Endovascular Therapy vs Medical Management for Patients With Acute Stroke With Medium Vessel Occlusion in the Anterior Circulation

Importance Randomized clinical trials have shown the efficacy of endovascular therapy (EVT) for acute large vessel occlusion strokes. The benefit of EVT in acute stroke with distal, medium vessel occlusion (DMVO) remains unclear. Objective To examine the efficacy and safety outcomes associated with EVT in patients with primary DMVO stroke when compared with a control cohort treated with medical management (MM) alone. Design, Setting, and Participants This multicenter, retrospective cohort study pooled data from patients who had an acute stroke and a primary anterior circulation emergency DMVO, defined as any segment of the anterior cerebral artery (ACA) or distal middle cerebral artery, between January 1, 2015, and December 31, 2019. Those with a concomitant proximal occlusion were excluded. Outcomes were compared between the 2 treatment groups using propensity score methods. Data analysis was performed from March to June 2021. Exposures Patients were divided into EVT and MM groups. Main Outcomes and Measures Main efficacy outcomes included 3-month functional independence (modified Rankin Scale [mRS] scores, 0-2) and 3-month excellent outcome (mRS scores, 0-1). Safety outcomes included 3-month mortality and symptomatic intracranial hemorrhage. Results A total of 286 patients with DMVO were evaluated, including 156 treated with EVT (mean [SD] age, 66.7 [13.7] years; 90 men [57.6%]; median National Institute of Health Stroke Scale [NIHSS] score, 13.5 [IQR, 8.5-18.5]; intravenous tissue plasminogen activator [IV tPA] use, 75 [49.7%]; ACA involvement, 49 [31.4%]) and 130 treated with medical management (mean [SD] age, 69.8 [14.9] years; 62 men [47.7%]; median NIHSS score, 7.0 [IQR, 4.0-14.0], IV tPA use, 58 [44.6%]; ACA involvement, 31 [24.0%]). There was no difference in the unadjusted rate of 3-month functional independence in the EVT vs MM groups (151 [51.7%] vs 124 [50.0%]; P = .78), excellent outcome (151 [38.4%] vs 123 [31.7%]; P = .25), or mortality (139 [18.7%] vs 106 [11.3%]; P = .15). The rate of symptomatic intracranial hemorrhage was similar in the EVT vs MM groups (weighted: 4.0% vs 3.1%; P = .90). In inverse probability of treatment weighting propensity analyses, there was no significant difference between groups for functional independence (adjusted odds ratio [aOR], 1.36; 95% CI, 0.84-2.19; P = .20) or mortality (aOR, 1.24; 95% CI, 0.63-2.43; P = .53), whereas the EVT group had higher odds of an excellent outcome (mRS scores, 0-1) at 3 months (aOR, 1.71; 95% CI, 1.02-2.87; P = .04). Conclusions and Relevance The findings of this multicenter cohort study suggest that EVT may be considered for selected patients with ACA or distal middle cerebral artery strokes. Further larger randomized investigation regarding the risk-benefit ratio for DMVO treatment is indicated

Large Genomic Deletions in CACNA1A Cause Episodic Ataxia Type 2

Episodic ataxia (EA) syndromes are heritable diseases characterized by dramatic episodes of imbalance and incoordination. EA type 2 (EA2), the most common and the best characterized subtype, is caused by mostly nonsense, splice site, small indel, and sometimes missense mutations in CACNA1A. Direct sequencing of CACNA1A fails to identify mutations in some patients with EA2-like features, possibly due to incomplete interrogation of CACNA1A or defects in other EA genes not yet defined. Previous reports described genomic deletions between 4 and 40 kb in EA2. In 47 subjects with EA (26 with EA2-like features) who tested negative for mutations in the known EA genes, we used multiplex ligation-dependent probe amplification to analyze CACNA1A for exonic copy number variations. Breakpoints were further defined by long-range PCR. We identified distinct multi-exonic deletions in three probands with classic EA2-like features: episodes of prolonged vertigo and ataxia triggered by stress and fatigue, interictal nystagmus, with onset during infancy or early childhood. The breakpoints in all three probands are located in Alu sequences, indicating errors in homologous recombination of Alu sequences as the underlying mechanism. The smallest deletion spanned exons 39 and 40, while the largest deletion spanned 200 kb, missing all but the first three exons. One deletion involving exons 39 through 47 arose spontaneously. The search for mutations in CACNA1A appears most fruitful in EA patients with interictal nystagmus and onset early in life. The finding of large heterozygous deletions suggests haploinsufficiency as a possible pathomechanism of EA2

The Society of Vascular and Interventional Neurology (SVIN) Mechanical Thrombectomy Registry: Methods and Primary Results

Background A better understanding of real‐world practice patterns in the endovascular treatment for large vessel occlusion acute ischemic stroke is needed. Here, we report the methods and initial results of the Society of Vascular and Interventional Neurology (SVIN) Registry. Methods The SVIN Registry is an ongoing prospective, multicenter, observational registry capturing patients with large vessel occlusion acute ischemic stroke undergoing endovascular treatment since November 2018. Participating sites also contributed pre‐SVIN Registry data collected per institutional prospective registries, and these data were combined with the SVIN Registry in the SVIN Registry+ cohort. Results There were 2088 patients treated across 11 US centers included in the prospective SVIN Registry and 5372 in SVIN Registry+. In the SVIN Registry cohort, the median number of enrollments per institution was 160 [interquartile range 53–243]. Median age was 67 [58–79] years, 49% were women, median National Institutes of Health Stroke Scale 16 [10–21], Alberta stroke program early CT score 9 [7–10], and 20% had baseline modified Rankin scale (mRS)≥2. The median last‐known normal to puncture time was 7.7 [3.1–11.5] hours, and puncture‐to‐reperfusion was 33 [23–52] minutes. The predominant occlusion site was the middle cerebral artery‐M1 (45%); medium vessel occlusions occurred in 97(4.6%) patients. The median number of passes was 1 [1–3] with 93% achieving expanded Treatment In Cerebral Ischemia2b50–3 reperfusion and 51% expanded Treatment In Cerebral Ischemia3/complete reperfusion. Symptomatic intracranial hemorrhage occurred in 5.3% of patients, with 37.3% functional independence (mRS0–2) and 26.4% mortality rates at 90‐days. Multivariable regression indicated older age, longer last‐normal to reperfusion, higher baseline National Institutes of Health Stroke Scale and glucose, lower Alberta stroke program early CT score, heart failure, and general anesthesia associated with lower 90‐day chances of mRS0–2 at 90‐days. Demographic, imaging, procedural, and clinical outcomes were similar in the SVIN Registry+. A comparison between AHA Guidelines‐eligible patients from the SVIN Registry against the Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke Trials study population demonstrated comparable clinical outcomes. Conclusions The prospective SVIN Registry demonstrates that satisfactory procedural and clinical outcomes can be achieved in real‐world practice, serving as a platform for local quality improvement and the investigation of unexplored frontiers in the endovascular treatment of acute stroke

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Abstract 1122‐000128: Imaging Follow‐Up in Carotid Webs: Is There Vascular Remodeling?

Introduction: Carotid web (CaW) is a shelf‐like fibrotic projection at the carotid bulb and constitutes an underrecognized cause of ischemic stroke. Atherosclerotic lesions are known to have dynamic remodeling with time however, little is known regarding the evolution of CaW over time. We aimed to better understand if CaW is a static or dynamic entity on delayed vascular imaging. Methods: This was a retrospective analysis of the CaW database at our comprehensive stroke center, including patients diagnosed with CaW between September 2014 through June 2021. Patients who had at least two good quality CT angiograms (CTAs) that were at least 6 months apart were included (CTAs with CaW and superimposed thrombus were excluded). CaW were quantified with 3‐D measurements using Horos software. This was done via volumetric analysis of free‐hand delineated CaW borders on thin cuts of axial CTA (Figure 1 Panel A). NASCET criteria was used to evaluate the degree of stenosis. Results: Sixteen CaW in 13 patients were identified and included. The median imaging follow‐up window was 16 months (IQR 12–22, range 6–29). Median patient age was 45.5 years‐old, 69% were women, 25% had hypertension, 38% hyperlipidemia, 25% diabetes mellitus, 0% atrial fibrillation, and 13% active smokers. 75% of the included CaW were symptomatic while 25% were asymptomatic. Median volume of CaW on initial CTA (8.52 mm3 [IQR 3.7‐13], range 2.2‐30.4) was comparable to median volume of CaW on most recent CTA (8.47 mm3 [IQR 4.0‐12.8], range 2.3‐29.4; p = <0.001 (Figure 1 Panel B). The CaW volumetric measurement correlation between the initial and most recent CTA was near perfect (rs = ‐0.99, p = <0.001). The median change in measured volume of CaW between first and last CTA was ‐0.19 mm3 [IQR ‐0.6‐0.4], range ‐1‐0.8. Median degree of stenosis was 8.1% [IQR 4.5‐17.1], range 0.4‐31.2. The duration of follow‐up imaging was not correlated with the change in CaW volume (Kendall tau‐b[τb] = ‐0.17, p = 0.93). The initial CaW volume was not found to be correlated to the degree of stenosis (τb = ‐0.08, p = 0.65). Conclusions: The volume of the CaW was not found to change over time, reinforcing the idea that this is a relatively static lesion. The CaW volume was not found to correlate with the degree of stenosis caused by it. Further longitudinal studies with longer follow‐up intervals are warranted

Abstract Number ‐ 51: Automated Versus Human Hyperdense Vessel Sign Detection Using Non‐Contrast Computed Tomography Scans

Introduction Rapid detection of large vessel occlusion (LVO) is very crucial in triaging stroke patients potentially candidates for mechanical thrombectomy (MT). Hyperdense vessel sign (HDVS) is one of the earliest ischemic changes in non‐contrast CT scan (NCCT) indicating LVO stroke. Artificial intelligence emerged to detect HDVS with the advantages of faster acquisition, less variation, and a lower need for experience than the usual detection. We aimed to identify the diagnostic performance of automated software (e‐Stroke, Brainomix) in HDVS detection. Methods A prospectively collectedMT database from March 2020 to August 2021 was reviewed. Patients were included if they had intracranial internal carotid artery or middle cerebral artery M1 or M2 occlusion. Cases with HDVS were identified through the routine 2.5‐mm slice thickness NCCT scans after being correlated with patients’ clinical information and confirmed with CT angiography (CTA) scans. NCCT scans were classified according to slice thickness into two groups: 2.5‐mm scans and 0.625‐mm generated scans. All NCCT scans were read by e‐Stroke software, then deidentified and reviewed by two stroke neurologists who were blinded to any clinical, other imaging, or therapeutic information. They were required to record the presence/laterality of HDVS before and after observing other NCCT early ischemic changes like gaze deviation, loss of insular ribbon, caudate or lentiform hypodensity. ROC curve analysis was used to estimate sensitivity and specificity and the area under the curve (AUC) was compared using DeLong’s test. Inter‐rater agreement between the two readers’ final reads, e‐Stroke, and the standard read was measured using the Fleiss Kappa test. Results Among 304 patients included in the study, 37.7% had HDVS. Approximately 44% of the scans had 2.5‐mm slice thickness and 56% had 0.625‐mm slice thickness. The e‐Stroke software identified HDVS with a sensitivity of 63% and a specificity of 71% (Table 1). The mean AUC value of e‐Stroke HDVS detection (0.67[0.61‐0.74]) was similar to reader‐1 (0.68[0.62‐0.74];p = 0.87) and reader‐2 (0.63[0.57‐0.70];p = 0.56). HDVS detection improved by reader‐1(0.78[0.72‐0.83];p = 0.03) after observing other early ischemic changes on the same scans, but reader‐2 performance remained similar to e‐Stroke (0.69[0.63‐0.76];p = 0.71). AUC, sensitivity and specificity ofHDVS detection by e‐Stroke were significantly higher using 2.5‐mm compared to 0.625‐mm sliced NCCT scans (0.78[0.70‐0.86],sensitivity 70%,specificity 86%;p< 0.001) vs (0.58[0.50‐0.67],sensitivity 56%,specificity 61%;p = 0.06) respectively;p = 0.01. The readers also had higher AUC values with 2.5‐mm scans but not statistically significant, (0.74[0.66‐0.83] vs 0.64[0.56‐0.73];p = 0.18) for reader‐1 and (0.68[0.59‐0.77] vs 0.57[0.48‐0.66];p = 0.23) for reader‐2. The same after the final read, (0.85[0.78‐0.92] vs 0.75[0.67‐0.82];p = 0.08) for reader‐1 and (0.73[0.65‐0.82] vs 0.67[0.58‐0.76];p = 0.43) for reader‐2. Similarly, inter‐rater agreement was higher using 2.5‐mm sliced scans, k = 0.50(0.43‐0.75) compared to0.625‐mm scans,k = 0.27(0.21‐0.33). Conclusions Artificial intelligence (e‐Stroke software) has comparable sensitivity and specificity to human readers in HDVS detection. For e‐Stroke software, 2.5‐mm sliced CT scans are better to identifyHDVS compared to 0.625‐mm scans

Abstract Number ‐ 10: Stroke Patients with Carotid Artery Web Have High RoPE Scores and Low Frequency of PFO

Introduction PFO‐associated stroke is more common in young patients (<60 years) with less vascular risk factors, and with an infarct pattern consistent with embolic phenomena. These features are included in the Risk of Paradoxical Embolization (RoPE) score in which a high score (≥ 7) indicates a high likelihood of a symptomatic PFO. However, carotid artery webs (CaW) have been reported in patients with the same profile in which a PFO might be detected. In this study, we calculated RoPE score for patients with symptomatic CaW related strokes to identify how many of these patients would have been potentially misclassified as having a PFO‐associated stroke. Methods Patients presenting with ESUS and ipsilateral symptomatic CaW were included. Stroke work up was completed including cervicocranial vascular imaging that was reviewed by a neuroradiologist and an interventional neurologist. Shunt study was done with a TTE, TEE, and/or TCD, all with a bubble study. RoPE score of ≥ 7 was considered high. Results A total of 75 patients fulfilled the inclusion criteria of having an ipsilateral symptomatic CaW as the etiology of ESUS with no competing etiologies aside from PFO. The baseline characteristics are described in the table. The rates of vascular risk factors were generally low which is reflected by a high median RoPE score of 7 [IQR 5‐8], with 52% (n = 39) of patients having a score of ≥ 7. Ten patients (13%) had a PFO, of which 3 had high‐risk features. There was no significant difference in median RoPE score between patients with and without PFO (8 [6‐8] vs 6 [5‐8], p = 0.238), nor in the rate of patients with high RoPE score (78% vs 44%, p = 0.06). Recurrence happened in 16% (n = 12) of the patients and was always ipsilateral to the symptomatic CaW. No significant difference was detected in the rates of recurrence between high vs low RoPE scores (20.5% vs 11.1%, p = 0.351). Patients with a PFO had higher rates of recurrence compared to those without a PFO (40%, n = 4 vs 12.3%, n = 8, p = 0.048); however, none of the PFO patients with a recurrent stroke had a high‐risk PFO. A superimposed thrombus was seen on the CaW in 12.2% (n = 9) and was more commonly seen in patients who had recurrence (36%, n = 4 vs 8%, n = 5, p = 0.024). Conclusions Patients with ESUS from a presumably symptomatic CaW‐related stroke have high RoPE scores. The recurrence rates were high in this population and were always ipsilateral to the side of the CaW including in the PFO population. The PFO is likely incidental in this population despite having a high RoPE score. Neurologists should carefully evaluate the cervical vasculature before concluding that a PFO is stroke‐related and committing patients to PFO treatment

Abstract Number ‐ 50: Multiplane Reconstruction Modifies The Diagnostic Performance Of CTA Imaging In Carotid Web Cases

Introduction Carotid Web (CaW) represents an important and overlooked etiology for ischemic stroke and has been associated with high rates of stroke recurrence. Computed tomography angiography (CTA) has been shown to have comparable performance to digital subtraction angiography (DSA) and has been suggested to be the non‐invasive imaging of choice for CaW detection. However, misdiagnosis has been demonstrated to be common even in specialized centers. We evaluated the impact of adding CTA multiplane reconstruction (MPR) andthree‐dimensional maximum intensity projection (3D MIP) reformat on the diagnostic performance of CTA in CaW detection. Methods After exclusion of patients aged >65 years old and patients with no available/poor quality CTA,CaW cases (n = 31 consecutive patients leading to 31 ipsilateral carotids to the stroke derived from out prospective CaW database), as well as two other groups: 1)carotid atherosclerosis (n = 27consecutivepatients from out carotid stenting database leading to 27 carotids contralateral to the index lesion) and 2) consecutive normal carotid cases (n = 49 patients with normal carotids extracted from the electronic medical records for patients imaged due to suspected blunt cerebrovascular trauma) were included. All CTA images were deidentified and reviewed independently by three stroke neurologists to record the diagnosis and level of diagnostic certainty (in form of a scale (1[lowest]‐to‐5[highest]) after evaluating the CTA axial plane alone, then after sagittal and coronal planes (MPR) reconstructions, and then after evaluation of3D MIP reformatted images.The analyses were made for the total number of observations for all readers (93 CaWs, 81 atherosclerosis cases and 147 normal carotids). Results On reviewing CTA axial projection alone, raters correctly diagnosed 44.1% of CaW, 87.7% of carotid atherosclerosis and 83% of normal carotid images. Sagittal and coronal MPR significantly increased the rate of accurate CaW diagnosis (76.3%‐Table 1) The certainty level for CaW diagnosis was lower when compared to atherosclerosis as well as normal carotid using the CTA axial projection alone (3.0[3.0‐4.0] vs 4.0[3.0‐5.0];p< 0.001 and vs 4.0[3.0‐5.0];p< 0.001) as well as after adding sagittal/coronal MPR (4.0[3.0‐5.0] vs 5.0[4.0‐5.0],p = 0.01; and vs 4.0[4.0‐5.0],p< 0.001). The certainty level became similar between CaW and atherosclerosis as well as normal carotids with the addition of 3D MIP (5.0[5.0‐5.0] vs 5.0[4.5‐5.0], p = 0.61; and vs 5.0[5.0‐5.0],p = 0.15) respectively. Inter‐rater agreement in CaW detection increased from k = 0.46(0.35‐0.57);p< 0.05usingaxial section to k = 0.80(0.69‐0.91);p< 0.05 with MPR. Axial projection alone had lower sensitivity in CaW detection (AUC = 0.69(0.62‐0.76),sensitivity = 44%,specificity = 95%,p< 0.05) compared to MPR (AUC = 0.86(0.80‐0.91),sensitivity = 76%,specificity = 96%,p< 0.05). Misdiagnosed CaW cases, after using all planes with 3D MIP (n = 23/93), were older (56[46‐61] vs 52[46‐57] years,p = 0.04) and lower length/base ratio (0.51[0.49‐0.87] vs 0.92[0.74‐1.19],p< 0.001) compared to the correctly diagnosed CaW cases (n = 70/93). Conclusions CTA axial plane alone is unreliable to detect CaW and the addition of sagittal/coronal MPR and 3D MIPs are important to increase accurate diagnosis and perceived reader diagnostic certainty