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BACKGROUND AND PURPOSE: Little is known on long-term follow-up after thrombolysis in ischemic stroke patients because the majority of studies evaluated outcome at 3 to 12 months. We aimed to assess 5-year outcome after intravenous thrombolysis (IVT). METHODS: Cohort study based on the prospective registry of all consecutive ischemic stroke patients submitted to IVT in our Stroke Unit. Five-year outcome, including living settings, functional outcome, stroke recurrence, and mortality, was ascertained by telephonic interviews and additional review of clinical records. Multivariate analyses were performed to identify predictors of outcome and mortality. Excellent outcome was defined as modified Rankin scale 0 to 1. RESULTS: Five-year outcome was available for 155/164 patients submitted to IVT. At 5 years, 32.9% of patients had an excellent outcome (95% confidence interval (CI) =25.5-43.3) and mortality was 43.9% (95%CI=36.1-51.7). Increasing age (odds ratio =0.93, 95% CI =0.90-0.97) and increasing National Institute of Health Stroke Scale (NIHSS) 24 h after thrombolysis (odds ratio =0.81, 95% CI =0.74-0.90) were independently associated with a lower likelihood of an excellent 5-year outcome. Age (hazards ratio =1.07, 95% CI =1.03-1.11) and excellent functional outcome 3 months after thrombolysis (hazards ratio =0.28, 95%CI=0.12-0.66) were independently associated with mortality during follow-up. CONCLUSIONS: One third of ischemic stroke patients have excellent 5-year outcome after IVT. Younger age, lower NIHSS 24 h after IVT, and excellent 3-month functional outcome are independent predictors of excellent 5-year outcome.

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BACKGROUND AND PURPOSE: Dramatic recovery (DR) after thrombolysis is dependent of vessel recanalization and is predictive of favorable clinical outcome. Successful recanalization is not equivalent to DR. Our objective was to assess its frequency and evaluate clinical and biochemical predictors and their prognosis. METHODS: We analyzed prospectively registered data from January 2007 to September 2012. All patients with anterior circulation stroke and NIHSS≥10 were included. Improvement of ≥10 or a score ≤3 24h after thrombolysis was defined as DR. RESULTS: In the 230 patients included, DR frequency was 23% (53 patients). DR group had lower admission NIHSS (14 vs 17, p=0.024), less total anterior circulation infarcts (p=0.009), more partial anterior circulation infarcts (p=0.003) and lower blood glucose on admission (118 vs 128mg/dL, p=0.013). All patients with DR had an Alberta Stroke Program Early CT Score (ASPECTS) ≥7, vs 89.3% without DR (p=0.013). Arterial recanalization, defined as hyperdense middle cerebral artery sign disappearance on control CT, was more frequent in the DR group (68.4% vs 14.1%, p<0.001). Intracranial hemorrhage on 24h-control CT scan was less frequent in the DR group (p<0.001). Multinomial logistic regression analysis showed that ASPECTS score was an independent predictor of DR (OR=2.35, 95%CI=1.32-4.16, p=0.003) and CT evidence of recanalization was independently associated with DR (OR=11.60, 95%CI, 3.02-44.53, p<0.001). CONCLUSION: DR is a frequent occurrence. ASPECTS score is an independent predictor of DR, which is also independently associated with CT evidence of middle cerebral artery recanalization.

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It was suggested that intravenous thrombolysis (IT) leads to larger extent recanalization in cardioembolic stroke. In this work we assess if this has beneficial clinical traduction. METHOD: We evaluated 177 patients undergoing IT, which were categorized into cardioembolic (CE) and non-cardioembolic (NCE). National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale were compared. RESULTS: The mean age was 67.4±12.01 and 53.8 percent were male. The mean NIHSS was: 14 (admission), 9 (24 h) and 6 (discharge), similar in subgroups. The difference between NIHSS at admission and 24 hours was 4.17±4.92 (CE: 4.08±4.71; NCE: 4.27±5.17, p=0.900) and at admission and discharge there was an average difference of 6.74±5.58 (CE: 6.97±5.68; NCE: 6.49±5.49, p=0.622). The mRS at discharge and 3 months was not significantly different by subtype, although individuals whose event was NCE are more independent at 3 months. CONCLUSION: Ours findings argue against a specific paper of IT in CE. It can result from heterogeneity of NCE group.

Alguns estudos sugerem que a trombólise endovenosa (TE) conduz a melhor recanalização nos acidentes vasculares cerebrais isquêmicos (AVCI) cardioembólicos. Neste trabalho questionamos se isto terá tradução em benefício clínico. MÉTODO: Avaliamos 177 doentes submetidos a TE, os quais foram categorizados como cardioembólicos (CE) e não cardioembólicos (NCE). Compararam-se a National Institutes of Health Stroke Scale (NIHSS) e escala de Rankin modificada. RESULTADOS: A idade média foi 67,4±12,01 e 53,8 por cento eram homens. NIHSS média foi: 14 (admissão), 9 (24 h), 6 (alta), semelhante nos subgrupos. A diferença entre NIHSS à admissão e 24 h foi de 4,17±4,92 (CE: 4,08±4,71; NCE: 4,27±5,17, p=0,900) e entre a admissão e a alta de 6,74±5,58 (CE: 6,97±5,68; NCE: 6,49±5,49, p=0,622). A classificação na mRS não foi significativamente diferente nos subgrupos (alta e 3 meses), mas os doentes com eventos NCE estavam mais independentes aos 3 meses. CONCLUSÃO: Os nossos resultados não documentam um papel específico da TE nos CE, o que pode resultar da heterogeneidade do grupo NCE.

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UNLABELLED: It was suggested that intravenous thrombolysis (IT) leads to larger extent recanalization in cardioembolic stroke. In this work we assess if this has beneficial clinical traduction. METHOD: We evaluated 177 patients undergoing IT, which were categorized into cardioembolic (CE) and non-cardioembolic (NCE). National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale were compared. RESULTS: The mean age was 67.4 ± 12.01 and 53.8% were male. The mean NIHSS was: 14 (admission), 9 (24 h) and 6 (discharge), similar in subgroups. The difference between NIHSS at admission and 24 hours was 4.17 ± 4.92 (CE: 4.08 ± 4.71; NCE: 4.27 ± 5.17, p=0.900) and at admission and discharge there was an average difference of 6.74 ± 5.58 (CE: 6.97 ± 5.68; NCE: 6.49 ± 5.49, p=0.622). The mRS at discharge and 3 months was not significantly different by subtype, although individuals whose event was NCE are more independent at 3 months. CONCLUSION: Ours findings argue against a specific paper of IT in CE. It can result from heterogeneity of NCE group.

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Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.

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BACKGROUND: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. METHODS: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. RESULTS: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.

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