Browsing by Author "Ferro, J"
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- Cerebral venous thrombosis causing posterior fossa lesions: description of a case series and assessment of safety of anticoagulation.Publication . Sousa, D; Ferro, J; Canhão, P; Barinagarrementeria, F; Bousser, MG; Stam, J; Pinto, A; Baptista, M; Béjot, Y; Dequatre-Poncelle, NBACKGROUND: Isolated posterior fossa parenchymal lesions associated with cerebral venous thrombosis (CVT) are rare. Posterior fossa lesions are an independent predictor of death in CVT. We aim to describe the characteristics and outcome of patients with CVT and isolated posterior fossa lesions and assess the safety of anticoagulation in patients with posterior fossa lesions associated with CVT. METHODS: We retrieved data from all patients with posterior fossa parenchymal lesions in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort related to clinical features, therapy and outcome. Fisher's exact test was used to evaluate associations. To assess the safety of anticoagulation in CVT patients with posterior fossa lesions we considered all patients with a lesion in this topography, either isolated or with concomitant supratentorial lesions, and compared the rate of new intracranial haemorrhages on repeated imaging with the remaining cohort. RESULTS: Out of 624 patients, 12 had isolated posterior fossa lesions and 14 had posterior fossa lesion with accompanying supratentorial lesions. The lateral sinus was most frequently occluded (n = 11). Involvement of the superior sagittal sinus was significantly less frequent compared to the remaining patients of the cohort (p = 0.013). None of the patients with isolated posterior fossa lesion died but 3 remained dependent on follow-up. Poor outcome (modified Rankin Scale ≥3) was more frequent in patients with any posterior fossa lesion, even when on anticoagulation (29.2% vs. 11.9%; OR 3.04; 95% CI 1.2-7.6; p = 0.018). Of the 24 anticoagulated patients with a posterior fossa lesion, 3 (12.5%) had new haemorrhages on repeated imaging, compared with 30 out of 495 anticoagulated patients (6.1%) without posterior fossa lesions (p = 0.19). CONCLUSIONS: We describe the largest series of CVT patients with associated posterior fossa lesions. When compared to anticoagulated CVT patients without posterior fossa lesions, CVT patients with posterior fossa lesions on full anticoagulation did not have a significant increase in the rate of new intracranial haemorrhages.
- Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial)Publication . Dávalos, A; Alvarez-Sabin, J; Castillo, J; Diez-Tejedor, E; Ferro, J; Martinez-Vila, E; Serena, J; Segura, T; Cruz, V; Masjuan, J; Cobo, E; Secades, J; Salgado, AV; International Citicoline Trial on acUte Stroke (ICTUS) trial investigatorsBACKGROUND: Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis. We sought to confirm the efficacy of citicoline in a larger trial. METHODS: We undertook a randomised, placebo-controlled, sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany, Portugal, and Spain. Using a centralised minimisation process, patients were randomly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms (1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [2×500 mg oral tablets given every 12 h]). All study participants were masked. The primary outcome was recovery at 90 days measured by a global test combining three measures of success: National Institutes of Health Stroke Scale ≤1, modified Rankin score ≤1, and Barthel Index ≥95. Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator, neurological deterioration, and mortality. This trial is registered, NCT00331890. RESULTS: 2298 patients were enrolled into the study from Nov 26, 2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in Germany recruited patients. Of the 2298 patients who gave informed consent and underwent randomisation, 1148 were assigned to citicoline and 1150 to placebo. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. The final randomised analysis was based on data for 2298 patients: 1148 in citicoline group and 1150 in placebo group. Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364). No significant differences were reported in the safety variables nor in the rate of adverse events. INTERPRETATION: Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke.
- Diagnosis of stroke by the nonneurologist: a validation study.Publication . Ferro, J; Pinto, A; Falcão, I; Rodrigues, G; Ferreira, J; Falcão, F; Azevedo, E; Canhão, P; Melo, T; Rosas, MJ; Oliveira, V; Salgado, AVBACKGROUND AND PURPOSE: The first medical contact of an acute stroke victim is often a nonneurologist. Validation of stroke diagnosis made by these medical doctors is poorly known. The present study seeks to validate the stroke diagnoses made by general practitioners (GPs) and hospital emergency service physicians (ESPs). METHODS: Validation through direct interview and examination by a neurologist was performed for diagnoses of stroke made by GPs in patients under their care and doctors working at the emergency departments of 3 hospitals. RESULTS: Validation of the GP diagnosis was confirmed in 44 cases (85%); 3 patients (6%) had transient ischemic attacks and 5 (9%) suffered from noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in 169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most frequent conditions misdiagnosed as stroke were neurological in nature (cerebral tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo, 1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical disorders, 7). CONCLUSIONS: In the majority of cases, nonneurologists (either GPs or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke with drugs that do not cause serious side effects can be started before evaluation by a neurologist and CT scan.
- Kalirin: a novel genetic risk factor for ischemic strokePublication . Krug, T; Manso, H; Gouveia, L; Sobral, J; Xavier, J; Albergaria, I; Gaspar, G; Correia, M; Viana-Baptista, M; Simões, R; Pinto, A; Taipa, R; Ferreira, C; Fontes, J; Silva, M; Gabriel, J; Matos, I; Lopes, G; Ferro, J; Vicente, A; Oliveira, SCerebrovascular 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.
- Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients.Publication . Rosa, A; Fonseca, B; Krug, T; Manso, H; Gouveia, L; Albergaria, I; Gaspar, G; Correia, M; Viana-Baptista, M; Simões, R; Pinto, A; Taipa, R; Ferreira, C; Fontes, J; Silva, M; Gabriel, J; Matos, I; Lopes, G; Ferro, J; Vicente, A; Oliveira, SBACKGROUND: 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.
- Mutations of the GLA gene in young patients with stroke: the PORTYSTROKE study-screening genetic conditions in Portuguese young stroke patientsPublication . Baptista, V; Ferreira, S; Pinho-e-Melo, T; Carvalho, M; Cruz, V; Carmona, C; Silva, F; Tuna, A; Rodrigues, M; Ferreira, C; Pinto, A; Leitão, A; Gabriel, J; Calado, S; Oliveira, J; Ferro, JBACKGROUND AND PURPOSE: Fabry disease is an X-linked monogenic disorder caused by mutations in the GLA gene. Recent data suggest that stroke in young adults may be associated with Fabry disease. We aimed to ascertain the prevalence of this disorder among young adult patients with stroke in Portugal by GLA genotyping. METHODS: During 1 year, all patients aged 18 to 55 years with first-ever stroke, who were admitted into any of 12 neurology hospital departments in Portugal, were prospectively enrolled (n=625). Ischemic stroke was classified according to Trial of Org 10172 in Acute Stroke Treatment criteria. Alpha-galactosidase activity was further assayed in all patients with GLA mutations. RESULTS: Four hundred ninety-three patients (mean age, 45.4 years; 61% male) underwent genetic analyses: 364 with ischemic stroke, 89 with intracerebral hemorrhage, 26 with subarachnoid hemorrhage, and 14 with cerebral venous thrombosis. Twelve patients had missense GLA mutations: 9 with ischemic stroke (p.R118C: n=4; p.D313Y: n=5), including 5 patients with an identified cause of stroke (cardiac embolism: n=2; small vessel disease: n=2; other cause: n=1), 2 with intracerebral hemorrhage (p.R118C: n=1; p.D313Y: n=1), and one with cerebral venous thrombosis (p.R118C: n=1). Leukocyte alpha-galactosidase activity was subnormal in the hemizygous males and subnormal or low-normal in the heterozygous females. Estimated prevalence of missense GLA mutations was 2.4% (95% CI, 1.3% to 4.1%). CONCLUSIONS: Despite a low diagnostic yield, screening for GLA mutations should probably be considered in different types of stroke. Restricting investigation to patients with cryptogenic stroke may underestimate the true prevalence of Fabry disease in young patients with stroke.