XVII. European Stroke Conference
Nice, France
XVII. European Stroke Conference
Nice, France
Poster Session: Small vessel disease
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Brains of young spontaneously hypertensive rats show higher small vessel densities than normotensive rats: a possible role for VEGF?
F. Fluri
M.F.Ritz
S. Engelter
N. Schaeren-Wiemers
P. Lyrer
Neurobiology Laboratory, Department of Biomedicine, Univeristy Hospital Basel
SWITZERLAND
Background: Subcortical arteriosclerotic leucencephalopathy is a distinct form of cerebral angiopathy that causes leukoaraiosis resulting in functional and intellectual impairments. Middle-aged and older persons with hypertension are at high risk to develop this cerebrovascular disease. The molecular mechanisms involved in the progression of subcortical leucencephalopathy are not yet known, and only few studies have so far investigated the pathomechanismen of this disease. An adequate rat strain, the Spontaneously Hypertensive Rats (SHR) is sharing several similarities with human’s essential hypertension, and may represent a suitable model for studying early hypertension-induced vascular abnormalities. Methods: Brain tissue sections of SHR and normotensive Wistar Kyoto rats (WKY) at age of 2, 4, 6 and 9 months were used to study the number of vessels in the cortex and striatum. Immunofluorescent staining using collagen type IV (col4) as a specific marker for blood vessels revealed a difference in vessel density in SHR. In order to find an explanation for this observation, we analysed the expression pattern of VEGF (vascular endothelial growth factor), an important factor involved in vasculogenesis and angiogenesis, and calculated the percentage of VEGF-positive vessels in both strains. Results: SHR showed in general a higher density of col4-positive vessels in the cortex and in the striatum than WKY, with significant differences in 2 months old (pre-hypertensive) and 4 months old (hypertensive) rats. Preliminary results from 2 months old animals showed further a higher proportion of VEGF-positive vessels in SHR than in WKY, which colocalize with col4-positive vessels in the cortex and putamen. Discussion: Pre-hypertensive and young hypertensive SHR show a higher small vessel density in different regions of their brains. The higher proportion of VEGF-expressing vessels observed in pre-hypertensive rats compared to normotensive age-matched rats may indicate that angiogenesis is already induced in this strain before hypertension occurs.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
14
Vitamin B12 deficiency contributes to cerebral small vessel disease related white matter lesions, likely through blood-brain barrier damage.
B. Pieters
J. Staals
I. Knottnerus
R. Rouhl
R. van Oostenbrugge
P. Menheere
J. Lodder
University Hospital MAASTRICHT
THE NETHERLANDS
Background: blood-brain barrier dysfunction may be an early phenomenon in the development of the small vessel disease underlying ischemic white matter lesions (WML). Experimental and human evidence indicate that vitamin (Vit)B12 plays an independent role in maintaining blood-brain barrier integrity. Therefore, we studied the relationship between serum Vit B12 and WML severity in a population with a high frequency of WML: patients with a first lacunar stroke. Methods: 124 patients (not cardioembolic, no carotid stenosis > 50%) had full clinical workup, including 1.5 T MRI and Vit B12 measurement. WMLs were graded based on the Fazekas scale: severe deep WML = partially and large confluent lesions; severe periventricular (PVWML) = lesions extending into white matter. Results: 75 men and 49 women were aged 66.0 (SD 11.9) years. Mean VitB12 level was 202 pmol/L (SD 68.9;range 52 – 431).Taking 200 pmol/L as cutoff, 20/66 (30%) of patients below, and 16/58 (28%) > 200 pmol/L had severe deep WML; OR 1.14(95%CI 0.17-7.85). Figures for PVWML: 28/43 (65%), and 38/81 (47%); OR 2.11(95%CI 0.99-4.51), p=0.054. Multivariate logistic regression analysis showed low VitB12 and severe PVWML significantly related:p=0.04. Mean folate level in 50/100 patients with folate measured and with VitB12< 200 was 16.4 nmol/L, and 16.5 nmol/L in 50 with VitB12>200 pmol/L. Discussion: 1.VitB12 deficiency in small vessel stroke is highly prevalent. 2.VitB12 deficiency may underlie blood-brain barrier damage, leading to small vessel dysfunction, especially periventricular WMLs. 3.Our findings may offer potential for therapy.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
PROGRESSIVE LACUNAR STROKE: POSSIBLE ROLE OF HYPOGLYCEMIA
B. Piccardi
V. Saia
A. Del Bene
M. Lamassa
G. Pracucci
P. Nencini
D. Inzitari
Department of Neurological and Psychiatric Sciences, University of Florence
ITALY
BACKGROUND: About 30% of patients with acute lacunar stroke experience neurological worsening within the first days after onset. The mechanism of deterioration remains unclear. The aims of this study are to define frequency and clinical profile of progressive lacunar stroke (PLS) and to identify clinical predictors of deterioration. METHODS: Out of 844 consecutive ischemic strokes hospedalized in Stroke Unit during the 2002-2007 period, we identified 109 (13%) patients with symptomatic lacunar infarction (TOAST criteria). Patients with lacunar strokes were divided in two groups (PLS and no PLS) on the basis of neurological worsening (>/= 1 point of NIHSS) occurred in the first 72 hours. Demographic variables, vascular risks factors, clinical monitoring (blood pressure, body temperature, glycemia), lacunar syndromes, admission NIHSS, laboratory data, and status at discharge were analysed between the two groups (chi-square test). RESULTS: Twenty-four (22.2%) of the 109 lacunar strokes were classified as PLS (males 50%, mean age 72.3+/-12.2, mean admission NIHSS 3.6+/- 2.4). A significant difference between the two groups was found in glycemic control during the first 72 hours: two PLS patients had hypoglicemia (</= 0.60 g/L), whereas no hypoglicemic episodes were registered in the no PLS group (8.3% vs 0%; p=0,008). A CT congruent lesion was found in 80.3% of PLS and in 56.5% of no PLS (p=0.031). Regarding prognosis, a remarkably higher proportion of PLS was not discharged at home (60.9% PLS vs 32.9% no PLS; p=0.015). DISCUSSION: Progression of neurological deficit in lacunar stroke is relatively common and often causes poor functional status at discharge. Blood glucose fluctuactions in acute lacunar stroke may play a role in early clinical worsening.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
10
PHENOTYPIC FEATURES WITH POSSIBLE PREDICTIVE VALUE OF CADASIL (CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY)
F. PESCINI
S. NANNUCCI
C. SARTI
S. BIANCHI
M.T.DOTTI
A. FEDERICO
D. INZITARI
L. PANTONI
Department of Neurological and Psychiatric Sciences, University of Florence
ITALY
Background CADASIL is an inherited microangiopathy clinically characterized by the variable association of strokes, cognitive and mood disturbances, migraine and epilepsy. The diagnosis is made by genetic analisys. In order to limit laboratory costs and direct genetic test only to suspected cases, it would be important to find disease predictors among phenotypic features. Methods Since 2002, we performed genetic test for Notch3 mutations in 74 probands of different families presenting a picture suggestive of CADASIL. No pre-specified screening procedure was used for the selection. Familial, clinical, and neuroimaging findings were compared between CADASIL patients and patients without Notch3 mutations to detect possible differences with predictive value versus the genetic diagnosis. Results Out of the 74 patients evaluated, 15 (20%, mean age 61.4 yrs) were diagnosed with CADASIL because a mutation leading to a cysteine substitution within the epidermal growth factor-like repeats was found. In other 59 patients (80%, mean age 56.8 yrs) with complete genetic evaluation (exons 2-23) no mutation was found (Notch3-negative group). The comparison of personal and familial histories, and neuroimaging findings showed that there were statistically significant differences between the 2 groups (Fisher’s exact test p<0.05) for history of migraine (73 vs. 38%), positive family history for stroke with onset before 60 yrs (69 vs. 32%), white matter changes extended to the anterior temporal lobes (93 vs. 43%), and presence of multiple lacunar infarcts (93 vs. 55%). Conclusions Some clinical and neuroimaging features seem to have a predictive value in the diagnosis of CADASIL but none is pathognomonic. These data may serve to develop an algorhythm to be applied in pre-genetic screening of CADASIL.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Regional gray matter atrophy reflects clinical progression in lacunar infarct patients with Mild Cognitive Impairment Vascular (MCI-V). A 18-month follow-up study
M. Grau-Olivares
D. Bartrés-Faz
A. Arboix
M. Rovira
C. Junqué
University of Barcelona
SPAIN
Background and purpouse: Very little data is available studying the progression of cognitive and cerebral changes in patients with mild cognitive impairment (MCI) related to small vessel disease. We studied long-term neuropsychological and structural brain changes in lacunar infart (LI) patients with MCI of vascular origin (MCI-V) and compared them to those in LI patients without cognitive impairment (NCI-V). Methods: Thirty patients with a first-ever LI (15 MCI-V and 15 NCI-V) were followed up a mean period of 18±6 months after the stroke. All cases underwent neurological, neuropsychological and MRI assessments at baseline and follow-up examinations. MRI measures included ratings of white matter hyperintensities (WMH) and automated regional gray matter volume measures. Results: MCI-V patients were more impaired overtime in attention and working memory (Digit Span of WAIS-III) as compared to NCI-V. No significant differences in WMH between baseline and follow-up evaluations were observed between groups. Conversely, MCI-V but not NCI-V patients presented extensive shrinkages of gray-matter volumes involving the frontal and temporal lobes (including the hippocampus) as well as the pons the cerebellum and the caudate nucleus. Gray matter volume losses at follow-up among MCI-V cases were unrelated to WMH ratings. Conclusions: Present findings indicate that the effects of small vessel disease on gray matter integrity are clearly different when considering patients with and without cognitive impairment. Since both groups were comparable at baseline examinations in terms of gray matter atrophy, it is possible that among MCI-V cases the lacunar event unleashes a neurodegenerative process that becomes independent of the primary vascular disease overtime.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
A-G-4G haplotype of PAI-1 gene polymorphisms G/A, HindIII, 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease
M. Adamski
W. Turaj
A. Slowik
D. Wloch
P. Wolkow
A. Szczudlik
Jagiellonian University College of Medicine
POLAND
Background: Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrynolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (-844 G/A, -675 4G/5G and HindIII G/C) with the odds of different causes of ischemic stroke. Methods and results: We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152), as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. -844 G/A and HindIII G/C PAI-1 polymorphisms were genotyped with RFLP technique, and -675 4G/5G PAI-1 polymorphism was genotyped with SSCP method. A-G-4G PAI-1 gene haplotype was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs. 35.7%; p = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. Conclusions: Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of -844 G/A, - 675 4G/5G and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke. Key words: ischemic stroke, etiology, risk factor, polymorphism, PAI-1
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Prevalence of Nephroangiosclerosis in Patients with Fatal Stroke
H. Abboud
J. Labreuche
C. Duyckaerts
J.-J.Hauw
P. Amarenco
Bichat-Claude Bernard University Hospital, Paris
FRANCE
Background: Glomerular filtration rate and decline in renal function in patients with stroke can be improved by global cardiovascular prevention. However, the prevalence of nephroangiosclerosis in patients with stroke is unknown. Methods: Using the Multiple Atherosclerosis Site in Stroke (MASS) study, which is a autopsy data bank, we studied the prevalence of nephroangiosclerosis in relation to hypertension and other risk factors in 820 consecutive autopsies of patients died from neurologic diseases and stroke. Results: 354 patients had pathologic evidences of stroke and 466 had other neurological diseases (OND). Nephroangiosclerosis (NAS) was found in 39.8% (95% CI, 34.7 to 44.9%) of patients with stroke versus 9.0% (95% CI, 6.4 to 11.6%) of patients with other neurologic diseases. Odds ratio (OR) adjusted for age and gender was 4.37 (95%CI, 2.92-6.52) and after further adjustment on cardiovascular risk factors was 2.94 (95%CI, 1.83-4.74). Among the 354 stroke patients, the prevalence of NAS was similar in patients with BI and those with BH, patients with or without parenchymal abnormalities-related to small vessel disease and across ischemic stroke subtypes except for those with coexisting causes. After multivariate analysis, NAS was independently associated with age in both stroke and OND patients and history of hypertension in stroke patients only. Conclusions: Nephroangiosclerosis is frequent in patients with fatal stroke. The association is independent of age, gender and other cardiovascular risk factors. Impaired renal function should be monitored and prevented in stroke patients with high blood pressure, particularly in case of history of cardiovascular disease and/or left ventricular hypertrophy.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Gait And Balance Abnormalities in CADASIL: The Relationship Between Clinical Impairment and MRI Lesion Burden
A. Viswanathan
O. Godin
E. Jouvent
M. O'Sullivan
A. Gschwendtner
M. Düring
C. Dufouil
M-G. Bousser
M. Dichgans
H. Chabriat
CHU Lariboisière, Assistance Publique des Hôpitaux de Paris
USA
Background: Gait and balance dysfunction(GBD) occurs in vascular cognitive impairment(VCI) and may predict the development of dementia. However, the precise relationship between GBD, cognitive impairment, and MRI lesions in VCI is not fully defined. CADASIL is a monogenic arteriopathy and a model of pure VCI. White matter hyperintensities(WMH), lacunar lesions(LL), cerebral microbleeds(CM), brain atrophy and tissue microstructural changes are seen on MRI. We hypothesized that increased MRI lesion burden would be independently associated with GBD in patients with CADASIL. We also sought to define relationship between GBD and clinical impairment in the disease. Methods:We collected clinical data and performed imaging on 146 patients. GBD was evaluated in each patient by a study neurologist. Degree of clinical impairment was assessed by modified Rankin scale(mRS) and Mattis dementia rating scale(MDRS). WMH and LL volume, number of CM, degree of atrophy, and whole-brain mean-ADC were determined. Results: Abnormal gait was present in 46 patients(31.5%). Of these, 71% also had evidence of balance dysfunction. In multivariate analyses, patients with abnormal gait were significantly more likely to have cognitive impairment(mean MDRS 119 v 137; p<0.0001) and disability(mean mRS 2.8 v 0.5; p<0.0001). Similar associations were seen in patients with balance dysfunction. All MRI markers except WMH volume were associated with GBD after correcting for age, sex and mRS. In the subgroup of independent patients(mRS<2; n=124) abnormalities of gait, but not abnormalities of balance, remained strongly associated with all MRI makers except WMH volume. Discussion:Gait and balance abnormalities are common in CADASIL, frequently coexist, and are associated with clinical impairment. Abnormal gait is strongly associated with increased MRI lesion burden, even in independent patients. These results suggest that GBD is sensitive clinical marker for both disease severity and MRI lesion burden in CADASIL. GBD may play similar role in other forms of VCI caused by small vessel disease.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
IS THE MIDDLE CEREBRAL ARTERY PULSATLITY INDEX (PI) USEFUL AS SMALL VESSEL DISEASE (SVD) MARKER?
M. Blanco
I. Rodríguez
R. Leira
M. Rodríguez-Yáñez
D. Santos
M. Millán
N. Pérez de la Ossa
J. Serena
A. Dávalos
J. Castillo
Deparment of Neurology, Hospital Clínico Universitario, Santiago de Compostela (Spain).
SPAIN
Background: Presence of SVD has been associated to the development of lacunar infarcts and cognitive impairment. Currently, its diagnosis is based in neuroimaging studies. A screening exam for population at risk would be very useful for the early detection of SVD. Our objective is to determine the value of the PI as potential marker for SVD. Methods: 150 patients (72.7 (8.6) age, 51.9% men) were included from a cerebrovascular disease ambulatory office. Cranial CT, supraaortic trunks and transcranial Doppler and minimental test were performed to all patients. The analysis PI value was obtained averaging 3 consecutive waves in both middle cerebral arteries. Leukoaraiosis was rated using the Fazekas scale. We considered PI<1.4 as low and high when PI≥1.4. Results: 69.3% of patients showed leukoaraiosis, 31.3% lacunar infarcts and 23.3% cognitive impairment. Patients with higher PI presented higher blood pressure (66% vs 40.8, p<0.0001), more leukoaraiosis (78.4% vs 31.1%, p<0.0001), larger lacunar infarct (40.2% vs 7.8%, p=0.0001) and bigger cognitive impairment (28.9% vs 6.8%, p<0.0001). Only the presence of leukoaraiosis (OR 6.1 CI95% 2.8-13-3) and lacunar infarct (OR 7.2 CI95% 2.8-18.5) showed an independent association in the logistical regression model. Conclusion: A PI≥1.4 increased more than 6 times the risk to develop lacunar infarct and/or leukoaraiosis. So, PI could be a useful screening test to detect EPV.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Sleep apnea and risk of silent white matter abnormalities on magnetic resonance imaging
M.G.Hickey
T.-E.J.Kiernan
L.A.Pearce
M.I.Aguilar
Mayo Clinic
USA
Background: Obstructive sleep apnea (OSA) is associated with hypertension (HTN) and cardiovascular disease. Although apneic events often parallel a surge in blood pressure, the exact mechanism relating OSA to cerebrovascular disease (CVD) has not been elucidated. White matter disease (WMD) seen on magnetic resonance imaging (MRI) is a manifestation of small vessel CVD. The most common risk factors for WMD are age and HTN. We hypothesize that OSA is an independent risk factor for WMD. Methods: Our institution’s sleep laboratory database was searched for subjects without HTN or CVD who had polysomnography and brain MRI in 2007. OSA was defined as an apnea/hypopnea index (AHI) above 5. MRIs were read by blinded neurologists with an inter-rater reliability of 85%. WMD was scored by the ARWMC scale (0 - 24 possible). A total score above 4 was considered significant WMD. Demographics were compared using Chi-square test for categorical and Mann-Whitney U test for continuous variables. A multivariate logistic regression model including the covariate age was planned to determine association of OSA with WMD. Results: These 60 subjects were 60% male with a median age of 64. OSA was diagnosed in 41 (68%), who were older (median 67 vs. 49, p < 0.001), and who had more WMD (median 2 vs. 0, p = 0.003). Significant WMD was diagnosed in 11 (22%), who were older (median 77 vs. 60 yrs, p < 0.001) and more often had OSA (100% vs. 61%, p = 0.012) than the 49 without WMD. In 43 subjects of age < 70, 1 had WMD and 26 (61%) had OSA. Discussion: Too few younger (</= 70 years) patients had significant WMD to assess the independent contribution of OSA on WMD regardless of age. Elderly patients with OSA commonly have both OSA and WMD. We suspect a relationship between OSA and WMD regardless of age and HTN and will evaluate a larger sample size in our ongoing research. The brain is an organ targeted by apneic episodes and hypoxia, with asymptomatic WMD on imaging likely being the earliest manifestation. Prompt recognition and early treatment of OSA could promote brain health.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Post-mortem 7-Tesla MRI combined with histopathology of cerebral small vessel disease – Rationale and design
R.P.Kloppenborg
P.J.Nederkoorn
E. Aronica
J.J.Geurts
J.J.Zwanenburg
M. Vermeulen
AMC Medical Center, University of Amsterdam
THE NETHERLANDS
Background Approximately 25% of all ischemic stroke is caused by small vessel disease (SVD), culminating in lacunar infarcts or leukoaraiosis. Pathophysiological causes of SVD are thought to differ from those in large vessel disease (i.e. thrombo-emboli) and include lipohyalinosis and inflammation of the vessel wall. Although techniques have improved significantly, recent histopathological studies in stroke are rare. Histopathological studies can now be combined with post-mortem MRI findings to enhance precision of tissue sampling, a method which has not yet been applied to stroke research. Moreover, novel 7-Tesla (7T) MRI increases accuracy in imaging SVD. This study aims to examine the pathology of SVD and compare it to large-vessel disease using these techniques. Methods Standardized 7T post-mortem MRI-protocols will be performed on the brain tissue of 40 cases with SVD and 20 controls. Directly after sections, 10-mm-thick coronal brain slices are cut and embedded in formalin. A perspex brain slice holder is used to contain the slices. Histopathological and immunocytochemical studies are performed on the radiologically identified areas with abnormalities due to SVD. Histopathological changes are correlated with post-mortem MRI findings and scores on the Fazekas scale. Results Currently, three cases were processed. Post-mortem 7T MRI showed ischemia due to SVD with superior resolution. Subsequent neuropathology showed no lipohyalinosis, although thickening of the intima was visible with leakage of albumin, and only marginal signs of thrombo-emboli. Discussion This study will gain insight in the pathophysiological mechanisms underlying SVD. The protocol enhances reliability in tissue sampling for histopathological research. To date, the combination of post-mortem 7T and neuropathology of SVD has not been performed. 7T MRI shows superior resolution in visualizing ischemia due to SVD in post-mortem cases.
