Clinically Asymptomatic Hemorrhagic Conversion Is Associated with Need for Inpatient Rehabilitation After Mechanical Thrombectomy for Anterior Circulation Ischemic Stroke.

BACKGROUND: Hemorrhagic conversion (HC) is a known complication after acute ischemic stroke (AIS) in patients undergoing mechanical thrombectomy (MT). Although symptomatic HC has been shown to lead to poor neurologic outcomes, the effect of asymptomatic HC (aHC) is unclear. This study aims to identify predictors of aHC and to determine the short-term outcomes. METHODS: This is a single-institution retrospective study of patients with anterior circulation stroke (AIS) who underwent MT between January 2016 and September 2022. Radiographic HC was identified on postoperative imaging. Asymptomatic hemorrhage was defined as no acute neurologic decline attributable to imaging findings. Baseline characteristics, technical aspects, and outcomes were compared between aHC and no-HC groups. Logistic regression and multivariate analysis were performed. RESULTS: A total of 615 patients underwent MT for AIS, of whom 496 met the inclusion criteria. A total of 235 patients (47.4%) had evidence of aHC. Diabetes mellitus (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.06-2.41; P = 0.03), hyperglycemia (OR, 1.01; 95% CI, 1.00-1.01; P = 0.002), greater number of passes (OR, 1.14; 95% CI, 1.00-1.31; P = 0.05), and longer time to reperfusion (OR, 1.02; 95% CI, 1.00-1.05; P = 0.05) were associated with aHC. Patients with aHC were significantly more likely to require rehabilitation, whereas those without HC were more likely to be discharged home (P < 0.001). There were no significant differences in long-term outcomes. CONCLUSIONS: HC occurred in up to half of patients who underwent MT for AIS, most of whom were clinically asymptomatic. Despite clinical stability, aHC was significantly associated with a greater need for inpatient rehabilitation. Predictors of aHC included hyperglycemia and a longer time to reperfusion.

Association of socioeconomic status with the management outcome of unruptured intracranial arteriovenous malformation.

OBJECTIVE: The longitudinal management of unruptured brain arteriovenous malformation (bAVM) is crucial. To date, no study in the United States has evaluated the impact of socioeconomic status (SES) on bAVM outcome. Herein, the authors aimed to clarify the impact of SES, as indicated by the area deprivation index (ADI), on bAVM outcome. METHODS: A retrospective analysis of an institutional bAVM database was conducted. Non-hereditary hemorrhagic telangiectasia patients with a single unruptured bAVM in the period from 1990 to 2021 were included in the analysis. The ADI was categorized as low (ADI ≤ 15th percentile), mid (15th percentile < ADI < 85th percentile), and high (ADI ≥ 85th percentile), with a low ADI indicating the most advantaged group. Patient baseline and follow-up data were analyzed. The primary outcome of interest was nonindependence (modified Rankin Scale [mRS] score > 2) at the last follow-up. A multivariable logistic regression model was performed. RESULTS: A total of 589 patients with unruptured bAVMs were included in the study. The mean patient age at diagnosis was 37.2 years, and 283 patients (48.0%) were male. Of the bAVMs, 238 (40.4%) had a low Spetzler-Martin grade (SMG < III), 194 (32.9%) had a moderate grade (SMG III), and 157 (26.7%) had a high grade (SMG > III). Sixty-nine patients (11.7%) were in the low-ADI group, 476 (80.8%) in the mid-ADI group, and 44 (7.5%) in high-ADI group. Increasing age (OR 1.02, 95% CI 1.01-1.04, p < 0.001), poor baseline mRS score (OR 3.27, 95% CI 1.32-7.88, p = 0.008), treatment with surgery plus radiosurgery with or without embolization (OR 3.21, 95% CI 1.03-9.81, p = 0.041), mid SMG (OR 1.94, 95% CI 1.11-3.44, p = 0.021), high SMG (OR 2.08, 95% CI 1.13-3.88, p = 0.020), longer follow-up (OR 1.05, 95% CI 1.03-1.08, p < 0.001), and mid ADI (OR 3.08, 95% CI 1.34-8.39, p = 0.015) were significantly associated with a poor outcome. A high ADI tended toward a poor outcome (OR 2.93, 95% CI 0.92-9.88, p = 0.071). Eventual obliteration of a bAVM was the only protective predictor of poor outcome (OR 0.55, 95% CI 0.30-0.98, p = 0.046). CONCLUSIONS: This study revealed that relatively disadvantaged patients with unruptured bAVMs are more likely to experience nonindependent outcomes at the last follow-up, after adjusting for confounding variables. An emphasis on social support may be beneficial for patients with a lower SES.

Management outcomes of peripontine arteriovenous malformation patients presenting with trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia as the presenting symptom of brain arteriovenous malformation (bAVM) has been rarely reported. Treatment of reported cases has been skewed toward surgery for these scarce, deeply located bAVMs. Here, the authors report their management and outcomes of bAVM patients presenting with ipsilateral trigeminal neuralgia (TN) at their institution. METHODS: This is a retrospective cohort study. The authors' institutional bAVM database was queried for non-hereditary hemorrhagic telangiectasia bAVMs in pontine, cistern, brainstem, trigeminal nerve, or tentorial locations. Patients with complete data were included in a search for trigeminal neuralgia or "facial pain" as the presenting symptom with TN being on the same side as the bAVM. Demographics, TN and bAVM characteristics, management strategies, and outcomes of bAVM and TN management were analyzed. RESULTS: Fifty-seven peripontine bAVMs were identified; 8 (14.0%) of these bAVMs were discovered because of ipsilateral TN, including 4 patients (50%) with facial pain in the V2 distribution. Five patients (62.5%) were treated with carbamazepine as the initial medical therapy, 2 (25%) underwent multiple rhizotomies, and 1 (12.5%) underwent microvascular decompression. None of the patients with TN-associated bAVMs presented with hemorrhage, compared with 25 patients (51%) with bAVMs that were not associated with TN (p < 0.01). TN-associated bAVMs were overall smaller than non-TN-associated bAVMs, but the difference was not statistically significant (1.71 cm vs 2.22 cm, p = 0.117), and the Spetzler-Martin grades were similar. Six patients (75%) underwent radiosurgery to the bAVM (mean dose 1800 cGy, mean target volume 0.563 cm3) and had complete resolution of TN symptoms (100%). The mean time from radiosurgery to TN resolution was 193 (range 21-360) days, and 83.3% of treated TN-associated bAVMs were obliterated via radiosurgery. Two patients (12.5%) were recommended for conservative management, with one undergoing subsequent rhizotomies and another patient died of hemorrhage during follow-up. CONCLUSIONS: TN-associated bAVM is a rare condition with limited evidence for management guidance. Radiosurgery can be safe and effective in achieving durable TN control in patients with TN-associated bAVMs. Despite their deep location and unruptured presentation, obliteration can reach 83.3% with radiosurgery.

The Natural History of Hemorrhage in Brain Arteriovenous Malformations-Poisson Regression Analysis of 1066 Patients in a Single Institution.

BACKGROUND AND OBJECTIVES: Natural history of hemorrhage in brain arteriovenous malformations (bAVM) is reported at 2%-4% per year. Published studies using survival analysis fail to account for recurrent hemorrhagic events. In this study, we present a large, single institution series to elucidate the natural history of bAVM using multivariable Poisson regression. METHODS: This is a retrospective cohort study. All patients with bAVM seen at our institution from 1990 to 2021 were included. Hemorrhages after detection of bAVM during the untreated interval were recorded. Natural history of hemorrhage was calculated by dividing number of hemorrhages by untreated interval. The frequency of hemorrhages followed a Poisson distribution. Multivariable Poisson regression with an offset variable of untreated interval in patient-years was constructed. Model selection was through a stepwise Akaike information criterion method. Stratified hemorrhagic rate was presented using different combinations of significant factors. RESULTS: A total of 1066 patients with nonhereditary hemorrhagic telangiectasia harboring a single bAVM were included. Ninety (8.44%) patients had 101 hemorrhages during an untreated interval of 3596.3344 patient-years, translating to an overall hemorrhagic rate of 2.81% per year. Significant factors increasing hemorrhage risk included ruptured presentation ( P < .001), increasing age ( P < .001), female sex ( P = .043), and deep location ( P = .040). Adult male patients with ruptured presentation and deep bAVMs sustained the highest annual risk at 10.81%, whereas no hemorrhages occurred in unruptured pediatric male patients or ruptured pediatric (younger than 18 years) male patients with superficial bAVMs. CONCLUSION: Hemorrhage after bAVM detection occurs in 8.41% of all patients, and the rate averages 2.81% per year. However, this risk varies from 0.00% to 10.81% per year depending on various risk factor combinations. Efforts should be made to stratify bAVM hemorrhage rate by risk factors for more precise estimation of bleeding risk if left untreated.

Management and outcome predictors of patients with ruptured deep-seated brain arteriovenous malformations.

OBJECTIVE: Decision-making for the management of ruptured deep-seated brain arteriovenous malformations (bAVMs) is controversial. This study aimed to shed light on the treatment outcomes of patients with ruptured deep-seated bAVMs. METHODS: Data on bAVM patients were retrieved from the authors' institutional database, spanning 1990-2021. The outcomes were annual hemorrhage risk (before and after intervention), number of follow-up hemorrhages, bAVM obliteration, poor modified Rankin Scale (mRS) score (i.e., mRS score > 2), worsened mRS score, and mortality. Multivariable Cox and logistic regression analyses were conducted to determine predictors of time-to-event and categorical outcomes, respectively. RESULTS: Of the 1066 patients in the database with brain bAVM, 177 patients harboring ruptured deep-seated bAVMs were included. The pretreatment annual hemorrhage risk was 8.24%, and the posttreatment risk was lowered to 1.65%. In multivariable Cox regression analysis, a prenidal aneurysm (HR 2.388, 95% CI 1.057-5.398; p = 0.036) was associated with a higher risk of follow-up hemorrhage, while definitive treatment (i.e., either surgery or radiosurgery vs endovascular embolization or conservative management) (HR 0.267, 95% CI 0.118-0.602; p = 0.001) was associated with a lower risk of follow-up hemorrhage. In multivariable logistic regression analysis, Spetzler-Martin grades IV and V (OR 0.404, 95% CI 0.171-0.917; p = 0.033) and brainstem arteriovenous malformation (AVM) (OR 0.325, 95% CI 0.128-0.778; p = 0.014) were associated with lower odds of obliteration, while definitive treatment (OR 8.864, 95% CI 3.604-25.399; p = 0.008) was associated with higher obliteration odds. Controlling for baseline mRS score, cerebellar AVM (OR 0.286, 95% CI 0.098-0.731; p = 0.013) and definitive treatment (OR 0.361, 95% CI 0.160-0.807; p = 0.013) were associated with lower odds of a poor mRS score, and definitive treatment (OR 0.208, 95% CI 0.076-0.553; p = 0.001) was associated with lower odds of a worsened mRS score. Furthermore, smoking (OR 6.068, 95% CI 1.531-25.581; p = 0.01) and definitive treatment (OR 0.101, 95% CI 0.024-0.361; p = 0.007) were associated with higher and lower mortality odds, respectively. CONCLUSIONS: A definitive treatment strategy seems to be beneficial in achieving higher obliteration and lower hemorrhage rates while decreasing the odds of a poor mRS score, worsened mRS score, and mortality. In this category of patients, prenidal aneurysms warrant treatment, and smoking cessation should be encouraged.

Cost-Effectiveness of a Direct-Aspiration First-Pass Technique versus Stent Retriever in Mechanical Thrombectomy.

OBJECTIVE: A direct-aspiration first-pass technique (ADAPT) in mechanical thrombectomy has been described in recent studies as an efficacious strategy compared with using a stent retriever (SR). We sought to evaluate for cost differences of ADAPT technique versus SR as an initial approach. METHODS: We conducted a retrospective analysis of consecutive patients with mechanical thrombectomy at our institution between 2022 and 2023. Patients were grouped into ADAPT with/without SR as a rescue strategy and SR as an initial approach with allowance of concomitant aspiration. Direct cost data (consumables) were obtained. Baseline demographics, stroke metrics, procedure outcomes and cost, and last follow-up outcomes in modified Rankin Scale were compared between 2 groups. RESULTS: Fifty-six patients were included. Thirty-seven (66.1%) underwent ADAPT, with 11 (29.7%) eventually requiring an SR. Mean age was 64.8 years. The average National Institutes of Health Stroke Scale score was 13.2 in the ADAPT group and 14.0 in the SR group (P = 0.68), with a similar proportion of tissue plasminogen activator (P = 0.53), site of occlusion (P = 0.66), and tandem occlusion (P = 0.69) between the groups. Recanalization was achieved in 94.6% of all patients, with an average of 1.9 passes, 89.3% being TICI 2B or above, with no differences between the 2 groups. Significantly lower cost (P < 0.01) was observed in ADAPT ($14,243.4) compared with SR ($19,003.6). Average follow-up duration was 180.2 days, with mortality of 23.2%. At last follow-up, 55.4% remained functionally independent (modified Rankin Scale score <3) with no difference (P = 0.56) between the ADAPT (59.5%) and SR (47.4%) groups. CONCLUSIONS: Outcomes were comparable between the ADAPT and SR groups. ADAPT reduced procedural consumables cost by approximately $5000 (25%), even if stent retrievers were allowed to be used for rescue. Establishing ADPAT as initial approach may bring significant direct cost savings while obtaining similar outcomes.

Racial disparities in functional outcomes following mechanical thrombectomy in a cohort of patients with ischemic stroke.

BACKGROUND: Non-Hispanic Black (NHB) patients experience increased prevalence of stroke risk factors and stroke incidence compared with non-Hispanic White (NHW) patients. However, little is known about >90-day post-stroke functional outcomes following mechanical thrombectomy. OBJECTIVE: To describe patient characteristics, evaluate stroke risk factors, and analyze the adjusted impact of race on long-term functional outcomes to better identify and limit sources of disparity in post-stroke care. METHODS: We retrospectively reviewed 326 patients with ischemic stroke who underwent thrombectomy at two centers between 2019 and 2022. Race was self-reported as NHB, NHW, or non-Hispanic Other. Stroke risk factors, insurance status, procedural parameters, and post-stroke functional outcomes were collected. Good outcomes were defined as modified Rankin Scale score ≤2 and/or discharge disposition to home/self-care. To assess the impact of race on outcomes at 3-, 6-, and 12-months' follow-up, we performed univariate and multivariate logistic regression. RESULTS: Patients self-identified as NHB (42%), NHW (53%), or Other (5%). 177 (54.3%) patients were female; the median (IQR) age was 67.5 (59-77) years. The median (IQR) National Institutes of Health Stroke Scale score was 15 (10-20). On univariate analysis, NHB patients were more likely to have poor short- and long-term functional outcomes, which persisted on multivariate analysis as significant at 3 and 6 months but not at 12 months (3 months: OR=2.115, P=0.04; 6 months: OR=2.423, P=0.048; 12 months: OR=2.187, P=0.15). NHB patients were also more likely to be discharged to rehabilitation or hospice/death than NHW patients after adjusting for confounders (OR=1.940, P=0.04). CONCLUSIONS: NHB patients undergoing thrombectomy for ischemic stroke experience worse 3- and 6-month functional outcomes than NHW patients after adjusting for confounders. Interestingly, this disparity was not detected at 12 months. Future research should focus on identifying social determinants in the short-term post-stroke recovery period to improve parity in stroke care.

Endovascular Thrombectomy versus Endovascular Thrombectomy Preceded by Intravenous Thrombolysis: A Systematic Review and Meta-Analysis.

BACKGROUND: Randomized controlled trials comparing endovascular thrombectomy (EVT) versus EVT preceded by intravenous thrombolysis (EVT + IVT) for acute ischemic stroke due to large artery occlusion remain controversial. This systematic review and meta-analysis seek to compare these 2 modalities. METHODS: Online Protocol is available at PROSPERO (york.ac.uk) (registration# CRD42022357506). MEDLINE, PubMed, and Embase were searched. The primary outcome was 90-day modified Rankin scale (mRS) ≤2. Secondary outcomes were 90-day mRS ≤1, 90-day mean mRS, National Institutes of Health Stroke Scale (NIHSS) at 1-3 and 3-7 days, 90-day Barthel Index, 90-day EQ-5D-5L (EuroQoL Group 5-Dimension 5-Level), the volume of infarction (mL), successful reperfusion, complete reperfusion, recanalization, 90-day mortality, any intracranial hemorrhage (ICH), symptomatic ICH, embolization in new territory, new infarction, puncture site complications, vessel dissection, and contrast extravasation. The certainty in the evidence was determined by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: Six randomized controlled trials yielding 2332 patients were included, of which 1163 and 1169 underwent EVT and EVT + IVT, respectively. The relative risk (RR) of 90-day mRS ≤2 was similar between the groups (RR = 0.96[0.88, 1.04]; P = 0.28). EVT was non-inferior to EVT + IVT because the lower bond of 95% confidence interval of the risk difference (RD = -0.02 [-0.06, 0.02]; P = 0.36) exceeded the -0.1 non-inferiority margin. The certainty in the evidence was high. The RR of successful reperfusion (RR = 0.96 [0.93, 0.99]; P = 0.006), any ICH (RR = 0.87 [0.77, 0.98]; P = 0.02), and puncture site complications (RR = 0.47 [0.25, 0.88]; P = 0.02) were lower with EVT. For EVT + IVT, the number needed to treat for successful reperfusion was 25, and the number needed to harm for any ICH was 20. The 2 groups were similar in other outcomes. CONCLUSION: EVT is non-inferior to EVT + IVT. In centers capable of both EVT and IVT, if timely EVT is feasible, it is reasonable to skip bridging IVT and keep rescue thrombolysis at the discretion of the interventionist for patients presenting within 4.5 hours of anterior ischemic stroke.

No Delayed Ruptures on Long-Term Follow-Up of a Case Series of Persistently Filling Saccular Internal Carotid Artery Aneurysms After Flow Diversion With the Pipeline Embolization Device.

BACKGROUND AND OBJECTIVES: Flow diversion of intracranial aneurysms results in high occlusion rates. However, 10% to 20% remain persistently filling at 1 year. Often, these are retreated, but benefits of retreatment are not well established. A better understanding of the long-term rupture risk of persistently filling aneurysms after flow diversion is needed. METHODS: Our institutional database of 974 flow diversion cases was queried for persistently filling saccular aneurysms of the clinoidal, ophthalmic, and communicating segments of the internal carotid artery treated with the pipeline embolization device (PED, Medtronic). Persistent filling was defined as continued flow into the aneurysm on 1 year catheter angiogram. The clinical record was queried for retreatments and delayed ruptures. Clinical follow-up was required for at least 2 years. RESULTS: Ninety-four persistent aneurysms were identified. The average untreated aneurysm size was 5.6 mm. A branch vessel originated separately in 55% of cases from the body of the aneurysm in 10.6% of cases and from the neck in 34% of cases. Eighteen percent of aneurysms demonstrated >95% filling at 1 year, and 61% were filling 5% to 95% of their original size. The mean follow-up time was 4.9 years, including 41 cases with >5 years. No retreatment was undertaken in 91.5% of aneurysms. There were no cases of delayed subarachnoid hemorrhage. CONCLUSION: Among saccular internal carotid artery aneurysms treated with PED that demonstrated persistent aneurysm filling at 1 year, there were no instances of delayed rupture on long-term follow-up. These data suggest that observation may be appropriate for continued aneurysm filling at least in the first several years after PED placement.

Surgery or Endovascular Treatment in Patients with Anterior Communicating Artery Aneurysm: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Although randomized controlled trials have compared surgery versus endovascular treatment for intracranial aneurysms, the literature is sparse in terms of subgroup analysis for anterior communicating artery (ACoA) aneurysm management. This systematic review and meta-analysis sought to compare surgical versus endovascular treatment for ACoA aneurysms. METHODS: Medline, PubMed, and Embase were searched from inception to December 12, 2022. Primary outcomes were post-treatment modified Rankin Scale (mRS) >2 and mortality. Secondary outcomes were aneurysm obliteration, retreatment and recurrence, rebleeding, technical failure, vessel rupture, aneurysmal subarachnoid hemorrhage-related hydrocephalus, symptomatic vasospasm, and stroke. RESULTS: Eighteen studies yielded 2368 patients, from which 1196 (50.5%) and 1172 (49.4%) patients underwent surgery and endovascular treatment, respectively. The odds ratio (OR) of mortality was similar in total (OR = 0.92 [0.63-1.37], P = 0.69), ruptured (OR = 0.92 [0.62-1.36], P = 0.66), and unruptured cohorts (OR = 1.58 [0.06-39.60], P = 0.78). The OR of mRS > 2 was similar in total (OR = 0.75 [0.50-1.13], P = 0.17), ruptured (OR = 0.77 [0.49-1.20], P = 0.25), and unruptured cohorts (OR = 0.64 [0.21-1.96], P = 0.44). The OR of obliteration was higher with surgery in the total (OR = 2.52 [1.49-4.27], P = 0.0008) and ruptured cohorts (OR = 2.61 [1.33-5.10], P = 0.005) and unruptured group (OR = 3.46 [1.30-9.20], P = 0.01). The OR of retreatment was lower with surgery in the total (OR = 0.37 [0.17-0.76], P = 0.007) and ruptured cohorts (OR = 0.31 [0.11-0.89], P = 0.03), thought it was similar in the unruptured group (OR = 0.51 [0.08-3.03], P = 0.46). The OR of recurrence was lower with surgery in the total (OR = 0.22 [0.10, 0.47], P = 0.0001), ruptured (OR = 0.16 [0.03, 0.90], P = 0.04), and mixed (un) ruptured cohorts (OR = 0.22 [0.09-0.53], P = 0.0009). The OR of rebleeding in ruptured group was similar (OR = 0.66 [0.29-1.52], P = 0.33). The ORs of other outcomes were similar. CONCLUSIONS: ACoA aneurysms may be safely treated with either surgery or endovascular treatment, although microsurgical clipping demonstrates higher obliteration rates and lower rates of retreatment and recurrence.

Microsurgery Versus Stereotactic Radiosurgery for Treatment of Patients With Brain Arteriovenous Malformation: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment decision-making for brain arteriovenous malformations (bAVMs) with microsurgery or stereotactic radiosurgery (SRS) is controversial. OBJECTIVE: To conduct a systematic review and meta-analysis to compare microsurgery vs SRS for bAVMs. METHOD: Medline and PubMed were searched from inception to June 21, 2022. The primary outcomes were obliteration and follow-up hemorrhage, and secondary outcomes were permanent neurological deficit, worsened modified Rankin scale (mRS), follow-up mRS > 2, and mortality. The GRADE approach was used for grading the level of evidence. RESULTS: Eight studies were included, which yielded 817 patients, of which 432 (52.8%) and 385 (47.1%) patients underwent microsurgery and SRS, respectively. Two cohorts were comparable in age, sex, Spetzler-Martin grade, nidus size, location, deep venous drainage, eloquence, and follow-up. In the microsurgery group, the odds ratio (OR) of obliteration was higher (OR = 18.51 [11.05, 31.01], P < .000001, evidence: high) and the hazard ratio of follow-up hemorrhage was lower (hazard ratio = 0.47 [0.23, 0.97], P = .04, evidence: moderate). The OR of permanent neurological deficit was higher with microsurgery (OR = 2.85 [1.63, 4.97], P = .0002, evidence: low), whereas the OR of worsened mRS (OR = 1.24 [0.65, 2.38], P = .52, evidence: moderate), follow-up mRS > 2 (OR = 0.78 [0.36, 1.7], P = .53, evidence: moderate), and mortality (OR = 1.17 [0.41, 3.3], P = .77, evidence: moderate) were comparable between the groups. CONCLUSION: Microsurgery was superior at obliterating bAVMs and preventing further hemorrhage. Despite a higher rate of postoperative neurological deficit with microsurgery, functional status and mortality were comparable with patients who underwent SRS. Microsurgery should remain a first-line consideration for bAVMs, with SRS reserved for inaccessible locations, highly eloquent areas, and medically high-risk or unwilling patients.

Sacrifice or preserve the superior petrosal vein in microvascular decompression surgery: a systematic review and meta-analysis.

OBJECTIVE: In microvascular decompression (MVD) surgery through the retrosigmoid approach, the surgeon may have to sacrifice the superior petrosal vein (SPV). However, this is a controversial maneuver. To date, high-level evidence comparing the operative outcomes of patients who underwent MVD with and without SPV sacrifice is lacking. Therefore, this study sought to bridge this gap. METHODS: The authors searched the Medline and PubMed databases with appropriate Medical Subject Heading (MeSH) terms and keywords. The primary outcome was vascular-related complications; secondary outcomes were new neurological deficit, cerebrospinal fluid (CSF) leak, and neuralgia relief. The pooled proportions of outcomes and OR (95% CI) for categorical data were calculated by using the logit transformation and Mantel-Haenszel methods, respectively. RESULTS: Six studies yielding 1143 patients were included, of which 618 patients had their SPV sacrificed. The pooled proportion (95% CI) values were 3.82 (0.87-15.17) for vascular-related complications, 3.64 (1.0-12.42) for new neurological deficits, 2.85 (1.21-6.58) for CSF leaks, and 88.90 (84.90-91.94) for neuralgia relief. The meta-analysis concluded that, whether the surgeon sacrificed or preserved the SPV, the odds were similar for vascular-related complications (2.5% vs 1.5%, OR [95% CI] 1.01 [0.33-3.09], p = 0.99), new neurological deficits (1.2% vs 2.8%, OR [95% CI] 0.55 [0.18-1.66], p = 0.29), CSF leak (3.1% vs 2.1%, OR [95% CI] 1.16 [0.46-2.94], p = 0.75), and neuralgia relief (86.6% vs 87%, OR [95% CI] 0.96 [0.62-1.49], p = 0.84). CONCLUSIONS: SPV sacrifice is as safe as SPV preservation. The authors recommend intentional SPV sacrifice when gentle retraction fails to enhance surgical field visualization and if the surgeon encounters SPV-related neurovascular conflict and/or anticipates impeding SPV-related bleeding.

Absence of Ischemic Injury after Sacrificing the Superior Petrosal Vein during Microvascular Decompression.

BACKGROUND: Sacrificing the superior petrosal vein (SPV) is controversial during a microvascular decompression (MVD). There have been multiple reports of complications including life-threatening brainstem infarction and cerebellar edema. OBJECTIVE: To analyze the potential for vascular complications when the SPV is sacrificed during an MVD. METHODS: Retrospective chart review was performed to identify all MVDs for trigeminal neuralgia and hemifacial spasm from 2007 to 2018 at 1 institution. Cases with ≥1 mo of follow-up were included and SPV sacrifice was noted. The primary outcome was complications related to SPV sacrifice including sinus thrombosis, cerebellar edema, and midbrain or pontine infarction. Imaging was used to confirm all potential vascular complications noted in medical records. Fisher's exact test and unpaired t-tests were used to compare between groups. RESULTS: A total of 732 MVD cases were identified and 592 met inclusion criteria with an average follow-up of 11.8 ± 16.4 mo and a male-to-female ratio of 1:2.2. The SPV was sacrificed in 217 cases and retained in 375 cases. No SPV-related vascular complications were found in this study. Two unrelated cases of vascular complications were identified and both were in the nonsacrificed group. One case involved cerebellar bleeding while the other was an ipsilateral transverse sinus thrombosis that was present preoperatively. CONCLUSION: In MVDs, there is no difference in the rate of vascular complications when the SPV is sacrificed compared to preserved. To best visualize a cranial nerve and optimize safe decompression, surgeons should feel free to sacrifice the SPV.

Combination anti-CXCR4 and anti-PD-1 immunotherapy provides survival benefit in glioblastoma through immune cell modulation of tumor microenvironment.

BACKGROUND: Emerging evidence suggests that myeloid cells play a critical role in glioblastoma (GBM) immunosuppression. Disappointing results of recent checkpoint inhibitor trials suggest that combination immunotherapy with alternative agents could be fruitful in overcoming immunosuppression. Overexpression of chemokine receptor CXCR4 is associated with poor prognosis in GBM. We investigate the treatment effects of combination immunotherapy with anti-PD-1 and anti-CXCR4 in a murine glioma model. METHODS: C57BL/6 mice were implanted with GL261-Luc+ glioma cells and randomized into 4 arms: (1) control (2) anti-PD-1 (3) anti-CXCR4, and (4) anti-PD-1 and anti-CXCR4 therapy. Overall survival and median survival were assessed. Cell populations were assessed by flow cytometry. RESULTS: Combination therapy conferred a significant survival benefit compared to control and monotherapy arms. Mice that received combination therapy demonstrated immune memory and decreased populations of immunosuppressive tumor-infiltrating leukocytes, such as monocytic myeloid-derived suppressor cells and microglia within the brain. Furthermore, combination therapy improved CD4+/CD8+ ratios in the brain as well as contributed to increased levels of pro-inflammatory cytokines. CONCLUSIONS: Anti-CXCR4 and anti-PD-1 combination immunotherapy modulates tumor-infiltrating populations of the glioma microenvironment. Targeting myeloid cells with anti-CXCR4 facilitates anti-PD-1 to promote an antitumor immune response and improved survival rates.

Retrosigmoid approach for glycerin rhizotomy in the treatment of trigeminal neuralgia without overt arterial compression: updated case series.

OBJECTIVE: Trigeminal neuralgia (TN) is a neuropathic pain disorder characterized by severe, lancinating facial pain that is commonly treated with neuropathic medication, percutaneous rhizotomy, and/or microvascular decompression (MVD). Patients who are not found to have distinct arterial compression during MVD present a management challenge. In 2013, the authors reported on a small case series of such patients in whom glycerin was injected intraoperatively into the cisternal segment of the trigeminal nerve. The objective of the authors' present study was to report their updated experience with this technique to further validate this novel approach. METHODS: The authors performed a retrospective analysis of data obtained in patients in whom glycerin was directly injected into the inferior third of the cisternal portion of the trigeminal nerve. Seventy-four patients, including 14 patients from the authors' prior study, were identified, and demographic information, intraoperative findings, postoperative course, and complications were recorded. Fisher's exact test, unpaired t-tests, and Kaplan-Meier survival curves using Mantel log-rank test were used to compare the 74 patients with a cohort of 476 patients who received standard MVD by the same surgeon. RESULTS: The 74 patients who underwent MVD and glycerin injection had an average follow-up of 19.1 ± 18.0 months, and the male/female ratio was 1:2.9. In 33 patients (44.6%), a previous intervention for TN had failed. On average, patients had an improvement in the Barrow Neurological Institute Pain Intensity score from 4.1 ± 0.4 before surgery to 2.1 ± 1.2 after surgery. Pain improvement after the surgery was documented in 95.9% of patients. Thirteen patients (17.6%) developed burning pain following surgery. Five patients developed complications (6.7%), including incisional infection, facial palsy, CSF leak, and hearing deficit, all of which were minor. CONCLUSIONS: Intraoperative injection of glycerin into the trigeminal nerve is a generally safe and potentially effective treatment for TN when no distinct site of arterial compression is identified during surgery or when decompression of the nerve is deemed to be inadequate.

The Effect of Flow-Related Aneurysms on Hemorrhagic Risk of Intracranial Arteriovenous Malformations.

BACKGROUND: Previous reports indicated an association between hemorrhagic presentation and flow-related aneurysms in arteriovenous malformation (AVM) patients. However, it remains unclear whether these flow-related aneurysms result in the hemorrhage of AVM. OBJECTIVE: To characterize this hemorrhage risk using our institutional experience over 25 yr. METHODS: We retrospectively reviewed records of patients at our institution diagnosed with AVM from 1990 to 2015. Patients without associated aneurysms (AVM only) and those with flow-related aneurysms (AVM-FA) were compared. Those with intranidal or unrelated aneurysms were excluded. Annual risk of AVM-related hemorrhage was calculated using the birth-to-treatment approach and compared using Poisson rate ratio test. RESULTS: Among 526 patients, there were 457 AVM only patients and 69 with flow-related aneurysms. AVM-FA patients were older (P = .005). AVMs with flow-related aneurysms were more likely located in the cerebellar vermis and hemispheres (P = .023 and .001, respectively). Presence of flow-related aneurysms increased the risk of presentation with subarachnoid hemorrhage (P < .001). Interestingly, no significant differences in presenting hemorrhage due to AVM rupture were found (P > .356). The majority of aneurysms were untreated (69.5%), and only 8 (9.8%) had ruptured presentation. At follow-up (mean = 5.3 yr), patients with flow-related aneurysms were less likely to develop seizures (P = .004). The annual risk of AVM hemorrhage was 1.33% and 1.05% for AVM only patients and AVM-FA patients, respectively (P = .248). CONCLUSION: Despite increased risk of subarachnoid hemorrhage at presentation, there was no increased likelihood of rupture in AVMs with flow-related aneurysms. More studies are warranted, as clarifying the competing risks of AVM vs aneurysm rupture may be critical in determining optimal treatment strategy.

Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system.

Immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) is emerging as an important treatment strategy in a growing list of cancers, yet its clinical benefits are limited to a subset of patients. Further investigation of tumor-intrinsic predictors of response and how extrinsic factors, such as iatrogenic immunosuppression caused by conventional therapies, impact the efficacy of anti-PD-1 therapy are paramount. Given the widespread use of corticosteroids in cancer management and their immunosuppressive nature, this study sought to determine how corticosteroids influence anti-PD-1 responses and whether their effects were dependent on tumor location within the periphery versus central nervous system (CNS), which may have a more limiting immune environment. In well-established anti-PD-1-responsive murine tumor models, corticosteroid therapy resulted in systemic immune effects, including severe and persistent reductions in peripheral CD4+ and CD8 + T cells. Corticosteroid treatment was found to diminish the efficacy of anti-PD-1 therapy in mice bearing peripheral tumors with responses correlating with peripheral CD8/Treg ratio changes. In contrast, in mice bearing intracranial tumors, corticosteroids did not abrogate the benefits conferred by anti-PD-1 therapy. Despite systemic immune changes, anti-PD-1-mediated antitumor immune responses remained intact during corticosteroid treatment in mice bearing intracranial tumors. These findings suggest that anti-PD-1 responses may be differentially impacted by concomitant corticosteroid use depending on tumor location within or outside the CNS. As an immune-specialized site, the CNS may potentially play a protective role against the immunosuppressive effects of corticosteroids, thus sustaining antitumor immune responses mediated by PD-1 blockade.

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM.

The use of inhibitory checkpoint blockade in the management of glioblastoma has been studied in both preclinical and clinical settings. TIGIT is a novel checkpoint inhibitor recently discovered to play a role in cancer immunity. In this study, we sought to determine the effect of anti-PD-1 and anti-TIGIT combination therapy on survival in a murine glioblastoma (GBM) model, and to elucidate the underlying immune mechanisms. Using mice with intracranial GL261-luc+ tumors, we found that TIGIT expression was upregulated on CD8+ and regulatory T cells (Tregs) in the brain compared to draining cervical lymph nodes (CLN) and spleen. We then demonstrated that treatment using anti-PD-1 and anti-TIGIT dual therapy significantly improved survival compared to control and monotherapy groups. The therapeutic effect was correlated with both increased effector T cell function and downregulation of suppressive Tregs and tumor-infiltrating dendritic cells (TIDCs). Clinically, TIGIT expression on tumor-infiltrating lymphocytes was shown to be elevated in patient GBM samples, suggesting that the TIGIT pathway may be a valuable therapeutic target. Expression of the TIGIT ligand, PVR, further portended a poor survival outcome in patients with low-grade glioma. We conclude that anti-TIGIT is an effective treatment strategy against murine GBM when used in combination with anti-PD-1, improving overall survival via modifications of both the T cell and myeloid compartments. Given evidence of PVR expression on human GBM cells, TIGIT presents as a promising immune therapeutic target in the management of these patients.

Ventricular Volume Dynamics During the Development of Adult Chronic Communicating Hydrocephalus in a Rodent Model.

INTRODUCTION: The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood. OBJECTIVE: To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms. METHODS: Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings. RESULTS: There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013). CONCLUSIONS: Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended.

Immediate and Long-Term Outcomes of Microvascular Decompression for Mixed Trigeminal Neuralgia.

BACKGROUND: Classic trigeminal neuralgia (TN) involves sharp, shooting pain in any trigeminal nerve distribution, whereas atypical TN presents with constant aching, numbness, or burning that can appear with classic features, leading to a mixed presentation. Microvascular decompression (MVD) is an effective treatment for classic TN, but its utility in treating mixed TN has been less well studied. METHODS: We retrospectively studied 73 adult patients with mixed TN and 386 patients with classic TN who underwent MVD between December 2007 and October 2016. Recorded variables included demographic data, graded radiologic and intraoperative findings, and graded pain outcomes in the immediate postoperative period (up to 3 months after MVD) and during long-term follow-up. RESULTS: The mean age of the 73 patients with mixed TN was 53.2 years. In terms of immediate postoperative outcomes, 67 patients (91.8%) experienced pain relief including improvement of atypical pain, whereas 6 patients (8.2%) had no pain relief. Having a preexisting pain syndrome (P = 0.001) or distortion of the trigeminal nerve intraoperatively (P = 0.001) was associated with poor surgical outcome in the patients with mixed TN. The mean duration of follow-up was 20.6 months. Forty-four patients (60.3%) developed recurrence of any TN pain. In comparison, 93% of the patients with classic TN experienced pain relief in the immediate postoperative period, and the recurrence rate was 19.9% in these patients. CONCLUSIONS: Patients with mixed TN suffer from both classic and atypical TN symptoms. Following MVD, 91.8% of our patients with mixed TN reported partial or complete pain relief, including improvement of atypical pain, in the immediate postoperative stage, compared with 93% of those with classic TN. Recurrence eventually developed in 60.3% of the patients with mixed TN.