We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all ...meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1 E17K , a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ∼5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive—nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.
BACKGROUND AND PURPOSE—After large-vessel intracranial occlusion, the fate of the ischemic penumbra, and ultimately final infarct volume, largely depends on tissue perfusion. In this study, we ...evaluated whether blood pressure reduction and sustained relative hypotension during endovascular thrombectomy are associated with infarct progression and functional outcome.
METHODS—We identified consecutive patients with large-vessel intracranial occlusion ischemic stroke who underwent mechanical thrombectomy at 2 comprehensive stroke centers. Intraprocedural mean arterial pressure (MAP) was monitored throughout the procedure. ΔMAP was calculated as the difference between admission MAP and lowest MAP during endovascular thrombectomy until recanalization. Sustained hypotension was measured as the area between admission MAP and continuous measurements of intraprocedural MAP (aMAP). Final infarct volume was measured using magnetic resonance imaging at 24 hours, and functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using linear and ordinal multivariable logistic regression.
RESULTS—Three hundred ninety patients (mean age 71±14 years, mean National Institutes of Health Stroke Scale score of 17) were included in the study; of these, 280 (72%) achieved Thrombolysis in Cerebral Infarction 2B/3 reperfusion. Eighty-seven percent of patients experienced MAP reductions during endovascular thrombectomy (mean 31±20 mm Hg). ΔMAP was associated with greater infarct growth (P=0.036) and final infarct volume (P=0.035). Mean ΔMAP among patients with favorable outcomes (modified Rankin Scale score, 0–2) was 20±21 mm Hg compared with 30±24 mm Hg among patients with poor outcome (P=0.002). In the multivariable analysis, ΔMAP was independently associated with higher (worse) modified Rankin Scale scores at discharge (adjusted odds ratio per 10 mm Hg, 1.17; 95% CI, 1.04–1.32; P=0.009) and at 90 days (adjusted odds ratio per 10 mm Hg, 1.22; 95% CI, 1.07–1.38; P=0.003). The association between aMAP and outcome was also significant at discharge (P=0.002) and 90 days (P=0.001).
CONCLUSIONS—Blood pressure reduction before recanalization is associated with larger infarct volumes and worse functional outcomes for patients affected by large-vessel intracranial occlusion stroke. These results underscore the importance of BP management during endovascular thrombectomy and highlight the need for further investigation of blood pressure management after large-vessel intracranial occlusion stroke.
BACKGROUND AND PURPOSE—Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular ...thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds.
METHODS—We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy–derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days.
RESULTS—Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 95% CI, 1.3–2.7 P=0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%, P=0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach.
CONCLUSIONS—Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.
While the benefit of mechanical thrombectomy (MT) for patients with anterior circulation acute ischemic stroke with large-vessel occlusion (AIS-LVO) has been clearly established, difficult vascular ...access may make the intervention impossible or unduly prolonged. In this study, the authors evaluated safety as well as radiographic and functional outcomes in stroke patients treated with MT via direct carotid puncture (DCP) for prohibitive vascular access.
The authors retrospectively studied patients from their prospective AIS-LVO database who underwent attempted MT between 2015 and 2018. Patients with prohibitive vascular access were divided into two groups: 1) aborted MT (abMT) after failed transfemoral access and 2) attempted MT via DCP. Functional outcome was assessed using the modified Rankin Scale at 3 months. Associations with outcome were analyzed using ordinal logistic regression.
Of 352 consecutive patients with anterior circulation AIS-LVO who underwent attempted MT, 37 patients (10.5%) were deemed to have prohibitive vascular access (mean age ± SD 82 ± 11 years, mean National Institutes of Health Stroke Scale NIHSS score 17 ± 5, with females accounting for 75% of the patients). There were 20 patients in the DCP group and 17 in the abMT group. The two groups were well matched for the known predictors of clinical outcome: age, sex, and admission NIHSS score. Direct carotid access was successfully obtained in 19 of 20 patients. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 16 (84%) of 19 patients in the DCP group. Carotid access complications included an inability to catheterize the carotid artery in 1 patient, neck hematomas in 4 patients, non-flow-limiting common carotid artery (CCA) dissections in 2 patients, and a delayed, fatal carotid blowout in 1 patient. The neck hematomas and non-flow-limiting CCA dissections did not require any subsequent interventions and remained clinically silent. Compared with the abMT group, patients in the DCP group had smaller infarct volumes (11 vs 48 ml, p = 0.04), a greater reduction in NIHSS score (-4 vs +2.9, p = 0.03), and better functional outcome (shift analysis for 3-month modified Rankin Scale score: adjusted OR 5.2, 95% CI 1.02-24.5; p = 0.048).
DCP for emergency MT in patients with anterior circulation AIS-LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates, smaller infarct volumes, and improved functional outcome compared with patients with abMT after failed transfemoral access. DCP should be considered in this patient population.
Paravertebral pseudoaneurysms are infrequent following vertebral augmentation but can be difficult to manage due to their proximity to the arterial supply of the spinal cord. Here, we present two ...distinct manifestations of this complication with associated anatomy and management. In the first, a pseudoaneurysm developed following radiofrequency ablation and kyphoplasty at the L2 and L4 levels. Direct puncture embolization initially failed to close the pseudoaneurysm, but stasis was ultimately achieved via trans-arterial embolization. In the second, vertebral augmentation at the T9 and T11-L3 levels was complicated by formation of a pseudoaneurysm fed by a segmental artery and a long paravertebral anastomotic vein. Due to the patient's poor medical status, intervention was not performed. Understanding vertebral arterial anatomy is crucial for preventing and treating vascular injury in vertebral augmentation.
•Pseudoaneurysm formation following vertebral augmentation is rare and difficult to manage due to the atypical location.•Embolization may be performed via direct puncture or a trans-arterial approach, as with pseudoaneurysms in other locations.•Appropriate management hinges on a comprehensive understanding of spinal arterial anatomy.
Background Timely imaging is essential for patients undergoing mechanical thrombectomy (MT). Our objective was to evaluate the safety and feasibility of low‐field portable magnetic resonance imaging ...(pMRI) for bedside evaluation following MT. Methods Patients with suspected large‐vessel occlusion undergoing MT were screened for eligibility. All pMRI examinations were conducted in the standard ferromagnetic environment of the interventional radiology suite. Clinical characteristics, procedural details, and pMRI features were collected. Subsequent high‐field conventional MRI within 72±12 hours was analyzed. If a conventional MRI was not available for comparison, computed tomography within the same time frame was used for validation. Results Twenty‐four patients were included (63% women; median age, 76 years interquartile range, 69–84 years). MT was performed with a median access to revascularization time of 15 minutes (interquartile range, 8–19 minutes), and with a successful outcome as defined by a thrombolysis in cerebral infarction score of ≥2B in 90% of patients. The median time from the end of the procedure to pMRI was 22 minutes (interquartile range, 16–32 minutes). The median pMRI examination time was 30 minutes (interquartile range, 17–33 minutes). Of 23 patients with available subsequent imaging, 9 had infarct progression compared with immediate post‐MT pMRI and 14 patients did not have progression of their infarct volume. There was no adverse event related to the examination. Conclusion Low‐field pMRI is safe and feasible in a post‐MT environment and enables timely identification of ischemic changes in the interventional radiology suite. This approach can facilitate the assessment of baseline infarct burden and may help guide physiological interventions following MT.
INTRODUCTION Prior studies have suggested a predictive value of computed tomography (CT)-based clot characteristics including location on clinical outcome after mechanical thrombectomy (MT) for ...anterior circulation acute ischemic stroke (AIS). This meta-analysis aims to provide an up-to-date evaluation of these characteristics on clinical outcome and recanalization success. METHODS We searched Cochrane Library, Embase, and MEDLINE databases for English articles reporting the effects of CT-based clot characteristics on outcomes after AIS between 2000–2019. The primary outcome was good functional status, as defined by modified Rankin Scale (mRS) ≤ 2 at 90 days. Secondary outcomes were recanalization success, symptomatic intracerebral hemorrhage (sICH), and mortality. The results were pooled with random and fixed effect models. RESULTS 2,933 records were identified through database searches. Of these, 33 studies were included in the qualitative synthesis. Clot burden score, location, distance to ICA terminus, length, volume, and attenuation were independent variables of interest. Of these variables, only clot location contained sufficient quantitative data for meta-analysis. Seven articles enrolling 2,306 patients with data on clot location and dichotomized mRS were identified. These included patients from a total of 8 randomized trials and 12 institutional cohorts. MCA occlusion was associated with a good functional outcome (pooled odds ratio OR: 1.38, 95% confidence interval CI: 1.12-1.70 for M1; pooled OR: 1.74, 95% CI: 1.16-2.62 for M2 and beyond) compared to ICA occlusion. Of the studies with the primary outcome of interest, 4 reported on recanalization outcomes and 3 reported on sICH and mortality. ICA occlusion was associated with increased mortality (pooled OR: 2.23, 95% CI: 1.64-3.04) compared to MCA occlusion. There were no differences in recanalization success and sICH by clot location. CONCLUSION In patients undergoing MT for AIS, ICA compared to MCA clot location as determined by pre-intervention CT angiography is associated with lower odds of good functional outcome and higher odds of mortality. Due to a lack of quantitative data in the published literature, the impact of other clot characteristics on stroke outcomes is better investigated by systematic review.
Abstract only Background and Aims: MRI is critical for diagnosing acute stroke and guiding candidate selection for potential reperfusion therapy. However, rapid stroke evaluation using MRI is often ...dissuaded by the time required for patients to travel to access-controlled, high-field (1.5-3T) systems. Advances in low-field MRI enable the acquisition of clinically valuable images at the bedside. We report neuroimaging in patients presenting to the Emergency Department (ED) with stroke symptoms using a low-field portable MRI (pMRI) device. Methods: A 64mT pMRI device was deployed in the Yale-New Haven Hospital ED from August 2020 to July 2021. Patients presenting as a “Stroke Code” or “Intracranial Hemorrhage Alert” with no MRI contraindications were scanned. Exams were performed at the bedside, in the vicinity of ED room equipment. Research staff acquired imaging via tablet, with images available immediately after acquisition. Sequences obtained and axial scan times (in minutes) included T1-weighted imaging (4:54), T2-weighted imaging (7:03), fluid-attenuated inversion recovery imaging (9:31), and diffusion-weighed imaging with apparent diffusion coefficient mapping (9:04). Patients’ demographic information, hours from the time of patients' last known normal (LKN) to time of scan, and discharge diagnoses (determined from final imaging interpretation) were assessed. Results: pMRI exams were obtained on 54 patients (28 females, 51.9%; median age 71 years, 20-98 years). Discharge diagnoses included ischemic stroke (42.6%) no intracranial abnormality (31.5%), intraparenchymal hemorrhage (7.4%), atherosclerosis (7.4%), tumor (5.6%), subdural hematoma (3.7%), and intraventricular hemorrhage (1.9%). Patient LKN times ranged from 2 to 144 hours (median of 12 hours; 3 patients with no LKN excluded). The pMRI did not interfere with ED equipment and no significant adverse events occurred. Conclusion: We report the use of a pMRI for bedside neuroimaging in the ED. This approach suggests that pMRI may be viable for supporting rapid diagnosis and treatment candidate selection in patients presenting with stroke symptoms to the ED.
Abstract only Background: Endovascular therapy (EVT) has been demonstrated to be beneficial regardless of baseline blood pressure (BP). However, questions concerning optimal BP management during EVT ...remain unanswered. Lowering BP may reduce penumbral perfusion resulting in increased infarct volume and poor outcomes. In this study, we examined the relationship between reductions in intra-procedural BP during EVT and functional outcome. Methods: We prospectively enrolled patients with acute large-vessel occlusion ischemic stroke undergoing EVT at Yale-New Haven Hospital. Baseline BP was measured at the start of EVT and monitored throughout the procedure. Reductions in BP were calculated as the difference between baseline systolic BP (SBP) and lowest SBP during the intervention. In addition, to distinguish between one time SBP reductions and sustained hypotension, we measured the area between baseline SBP and continuous measurements of intra-procedural SBP. Functional outcome was assessed using the modified Rankin scale (mRS) at discharge and 90 days. Associations between BP reduction and outcome were assessed using ordinal logistic regression. Results: 68 patients (mean age 73+/-16.7, 36F, mean NIHSS 17) were included in the study. Mean baseline BP was 152/82 mmHg. The median SBP reduction among patients with favorable outcome (mRS ≤2) was 23 mmHg (IQR 11-52) compared to 54 mmHg (IQR 28-86) in the group with poor outcome (p=0.03). A decrease in SBP from initial levels during EVT was independently associated with an increased likelihood for higher (worse) scores on the mRS at discharge (p=0.02) and 3 months (p=0.03) after adjusting for age and admission NIHSS. Every 10 mmHg reduction in SBP from baseline was associated with a 1.4 fold increase in the odds of an unfavorable outcome at 90 days. Conclusions: BP reduction during EVT may be harmful and lead to worse functional outcomes for patients affected by large-vessel stroke. Even modest, one time reductions in SBP, as frequently occurs during induction of anesthesia, appear to be associated with increased risk for worsened functional status. These results underline the importance of BP management during EVT, and highlight the need for further investigation of active BP management strategies to optimize clinical outcomes.
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