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1.
N Engl J Med ; 390(18): 1677-1689, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38718358

ABSTRACT

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).


Subject(s)
Infarction, Anterior Cerebral Artery , Stroke , Thrombectomy , Thrombolytic Therapy , Aged , Aged, 80 and over , Female , Humans , Male , Cerebral Hemorrhage/etiology , Combined Modality Therapy , Endovascular Procedures , Magnetic Resonance Imaging , Stroke/diagnostic imaging , Stroke/etiology , Stroke/therapy , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/methods , Tomography, X-Ray Computed , Brain Infarction/diagnostic imaging , Brain Infarction/etiology , Brain Infarction/therapy , Acute Disease , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/surgery , Cerebral Arterial Diseases/complications , Cerebral Arterial Diseases/diagnostic imaging , Cerebral Arterial Diseases/pathology , Cerebral Arterial Diseases/surgery , Infarction, Anterior Cerebral Artery/diagnostic imaging , Infarction, Anterior Cerebral Artery/pathology , Infarction, Anterior Cerebral Artery/surgery
3.
Cortex ; 160: 55-66, 2023 03.
Article in English | MEDLINE | ID: mdl-36745966

ABSTRACT

Apathy occurs in approximately one third of people after stroke. Despite its frequency and functional consequences, the determinants of apathy have only been partially defined. The major difficulty lies in disentangling the reduction in activity due to apathy itself from those secondary to comorbidities, such as depression, sensorimotor deficits, and cognitive impairment. Here, we aimed to examine the prevalence of apathy, identify confounding sources of hypoactivity, and define its neuroimaging determinants using multivariate voxel lesion symptom-mapping (mVLSM) analyses. We assessed apathy in a subgroup (n = 325, mean age: 63.8 ± 10.5 years, 91.1% ischemic stroke) of the GRECogVASC cohort using the validated Behavioral Dysexecutive Syndrome Inventory, interpreted using GREFEX criteria, as well as confounding factors (depression, anxiety, severity of the neurological deficit, and gait disorders). mVLSM analysis was used to define neuroimaging determinants and was repeated after controlling for confounding factors. Apathy was present for 120 patients (36.9%, 95% CI: 31.7-42.2). Stepwise linear regression identified three factors associated with apathy: depressive symptoms (R2 = .3, p = .0001), cognitive impairment (R2 = .015, p = .02), and neurological deficit (R2 = .110, p = .0001). Accordingly, only 9 (7.5%) patients had apathy without a confounding factor, i.e., isolated apathy. In conventional VLSM analysis, apathy was associated with a large number of subcortical lesions that were no longer considered after controlling for confounding factors. Strategic site analysis identified five regions associated with isolated apathy: the F3 orbitalis pars, left amygdala, left thalamus, left pallidum, and mesencephalon. mVLSM analysis identified four strategic sites associated with apathy: the right corticospinal tract (R2 = .11; p = .0001), left frontostriatal tract (R2 = .11; p = .0001), left thalamus (R2 = .04; p = .0001), and left amygdala (R2 = .01; p = .013). These regions remained significant after controlling for confounding factors but explained a lower amount of variance. These findings indicate that poststroke apathy is more strongly associated with depression, neurological deficit, and cognitive impairment than with stroke lesions locations, at least using VLSM analysis.


Subject(s)
Apathy , Cognitive Dysfunction , Stroke , Humans , Middle Aged , Aged , Magnetic Resonance Imaging , Neuropsychological Tests , Cognitive Dysfunction/psychology , Cognition , Depression
4.
Stroke ; 53(11): 3304-3312, 2022 11.
Article in English | MEDLINE | ID: mdl-36073368

ABSTRACT

BACKGROUND: 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 (≥4 National Institutes of Health Stroke Scale points increase within 24 hours), and secondary outcomes were END within 7 days (END7d) 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 END7d 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, END7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END7d: 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). END7d 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. CONCLUSIONS: 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.


Subject(s)
Arterial Occlusive Diseases , Brain Ischemia , Carotid Artery Diseases , Ischemic Stroke , Stroke , Thrombosis , Humans , Fibrinolytic Agents/therapeutic use , Thrombolytic Therapy/methods , Carotid Artery, Internal/diagnostic imaging , Retrospective Studies , Treatment Outcome , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/drug therapy , Arterial Occlusive Diseases/complications , Stroke/diagnostic imaging , Stroke/drug therapy , Stroke/etiology , Carotid Artery Diseases/complications , Thrombosis/drug therapy , Anticoagulants/therapeutic use , Brain Ischemia/diagnostic imaging , Brain Ischemia/drug therapy , Brain Ischemia/complications , Thrombectomy/methods
5.
Eur J Neurol ; 29(7): 1972-1982, 2022 07.
Article in English | MEDLINE | ID: mdl-35276029

ABSTRACT

BACKGROUND AND PURPOSE: The aim of this study was to determine the contributions of background disorders responsible for participation restriction as indexed by a structured interview for the modified Rankin Scale (mRS-SI). METHODS: A subset of 256 patients was assessed at 6 months after stroke using the National Institutes of Health Stroke Scale (NIHSS), gait score, comprehensive cognitive battery (yielding a global cognitive Z-score), behavioral dysexecutive disorders (DDs), anxiety and depressive symptoms, epilepsy, and headache. Following bivariate analyses, determinants of participation restriction were selected using ordinal regression analysis with partial odds. RESULTS: Poststroke participation restriction (mRS-SI score > 1) was observed in 59% of the patients. In bivariate analyses, mRS-SI score was associated with prestroke mRS-SI score, 6-month NIHSS score, gait score, global cognitive Z-score, behavioral DDs, and presence of anxiety and depression (all: p = 0.0001; epilepsy: p =0.3; headache: p = 0.7). After logistic regression analysis, NIHSS score was associated with increasing mRS-SI score (p = 0.00001). Prestroke mRS-SI score (p = 0.00001), behavioral DDs (p = 0.0008) and global cognitive Z-score (p = 0.01) were associated with both mRS-SI score > 1 and mRS-SI score > 2. In addition, gait score was associated with mRS-SI score > 2 (p = 0.00001). This model classified 85% of mRS-SI scores correctly (p = 0.001). Structural equation modeling showed the contributions of gait limitation (standardized coefficient [SC]: 0.68; p = 0.01), prestroke mRS-SI (SC: 0.41; p = 0.01), severity of neurological impairment (SC: 0.16; p = 0.01), global cognitive Z-score (SC: -0.14; p = 0.05), and behavioral DDs (SC: 0.13; p = 0.01). CONCLUSION: These results provide a statistical model of weights of determinants responsible for poststroke participation restriction and highlight a new independent determinant: behavioral DDs.


Subject(s)
Disabled Persons , Stroke , Disability Evaluation , Headache , Humans , Stroke/diagnosis , Time Factors
6.
JAMA Neurol ; 78(3): 321-328, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33427887

ABSTRACT

Importance: The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy. Objective: To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO. Design, Setting, and Participants: This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019. Main Outcomes and Measures: ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause. Results: Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively. Conclusions and Relevance: The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.


Subject(s)
Administration, Intravenous/trends , Cerebrovascular Disorders/therapy , Mechanical Thrombolysis/trends , Stroke/therapy , Thrombolytic Therapy/trends , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous/methods , Aged , Aged, 80 and over , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/epidemiology , Cohort Studies , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Mechanical Thrombolysis/methods , Middle Aged , Nervous System Diseases/diagnostic imaging , Nervous System Diseases/epidemiology , Nervous System Diseases/therapy , Predictive Value of Tests , Retrospective Studies , Stroke/diagnostic imaging , Stroke/epidemiology , Thrombolytic Therapy/methods
7.
Neurology ; 91(21): e1979-e1987, 2018 11 20.
Article in English | MEDLINE | ID: mdl-30333160

ABSTRACT

OBJECTIVE: To validate the ability of a specifically developed cognitive risk score to identify patients at risk of poststroke neurocognitive disorders (NCDs) who are eligible for a comprehensive cognitive assessment. METHODS: After assessing 404 patients (infarct 91.3%) in the Groupe de Réflexion pour l'Evaluation Cognitive VASCulaire (GRECogVASC) cross-sectional study with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network battery 6 months after stroke, we used multivariable logistic regression and bootstrap analyses to determine factors associated with NCDs. Independent, internally validated factors were included in a cognitive risk score. RESULTS: Cognitive impairment was present in 170 of the 320 patients with a Rankin Scale score ≥1. The backward logistic regression selected 4 factors (≥73% of the permutations): NIH Stroke Scale score on admission ≥7 (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.29-4.3, p = 0.005), multiple strokes (OR 3.78, 95% CI 1.6-8, p = 0.002), adjusted Mini-Mental State Examination (MMSEadj) score ≤27 (OR 6.69, 95% CI 3.9-11.6, p = 0.0001), and Fazekas score ≥2 (OR 2.34, 95% CI 1.3-4.2, p = 0.004). The cognitive risk score computed with these 4 factors provided good calibration, discrimination (overoptimism-corrected C = 0.793), and goodness of fit (Hosmer-Lemeshow test p = 0.99). A combination of Rankin Scale score ≥1, cognitive risk score ≥1, and MMSEadj score ≥21 selected 230 (56.9%) of the 404 patients for a comprehensive assessment. This procedure yielded good sensitivity (96.5%) and moderate specificity (43%; positive predictive value 0.66, negative predictive value 0.91) and was more accurate (p ≤ 0.03 for all) than the sole use of screening tests (MMSE or Montréal Cognitive Assessment). CONCLUSION: The GRECogVASC cognitive risk score comprises 4 easily documented factors; this procedure helps to identify patients at risk of poststroke NCDs who must therefore undergo a comprehensive assessment. CLINICALTRIALSGOV IDENTIFIER: NCT01339195.


Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/etiology , Neuropsychological Tests , Stroke/complications , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
8.
Stroke ; 49(11): 2666-2673, 2018 11.
Article in English | MEDLINE | ID: mdl-30355190

ABSTRACT

Background and Purpose- We aimed to define the neuroimaging determinants of poststroke cognitive performance and their relative contributions among a spectrum of magnetic resonance imaging markers, including lesion burden and strategic locations. Methods- We prospectively included patients with stroke from the GRECogVASC study (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) who underwent 3-T magnetic resonance imaging and a comprehensive standardized battery of neuropsychological tests 6 months after the index event. An optimized global cognitive score and neuroimaging markers, including stroke characteristics, cerebral atrophy markers, and small vessel diseases markers, were assessed. Location of strategic strokes was determined using a specifically designed method taking into account stroke size and cerebral atrophy. A stepwise multivariable linear regression model was used to identify magnetic resonance imaging determinants of cognitive performance. Results- Data were available for 356 patients (mean age: 63.67±10.6 years; 326 [91.6%] of the patients had experienced an ischemic stroke). Six months poststroke, 50.8% of patients presented with a neurocognitive disorder. Strategic strokes (right corticospinal tract, left antero-middle thalamus, left arcuate fasciculus, left middle frontal gyrus, and left postero-inferior cerebellum; R2=0.225; P=0.0001), medial temporal lobe atrophy ( R2=0.077; P=0.0001), total brain tissue volume ( R2=0.028; P=0.004), and stroke volume ( R2=0.013; P=0.005) were independent determinants of cognitive performance. Strategic strokes accounted for the largest proportion of the variance in the cognitive score (22.5%). The white matter hyperintensity burden, brain microbleeds, and dilated perivascular spaces were not independent determinants. Conclusions- Optimized global cognitive score and combined approach of both quantitative measures related to structure loss and qualitative measures related to the presence of strategic lesion are required to improve the determination of structure-function relationship of cognitive performance after stroke.


Subject(s)
Brain/diagnostic imaging , Cognition , Stroke/diagnostic imaging , Aged , Atrophy , Brain/pathology , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/epidemiology , Cerebral Small Vessel Diseases/psychology , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Neuropsychological Tests , Severity of Illness Index , Stroke/epidemiology , Stroke/psychology , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology , Thalamus/diagnostic imaging , Thalamus/pathology , White Matter/diagnostic imaging , White Matter/pathology
9.
Am J Emerg Med ; 35(5): 716-719, 2017 May.
Article in English | MEDLINE | ID: mdl-28096032

ABSTRACT

BACKGROUND AND PURPOSE: Following the reorganization of a University Medical Center onto a single campus, an Intensive Care Unit was created within the adult Emergency Department (ED ICU). We assessed the effects of these organizational changes on acute stroke management and the intravenous administration of recombinant tissue plasminogen activator (IV rtPA), as characterized by the thrombolysis rate, door-to-needle time (DNT) and outcome at 3months. METHODS: Between October 2013 and September 2015, we performed a retrospective, observational, single-center, comparative study of patients admitted for ischemic stroke and treated with IV rtPA during two 321-day periods (before and after the creation of the ED ICU). All patients with ischemic stroke were included. Multivariable logistic regression models were performed. The DNT was stratified according to a threshold of 60min. A favorable long-term outcome was defined as a modified Rankin score≤2 at 3months. RESULTS: A total of 1334 ischemic stroke patients were included. Among them, 101 patients received IV rtPA. The frequency of IV rtPA administration was 5.8% (39 out of 676) before the creation of the ED ICU, and 9.3% (62 out of 668) afterwards (odds ratio (OR) [95% confidence interval (CI)]: 1.67 [1.08-2.60]; p=0.02). Additionally, the DNT was shorter (OR [95%CI]: 4.30 [1.17-20.90]; p=0.04) and there was an improvement in the outcome (OR [95%CI]=1.30 [1.01-2.10]; p=0.045). CONCLUSION: Our results highlight the benefits of a separate ED ICU within conventional ED for acute stroke management, with a higher thrombolysis rate, reduced intrahospital delays and better safety.


Subject(s)
Early Medical Intervention/organization & administration , Emergency Service, Hospital/organization & administration , Intensive Care Units/organization & administration , Organizational Innovation , Stroke/therapy , Thrombolytic Therapy/methods , Time-to-Treatment/statistics & numerical data , Administration, Intravenous , Aged , Brain Ischemia/diagnosis , Brain Ischemia/therapy , Early Medical Intervention/standards , Emergency Service, Hospital/trends , Female , Fibrinolytic Agents/administration & dosage , France , Humans , Intensive Care Units/trends , Male , Outcome and Process Assessment, Health Care , Patient Safety , Retrospective Studies , Stroke/diagnosis , Stroke/physiopathology , Time Factors , Tissue Plasminogen Activator/administration & dosage
10.
Neurology ; 87(23): 2416-2426, 2016 Dec 06.
Article in English | MEDLINE | ID: mdl-27815401

ABSTRACT

OBJECTIVE: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia. METHODS: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under ClinicalTrials.gov identifier no. NCT01614080. RESULTS: We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26-10.34). CONCLUSIONS: The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.


Subject(s)
Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Aged , Aged, 80 and over , Brain Ischemia/complications , Brain Ischemia/mortality , Cerebral Hemorrhage/complications , Disability Evaluation , Female , Fibrinolytic Agents/chemistry , Humans , Male , Middle Aged , Recombinant Proteins/chemistry , Recombinant Proteins/therapeutic use , Seizures/complications , Severity of Illness Index , Stroke/complications , Stroke/mortality , Time-to-Treatment , Tissue Plasminogen Activator/chemistry , Treatment Outcome
11.
Nat Genet ; 47(1): 78-83, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25420145

ABSTRACT

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.


Subject(s)
Alleles , Carotid Artery, Internal, Dissection/genetics , Microfilament Proteins/genetics , Polymorphism, Single Nucleotide , Vertebral Artery Dissection/genetics , Adult , Brain Ischemia/epidemiology , Brain Ischemia/genetics , Carotid Artery, Internal, Dissection/epidemiology , Female , Finland/epidemiology , Follow-Up Studies , Genetic Pleiotropy , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Hypercholesterolemia/epidemiology , Hypertension/epidemiology , Male , Microfilament Proteins/physiology , Middle Aged , Migraine Disorders/epidemiology , Myocardial Infarction/epidemiology , Obesity/epidemiology , Odds Ratio , Risk Factors , Vertebral Artery Dissection/epidemiology
12.
Int J Stroke ; 10(3): 360-3, 2015 Apr.
Article in English | MEDLINE | ID: mdl-23227939

ABSTRACT

BACKGROUND: Stroke in patients with acute cervical artery dissection may be anticipated by initial transient ischemic or nonischemic symptoms. AIM: Identifying risk factors for delayed stroke upon cervical artery dissection. METHODS: Cervical artery dissection patients from the multicenter Cervical Artery Dissection and Ischemic Stroke Patients study were classified as patients without stroke (n = 339), with stroke preceded by nonstroke symptoms (delayed stroke, n = 244), and with stroke at onset (n = 382). Demographics, clinical, and vascular findings were compared between the three groups. RESULTS: Patients with delayed stroke were more likely to present with occlusive cervical artery dissection (P < 0.001), multiple cervical artery dissection (P = 0.031), and vertebral artery dissection (P < 0.001) than patients without stroke. No differences were observed in age, smoking, arterial hypertension, hypercholesterolemia, migraine, body mass index, infections during the last week, and trauma during the last month, but patients with delayed stroke had less often transient ischemic attack (P < 0.001) and local signs (Horner syndrome and cranial nerve palsy; P < 0.001). CONCLUSIONS: Occlusive cervical artery dissection, multiple cervical artery dissection, and vertebral artery dissection were associated with an increased risk for delayed stroke. No other risk factors for delayed stroke were identified. Immediate cervical imaging of cervical artery dissection patients without ischemic stroke is needed to identify patients at increased risk for delayed ischemia.


Subject(s)
Stroke/diagnosis , Stroke/etiology , Vertebral Artery Dissection/complications , Adult , Databases, Factual/statistics & numerical data , Female , Humans , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/etiology , Male , Middle Aged , Predictive Value of Tests , Risk Factors
13.
Neurology ; 83(22): 2023-31, 2014 Nov 25.
Article in English | MEDLINE | ID: mdl-25355833

ABSTRACT

OBJECTIVE: In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. METHODS: We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. RESULTS: Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%-1.5%) from 17 families (0.9%, 0.5%-1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. CONCLUSIONS: In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.


Subject(s)
Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/genetics , Vertebral Artery Dissection/diagnosis , Vertebral Artery Dissection/genetics , Adult , Cohort Studies , Female , Humans , Internationality , Male , Middle Aged
15.
J Neurol ; 260(5): 1324-31, 2013 May.
Article in English | MEDLINE | ID: mdl-23263596

ABSTRACT

The objective of this observational study of consecutive patients hospitalized for cerebral venous thrombosis (CVT) was to determine the prevalence of post-CVT cognitive impairment and identify factors associated with this condition. Out of a total of 73 patients hospitalized for CVT, 52 were included in the study and 44 were assessed with a comprehensive neuropsychological battery. At the last outpatient visit (mean ± SD time since CVT: 22 ± 13 months), a standardized, neuropsychological assessment was administered. Cognitive impairment was defined as significant impairment (with a cut-off at the 5th percentile) in at least two of the cognitive domains tested in the neuropsychological battery or severe aphasia or cognitive disorders with MMSE score ≤ 17 out of 30. Cognitive impairment was observed in 16 patients (31 %; 95 % CI 18-43 %): 4 with major disability precluding comprehensive assessment (3 with severe aphasia, 1 with MMSE ≤ 17) and 12 with significant impairments in at least two cognitive domains. Determinants of long-term cognitive impairment were straight sinus involvement (OR 22.4; 95 % CI 1.79-278.95; p = 0.016) and the presence of parenchymal lesions on follow-up magnetic resonance imaging (OR 7.8; 95 % CI 1.40-43.04; p = 0.019). The sole predictor of failure to return to full-time employment was cognitive impairment (OR 21.0; 95 % CI 3.35-131.44; p = 0.001). Cognitive impairment persists in up to one-third of cases of CVT. It is more frequent in patients with deep CVT and persistent parenchymal lesions and is associated with failure to return to full-time employment.


Subject(s)
Cognition Disorders/etiology , Intracranial Thrombosis/complications , Venous Thrombosis/complications , Adult , Cognition Disorders/diagnosis , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Mental Status Schedule , Middle Aged , Neuropsychological Tests , Retrospective Studies
16.
J Stroke Cerebrovasc Dis ; 22(1): 80-6, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22421024

ABSTRACT

BACKGROUND: Frequencies of cognitive impairment and dementia have not been assessed in spontaneous intracerebral hemorrhage (ICH). The objective of this study was to determine the frequencies and patterns of cognitive impairment and dementia in a cross-sectional study of consecutive patients hospitalized in a single university medical center. METHODS: Of 183 consecutive patients hospitalized between 2002 and 2006, 80 survivors were contacted and 78 were included (mean time since stroke 40 months). Thirty patients were scored with the Informant Questionnaire on Cognitive Decline in the Elderly and Instrumental Activities of Daily Living in a telephone interview, and 48 underwent a comprehensive clinical and neuropsychological assessment. RESULTS: Dementia was observed in 18 of 78 patients (23%; 95% confidence interval [CI] 13-32%) and cognitive impairment without dementia was seen in 37 of 48 patients (77%; 95% CI 65-89%). The cognitive disorders mainly concerned episodic memory (52%), psychomotor speed (44%), and executive function (37%), followed by language and visuoconstructive abilities. In a logistic regression analysis, Rankin score >1 at discharge and hemorrhage volume were the initial factors to be selected as a predictor of long-term dementia. CONCLUSIONS: This single-center, cross-sectional study revealed that the prevalence of dementia and cognitive impairment without dementia after ICH are high and are similar to those observed in cerebral infarct. Further longitudinal, prospective studies are required to assess accurately the prevalence, mechanisms and predictors of post-ICH dementia.


Subject(s)
Cerebral Hemorrhage/epidemiology , Cognition Disorders/epidemiology , Cognition , Dementia/epidemiology , Hospitals, University , Aged , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/psychology , Chi-Square Distribution , Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Cross-Sectional Studies , Dementia/diagnosis , Dementia/psychology , Disability Evaluation , Executive Function , Female , France/epidemiology , Humans , Language , Male , Memory , Middle Aged , Motor Activity , Neuropsychological Tests , Prevalence , Risk Factors , Surveys and Questionnaires , Time Factors
17.
Ther Clin Risk Manag ; 8: 87-93, 2012.
Article in English | MEDLINE | ID: mdl-22399853

ABSTRACT

BACKGROUND: The purpose of this study was to determine whether the National Institutes of Health Stroke Scale (NIHSS) score was associated with inhospital neurological and medical complications (NMC) in patients with posterior circulation infarction. METHODS: This retrospective study included all patients admitted to our stroke unit during a one-year period (n = 289). NMC included neurological deterioration (ie, worsening by 4 points or more of the NIHSS score during the hospital stay) and all other medical complications based on what was recorded in the patients' charts. RESULTS: Seventy-nine patients (27%) experienced NMC. In posterior circulation infarction patients (n = 90), patients with NMC had a higher baseline NIHSS score (10.9 versus 2.2, P = 0.004) and a baseline NIHSS score >2 (78% versus 36%, P = 0.003). In stepwise logistic regression, an NIHSS score >2 (odds ratio: 8.2; 95% confidence interval: 1.64-41.0; P = 0.01) was associated with NMC. Similar results were observed for anterior circulation infarction patients but with a higher cutoff value for NIHSS score. CONCLUSION: In ischemic stroke patients, an increased baseline NIHSS score was associated with an increased risk of NMC. This association applied to anterior-circulation as well as posterior circulation stroke, although zero on the NIHSS for posterior circulation stroke does not mean the absence of NMC during hospitalization. The clinical significance of these findings requires further evaluation in larger prospective studies.

19.
Stroke ; 42(12): 3447-53, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21940971

ABSTRACT

BACKGROUND AND PURPOSE: Although intracranial artery calcification (IAC) has been reported to be a risk factor for ischemic stroke, the prognostic implications of IAC in stroke outcome are unknown. The purpose of this study was to determine the association between IAC and risk of vascular events and death in patients with stroke after hospital discharge. METHODS: All patients with ischemic stroke over a 1-year period were included (n=302). IAC, assessed by multidetector CT, was defined as hyperdense foci (peak density>130 Hounsfield units) and assessed in the 7 major cerebral arteries. The IAC scores ranged from 0 (no calcification) to 7. Follow-up information on major clinical events (including fatal or nonfatal ischemic stroke, cardiac and peripheral artery events, and all-cause death) was obtained by means of a structured phone interview. RESULTS: IAC was present in 260 patients (83%). With a mean follow-up of 773±223 days, 88 major clinical events occurred in 67 patients (22%): 45 new ischemic vascular events (ischemic stroke: n=22; cardiac event: n=15; peripheral artery event: n=8) and 43 deaths from any cause. Patients with the highest IAC scores had significantly higher rates of death and vascular events than those with the lowest IAC scores (log rank test, P=0.029). In the Cox proportional hazards regression model, the IAC score was significantly associated with major clinical events (hazard ratio, 1.34; 95% CI, 1.11-1.61; P=0.002). CONCLUSIONS: In patients with ischemic stroke, IAC detection may constitute a simple marker of a high risk of future major clinical events.


Subject(s)
Brain Ischemia/diagnostic imaging , Calcinosis/diagnostic imaging , Cerebral Arteries/diagnostic imaging , Stroke/diagnostic imaging , Adult , Aged , Aged, 80 and over , Brain Ischemia/mortality , Calcinosis/mortality , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Discharge , Prognosis , Radiography , Risk Factors , Stroke/mortality
20.
Stroke ; 42(6): 1712-6, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21474808

ABSTRACT

BACKGROUND AND PURPOSE: A screening test is required to improve the diagnosis of poststroke cognitive impairment. The Montreal Cognitive Assessment (MoCA), a newly designed screening test, has been found to be more sensitive than Mini-Mental State Examination (MMSE), but its clinical value has not been established by means of a comprehensive neuropsychological battery. This study was designed to assess the value of MoCA and MMSE to detect poststroke cognitive impairment determined by a neuropsychological battery. METHODS: Both screening tests and a neuropsychological battery were administered during the acute phase in 95 patients referred for recent infarct or hemorrhage. Raw MMSE and MoCA scores were used with published cutoffs and new cutoff scores for MMSE and MoCA were also computed after adjustment for age and education. RESULTS: Using raw scores, MoCA was more frequently impaired (P=0.0001) than MMSE. MoCA showed good sensitivity (sensitivity, 0.94) but moderate specificity (specificity, 0.42; positive predictive value, 0.77; negative predictive value, 0.76), whereas an inverse profile was observed for MMSE (sensitivity, 0.66; specificity, 0.97; positive predictive value, 0.98; negative predictive value, 0.58). Adjusted scores with new cutoffs (MMSE(adj) ≤24, MoCA(adj) ≤20) provided good sensitivity and very good specificity for both tests (MMSE(adj): sensitivity, 0.7, specificity, 0.97, positive predictive value, 0.98, negative predictive value, 0.61; MoCA(adj): sensitivity, 0.67, specificity, 0.9, positive predictive value, 0.93, negative predictive value, 0.57). On receiver operating characteristic curve analysis, areas under the curve of all scores were >0.88. CONCLUSIONS: The previously reported high sensitivity of MoCA is associated with low specificity. Both screening tests are moderately sensitive to acute poststroke cognitive impairment. This study provides indications for the diagnosis of poststroke cognitive impairment.


Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Neuropsychological Tests , Stroke/complications , Aged , Female , Humans , Male , Mental Status Schedule , Middle Aged , ROC Curve , Reproducibility of Results , Sensitivity and Specificity
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