Kallmes, David F.

Background There is limited evidence on the optimal endovascular strategy for treatment of distal medium-vessel occlusions (DMVO). The low-profile Tigertriever 13 stent-triever shows early promise as an adaptable device that can navigate the distal vasculature without increasing complication risk in DMVO. Methods Using Nested Knowledge, we screened literature for RCTs and cohort studies on the endovascular treatment of DMVO. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction (TICI) ≥ 2b and secondary outcomes included rate of symptomatic intracranial hemorrhage (sICH), mortality at 90 days, and modified Rankin scale (mRS) scores 0–2 at 90 days. A random-effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results Eleven studies with 1402 patients, 167 patients treated by Tigertriever 13 and 1235 patients treated by other devices, were included in the meta-analysis. The rate of reperfusion success was similar in patients treated by Tigertriever 13 (83.2% [95% CI: 71.5–96.7%]) versus other devices (81.6% [95% CI: 75.3–88.4%], p > 0.05). The rate of sICH was also similar in patients treated by Tigertriever 13 (7.2% [95% CI: 4.1–12.5%]) versus other devices (6.9% [95% CI: 5.5–8.8%]). There was significant heterogeneity in the reporting of mortality and mRS. Conclusions Tigertriever 13 had similar rates of reperfusion success and sICH as other devices used for the treatment of DMVO. Heterogeneity in data element reporting prevented further analyses. Further studies evaluating Tigertriever 13 and other potential devices in DMVO should attempt to harmonize data element reporting.

Background Computed tomography (CT) angiography collateral score (CTA-CS) is an important clinical outcome predictor following mechanical thrombectomy for ischemic stroke with large vessel occlusion (LVO). The present multireader study aimed to evaluate the performance of e-CTA software for automated assistance in CTA-CS scoring. Materials and Methods Brain CTA images of 56 patients with anterior LVO were retrospectively processed. Twelve readers of various clinical training, including junior neuroradiologists, senior neuroradiologists, and neurologists graded collateral flow using visual CTA-CS scale in two sessions separated by a washout period. Reference standard was the consensus of three expert readers. Duration of reading time, inter-rater reliability, and statistical comparison of readers’ performance metrics were analyzed between the e-CTA assisted and unassisted sessions. Results e-CTA assistance resulted in significant increase in mean accuracy (58.6% to 67.5%, p = 0.003), mean F1 score (0.574 to 0.676, p = 0.002), mean precision (58.8% to 68%, p = 0.007), and mean recall (58.7% to 69.9%, p = 0.002), especially with slight filling deficit (CTA-CS 2 and 3). Mean reading time was reduced across all readers (103.4 to 59.7 s, p = 0.001), and inter-rater agreement in CTA-CS assessment was increased (Krippendorff's alpha 0.366 to 0.676). Optimized occlusion laterality detection was also noted with mean accuracy (92.9% to 96.8%, p = 0.009). Conclusion Automated assistance for CTA-CS using e-CTA software provided helpful decision support for readers in terms of improving scoring accuracy and reading efficiency for physicians with a range of experience and training backgrounds and leading to significant improvements in inter-rater agreement.

Importance Patients with atrial fibrillation (AF) treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) have been reported to experience worse outcomes compared with patients without AF. Objective To assess differences between patients with AF and their counterparts without AF treated with MT for AIS, focusing on safety outcomes, clinical outcomes, and baseline characteristics in both groups. Data Sources A systematic literature review of the English language literature from inception to July 14, 2022, was conducted using Web of Science, Embase, Scopus, and PubMed databases. Study Selection Studies that focused on patients with and without AF treated with MT for AIS were included. Multiple reviewers screened studies to identify studies included in analysis. Data Extraction and Synthesis Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline to ensure accuracy. Data were pooled using a random-effects model. Main Outcomes and Measures The primary outcome of interest was rate of modified Rankin Scale (mRS) scores of 0 to 2 at 90 days. Secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction (TICI) scores of 2b to 3, 90-day mortality, symptomatic intracranial hemorrhage (SICH), and baseline patient characteristics. Results Of 1696 initially retrieved studies, 10 studies were included, with 6543 patients. Patients with AF were a mean of 10.17 (95% CI, 8.11-12.23) years older ( P < .001) and had higher rates of hypertension (OR, 1.89 [95% CI, 1.57-2.27]; P < .001) and diabetes (OR, 1.16 [95% CI, 1.02-1.31]; P = .02). Overall, there were comparable rates of mRS scores of 0 to 2 between patients with AF and patients without AF (odds ratio [OR], 0.72 [95% CI, 0.47-1.10]; P = .13), with significant heterogeneity among the included studies. After sensitivity analysis, the rate of mRS scores of 0 to 2 was significantly lower among patients with AF (OR, 0.65 [95% CI, 0.52-0.81]; P < .001). Successful reperfusion rates were similar between the groups (OR, 1.11 [95% CI, 0.78-1.58]; P = .57). The rate of SICH was similar between groups (OR, 1.05 [95% CI, 0.84-1.31]; P = .68). Mortality was significantly higher in the AF group (OR, 1.47 [95% CI, 1.12-1.92]; P = .005). Conclusions and Relevance In this systematic review and meta-analysis, patients with AF experienced worse 90-day outcomes, even in the setting of similar rates of successful reperfusion. This was likely associated with greater age and greater rates of comorbidities among patients with AF.

Background Delayed neurological improvement (DNI) is a phenomenon that involves patient improvement in the absence of early neurological change following treatment for acute ischemic stroke. The patient characteristics associated with this condition are largely unexplored. Methods Following the PRISMA guidelines, a systematic review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. We calculated pooled odds ratios (ORs), mean differences (MDs), and their corresponding 95% confidence intervals (CIs) to test the association between patient characteristics and achievement of DNI. Results Seven studies, with 3266 patients, were included in our analysis. All studies reported a different definition of DNI, with five studies focusing on rates of good functional outcome at 90 days post-treatment in the absence of early neurological improvement. Use of intravenous thrombolytics was associated with increased rates of DNI (OR 1.96, 95% CI 1.28 to 3.00; p = 0.002). Atrial fibrillation was associated with decreased rates of DNI (OR 0.69, 95% CI 0.57 to 0.82; p < 0.001), as was hypertension (OR 0.66, 95% CI 0.53 to 0.83, p < 0.001), and diabetes mellitus (OR 0.71, 95% CI 0.56 to 0.90; p = 0.005). On average, patients who achieved DNI were 6.30 years younger than their non-DNI counterparts ( MD −6.30, 95% CI −9.19 to −3.41; p < 0.001). There were modest associations between male sex and DNI (OR 1.36, 95% CI 1.01 to 1.74, p = 0.042), and smoking and DNI (OR 1.28, 95% CI 1.03 to 1.59, p = 0.027). Conclusions DNI is a phenomenon that is not presently well understood. Lack of uniformity among definitions of DNI hinders efforts to explore DNI and the factors associated with its occurrence. Future studies should work to establish a consensus definition of DNI to determine its causes and significance more accurately.

Background Covert cerebrovascular disease (CCD) has been shown to be associated with dementia in population‐based studies with magnetic resonance imaging (MRI) screening, but dementia risk associated with incidentally discovered CCD is not known. Methods and Results Individuals aged ≥50 years enrolled in the Kaiser Permanente Southern California health system receiving head computed tomography (CT) or MRI for nonstroke indications from 2009 to 2019, without prior ischemic stroke/transient ischemic attack, dementia/Alzheimer disease, or visit reason/scan indication suggestive of cognitive decline or stroke were included. Natural language processing identified incidentally discovered covert brain infarction (id‐CBI) and white matter disease (id‐WMD) on the neuroimage report; white matter disease was characterized as mild, moderate, severe, or undetermined. We estimated risk of dementia associated with id‐CBI and id‐WMD. Among 241 050 qualified individuals, natural language processing identified 69 931 (29.0%) with id‐WMD and 11 328 (4.7%) with id‐CBI. Dementia incidence rates (per 1000 person‐years) were 23.5 (95% CI, 22.9–24.0) for patients with id‐WMD, 29.4 (95% CI, 27.9–31.0) with id‐CBI, and 6.0 (95% CI, 5.8–6.2) without id‐CCD. The association of id‐WMD with future dementia was stronger in younger (aged <70 years) versus older (aged ≥70 years) patients and for CT‐ versus MRI‐discovered lesions. For patients with versus without id‐WMD on CT, the adjusted HR was 2.87 (95% CI, 2.58–3.19) for younger and 1.87 (95% CI, 1.79–1.95) for older patients. For patients with versus without id‐WMD on MRI, the adjusted HR for dementia risk was 2.28 (95% CI, 1.99–2.62) for younger and 1.48 (95% CI, 1.32–1.66) for older patients. The adjusted HR for id‐CBI was 2.02 (95% CI, 1.70–2.41) for younger and 1.22 (95% CI, 1.15–1.30) for older patients for either modality. Dementia risk was strongly correlated with id‐WMD severity; adjusted HRs compared with patients who were negative for id‐WMD by MRI ranged from 1.41 (95% CI, 1.25–1.60) for those with mild disease on MRI to 4.11 (95% CI, 3.58–4.72) for those with severe disease on CT. Conclusions Incidentally discovered CCD is common and associated with a high risk of dementia, representing an opportunity for prevention. The association is strengthened when discovered at younger age, by increasing id‐WMD severity, and when id‐WMD is detected by CT scan rather than MRI.

OBJECTIVE Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

Background Previous randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO. Methods Using Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0–3, and secondary outcomes included 90-day mRS score 0–2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results Four RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0–3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; P<0.001). Conclusions EVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH.

Background: New trials are planned regularly to provide the highest quality of evidence and invade new occlusion territories, which requires a pre-defined reporting strategy with consistent, common data elements for more straightforward collective evidence synthesis. We sought to review all active endovascular thrombectomy trials to investigate their patient selection criteria, intervention description, and reported outcomes. Methods: A literature search was systematically conducted on clinicaltrials.gov for active trials and all intervention, inclusion criteria, and outcomes reported were extracted. A qualitative synthesis of the frequency of study design types and data elements are graphically and narratively presented. Results: A total of 32 studies were tagged and included in the final qualitative analysis. The inclusion criteria were highly variable, including different cut-offs for the last well-known baseline National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and modified Rankin scale (mRS). Half of the studies (16/32) mentioned “thrombectomy” without defining which technique or device was used, and the final thrombolysis in cerebral infarction scale was provided in 19 (59.4%) studies. Heterogeneity was also present among the studies reporting a first-pass effect, both in how studies defined the outcome and in used ranges for mRS. Mortality and intracerebral hemorrhage (ICH) were more homogenous in their presentation and follow-up. Conclusions: There is a great degree of heterogeneity in the active thrombectomy trials concerning inclusion criteria, interventions used, and how outcomes are being reported.

Neurovascular catheter technology has rapidly evolved over the past decade. While performance characteristics are well known to the practitioner, the design features of these new-generation catheters and their implications on performance metrics remain a mystery to most clinicians due to the limited number of available resources. This knowledge gap hampers informed device choices and also limits collaboration between clinicians and engineers. To aid fellow neurointerventionalists, in this primer we have summarized the basic concepts of catheter design and construction.