The purpose of this study was to analyze whether treating ruptured intracranial aneurysms within 24 hours of subarachnoid hemorrhage improves clinical outcome.
An 11-year database of consecutive ...ruptured intracranial aneurysms treated with endovascular coiling or craniotomy and clipping was analyzed. Outcome was measured by the modified Rankin Scale at 6 months. Our policy is to treat all cases within 24 hours of subarachnoid hemorrhage. Treatment delays are due to nonclinical logistical factors.
Two hundred thirty cases were coiled or clipped within 24 hours of subarachnoid hemorrhage and 229 at >24 hours. No difference in age, gender, smoking, family history of subarachnoid hemorrhage, aneurysm size, or aneurysm location was found between the groups. Poor World Federation of Neurological Surgeons clinical grade patients were overrepresented in the ultra-early group. Increasing age and higher World Federation of Neurological Surgeons clinical grade were predictors of poor outcome. Eight point zero percent (16 of 199) of cases treated within 24 hours of SAH (ultra-early) were dependent or dead at 6 months compared with 14.4% (30 of 209) of those treated at >24 hours post-SAH (delayed; (χ2, P0.044) corrected. A total of 3.5% of cases coiled within 24 hours were dependent or dead at 6 months compared with 12.5% of cases coiled at 1 to 3 days, an 82% relative risk reduction and a 10.2% absolute risk reduction (χ2, P=0.040). These groups did not differ in age, World Federation of Neurological Surgeons clinical grade, aneurysm size, or aneurysm location.
Treatment of ruptured aneurysms within 24 hours is associated with improved clinical outcomes compared with treatment at >24 hours. The benefit is more pronounced for coiling than clipping.
BACKGROUND AND PURPOSE—Basilar artery occlusion is associated with high risk of disability and mortality. This study aimed to assess the prognostic value of a new radiological scorethe Basilar Artery ...on Computed Tomography Angiography (BATMAN) score.
METHODS—A retrospective analysis of consecutive stroke patients with basilar artery occlusion diagnosed on computed tomographic angiography was performed. BATMAN score is a 10-point computed tomographic angiography–based grading system which incorporates thrombus burden and the presence of collaterals. Reliability was assessed with intraclass coefficient correlation. Good outcome was defined as modified Rankin Scale score of ≤3 at 3 months and successful reperfusion as thrombolysis in cerebral infarction 2b-3. BATMAN score was externally validated and compared with the Posterior Circulation Collateral score.
RESULTS—The derivation cohort included 83 patients with 41 in the validation cohort. In receiver operating characteristic (ROC) analysis, BATMAN score had an area under receiver operating characteristic curve of 0.81 (95% confidence interval CI, 0.7–0.9) in derivation cohort and an area under receiver operating characteristic curve of 0.74 (95% CI, 0.6–0.9) in validation cohort. In logistic regression adjusted for age and clinical severity, BATMAN score of <7 was associated with poor outcome in derivation cohort (odds ratio, 5.5; 95% CI, 1.4–21; P=0.01), in validation cohort (odds ratio, 6.9; 95% CI, 1.4–33; P=0.01), and in endovascular patients, after adjustment for recanalization and time to treatment (odds ratio, 4.8; 95% CI, 1.2–18; P=0.01). BATMAN score of <7 was not associated with recanalization. Interrater agreement was substantial (intraclass coefficient correlation, 0.85; 95% CI, 0.8–0.9). BATMAN score had greater accuracy compared with Posterior Circulation Collateral score (P=0.04).
CONCLUSIONS—The addition of collateral quality to clot burden in BATMAN score seems to improve prognostic accuracy in basilar artery occlusion patients.
Summary
Objective
Endovascular therapy has recently become standard therapy for select patients with acute ischemic stroke. Infarcted brain tissue may undergo hemorrhagic transformation (HT) after ...endovascular therapy. We investigated the association between HT and occurrence of poststroke seizures in patients treated with endovascular therapy.
Methods
Consecutive patients treated with endovascular therapy for acute anterior circulation ischemic stroke were included. HT was assessed with computed tomography/magnetic resonance imaging (CT/MRI) at 24 h after stroke onset. Patients were followed for up to 2 years for seizure occurrence.
Results
A total of 205 (57.1% male) patients were analyzed. Median age was 69 years (interquartile range IQR 57‐78). Among patients with HT, 17.9% (10/56) developed poststroke seizures compared with 4.0% (6/149) among those without HT (hazard ratio HR 5.52; 95% confidence interval CI 2.00‐15.22; P = .001). The association remained significant after adjustment for cortical involvement, baseline National Institutes of Health Stroke Scale score, age and use of intravenous tissue plasminogen activator and clot retrieval (HR 4.85; 95% CI 1.60‐14.76; P = .005). In patients who developed seizures within the follow‐up period, median time to first seizure was 111 days (IQR 28‐369) in patients with HT and 36 days (IQR 0.5‐183) in patients without HT.
Significance
A patient who develops HT following endovascular therapy for acute ischemic stroke had a nearly 5 times higher rate of developing poststroke seizures within 2 years. HT may be used as an imaging biomarker for poststroke seizures.
Introduction
Untreated basilar artery occlusion (BAO) carries 70% mortality. Guidelines recommend thrombectomy with or without thrombolysis.
Aim
We compared Modified Rankin Scores (mRS) at 3 and 12 ...months post thrombectomy to determine benefit of long‐term follow up.
Methods
Retrospective, single centre analysis of BAO thrombectomies between 2015 and 2019. Inclusion criteria were symptomatic BAO on CT angiography, absent early ischemic changes, premorbid independence and intervention within 24 h. All received stroke ward care. Results were analysed with simple statistics and binary logistic regression as appropriate.
Results
Of 82 patients: most were male (61%, 50/82) with median age 68 years (IQR 17 years) and median NIHSS 14 (IQR 15). Median door‐to‐puncture time was 42 min (IQR 72 min). Total deaths were 34.1% (28/82) at 3 months, and 37.8% (31/82) at 12 months. Of 51 patients alive at 12 months: 41% (21/51) had improved mRS, 16% (8/51) had worse mRS and 43% (22/51) had unchanged mRS, compared to 3 months. Improvements to mRS were: one point in 57.1% (14/21), two points in 28.9% (6/21) and three points in 4.8% (1/21). Nursing home admission was avoided in 11.8% (6/51) who improved from mRS4. Increased age was associated with decreased likelihood of reaching the primary outcome OR 0.87, 95% CI 0.76–0.99 (p value = 0.03).
Conclusion
Over a quarter of patients improved beyond 3 months. Future studies should adopt long‐term follow up as primary outcome.
Basilar artery occlusion is generally treated with mechanical thrombectomy; standard follow‐up occurs after 3 months. Longer term follow up at 12 months show that many patients continue to improve thus should not have their neurological fate sealed at 3 months. Future studies should adopt longer‐term 12 month outcomes as the primary end point.
Abstract The mild cognitive impairment (MCI) stage of Alzheimer's disease (AD) may be optimal for clinical trials to test potential treatments for preventing or delaying decline to dementia. However, ...MCI is heterogeneous in that not all cases progress to dementia within the time frame of a trial and some may not have underlying AD pathology. Identifying those MCIs who are most likely to decline during a trial and thus most likely to benefit from treatment will improve trial efficiency and power to detect treatment effects. To this end, using multimodal, imaging-derived, inclusion criteria may be especially beneficial. Here, we present a novel multimodal imaging marker that predicts future cognitive and neural decline from F-18fluorodeoxyglucose positron emission tomography (PET), amyloid florbetapir PET, and structural magnetic resonance imaging, based on a new deep learning algorithm (randomized denoising autoencoder marker, rDAm). Using ADNI2 MCI data, we show that using rDAm as a trial enrichment criterion reduces the required sample estimates by at least five times compared with the no-enrichment regime and leads to smaller trials with high statistical power, compared with existing methods.
BACKGROUND AND PURPOSE—The benefit of endovascular therapy in extended time windows has been demonstrated in patients with anterior circulation large vessel occlusion ischemic stroke and favorable ...imaging profile. We evaluated whether collaterals and thrombus burden influence the associations between revascularization, time-to-treatment, and outcome in endovascular therapy-treated patients with basilar artery occlusion.
METHODS—We retrospectively analyzed clinical and imaging data of consecutive endovascular therapy-treated patients with basilar artery occlusion included in the multicenter Basilar Artery Treatment and Management Collaboration. The BATMAN (Basilar Artery on Computed Tomography Angiography score, which evaluates thrombus burden and collaterals) and the PC-CS (Posterior Circulation Collateral score, which evaluates collaterals) were assessed on computed tomography angiography, blinded to clinical outcome. Good outcome was defined as modified Rankin Scale score of ≤3 within 3 months; revascularization (successful reperfusion) as modified Thrombolysis in Cerebral Infarction 2b–3 (or TIMI Thrombolysis in Myocardial Infarction 2–3 in the BASICS Basilar Artery International Cooperation Study registry).
RESULTS—We included 172 patients with basilar artery occlusion treated with endovascular therapy (124 with mechanical thrombectomy)mean (SD) age 65 (13) years, median National Institutes of Health Stroke Scale 22 (interquartile range 12–30), 64 (37%) treated >6 hours. Revascularization (achieved in 79% of patients) was associated with good outcome (P=0.003). The use of new generation thrombectomy devices was associated with good outcome (P=0.03). In patients who achieved revascularization, 29/46 (63%) of patients with a favorable BATMAN score and 26/51 (51%) with favorable PC-CS had good outcomes. In logistic regression analysis (adjusted for age, National Institutes of Health Stroke Scale, and time-to-treatment ≤6/>6 hours), revascularization was associated with good outcome in patients with favorable BATMAN score (odds ratio, 15.8; 95% CI, 1.4–175; P=0.02) or PC-CS (odds ratio, 9.4; 95% CI, 1.4–64; P=0.02). In patients who achieved revascularization, early (time-to-treatment ≤6 hours) but not late treatment was associated with improved outcome in patients with unfavorable BATMAN score (18/52 35%; odds ratio, 15; 95% CI, 1.9–124; P=0.01) or PC-CS (16/44 36%; odds ratio, 5.5; 95% CI, 1.4–21; P=0.01).
CONCLUSIONS—Revascularization is associated with good outcome in patients with basilar artery occlusion with good collaterals and less extensive occlusion, even >6 hours after onset.
BACKGROUND AND PURPOSE—Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well ...established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU.
METHODS—Treatment time metrics for MSU patients receiving reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment modeled using quantile regression analysis. Time savings were subsequently converted to disability-adjusted life years avoided using published estimates.
RESULTS—In the first 365-day operation of the Melbourne MSU, prehospital thrombolysis was administered to 100 patients (mean age, 73.8 years; 62% men). The median time savings per MSU patient, compared with the control cohort, was 26 minutes (P<0.001) for dispatch to hospital arrival and 15 minutes (P<0.001) for hospital arrival to thrombolysis. The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes (95% CI, 36.0–49.0). In the same period, 41 MSU patients received EVT (mean age, 76 years; 61% men) with median dispatch-to-treatment time saving of 51 minutes (95% CI, 30.1–71.9, P<0.001). This included a median time saving of 17 minutes (95% CI, 7.6–26.4, P=0.001) for EVT hospital arrival to arterial puncture for MSU patients. Estimated median disability-adjusted life years saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.
CONCLUSIONS—The Melbourne MSU substantially reduced time to reperfusion therapies, with the greatest estimated disability avoidance driven by the more powerful impact of earlier EVT. These findings highlight the benefits of prehospital notification and direct triage to EVT centers with facilitated workflow on arrival by the MSU.
Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis. ...Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4). This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites. We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4. Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition. Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type. Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features. Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities. Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome. Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
BACKGROUND:Indications for external beam radiation therapy (EBRT) for atypical meningiomas (AMs) remain unclear.
OBJECTIVE:To analyze features associated with recurrence in AM patients after gross ...total resection (GTR) and to assess the relative benefit of EBRT in a retrospective cohort study.
METHODS:One hundred fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0 months) were examined for possible predictors of recurrence (age, sex, location, volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum tests were used to analyze the association between these predictors and use of EBRT. The impact on recurrence for these predictors and EBRT was analyzed with Kaplan-Meier and Cox regression.
RESULTS:Of 151 patients, 13 (8.6%) experienced recurrence after GTR (median, 47.0 months). Multivariate analysis identified elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of recurrence. Larger volume (P = .96) was not associated with recurrence but was more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months). The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/EBRT were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated no difference in progression-free survival or overall survival after GTR vs GTR/EBRT (P = .8, P > .99).
CONCLUSION:Brain invasion and high mitotic rates may predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR.
ABBREVIATIONS:AM, atypical meningiomaEBRT, external beam radiation therapyGTR, gross total resectionLC, local controlMI, mitotic indexOS, overall survivalPFS, progression-free survivalWHO, World Health Organization
The experimental observation that certain crystal faces do not grow, despite being in contact with supersaturated solution, is a widely reported phenomenon. This concept of a growth “dead zone” has ...been known for many years, but its origin remains an unresolved problem in crystal growth. Sometimes it seems to be an inherent feature of the solution growth process, while at others it appears that an impurity is an essential element for its appearance. Here we review existing data and provide new experimental evidence to confirm the widespread existence of the dead zone across a range of molecular materials. Available crystal growth kinetics are confronted with mechanistic models. Examination of the packing arrangements of appropriate crystal faces suggests that this behavior is linked to molecular-scale surface roughness.
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