty patients were included in our study, 155 who underwent endovascular thrombectomy with nursing-administered conscious sedation and 165 who underwent endovascular thrombectomy with monitored anesthesia care. After propensity score matching, there were 111 patients in each group. There was no difference in modified Rankin score 0-2 at 90 days (26.1% vs 35.1%, p = 0.190). Patients undergoing monitored anesthesia care received significantly more vasoactive medications (23.4% vs 49.5%, p < 0.001) and had a lower intraoperative minimum systolic blood pressure (134 vs 123 mmHg, p < 0.046). There was no difference in procedural efficacy, safety, intubation rates, and postoperative complications. CONCLUSION: Perioperative sedation with nursing-administered conscious sedation may be safe and effective in patients undergoing endovascular thrombectomy for ischemic stroke.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

BACKGROUND: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

Neuroendovascular Procedures in Patients with Ehlers-Danlos Type IV: Multicenter Case Series and Systematic Review.

BACKGROUND: Ehlers-Danlos type IV or vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited disorder characterized by profound vascular fragility resulting from defective production of type III procollagen. Cerebrovascular diseases including spontaneous dissections, cerebral aneurysms, and cavernous carotid fistulae are common. Endovascular therapies in this patient population are known to be higher risk, although many studies (before 2000) involved older techniques and equipment. The purpose of this study is to investigate the safety and efficacy of modern neuroendovascular techniques in the treatment of cerebrovascular diseases in patients with vEDS. METHODS: We combined a multi-institutional retrospective case series at 3 quaternary-care centers with a systematic literature review of individual case reports and case series spanning 2000-2021 to evaluate the safety and efficacy of neuroendovascular procedure in patients with vEDS with cerebrovascular diseases. RESULTS: Fifty-nine patients who underwent 66 neuroendovascular procedures were evaluated. Most of the patients had direct cavernous carotid fistulas (DCCF). Neuroendovascular procedures had a 94% success rate, with a complication rate of 30% and a mortality of 7.5%. CONCLUSIONS: Neuroendovascular procedures can be performed with a high rate of success in the treatment of cerebrovascular diseases in patients with vEDS, although special care is required because complication rates and mortality are high. Access site and procedure-related vascular injuries remain a significant hurdle in treating vEDS with cerebrovascular diseases, even with modern techniques.

Direct ventriculoatrial shunt in a pediatric patient: case report and technical note.

BACKGROUND /IMPORTANCE: The safety of direct cardiac shunts has been historically described in the pediatric population before the introduction of silastic catheters but are rarely utilized in modern practice. Herein, we describe several technical nuances regarding the placement of a direct ventriculoatrial catheter in a pediatric patient, including the creation of a sternal divot to accommodate for the movement of the catheter during growth. CLINICAL PRESENTATION: We report a complex case of a 2-year-old former premature infant with multiple systemic congenital abnormalities, including tracheal atresia (type 2), complete atrioventricular septal defect status post repair, and shunted hydrocephalus. She developed multiple shunt malfunctions secondary to abdominal malabsorption and shunt infections. CONCLUSION: Multiple options for distal shunt placement, including the atrium via open and endovascular techniques, the abdomen, gallbladder, and pleura, were considered, but the direct cardiac placement was felt to be the safest option given the patient's coexisting conditions. Placement requires a multidisciplinary team. Special consideration should be made for linear growth in children.

Association of Low-Grade Glioma Diagnosis and Management Approach with Mental Health Disorders: A MarketScan Analysis 2005-2014.

Low-grade gliomas (LGGs) comprise 13-16% of glial tumors. As survival for LGG patients has been gradually improving, it is essential that the effects of diagnosis and disease progression on mental health be considered. This retrospective cohort study queried the IBM Watson Health MarketScan® Database to describe the incidence and prevalence of mental health disorders (MHDs) among LGG patients and identify associated risk factors. Among the 20,432 LGG patients identified, 12,436 (60.9%) had at least one MHD. Of those who never had a prior MHD, as documented in the claims record, 1915 (16.7%) had their first, newly diagnosed MHD within 12 months after LGG diagnosis. Patients who were female (odds ratio (OR), 1.14, 95% confidence intervals (CI), 1.03-1.26), aged 35-44 (OR, 1.20, 95% CI, 1.03-1.39), and experienced glioma-related seizures (OR, 2.19, 95% CI, 1.95-2.47) were significantly associated with MHD incidence. Patients who underwent resection (OR, 2.58, 95% CI, 2.19-3.04) or biopsy (OR, 2.17, 95% CI, 1.68-2.79) were also more likely to develop a MHD compared to patients who did not undergo a first-line surgical treatment. These data support the need for active surveillance, proactive counseling, and management of MHDs in patients with LGG. Impact of surgery on brain networks affecting mood should also be considered.

Risk Factors Associated with ICU-Specific Care in Patients Undergoing Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: Multiple studies suggest routine postoperative intensive care unit (ICUs) stays in presumed high-risk neurosurgical procedures may be unnecessary. Our objective was to evaluate the risk factors associated with ICU-specific needs in patients undergoing elective endovascular treatment of unruptured intracranial aneurysms. METHODS: A retrospective review of consecutive patients undergoing elective endovascular treatment of unruptured aneurysms was performed between January 2010 and January 2020 in a single academic medical center. Patient demographic information, aneurysm and treatment characteristics, intraoperative and postoperative complications, as well as ICU-specific needs, were abstracted. The primary outcome was ICU-specific needs. RESULTS: A total of 382 patient encounters in 344 unique patients were abstracted. 13.6% (52 of 382) of patient encounters had an ICU-specific need. Multivariate analysis revealed that age [adjusted odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.07, p = 0.03], procedure duration greater 200 min (adjusted OR 2.75, 95% CI 1.34-5.88, p = 0.007), and any intraoperative complication (adjusted OR 20.41, CI 7.97-56.57, p < 0.001) were independent predictors of postoperative ICU-specific needs. The majority of ICU-specific needs (94%, 49 of 52) occurred within 6 h of surgery. CONCLUSIONS: Our results show that age, procedure duration greater than or equal to 200 min, and intraoperative complication were independent predictors of postoperative ICU-specific needs in patients presenting for elective endovascular treatment of unruptured intracranial aneurysms. The majority of ICU-specific needs and associated complications occurred in the immediate postoperative period. This data can be used to help decide the appropriate postoperative level of care in this patient population.

Balloon-Assisted Roadmap Technique to Enable Flow Diversion of a High-Flow Direct Carotid-Cavernous Fistula.

BACKGROUND: The use of flow diverters as a first-line treatment for direct carotid cavernous fistula (CCF) is a relatively new approach in the neurointerventional field which allows obliteration of the fistula with less mass effect from coils in the cavernous sinus. Safe and successful deployment of a flow diverter requires adequate imaging of the parent vessel, which may be challenging in the setting of high-flow CCF without antegrade flow. OBJECTIVE: To facilitate adequate parent vessel imaging in the setting of high-flow CCF to enable the safe development of a flow diverter device. METHODS: Here we present the case of a patient with delayed presentation of post-traumatic direct CCF after a motor vehicle accident, with no antegrade flow past the fistulous connection. We used temporary balloon occlusion of the fistulous connection to enable road-map imaging of the parent vessel and flow-diverter placement. "Drag and drop" device opening in the middle cerebral artery facilitated better deployment of the flow-diverter against retrograde cavernous flow through the fistula. RESULTS: Temporary balloon occlusion of the fistulous connection was used to acquire a roadmap to facilitate safe deployment of a flow diverter and subsequent treatment of the CCF with transvenous coil embolization, with complete resolution of symptoms. CONCLUSION: Balloon-assisted roadmap use is a novel means of visualizing the parent vessel in direct CCF to facilitate safe flow diverter deployment.

VEGF and Immune Checkpoint Inhibition for Prevention of Brain Metastases: Systematic Review and Meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the role of VEGF inhibitors and immune checkpoint inhibitors (ICIs) in preventing the development of brain metastasis (BMs). METHODS: We searched MEDLINE, EMBASE, Cochrane Database, Google Scholar between January 1, 2000 and June 1, 2020. Included studies were randomized controlled trials (RCTs) of adults with systemic cancer which reported incidence of BMs treated with and without VEGF inhibitors, and observational studies of adults with systemic cancer which reported incidence of BMs treated with and without ICIs (there were no RCTs addressing the ICI question). Pooled relative risks (RR) were computed utilizing a binary random-effects model. RESULTS: A search for VEGF and incidence of new BMs revealed 7 studies (6212 patients with breast, colon and non-small cell lung cancer). Meta-analysis showed a lower incidence of new BMs compared to control (RR 0.71, 95% CI: 0.56-0.89, p=0.003). A search for ICIs and incidence of new BMs yielded 8 studies (732 patients with non-small cell lung cancer or metastatic melanoma) where ICIs were used as an adjunct to radiosurgery. Meta-analysis showed a lower incidence of out-of-treatment-field BMs with ICI inhibitors compared to controls at 1 year (RR 0.65, 95% CI: 0.49-0.88, p=0.005). The overall GRADE score for the evidence evaluating the role of bevacizumab and immune checkpoint inhibitors was high and moderate, respectively. CONCLUSION: VEGF and immune checkpoint inhibitors may have a role in prophylaxis against brain metastases in patients with solid tumors.

Aneurysmal and arteriovenous malformation hemorrhage during pregnancy: An update on the epidemiology, risk factors and prognosis.

INTRODUCTION: Intracranial hemorrhage (ICH) is a devastating condition with a high rate of morbidity and mortality. Aneurysm or arteriovenous malformation (AVM) rupture are two common etiologies leading to ICH. Here we provide an update on ICH during pregnancy with a focus on those caused by aneurysm or AVM rupture. METHODS: Here we systematically review 25 studies reported in the literature to provide an update on ICH during pregnancy focusing on aneurysm or AVM rupture. We also reviewed the prognosis of ICH during puerperium. RESULTS: Discrepancies exist between studies supporting or refuting the hypothesis of a higher rate of ICH during pregnancy, obscuring the overall rate of aneurysm and AVM rupture in pregnant ICH patients. However, risk factors such as maternal age and hypertension have shown to increase the frequency of ICH in pregnant patients. We also show increased morbidity and mortality in patients suffering from preeclampsia/eclampsia. DISCUSSION: ICH is rare, but the various studies demonstrating its increased frequency, morbidity, and mortality during pregnancy should raise our awareness of this condition. The management and treatment decisions for a pregnant ICH patient should follow the same principles as nonpregnant patients, but with the knowledge that not all medications are appropriate for use in the pregnant patient. Although there seems to be a higher frequency of AVM rupture, further research must be conducted in order to fully determine the effects of pregnancy on aneurysm and AVM ruptures.