XVII. European Stroke Conference
Nice, France
XVII. European Stroke Conference
Nice, France
Oral Session:
Etiology of stroke
Date:
Friday 16 May 2008
Time:
8:00 - 8:10
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
01
Ischaemic heart disease (IHD) risks after different ischaemic stroke subtypes in a prospective hospital-based study: evidence for a distinct lacunar ischaemic stroke arteriopathy?
C. Jackson
M. Dennis
J. Wardlaw
S. Lewis
A. Hutchison
C. Sudlow
University of Edinburgh
UNITED KINGDOM
Introduction The arteriopathy of lacunar stroke may differ from the atherothrombotic processes causing most other ischaemic strokes. Previous reports of a lower prevalence of prior IHD (a marker of atherothrombotic disease) in lacunar versus non-lacunar ischaemic stroke support a distinct lacunar arteriopathy. A lower risk of IHD during follow-up after lacunar versus non-lacunar ischaemic stroke could provide further supportive evidence, but data published so far from observational studies comparing IHD risk after well-characterised ischaemic stroke subtypes are scarce. Methods We used multiple overlapping methods to follow a hospital-based cohort of 1008 first-ever ischaemic stroke patients over 1-4 years for vascular outcomes, including myocardial infarction (MI) and death. We used clinical features and CT/MR brain imaging to assign baseline stroke subtypes. We assessed differences in IHD risk between subtypes with survival methods, comparing rates of MI and of MI or cardiac death following lacunar versus non-lacunar anterior circulation ischaemic stroke. Results Of 282 lacunar patients, 8 (3%) had an MI and 11 (4%) had an MI or cardiac death. Of 527 non-lacunar patients, 25 (5%) had an MI and 33 (6%) had an MI or cardiac death. Survival analyses showed a non-significant trend towards lower rates of both IHD outcomes in lacunar patients (rate ratio lacunar vs non-lacunar for MI: 0.5, 95% CI 0.2 to 1.1, p=0.1; for MI or cardiac death: 0.5, 95% CI 0.3 to 1.1, p=0.07). Discussion Our results suggest a lower IHD risk after lacunar versus non-lacunar ischaemic stroke. However, although our study accrued more MIs than any published similar cohort study, IHD outcome numbers were still small and a pooled analysis of individual patient data from similar cohorts is now needed.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
8:10 - 8:20
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
02
Is the recently identified SNP on chromosome 9p a cardiospecific genetic risk factor?
Results from three case-control studies
R. Lemmens
S. Abboud
W. Robberecht
L. Vanhees
M. Pandolfo
V. Thijs
A. Goris
KULeuven, Leuven ULB, Brussels
BELGIUM
Background: Recently, several highly correlated polymorphisms on chromosome 9 were found to be associated with myocardial infarction. We investigated whether this association was also present in a Belgian population of coronary heart disease patients. Additionally we studies whether variants in this region were also associated with cerebrovascular disease by performing two case-control studies in patients with ischemic stroke or TIA. Methods: A total of 933 patients with coronary heart disease were included from the CAREGENE (CArdiac REhabilitation and GENetics of Exercise performance) study. The first case-control study in patients with TIA or stroke prospectively selected 317 Caucasians. Two hundred seventeen individuals without a history of cerebrovascular disease and 296 patients with amyotrophic lateral sclerosis (ALS) were chosen as controls. An additional population of 222 patients with lacunar stroke or stroke due to large vessel atheroclerosis and 313 controls were studied. SNP rs10757278 on chromosome 9 was genotyped in all. Results: The frequency of the MI risk allele rs10757278*G was 55% in Caregene cases versus 47% in controls, p=1x10-5, OR=1.40 (1.21-1.62), consistent with various other studies. However in 317 stroke or TIA patients we did not find any association the G-allele frequency being 48% (OR= 1.03, p= 0.71) nor did we identify an association between genotype and stroke or TIA (G/G genotype 22.9% in cases versus 22.8% in controls, p=0.97). Furthermore the G-allele frequencies in the second case-control study also did not significantly differ between cases and controls, 51 % versus 50 % respectively (OR= 1.03, p=0.80). Conclusions/Relevance: We replicated a locus on chromosome 9, rs10757278 to be strongly associated with coronary heart disease in a Belgian population, but did not identify a genetic association with stroke or TIA in two independent populations. These results underscore the complex genetic background of stroke possibly due to the heterogeneous nature of stroke etiologic mechanisms.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
8:20 - 8:30
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
03
A CEREBRAL ANGIOPATHY ASSOCIATED WITH CANNABIS USE IS A MAIN CAUSE OF ISCHEMIC STROKE IN A PROSPECTIVE SERIES OF 48 YOUNG PATIENTS
V. WOLFF
V. LAUER
F. BOUJAN
C. SABOURDY
J. SCHOLLY
P. VILLANOVA
O. ROUYER
C. JAHN
R. BEAUJEUX
C. MARESCAUX
Centre Hospitalier et Uuniversitaire de Strasbourg
FRANCE
Objective: The aim of our work was to evaluate the relationship between cannabis use and ischemic stroke in a young adult population. Methods: The study was based on a prospective population of 48 consecutive young patients (less than 45 years old), admitted in our department for an acute ischemic stroke (confirmed by cerebral imaging) from October 2005 to September 2007. A systematic first-line screening was performed including blood tests, cardio-vascular investigations and urine analysis for cannabinoids. If there was no etiology after those investigations, a second-line screening was performed with trans-femoral conventional angiography and cerebrospinal fluid analysis. In patients with intracranial stenosis, a control was planned through neurovascular imaging within 3-6 months. Results: In this series, 13 patients were cannabis users, and most of them had multifocal intracranial stenosis (n=10). This suggested there was a link between cannabis use and this arterial characteristic in ischemic stroke. In fact, control through vascular imaging showed partial or total reversibility of arterial vasoconstriction. Among those 48 ischemic strokes, there was a multifocal intracranial angiopathy associated with cannabis use in 21%, a cervical artery dissection in 19%, a cardioembolism in 12.5%, an isolated intra-cranial stenosis with unknown etiology in 12.5%, an intra-cranial atherosclerosis stenosis in 6%, a vascularitis associated with HIV in 2%, an intra-petrosal carotid dissection in 2%. Exhaustive screening didn’t show any etiology in 25%. Conclusion : Even if there are few case-reports associating stroke and cannabis use in medical literature, we think that a cerebral angiopathy, involving several arteries, associated with cannabis consumption could be a main cause of ischemic stroke in young people. We suggest to look for evidence of cannabis abuse and implement neuro-vascular imaging in case of cryptogenic ischemic stroke in young adults.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
8:30 - 8:40
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
04
Is Moderate Atherosclerotic Stenosis in Middle Cerebral Artery a Cause or a Coincidental Finding in Ischemic Stroke ?
I. Klein
J. Labreuche
P. Lavallée
M. Mazighi
C. Duyckaerts
J.J.Hauw
P. Amarenco
Bichat Hospital, Denis Diderot University and Medical School
FRANCE
Background: Few pathological data have focused on the causal link between intracranial atherosclerotic disease and parent artery stroke. Objective: To study the causality of middle cerebral artery (MCA) atherosclerotic disease in patients with fatal stroke. Methods: In 123 patients with unilateral middle cerebral artery (MCA) territory infarction we performed a case-control autopsy study evaluating the frequency of atherosclerotic plaque and stenosis in ipsilateral vs. controlateral MCA and internal carotid artery. Clinical history, risk factors, imaging data, pathologic analysis of the entire cerebral arterial tree and general autopsy reports were available. Results: The overall prevalence of MCA atherosclerosis (moderate or severe stenosis) was much higher in ipsilateral (21.1%, n=26) than contralateral side (8.1%, n=10). The corresponding OR for presence of atherosclerosis in MCA ipsilateral relative to MCA contralateral of the infarction was 6.33 (95%CI, 1.87-21.40) ). This significant difference was found with moderate (OR=5.75; 95%CI, 1.45 to 22.76) and severe stenosis (OR=7.18; 95%CI, 1.58 to 32.73) Conclusion: Moderate MCA atherosclerotic stenosis might be responsible for parent territorial stroke. Novel arterial wall MR imaging techniques should now investigate the hypothesis that moderate MCA stenosis is a potential explanation in patients with nonfatal stroke of unknown cause.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
8:40 - 8:50
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
05
Recurrent stroke rates and subtype patterns among lacunar versus non-lacunar ischaemic stroke patients in a hospital-based cohort – evidence for distinct vascular pathologies?
C. Jackson
M. Dennis
J. Wardlaw
S. Lewis
A. Hutchison
C. Sudlow
University of Edinburgh
UNITED KINGDOM
Introduction The vascular pathology of lacunar ischaemic stroke, and any differences from the atherothrombotic pathology causing most other ischaemic strokes, is poorly understood. Different recurrent stroke rates and subtype patterns between lacunar and non-lacunar ischaemic stroke might reflect distinct vascular pathologies. Methods We used multiple overlapping methods prospectively to follow a hospital-based cohort of 1008 first-ever ischaemic stroke patients for recurrent strokes over 1-4 years. We used clinical assessment and CT/MR brain imaging to assign stroke subtypes, and compared recurrence rates and subtype patterns in lacunar versus non-lacunar anterior circulation ischaemic stroke patients. Results All patients had brain imaging after their first-ever stroke. 94% of those with recurrent stroke had brain imaging (57% diffusion weighted MRI). 36/282 (13%) lacunar and 73/527 (14%) non-lacunar patients had a recurrence. There was no significant difference in recurrence rate over the entire follow-up (age and sex-adjusted hazard ratio non-lacunar vs lacunar: 1.2, 95% CI 0.8 to 1.8), but early (first 1-2 weeks) recurrence rate was higher in non-lacunar patients. Recurrences were significantly more often lacunar if first-ever ischaemic stroke was lacunar (relative risk of lacunar recurrence after lacunar vs non-lacunar first-ever stroke: 4.1, 95% CI 1.9 to 8.6). Discussion High rates of brain imaging allowed accurate subtyping of first and recurrent strokes. The higher early recurrence rate among non-lacunar patients reflects a higher prevalence of thromboemboli, but does not necessarily imply a distinct vascular pathology for lacunar stroke. However, the tendency for recurrences to have the same subtype as the first stroke supports distinct vascular pathologies.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
8:50 - 9:00
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
06
Atypical Lacunar Syndromes: Same disease as classic lacunar infarcts?
The Secondary Prevention of Small Subcortical Strokes (SPS3) Study
O. Benavente
A. Arboix
C. Bazan
F. Rubio
C. Coffey
L. McClure
N. Nair
A. Roldan
C. White
R. Hart
University of Texas
USA
Background In contrast to well defined classic or typical lacunar syndromes, there is scant information about atypical lacunar syndromes. It is postulated that atypical syndromes may represent a different entity. Methods The aim of this study was to compare characteristics between patients with an atypical lacunar syndrome (ALS) and those with a typical lacunar syndrome (TLS). The analysis included participants from the SPS3 study, a multicenter trial enrolling patients with MRI proven lacunar stroke. The classification was based on clinical presentation of the index event. A TLS was considered with one of the following syndromes: pure motor, pure sensory, sensorimotor, ataxic hemiparesis and dysarthria clumsy hand. The rest were classified as ALS. Results Among 1560 patients, 622 (40%) had an ALS and the remainder TLS. Significant differences between patients with ALS vs. TLS were only for age (ALS: 62 ± 11.1 vs. TLS: 64 ± 11.1; p = 0.005) and prevalence of coronary artery disease (ALS: 15% vs. TLS: 10%; p = 0.004). The frequency of ALS vs. TLS did not differ by gender or ethnicity. There were no differences in frequency of hypertension (90% vs 91 %), diabetes (38%, vs 36%) and hyperlipidemia (55% vs 52%), p-values >0.05. Finally, there were no differences with respect to intracranial stenosis (5% vs. 4%, p=0.59), severe white matter disease (14% vs 14% p=0.28) nor anatomical localization for ALS and TLS (basal ganglia, 46% vs. 51%), (pons, 27% vs. 26%) and (thalamus; 26% vs. 22%), p-values >0.05. Disability was similar in both groups (66% of ALS and 65% of TLS had a Rankin of 0-1, p=0.7). Conclusions These results suggest that typical and atypical lacunar syndromes are the result of similar vascular processes. The presence of an atypical lacunar syndrome should not exclude the underlying mechanism of small vessel disease and should not alter the management of these patients.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
9:00 - 9:10
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
07
Pathophysiology of lacunar stroke: a new mechanism?
J.M.Wardlaw
F. Doubal
P.A.Armitage
F. Chappell
A.J.Farrall
C. Sudlow
M.S.Dennis
University of Edinburgh
UNITED KINGDOM
Introduction: The cause of most lacunar stroke is unknown, but is related to intrinsic cerebral small vessel disease, may be associated with endothelial dysfunction, and is generally considered to be ischaemic. However, the appearance of the cerebral small vessels and brain lesions could be due to failing blood-brain barrier (BBB). We compared whole brain BBB permeability in patients with lacunar stroke and controls with cortical stroke. Methods: We recruited patients with ischaemic stroke of lacunar and mild cortical type. We assessed BBB leak using MR imaging with i.v. gadolinium (Gd) at least 1 month after stroke to avoid any acute stroke effects. We extracted signal change pre- and for 30 minutes post-Gd from grey and white matter, CSF, and blood using manually placed regions-of-interest and tissue segmentation by statistical parametric mapping. We compared the signal/time curves in each tissue between lacunar and cortical patients with general linear modeling, and tested the effect of age, white matter lesions and other risk factors. Results: We recruited 97 patients, 51 lacunar, 46 cortical. The two groups had similar mean ages, proportions with hypertension, diabetes and white matter lesions. Signal change post-contrast was higher in lacunar than in cortical stroke patients in white matter (p<0.001) and CSF (p<0.003) but there was no difference in grey matter or blood. On multivariate analyses, the only factors that influenced the magnitude of signal change post contrast were increasing age, weight and enlarged perivascular spaces, but these had no effect on the lacunar-cortical differences. Conclusion: The BBB may be dysfunctional in lacunar disease, allowing contrast to leak into small vessel walls and brain throughout subcortical white matter and thence into CSF. More studies are needed to confirm these findings and determine whether abnormal BBB pre-dates clinically-evident lacunar disease. BBB dysfunction, not just ischaemia, may be an important mechanism for brain damage in cerebral small vessel disease.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
9:10 - 9:20
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
08
Presence of Retinopathy does not differ in Ischaemic Stroke Subtypes
F.N.Doubal
B. Dhillon
M.S.Dennis
J.M.Wardlaw
University of Edinburgh
UNITED KINGDOM
Introduction Lacunar stroke is associated with an intrinsic cerebral small vessel disorder of unknown cause. Retinal arterioles are developmentally and physiologically similar to cerebral small vessels, stroke risk is associated with retinopathy and retinal features could be related to stroke subtype. We hypothesized that there would be higher rates of retinopathy due to small vessel effects in patients with lacunar versus cortical stroke. Methods We prospectively recruited patients presenting with lacunar and cortical ischaemic stroke. Stroke was diagnosed and subtyped by an experienced stroke physician based on clinical features and cerebral magnetic resonance imaging. All patients had 6 dilated digital retinal photographs performed of each eye. Retinopathy (one or more of hard or soft exudates, microaneurysms or haemorrhages) was graded blinded to stroke type by a trained physician as definitely present/absent or questionable. Questionable lesions were graded by an ophthalmologist. Results We recruited 204 patients. 2 pts were excluded with ungradeable photographs leaving 202 patients for analysis (102 lacunar and 100 cortical strokes). Mean age was 68 (SD13) and mean NIHSS 2. Similar proportions of each group had diabetes (19% lacunar v 12 % cortical) and hypertension (58% lacunar and 66% cortical). There was no difference in age between the groups (lacunar mean 66 yrs v cortical mean 70 yrs). 19% of lacunar and 25% of cortical patients had some evidence of retinopathy. This difference is not significant. Conclusions We have not demonstrated a strong association between presence of retinopathy and ischaemic stroke subtype. However larger samples or assessment of other retinal vascular abnormalities may yield promising results. Further analyses are required to adjust for risk factors and test associations with white matter lesions and related brain abnormalities.
Etiology of stroke
Date:
Friday 16 May 2008
Time:
9:20 - 9:30
- Room:
Calliope
Chair: H. Ay, Turkey and P. Kelly, Ireland
09
Prevalence of Fabry disease and CADASIL in young patients with first-ever stroke: The PORTYSTROKE – screening genetic conditions in PORTuguese Young STROKE patients
M. Viana-Baptista
S.M.Ferreira
T.P.Melo
M. Carvalho
V.T.Cruz
C. Carmona
F.A.Silva
J.P.Oliveira
J.M.Ferro
PORTYSTROKE investigators
Hospital Garcia deOrta, Almada
PORTUGAL
Background: Despite extensive investigation, frequently the cause of stroke in young adults remains unclear. Fabry disease and CADASIL are monogenic disorders associated with early onset of stroke. Atypical phenotypes have been recognized and the diseases are probably under diagnosed in the stroke population. Methods: Between 11/06 and 10/07 all patients aged 18-55 years, with first-ever stroke, were considered for screening of these disorders in twelve Neurology Departments. From a total of 625 we studied 493 patients, mean age 45.4, 61% male (132 patients refused to participate, died before inclusion or were lost for other reasons): 74% ischemic stroke, 23% hemorrhagic stroke (including 26 with subarachnoid hemorrhage) and 3% cerebral venous thrombosis. All patients underwent extensive investigation. Ischemic strokes were classified according to TOAST criteria. The entire alpha-GAL gene and exons 4, 11, 18/19 of NOTCH3 gene were screened for mutations (up to now in 401 and 493 patients, respectively). Results: 11 mutations were found in the alpha-GAL gene and 8 mutations were found in the NOTCH3 gene, (prevalence of 2.7 IC:1.5;4.7 and 1.6 IC:0.8;3.1, respectively). Mutations in the alpha-GAL gene were found in ischemic stroke (2 cardioembolic, 3 Lacunar, 1 other cause, 3 unknown cause) and primary intracerebral hemorrhage (2), yield 2.2% IC (1.1;4.1) for ischemic and 0.5% (IC 0.1;1.6) for hemorrhagic stroke. Mutations in the NOTCH3 gene were found in 6 ischemic strokes (1 cardioembolic, 2 lacunar, 3 unknown cause), yield 1.2% (IC 0.5;2.5) and 2 primary intracerebral hemorrhage, yield 0.4% (Ic 0.1;1.3). Conclusion: Screening for Fabry disease and CADASIL seems to have a low yield. In spite of this, both diseases should be considered for ischemic and hemorrhagic stroke. Supported by GENZYME-Portugal
