Profile of and risk factors for poststroke cognitive impairment in diverse ethno-regional groups

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethno-racial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethno-racial differences that warrant attention in the development of prevention strategies.OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.Peer reviewe

Distinctive Effects of CCR5, CCR2, and SDF1 Genetic Polymorphisms in AIDS Progression

The Genetics of Resistance to Infection by HIV-1 (GRIV) cohort represents 200 nonprogressor/slow-progressor (Slowprog) and 90 fast-progressor (Fastprog) HIV-1-infected patients. Using this unique assembly, we performed genetic studies on three recently discovered polymorphisms of CCR5, CCR2, and SDFI, which have been shown to slow the rate of disease progression. The increased prevalence of mutant alleles among Slowprogs from the GRIV cohort was significant for CCR5 (p \u3c .0001) but not for CCR2 (p = .09) or SDF1 (p = .12), emphasizing the predominant role of CCR5 as the major HIV-1 coreceptor. However, the prevalence of the CCR2 mutant allele (64I) was significantly increased among Slowprogs homozygous for wild-type CCR5 compared with Fastprogs (p = .04). The prevalence of double mutants SDF1- 3\u27A/3\u27A genotypes was also increased among Slowprogs homozygous for wild-type CCR5 compared with Fastprogs (p = .05). The effects of the CCR2 and SDF1 mutations are overshadowed by the protective effects of the CCR5 deletion. Predictive biologic markers such as CD4 cell counts or viral load in the Slowprog population did not show significant differences between Slowprog groups with wild-type or mutant alleles for the three genes. Thus, our data suggest that the effects of these genes are exerted earlier in infection and no longer evident in the Slowprog of the GRIV cohort whose average duration of HIV infection is 12 years. We conclude that these genes, whose products serve as viral coreceptors or their ligands, may play a role early in infection and delay the onset of disease. However, among Slowprogs, whose duration of infection is \u3e8 years, they are no longer influential for maintenance of their longterm nonprogression status. Other genetic determinants may be responsible for late protective effects

Should Patients With Acute Minor Ischemic Stroke With Isolated Internal Carotid Artery Occlusion Be Thrombolysed?

International audienceBACKGROUND: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT-as compared to no-IVT-may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation. METHODS: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score <6) isolated internal carotid artery occlusion patients treated within 4.5 hours of symptoms onset with either IVT or antithrombotic therapy between 2006 and 2020 (inclusion date varied among centers). Primary outcome was END within 24 hours (≥q4 National Institutes of Health Stroke Scale points increase within 24 hours), and secondary outcomes were END within 7 days (END(7d)) and 3-month modified Rankin Scale score 0 to 1. RESULTS: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END(7d) occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07-3.92]; P=0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P=0.09). However, END(7d) and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END(7d): adjusted hazard ratio, 1.29 [95% CI, 0.75-2.23]; P=0.37; modified Rankin Scale score of 0-1: adjusted odds ratio, 1.1 [95% CI, 0.6-2.2]; P=0.71). END(7d) occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9-10.1) versus 20.4 hours (interquartile range, 7.8-34.4), respectively, P<0.01. CONCLUSION: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END-particularly END due to artery-to-artery embolism-occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population

Thrombus Length Predicts Lack of Post-Thrombolysis Early Recanalization in Minor Stroke With Large Vessel Occlusion

International audienceBackground and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results- Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2-4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4-13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21-1.92; P<0.001). The C statistic of susceptibility vessel sign length for no-ER prediction was 0.82 (95% CI, 0.73-0.92), and the optimal cutoff (Youden) was 9 mm. Sensitivity and specificity of this cutoff for no-ER were 67.8% (95% CI, 55.9-79.7) and 84.6% (95% CI, 70.7-98.5), respectively. Conclusions- ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population