Marie Bodenant

Cervical artery dissection: trauma and other potential mechanical trigger events.

Objective: To examine the import of prior cervical trauma (PCT) in patients with cervical artery dissection (CeAD). Methods: In this observational study, the presence of and the type of PCT were systematically ascertained in CeAD patients using 2 different populations for comparisons: 1) age- and sex-matched patients with ischemic stroke attributable to a cause other than CeAD (non–CeAD-IS), and 2) healthy subjects participating in the Cervical Artery Dissection and Ischemic Stroke Patients Study. The presence of PCT within 1 month was assessed using a standardized questionnaire. Crude odds ratios (ORs) with 95% confidence intervals (CIs) and ORs adjusted for age, sex, and center were calculated. Results: We analyzed 1,897 participants (n = 966 with CeAD, n = 651 with non–CeAD-IS, n = 280 healthy subjects). CeAD patients had PCT in 40.5% (38.2%–44.5%) of cases, with 88% (344 of 392) classified as mild. PCT was more common in CeAD patients than in non–CeAD-IS patients (ORcrude 5.6 [95% CI 4.20–7.37], p < 0.001; ORadjusted 7.6 [95% CI 5.60–10.20], p < 0.001) or healthy subjects (ORcrude 2.8 [95% CI 2.03–3.68], p < 0.001; ORadjusted 3.7 [95% CI 2.40–5.56], p < 0.001). CeAD patients with PCT were younger and presented more often with neck pain and less often with stroke than CeAD patients without PCT. PCT was not associated with functional 3-month outcome after adjustment for age, sex, and stroke severity. Conclusion: PCT seems to be an important environmental determinant of CeAD, but was not an independent outcome predictor. Because of the characteristics of most PCTs, the term mechanical trigger event rather than trauma may be more appropriate.

Measures of Abdominal Adiposity and the Risk of Stroke The MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Study

Background and Purpose— Excess fat accumulates in the subcutaneous and visceral adipose tissue compartments. We tested the hypothesis that indicators of visceral adiposity, namely, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), are better predictors of stroke risk than body mass index (BMI). Methods– The association of BMI, WC, WHR, and WHtR with stroke was assessed in 31 201 men and 23 516 women, free of vascular disease at baseline, from the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study. During a mean follow-up of 11 years, 1130 strokes were recorded. Relative risks (95% CI) were calculated by Cox regression after stratification for center and adjustment for age, smoking, educational level, alcohol consumption, hypertension, diabetes, total cholesterol, high-density lipoprotein cholesterol, and BMI and model fit was assessed using log-likelihoods. Results— BMI, WC, WHR, and WHtR were associated with the risk of stroke in men. After full adjustment including BMI, the relative risks for stroke remained significant for WC (1.19 [1.02 to 1.34] per 1 SD increase in WC), WHR (1.14 [1.03 to 1.26]), and WHtR (1.50 [1.28 to 1.77]). Among women, the extent of the associations with stroke risk was similar for WHtR (1.31 [1.04 to 1.65]), WC (1.19 [0.96 to 1.47]), and WHR (1.08 [0.97 to 1.22]). Further analyses by World Health Organization obesity categories showed that WC, WHR, and WHtR were associated with the risk of stroke also in lean men and women (BMI <25 kg/m2), independently of confounders, cardiovascular risk factors, and BMI. Conclusions— Indicators of abdominal adiposity, especially WHtR, are more strongly associated with stroke risk than BMI. These results emphasize the importance of measuring abdominal adiposity, especially in lean subjects.

Intravenous Thrombolysis for Acute Cerebral Ischaemia: Comparison of Outcomes between Patients Treated at Working versus Nonworking Hours

Background: Stroke outcomes are worse in patients admitted at nonworking hours (NWH), but whether this is also true in patients treated with intravenous (i.v.) thrombolysis has not been definitely proven. Objective: Our aim was to test the hypothesis that stroke patients treated by i.v. rt-PA at NWH have a worse outcome than those treated at working hours (WH). Methods: We compared outcomes at 7 days and at 3 months, between patients treated at NWH and at WH in the stroke unit of the Lille University Hospital. Results: Of 252 consecutive patients [median age: 69 years; 132 men (52.4%); median National Institutes of Health Stroke Scale score: 14; median onset-to-needle time: 150 min], 134 (53.2%) were treated at NWH. They did not differ for baseline characteristics and proportion of patients with modified Rankin Scale scores 0–1 and 0–2 at 3 months. Patients treated at WH were more likely to die before 7 days (12.7 vs. 4.5%; adjusted odds ratio: 3.6; 95% confidence interval: 1.2–10.4) and at 3 months (21.6 vs. 11.4%; adjusted odds ratio: 2.2; 95% confidence interval: 1.02–4.7). The causes of death did not differ between NWH and WH. At NWH, there was no difference in baseline characteristics and outcomes of patients treated by stroke- and nonstroke neurologists. Conclusion: The case fatality rates were unexpectedly higher at WH than at NWH. If this finding can be reproduced and is not a chance finding, we should identify explanations, especially organisational issues, chronobiological factors or summation of subtle – nonsignificant – baseline differences.

Relationship Between Onset-to-Door Time and Door-to-Thrombolysis Time: A Pooled Analysis of 10 Dedicated Stroke Centers

Background and Purpose— Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers. Methods— Prospectively collected data of consecutive ischemic stroke patients from 10 centers who received IV thrombolysis within 4.5 hours from symptom onset were merged (n=7106). DNT was analyzed as a function of demographic and prehospital variables using regression analyses, and change over time was considered. Results— In 6348 eligible patients with known treatment delays, median DNT was 42 minutes and kept decreasing steeply every year (P<0.001). Median DNT of 55 minutes was observed in patients with ODT ⩽30 minutes, whereas it declined for patients presenting within the last 30 minutes of the 3-hour time window (median, 33 minutes) and of the 4.5-hour time window (20 minutes). For ODT within the first 30 minutes of the extended time window (181–210 minutes), DNT increased to 42 minutes. DNT was stable for ODT for 30 to 150 minutes (40–45 minutes). We found a weak inverse overall correlation between ODT and DNT (R2=−0.12; P<0.001), but it was strong in patients treated between 3 and 4.5 hours (R2=−0.75; P<0.001). ODT was independently inversely associated with DNT (P<0.001) in regression analysis. Octogenarians and women tended to have longer DNT. Conclusions— DNT was decreasing steeply over the last years in dedicated stroke centers; however, significant oscillations of in-hospital treatment delays occurred at both ends of the time window. This suggests that further improvements can be achieved, particularly in the elderly.

Does pre-existing cognitive impairment no-dementia influence the outcome of patients treated by intravenous thrombolysis for cerebral ischaemia?

Approximately 10% of patients with a first-ever stroke and 30% with a recurrent stroke have pre-existing dementia,1 and many others have cognitive impairment no-dementia (CIND). A recent trial and an updated meta-analysis showed that rt-PA is also beneficial after 80 years of age. Cognitive impairment being frequent in elderly subjects, more patients eligible for rt-PA will have prestroke cognitive impairment. They often have an underlying brain pathology associated with an increased bleeding risk: brain microbleeds and leukoaraiosis are frequent and usually associated with cerebral amyloid angiopathy in Alzheimers disease or hypertensive microangiopathy in vascular dementia. They are also less likely to recover because of pre-existing brain lesions, impaired brain plasticity and possibly higher sensitivity to the neurotoxic effects of rt-PA. Three studies evaluated the influence of pre-existing dementia on outcome after thrombolysis.2–4 They provided conflicting results, that is, a tendency towards increased in-hospital mortality and symptomatic haemorrhagic transformation (sHT),3 increased in-hospital mortality without increase in sHT4 and no significant difference in outcome.5 However, they did not take into account important predictors of outcome such as baseline stroke severity and did not evaluate the proportion of independent survivors at 3 months. Moreover, they did not take into account CIND. Therefore, the question of whether rt-PA is safe and effective in ischaemic stroke patients with cognitive impairment …

Isolated Subarachnoidal Hemorrhage following Carotid Endarterectomy.

Cerebral hyperperfusion syndrome is a rare but well-described complication following carotid endarterectomy or stenting. Clinical signs are ipsilateral, throbbing, unilateral headache with nausea or vomiting, seizures, and neurological deficits, with or without intracerebral abnormalities on CT scan, such as brain edema or intracerebral hemorrhage. Subarachnoidal hemorrhage is rarely described especially if it occurs isolated. We describe a 74-year-old man with a history of high blood pressure, hypercholesterolemia, atrioventricular block with pacemaker, and ischemic cardiopathy with coronary bypass. He underwent right carotid endarterectomy for a 90% NASCET asymptomatic stenosis. Four days after surgery, he complained of unusual headaches with right, throbbing hemicrania. Nine days after surgery, he presented with left hemiplegia and a partial motor seizure. He had fluctuant altered consciousness, left hemiplegia, and left visual and sensory neglect. Brain CT showed right frontal subarachnoidal hemorrhage without parenchymal bleeding. Cerebral angiography found no cerebral aneurysm, no vascular malformation, but a vasospasm of the left middle cerebral artery. Transcranial Doppler confirmed this vasospasm. Evolution was favorable with no recurrence of seizures but with an improvement of the neurological deficits and vasospasm. Physicians should bear in mind this very rare complication of endarterectomy and immediately perform neuroimaging in case of unusual headache following endarterectomy or angioplasty.

Intravenous Thrombolysis for Acute Cerebral Ischemia in Belgrade, Serbia: Comparison with Lille, France

Background: Worse socioeconomic situation is associated with worse outcomes in stroke cases. Whether it also influences outcomes in patients treated with intravenous thrombolysis remains unknown. The aim of this study was to test the hypothesis that outcomes are less favorable in patients treated with intravenous thrombolysis in Belgrade, Serbia, than in Lille, France. Methods: We compared outcomes at day 7 and month 3, between 123 consecutive stroke patients treated with intravenous thrombolysis in Belgrade and 273 in Lille. Results: At month 3, there was no significant difference between Belgrade and Lille in patients’ excellent outcomes [modified Rankin Scale 0–1; 49.6 vs. 45.4%, odds ratio (OR): 1.21, 95% confidence interval (CI): 0.79–1.86] or in death (11.4 vs. 16.1%, OR 0.67, 95% CI: 0.35–1.27). However, compared with a subgroup of age-matched patients from Lille, Belgrade patients tended to have worse outcomes. Patients from Belgrade were 16 years younger (p < 0.0001), more likely to be men (OR 2.40, 95% CI: 1.52–3.78), and more likely to be smokers (OR 2.24, 95% CI: 1.43–3.51). Also, a trend for a slightly higher rate of symptomatic hemorrhagic transformation was registered in this group (7.3 vs. 3.3%, OR 2.32, 95% CI: 0.90–5.99). In Belgrade, patients arrived 27 min earlier to the hospital (p < 0.0001), but their door-to-needle time was 37 min longer (p < 0.0001). Compared with a subgroup of age-matched patients from Lille, they tended to have worse outcomes. Conclusion: Intravenous thrombolysis-treated stroke patients in Belgrade have similar outcomes and rates of complications as those from Lille.

Are the results of intravenous thrombolysis trials reproduced in clinical practice? Comparison of observed and expected outcomes with the stroke-thrombolytic predictive instrument (STPI)

AIM In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice. METHOD Data from a registry of consecutive patients treated by rt-PA at Lille University Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale (mRS) scores, at 3 months. The observed outcomes were then compared with the probability of good (mRS 0-1) and of catastrophic (mRS 5-6) outcomes, as predicted by the stroke-thrombolytic predictive instrument (STPI). RESULTS Of the 1000 consecutive patients (469 male, median age 74 years, median baseline National Institutes of Health Stroke Scale 11, median onset-to-needle time 143min), 438 (43.8%) had a good outcome, 565 (56.5%) had an mRS score 0-2 or similar to their pre-stroke mRS, 155 (15.5%) died within 3 months and 74 (7.4%) developed symptomatic intracerebral hemorrhage according to ECASS-II (Second European-Australasian Acute Stroke Study) criteria. Of the 613 patients (61.3%) eligible for evaluation by the s-TPI, the observed rate of good outcomes was 41.3% (95% CI: 37.5-45.3%), while expected rates with and without rt-PA were 48.8% (95% CI: 44.8-52.7%) and 32.5% (95% CI: 28.8-36.2%), respectively; the observed rate of catastrophic outcomes was 17.0% (95% CI: 14.0-19.9%), while the expected rate was 19.2% (95% CI: 16.1-22.4%) with or without rt-PA. CONCLUSION In clinical practice, the rate of good outcomes is slightly lower than expected, according to the s-TPI, except for the most severe cases, whereas the rate of catastrophic outcomes is roughly similar. However, the rate of good outcomes is higher than predicted without treatment. This finding suggests that rt-PA is effective for improving outcomes in clinical practice.

Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke

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.