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

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 ‐ 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

Infarct Patterns in Patients With Symptomatic Carotid Webs

Background Carotid webs (CaWs) may explain embolic strokes particularly in young patients with cerebral embolism of otherwise undetermined cause. We aim to describe the radiological patterns of infarction in patients with symptomatic CaWs. Methods Retrospective analysis of a symptomatic CaW database (September 2014–July 2019) from 2 comprehensive stroke centers. Magnetic resonance imaging scans were reviewed independently by 2 blinded raters. Patterns of acute infarction included territorial (involving ≥2 arterial subdivisions), cortical (affecting 1 arterial subdivision), 1or multiple small cortical infarcts, borderzone infarcts (cortical or internal), striatocapsular lacunes (<1.5 cm in size), or ≥1 deep vascular territory (involving subcortical contiguous deep structures). Different concomitant patterns could coexist. Prior strokes and leukoaraiosis severity (modified Fazekas scale) were evaluated. Results Forty symptomatic patients with CaW who had infarction were identified. The median age of patients was 49 years (interquartile range, 41–57 years), 22% were women, and 78% were of Black race. The median National Institute of Health Stroke Scale was 13 (interquartile range, 4–17), noncontrast Alberta Stroke Program Early CT Score was 8 (interquartile range, 7–8), and 13 (33%) patients received intravenous alteplase. Thirty‐four (85%) individuals presented with large vessel occlusion strokes (9% intracranial internal carotid artery, 62% middle cerebral artery M1 segment, 29% M2 segment). Sixty‐three percent of patients had right hemispheric strokes and 85% large vessel occlusion. Most patients (98%) had cortical infarcts: 30% were territorial, 38% affected 1 subdivision, and 63% had ≥1 small cortical infarct. Ten percent of the patients had infarcts involving borderzone areas. Fifteen percent of patients had striatocapsular lacunes, all of which had a concomitant cortical infarction. Five percent of patients had imaging evidence of previous strokes (all cortical and within the CaW vascular territory) and 20% had leukoaraiosis (18% grade 1 and 2% grade 2). Conclusion Acute cerebral infarction attributed to CaW were all compatible with an embolic mechanism. CaW should be considered in the workup of patients with cryptogenic strokes as a potential source of embolism

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