Strength of Association between Infarct Volume and Clinical Outcome Depends on the Magnitude of Infarct Size: Results from the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the association of infarct volume and clinical outcome changes with the magnitude of infarct size. MATERIALS AND METHODS: Data were derived from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, in which patients with acute stroke with large-vessel occlusion were randomized to endovascular treatment plus either nerinetide or a placebo. Infarct volume was manually segmented on 24-hour noncontrast CT or DWI. The relationship between infarct volume and good outcome, defined as mRS 0-2 at 90 days, was plotted. Patients were categorized on the basis of visual grouping at the curve shoulders of the infarct volume/outcome plot. The relationship between infarct volume and adjusted probability of good outcome was fitted with linear or polynomial functions as appropriate in each group. RESULTS: We included 1099 individuals in the study. Median infarct volume at 24 hours was 24.9 mL (interquartile range [IQR] = 6.6-92.2 mL). On the basis of the infarct volume/outcome plot, 4 infarct volume groups were defined (IQR = 0-15 mL, 15.1-70 mL, 70.1-200 mL, >200 mL). Proportions of good outcome in the 4 groups were 359/431 (83.3%), 219/337 (65.0%), 71/201 (35.3%), and 16/130 (12.3%), respectively. In small infarcts (IQR = 0-15 mL), no relationship with outcome was appreciated. In patients with intermediate infarct volume (IQR = 15-200 mL), there was progressive importance of volume as an outcome predictor. In infarcts of > 200 mL, outcomes were overall poor. CONCLUSIONS: The relationship between infarct volume and clinical outcome varies nonlinearly with the magnitude of infarct size. Infarct volume was linearly associated with decreased chances of achieving good outcome in patients with moderate-to-large infarcts, but not in those with small infarcts. In very large infarcts, a near-deterministic association with poor outcome was seen.

Considerations for Antiplatelet Management of Carotid Stenting in the Setting of Mechanical Thrombectomy: A Delphi Consensus Statement.

BACKGROUND AND PURPOSE: There are only few data and lack of consensus regarding antiplatelet management for carotid stent placement in the setting of endovascular stroke treatment. We aimed to develop a consensus-based algorithm for antiplatelet management in acute ischemic stroke patients undergoing endovascular treatment and simultaneous emergent carotid stent placement. MATERIALS AND METHODS: We performed a literature search and a modified Delphi approach used Web-based questionnaires that were sent in several iterations to an international multidisciplinary panel of 19 neurointerventionalists from 7 countries. The first round included open-ended questions and formed the basis for subsequent rounds, in which closed-ended questions were used. Participants continuously received feedback on the results from previous rounds. Consensus was defined as agreement of ≥70% for binary questions and agreement of ≥50% for questions with >2 answer options. The results of the Delphi process were then summarized in a draft manuscript that was circulated among the panel members for feedback. RESULTS: A total of 5 Delphi rounds were performed. Panel members preferred a single intravenous aspirin bolus or, in jurisdictions in which intravenous aspirin is not available, a glycoprotein IIb/IIIa receptor inhibitor as intraprocedural antiplatelet regimen and a combination therapy of oral aspirin and a P2Y12 inhibitor in the postprocedural period. There was no consensus on the role of platelet function testing in the postprocedural period. CONCLUSIONS: More and better data on antiplatelet management for carotid stent placement in the setting of endovascular treatment are urgently needed. Panel members preferred intravenous aspirin or, alternatively, a glycoprotein IIb/IIIa receptor inhibitor as an intraprocedural antiplatelet agent, followed by a dual oral regimen of aspirin and a P2Y12 inhibitor in the postprocedural period.

Antiplatelet Management for Stent-Assisted Coiling and Flow Diversion of Ruptured Intracranial Aneurysms: A DELPHI Consensus Statement.

BACKGROUND AND PURPOSE: There is a paucity of data regarding antiplatelet management strategies in the setting of stent-assisted coiling/flow diversion for ruptured intracranial aneurysms. This study aimed to identify current challenges in antiplatelet management during stent-assisted coiling/flow diversion for ruptured intracranial aneurysms and to outline possible antiplatelet management strategies. MATERIALS AND METHODS: The modified DELPHI approach with an on-line questionnaire was sent in several iterations to an international, multidisciplinary panel of 15 neurointerventionalists. The first round consisted of open-ended questions, followed by closed-ended questions in the subsequent rounds. Responses were analyzed in an anonymous fashion and summarized in the final manuscript draft. The statement received endorsement from the World Federation of Interventional and Therapeutic Neuroradiology, the Japanese Society for Neuroendovascular Therapy, and the Chinese Neurosurgical Society. RESULTS: Data were collected from December 9, 2019, to March 13, 2020. Panel members achieved consensus that platelet function testing may not be necessary and that antiplatelet management for stent-assisted coiling and flow diversion of ruptured intracranial aneurysms can follow the same principles. Preprocedural placement of a ventricular drain was thought to be beneficial in cases with a high risk of hydrocephalus. A periprocedural dual, intravenous, antiplatelet regimen with aspirin and a glycoprotein IIb/IIIa inhibitor was preferred as a standard approach. The panel agreed that intravenous medication can be converted to oral aspirin and an oral P2Y12 inhibitor within 24 hours after the procedure. CONCLUSIONS: More and better data on antiplatelet management of patients with ruptured intracranial aneurysms undergoing stent-assisted coiling or flow diversion are urgently needed. Panel members in this DELPHI consensus study preferred a periprocedural dual-antiplatelet regimen with aspirin and a glycoprotein IIb/IIIa inhibitor.

Imaging Triage of Patients with Late-Window (6-24 Hours) Acute Ischemic Stroke: A Comparative Study Using Multiphase CT Angiography versus CT Perfusion.

BACKGROUND AND PURPOSE: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT. MATERIALS AND METHODS: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients' eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion. RESULTS: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0-2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0-2 (P interaction = .007). The multiphase CTA-based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77-0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models. CONCLUSIONS: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window.

Optimizing fast first pass complete reperfusion in acute ischemic stroke - the BADDASS approach (BAlloon guiDe with large bore Distal Access catheter with dual aspiration with Stent-retriever as Standard approach).

Introduction: Endovascular therapy is the standard of care for acute ischemic stroke due to large vessel occlusions. The ultimate goal is to achieve fast first pass complete reperfusion, since delayed and/or incomplete reperfusion increases complication rates and costs and deteriorates patient outcome. Achieving optimal results can sometimes be challenging, particularly in patients with tortuous vessels. Several techniques have been described lately to optimize recanalization, including first line aspiration and various stent-retriever assisted techniques. In our experience, mechanical thrombectomy with a BAlloon guide catheter, large bore Distal access catheter, Dual Aspiration and Stent-retriever as Standard approach (BADDASS) is the most efficient technique to succeed, since it combines the advantages of stent-retrievers and distal aspiration.Areas covered: The purpose of this review is to enable neurointerventionalists to achieve fast first pass complete reperfusion by outlining the BADDASS approach step-by-step and sharing additional tips for navigating through challenging internal carotid artery segments.Expert opinion: In our experience, the BADDASS approach is the safest and most effective way to achieve fast first pass complete reperfusion.

Dismantling the ability of CT and MRI to identify the target mismatch profile in patients with anterior circulation large vessel occlusion beyond six hours from symptom onset.

PURPOSE: Patients with large vessel occlusion and target mismatch on imaging may be thrombectomy candidates in the extended time window. However, the ability of imaging modalities including non-contrast CT Alberta Stroke Program Early Computed Tomographic Scoring (CT ASPECTS), CT angiography collateral score (CTA-CS), diffusion-weighted MRI ASPECTS (DWI ASPECTS), DWI lesion volume, and DWI volume with clinical deficit (DWI + NIHSS), to identify mismatch is unknown. METHODS: We defined target mismatch as core infarct (DWI volume) of < 70 mL, mismatch volume (tissue with TMax > 6 s) of ≥ 15 mL, and mismatch ratio of ≥ 1.8. Using experimental dismantling design, ability to identify this profile was determined for each imaging modality independently (phase 1) and then with knowledge from preceding modalities (phase 2). We used a generalized mixed model assuming binary distribution with PROC GLIMMIX/SAS for analysis. RESULTS: We identified 32 patients with anterior circulation occlusions, presenting > 6 h from symptom onset, with National Institute of Health Stroke Scale of ≥ 6, who had CT and MR before thrombectomy. Sensitivities for identifying target mismatch increased modestly from 88% for NCCT to 91% with the addition of CTA-CS, and up to 100% for all MR-based modalities. Significant gains in specificity were observed from successive tests (29, 19, and 16% increase for DWI ASPECTS, DWI volume, and DWI + NIHSS, respectively). CONCLUSIONS: The combination of NCCT ASPECTS and CTA-CS has high sensitivity for identifying the target mismatch in the extended time window. However, there are gains in specificity with MRI-based imaging, potentially identifying treatment candidates who may have been excluded based on CT imaging alone.

Imaging of Patients with Suspected Large-Vessel Occlusion at Primary Stroke Centers: Available Modalities and a Suggested Approach.

The overwhelming benefit of endovascular therapy in patients with large-vessel occlusions suggests that more patients will be screened than treated. Some of those patients will be evaluated first at primary stroke centers; this type of evaluation calls for standardizing the imaging approach to minimize delays in assessing, transferring, and treating these patients. Here, we propose that CT angiography (performed at the same time as head CT) should be the minimum imaging approach for all patients with stroke with suspected large-vessel occlusion presenting to primary stroke centers. We discuss some of the implications of this approach and how to facilitate them.

Genetic selection pressure in TLR9 gene may enforce risk for SLE in Indian Tamils.

Objectives Lupus is a classical systemic autoimmune disease with genetics as one of the well known causative factors for the disease pathogenesis. Toll-like receptors are the major pattern recognition receptors associated with innate immunity and also act as an interface with the adaptive immunity. Genetic polymorphisms in genes encoding TLRs were implicated in the development of infections, malignancies and autoimmune diseases. TLR9 is a member of TLR family, and recognizes the CpG DNA motifs of pathogens. Though the incidence rate of lupus in Asians was reported to be low (30 - 50/100,000 population), poor disease prognosis due to higher incidence of renal complications and aggressive disease worsens the scenario. The ability of TLR9 to detect and elicit an immune response against double-stranded DNA makes TLR9 a relevant factor to be tested for its association with the clinical and serological phenotypes of lupus. However, lack of relevant genetic data on normative frequencies of the TLR9 (rs187084) polymorphism may serve as a constraint to derive the sample size to conduct case control association studies. Hence this study was conducted to establish the normative frequency of TLR9 (rs187084) polymorphism in Indian Tamils. Materials and methods The TLR9 (rs187084) polymorphism was screened in South Indian Tamils ( n = 208) by PCR-RFLP. Results and discussion We observed a higher occurrence of the mutant allele (65%) in South Indian Tamils. No gender disparity with respect to the mutant allele frequency was observed. The higher incidence of mutant allele in both genders suggests that this population had undergone a genetic selection pressure as an evolutionary genetic measure to withstand the prevailing endemic infections like TB and malaria. Though the enhanced expression of TLR9 was protective against infections, it may also influence the development of autoimmune diseases. Conclusion The higher incidence of theTLR9 (rs187084) over-expression mutation in Indian Tamils is suggestive of a genetic adaptation or selection pressure to withstand the prevailing endemic infectious and parasitic diseases. However, this genetic adaptation poses a greater risk to develop autoimmune diseases like SLE etc through complex gene environment interactions. The normative frequency of the TLR9 (rs187084) polymorphism established in our population could now be used to define the sample size for future case control studies.

Evaluation of some aromatic plant extracts for mosquito larvicidal potential against Culex quinquefasciatus, Aedes aegypti, and Anopheles stephensi.

In the present investigation, larvicidal potential of hexane, choloroform, ethyl acetate, acetone, and methanol extracts of seven aromatic plants, viz., Blumea mollis, Chloroxylon swietenia, Clausena anisata, Feronia limnonia, Lantana camera, Plectranthus amboinicus, and Tagetes erecta were screened against Culex quinquefasciatus, Aedes aegypti, and Anopheles stephensi. The larval mortality was observed after 12 and 24 h of exposure period. The results revealed that all the extracts showed varied levels of larvicidal activity against the mosquito species tested. However, the ethyl acetate extract of Chloroxylon swietenia showed the remarkable larvicidal activity against C. quinquefasciatus, Ae. aegypti, and An. stephensi. After 12 h of exposure period, the larvicidal activity was LC50 = 194.22 and LC90 = 458.83 ppm (C. quinquefasciatus), LC50 = 173.04 and LC90 = 442.73 ppm (Ae. aegypti), and LC50 = 167.28 and LC90 = 433.07 ppm (An. stephensi), and the larvicidal activity after 24-h exposure period was LC50 = 94.12 and LC90 = 249.83 ppm (C. quinquefasciatus), LC50 = 80.58 and LC90 = 200.96 ppm (Ae. aegypti), and LC50 = 76.24 and LC90 = 194.51 ppm (An. stephensi). The larvicidal potential of other plant extracts were in order of ethyl acetate extract of Clausena anisata > methanol extract of P. amboinicus > acetone extract of F. limonia > methanol extract of T. erecta > methanol extract of B. mollis > and methanol extract of L. camera. The results of the present study offer a possible way for further investigations to find out the active molecule responsible for the activity.

Direct costs associated with chronic kidney disease among type 2 diabetic patients in India.

The aim of this study was to estimate the direct costs of medical care among hospitalized type 2 diabetic patients with chronic kidney disease (CKD). A total of 209 (M:F, 133:76) patients were divided into groups based on the severity of kidney disease. Group 1 subjects had undergone renal transplantation (n = 12), group 2 was CKD patients on hemodialysis (n = 45), group 3 was patients with CKD, prior to end-stage renal disease (ESRD) (n = 66), and group 4 (n = 86) consisted of subjects without any complications. Details about expenditure per hospitalization, length of stay during admission, direct medical and nonmedical cost, expenditure for the previous two years, and source of bearing the expenditure were recorded in a questionnaire. Diabetic patients with CKD prior to ESRD spend more per hospitalization than patients without any complications. [Median ₹ 12,664 vs. 3,214]. The total median cost of CKD patients on hemodialysis was significantly higher than other CKD patients (INR 61,170 vs. 12,664). The median cost involved in kidney transplantation was ₹ 392,920. The total expenditure for hospital admissions in two years was significantly higher for dialysis than transplantation. Patients on hemodialysis or kidney transplantation tend to stay longer as inpatient admissions. The source of funds for the expenditure was mainly personal savings (46%). The expenditure on hospital admissions for CKD was considerably higher, and so, there is a need to develop a protocol on a cost-effective strategy for the treatment of CKD.

Endovascular treatment of acute carotid occlusion.

OBJECTIVES: Acute cervical carotid occlusion is one of the most challenging scenarios encountered in endovascular stroke treatment. PATIENTS AND METHODS: A retrospective analysis of 11 consecutive non-dissection stroke patients with concomitant cervical carotid and intracranial occlusion treated with intraarterial (IA) mechanical thrombectomy and/or pharmacologic thrombolysis over five years at two academic hospitals was performed. Data was analyzed using Fisher's exact test. RESULTS: Patients included 3 females and 8 males. Average age was 64.7 years (range 30-94 years). All patients had both cervical carotid and intracranial occlusions. Intracranial occlusion involved the internal carotid artery in 7 patients and the middle cerebral artery in 4 patients. All of the patients received intracranial IA Tissue Plasminogen Activator (tPA). Six patients received carotid stents for cervical occlusion as part of their treatment. Five patients received only IA tPA via collateral circulation. Of the patients receiving stents, 5 of 6 (83.3%) had successful recanalization (Thrombolysis in Cerebral Ischemia 2b or 3 flow). Only 1 of 5 (20%) patients who did not receive stents prior to intracranial treatment had successful recanalization. The difference in recanalization rates approached statistical significance (p=.08). There were 4 total in-hospital mortalities: 2 in the group that received stents prior to thrombolysis and 2 in the non-stent group. There were 2 clinically significant hemorrhages in the study, both in the stent group. CONCLUSIONS: Revascularization of the cervical carotid occlusion prior to treatment of the intracranial occlusion led to increased rates of recanalization in patients with tandem extracranial and intracranial occlusions. Whether a clinical benefit can be consistently derived likely relies on other factors, including the evaluation of cerebral perfusion.

The clinical and radiographic importance of distinguishing partial from near-complete reperfusion following intra-arterial stroke therapy.

BACKGROUND AND PURPOSE: Reperfusion following intra-arterial stroke therapy is associated with improved clinical outcomes. However, the degree of reperfusion needed to achieve successful outcomes is unknown. The purpose of this analysis was to determine whether the degree of reperfusion has an impact on final infarct volumes and clinical outcomes. MATERIALS AND METHODS: A retrospective analysis identified 88 consecutive patients who underwent intra-arterial therapy for acute anterior circulation stroke. Reperfusion was graded by using the TICI scale into none (TICI 0 or 1), partial (TICI 2a), or near-complete (TICI 2b/3). Baseline characteristics were compared. For each of these groups, we compared discharge disposition and final infarct volumes. RESULTS: Near-complete, partial, and no reperfusion occurred in 44.3%, 26.1%, and 29.6% of patients, respectively. Baseline characteristics were similar across all 3 groups. The median NIHSS score was 15. Significant differences in discharge disposition were seen, with 41.0% of the TICI 2b/3 group discharged home versus 17.4% of TICI 2a and 7.7% of TICI 0/1. In-hospital mortality was 12.8% for TICI 2b/3 compared with 39.1% for TICI 2a and 34.6% for TICI 0/1. Patients with near-complete reperfusion were significantly more likely to have infarct volumes ≤70 mL (OR = 12.1; 95% CI, 2.7-54.2), compared with patients with partial reperfusion (OR = 2.2; 95% CI, 0.5-9.6). CONCLUSIONS: Significant differences exist in outcomes and infarct volumes between partial (TICI 2a) and near-complete (TICI 2b/3) reperfusion following intra-arterial stroke therapy. Further trials should separately report these groups to facilitate comparison among treatment paradigms.

Chemical constituents and larvicidal potential of Feronia limonia leaf essential oil against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus.

In the present investigation, the leaf essential oil of Feronia limonia was evaluated for chemical constituents and mosquito larvicidal activity against the larvae of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus. GC and GC-MS analyses revealed that the essential oil contain 51 compounds. Estragole (34.69 %) and ß-pinene(23.59 %) were identified as the major constituents followed by methyl (Z)-caryophyllene (11.05 %), eugenol (6.50 %), linalool (3.97 %), phytol (3.27 %), sabinene (2.41 %) and limonene (2.27 %). Larval mortality was observed after 12 and 24 h of exposure period. The oil showed remarkable larvicidal activity against A. stephensi (LC(50) = 38.93 and LC(90) = 108.64 ppm (after 12 h); LC(50) = 15.03 and LC(90) = 36.69 ppm (after 24 h)), A. aegypti (LC(50) = 37.60 and LC(90) = 104.69 ppm (after 12 h); LC(50) = 11.59 and LC(90) = 42.95 ppm (after 24 h)) and C. quinquefasciatus (LC(50) = 52.08 and LC(90) = 124.33 ppm (after 12 h); LC(50) = 22.49 and LC(90) = 60.90 ppm (after 24 h)). Based on the results, the essential oil of F. limonia can be considered as a new source of larvicide for the control of vector mosquitoes.

Clinical stroke penumbra: use of National Institutes of Health stroke scale as a surrogate for CT perfusion in patient triage for intra-arterial middle cerebral artery stroke therapy.

BACKGROUND AND PURPOSE: CTP may help triage acute stroke patients for IAT, but requires additional contrast agent, radiation, and imaging time. Our aim was to determine whether clinical examination (NIHSS) with NCCT and CTA can substitute for CTP without significantly affecting IAT triage of patients with acute MCA stroke. MATERIALS AND METHODS: We reviewed NCCT, CTA, and CTP imaging performed within 8 hours of symptom onset in 36 patients presenting with MCA territory stroke (September 2007-October 2009). Two neuroradiologists reviewed, independently and by consensus, NCCT, CTA, and CTP (CTP group), and 2 different neuroradiologists blinded to CTP reviewed NCCT, CTA, and NIHSS (stroke scale group) to determine IAT eligibility: M1 or proximal M2 occlusion; infarct core <1/3 MCA territory; and ischemic penumbra >20% infarct core. The stroke scale group estimated infarct core from NCCT and CTA source images and ischemic penumbra from core size relative to NIHSS score and re-evaluated patients after unblinding to CTP. We computed intragroup and intergroup κ scores for IAT treatment recommendation and used the McNemar test to determine whether CTP significantly affected the stroke scale group's decisions. RESULTS: IAT was recommended in 16/36 (44%) and 17/36 (47%) patients by the CTP and stroke scale groups, respectively, with intragroup κ scores of 0.78 ± 0.11 versus 0.83 ± 0.09. The intergroup κ score was 0.83 ± 0.09. When unblinded to CTP, the stroke scale group revised 2/36 (5.6%) decisions, which was insignificant (P = .48, McNemar test). CONCLUSIONS: NIHSS interpreted with NCCT and CTA may be an effective substitute for CTP-derived measures in the IAT triage of patients with acute MCA stroke. Replacing CTP may potentially reduce radiation and contrast dose and time to treatment.

Incidence of extrinsic compression of the internal jugular vein in unselected patients undergoing CT angiography.

BACKGROUND AND PURPOSE: Little is known about how commonly the internal jugular vein is compressed by extrinsic structures in the upper neck. The purpose of this paper was to identify the frequency and cause of external compression of the superior segment of the internal jugular vein. MATERIALS AND METHODS: Retrospective review of CT angiograms of the neck was performed in 108 consecutive patients. Axial source images were evaluated for moderate (>50%) or severe (>80%) stenosis of the internal jugular vein on the basis of external compression. The cause of extrinsic compression was also recorded. In cases with stenosis, the presence of ipsilateral isoattenuated collateral veins was recorded and considered representative of collateral flow. RESULTS: Moderate stenosis was seen in 33.3% of right and 25.9% of left internal jugular veins. Severe stenosis was seen in 24.1% of right and 18.5% of left internal jugular veins. The most common causes of extrinsic compression included the styloid process and the posterior belly of the digastric muscle. In patients with severe internal jugular vein stenosis, 53.8% of right sides and 55% of left sides had associated condylar collaterals. CONCLUSIONS: Extrinsic compression of the superior segment of the internal jugular vein is a common finding in unselected patients, often caused by the styloid process or the posterior belly of the digastric muscle. Presence of severe stenosis is not universally associated with collateral formation.