Hemodynamic alterations in vertebrobasilar large artery disease assessed by arterial spin-labeling MR imaging.

BACKGROUND AND PURPOSE: VB artery stenosis is associated with a high risk of recurrent ischemic events, and knowledge about the hemodynamic relevance of VB stenosis is important for clinical decision making. In this study, multiple inflow pulsed ASL MR imaging was assessed for its ability to measure CBF and ATT in patients with VB disease. MATERIALS AND METHODS: ASL was performed on a 3T MR imaging scanner in 41 participants. Twenty-one patients had a history of ischemic events in the VB circulation (14 men, 7 women, age 66 ± 11 years). Clinical data and CE-MRA were used to classify VB disease severity. Twenty age-matched adults were controls. Group and within-VB analyses were performed. Mean CBF and ATT values in the ROIs were adjusted by excluding voxels that did not produce a reliable ASL estimate. RESULTS: CBF was reduced (P < .003) in patients compared with controls, which was significant after excluding voxels with a poor fit. Differences in ATT between patients and controls were not significant after voxel correction. There was a strong correlation between CBF and ATT among patients. Finally, ATT was significantly correlated with VB disease severity (P = .026). CONCLUSIONS: Multiple inflow ASL distinguished patients with VB disease from age matched-controls. VB disease rating was associated with prolonged ATT downstream. ASL may have diagnostic potential among patients in whom risk of intervention is high.

Association between cortical metabolite levels and clinical manifestations of migrainous aura: an MR-spectroscopy study.

Previous studies suggest an abnormal cerebral cortical energy metabolism in migraineurs. If causally related to the pathophysiology of migraine, these abnormalities might show a dose-response relationship with the duration and severity of aura symptoms. While such a trend has been suggested in phosphorus spectroscopy (31P-MRS) studies, it has not been considered in proton spectroscopy (1H-MRS) studies and it has not been studied in cerebral white matter. We aimed to determine whether for any of the metabolites measured by 31P-MRS or 1H-MRS there was a dose-response relationship with aura duration and severity, and whether such an association was also present in cerebral white matter. We studied patients with migraine with aura and healthy controls with 31P-MRS and with 1H-MRS. We measured metabolite ratios in grey and in white matter and in the patients, we related metabolite levels to the clinical characteristics and duration of the aura. In patients, the phosphocreatine/phosphate (PCr/Pi) ratio decreased significantly with increasing aura duration and was significantly lower in patients with hemiplegic migraine than in patients with non-motor aura. Overall the metabolite ratios did not differ significantly between patients and controls, but compared with controls the PCr/Pi ratio in patients with hemiplegic migraine and in patients with persistent aura >7 days was significantly lower. These changes were only present in grey matter. Results for 1H-MRS did not differ significantly between patients and controls, and they showed no association with duration or severity of symptoms. In this study, metabolite ratios differed significantly between patients with different aura phenotypes and with increasing aura duration. In addition, only in some patient subgroups were metabolite ratios significantly different from controls. These findings support the concept that migraine with aura is a heterogeneous disorder with distinct pathophysiological subtypes. They further suggest that rather than determining the susceptibility to developing a migraine attack, changes in cortical energy metabolism may determine the clinical manifestations of the migrainous aura once an attack has started.

Presence of acute ischaemic lesions on diffusion-weighted imaging is associated with clinical predictors of early risk of stroke after transient ischaemic attack.

BACKGROUND: Early risk of stroke after a transient ischaemic attack (TIA) can be reliably predicted with risk scores based on clinical features of the patient and the event, but it is unclear how these features correlate with findings on brain imaging and few studies have investigated this in the subacute phase. METHODS: Two hundred consecutive patients attending a specialist clinic underwent diffusion-weighted brain imaging (DWI) on the day of the clinic (> or =3 days after a TIA) and the presence of recent lesions (positive DWI) was related to the presence of clinical features associated with a high stroke risk and to 2 validated risk scores (ABCD and California). RESULTS: Thirty-one patients (16%) had positive DWI. Increasing ABCD and California scores were associated with positive DWI (p = 0.02 for both) independent of the delay from TIA to scan. CONCLUSION: Presence of recent ischaemic lesions on DWI correlates with validated clinical scores for risk of stroke after TIA in patients scanned subacutely. Future prognostic studies of DWI after TIA should adjust for the risk scores to determine the independent predictive value of DWI and hence the likely role of DWI in refinements of the scores.

Evolution of the diffusion-weighted signal and the apparent diffusion coefficient in the late phase after minor stroke: a follow-up study.

INTRODUCTION: Diffusion-weighted imaging (DWI) is mainly used in acute stroke, and signal evolution in the acute phase has been studied extensively. However, patients with a minor stroke frequently present late. Recent studies suggest that DWI may be helpful at this stage, but only very few published data exist on the evolution of the DW-signal in the weeks and months after a stroke. We performed a follow-up study of DWI in the late stages after a minor stroke. METHODS: 28 patients who presented 48 hours to 14 days after a minor stroke underwent serial MRI at baseline, 4 weeks, 8 weeks, 12 weeks, 6 months and>or=9 months after their event. Signal intensity within the lesion was determined on T2-weighted images, DW-images and the Apparent Diffusion Coefficient (ADC) map at each time-point, and ratios were calculated with contralateral normal values (T2r, DWIr, ADCr). RESULTS: T2r was increased in all patients from the beginning, and showed no clear temporal evolution. ADCr normalized within 8 weeks in 83% of patients, but still continued to increase for up to 6 months after the event. The DW-signal decreased over time, but was still elevated in 6 patients after>or=6 months. The evolution of ADCr and DWIr showed statistically highly significant inter-individual variation (p<0.0001), which was not accounted for by age, sex, infarct size or infarct location. CONCLUSION: The ADC and the DW-signal may continue to evolve for several months after a minor ischaemic stroke. Signal evolution is highly variable between individuals. Further studies are required to determine which factors influence the evolution of the ADC and the DW-signal.

Heritability of ischemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies.

UNLABELLED: Background- Appropriate design of molecular genetic studies of ischemic stroke requires an understanding of the genetic epidemiology of stroke. However, there are no published population-based data on heritability of aetiological subtypes of ischemic stroke, confounding by heritability of other vascular risk factors, or the relationship between heritability and age of onset. METHODS: We studied family history of stroke (FHx(Stroke)) and of myocardial infarction (FHx(MI)) in first-degree relatives in 2 population-based studies (Oxford Vascular Study [OXVASC]; Oxfordshire Community Stroke Project [OCSP]). We related FHx(Stroke) and FHx(MI) to subtype of ischemic stroke, age, and the presence of vascular risk factors and performed a systematic review of all studies of FHx(Stroke) by stroke subtype. RESULTS: In our population-based studies and in 3 hospital-based studies, FHx(Stroke) was least frequent in cardioembolic stroke (OR=0.74, 95%CI=0.58 to 0.95, P=0.02) but was equally frequent in the other subtypes. In OXVASC and OCSP, FHx(Stroke) (P=0.02), FHx(MI) (P=0.04), and FHx of either (P=0.006) were associated with stroke at a younger age. Only FHx(Stroke) was associated with previous hypertension (OR=1.59, 95%CI=1.08 to 2.35, P=0.02). FHx(MI) was more frequent in large-artery stroke (OR=1.63, 95%CI=0.99 to 2.69, P=0.05). CONCLUSIONS: Consistent results in our population-based studies and previous hospital-based studies suggest that inclusion bias is not a major problem for studies of the genetic epidemiology of stroke. Molecular genetic studies might be best targeted at non-cardioembolic stroke and younger patients. However, genetic susceptibility to hypertension may account for a significant proportion of the heritability of ischemic stroke.

Differences in vascular risk factors between etiological subtypes of ischemic stroke: importance of population-based studies.

BACKGROUND: To understand the mechanisms of stroke and to target prevention, we need to know how risk factors differ between etiological subtypes. Hospital-based studies may be biased because not all stroke patients are admitted. If risk factors differ between patients who are admitted and those who are not, then case-control studies will be biased. If the likelihood of admission also depends on stroke subtype, then case-case comparisons may also be biased. METHODS: We compared risk factors and ischemic stroke subtypes (TOAST classification) in hospitalized and nonhospitalized patients in 2 population-based stroke incidence studies: the Oxford Vascular Study (OXVASC) and Oxfordshire Community Stroke Project (OCSP). We also performed a meta-analysis of risk factor-stroke subtype associations with other published population-based studies. RESULTS: In OXVASC and OCSP, stroke subtypes differed between hospitalized (293 of 647) and nonhospitalized patients (P<0.0001), with more cardioembolic strokes (odds ratio [OR], 1.8; 95% CI, 1.3 to 2.6) and fewer lacunar strokes (OR, 0.4; 95% CI, 0.3 to 0.7). Premorbid blood pressure and cholesterol were higher in hospitalized patients (both P<0.0001). Risk factor-stroke subtype associations in hospitalized patients were consequently biased (P=0.001). Meta-analysis of data from all patients in OXVASC, OCSP, and 2 other studies demonstrated consistent risk factor-stroke subtype associations. However, contrary to previous hospital-based studies, there was only a weak (OR, 1.4; 95% CI, 1.1 to 1.8) and inconsistent (P(heterogeneity)=0.01) association between small-vessel stroke and hypertension and no association with diabetes (OR, 1.0; 95% CI, 0.7 to 1.3). CONCLUSIONS: Prevalences of risk factors and stroke subtypes differ between hospitalized and nonhospitalized patients with ischemic stroke, which may bias hospital-based risk factor studies. Meta-analysis of population-based studies suggests that vascular risk factors differ between stroke subtypes.

Abnormalities on diffusion weighted magnetic resonance imaging performed several weeks after a minor stroke or transient ischaemic attack.

OBJECTIVES: Diffusion weighted brain imaging (DWI) is used in acute stroke, and also shows an acute ischaemic lesion in most transient ischamic attack (TIA) patients scanned acutely. However, it may also be useful in identifying subacute ischaemic lesions in patients with minor stroke or TIA who present several weeks after symptom onset. This study investigated the sensitivity and the observer reproducibility of DWI in cerebral TIA and minor ischaemic stroke patients scanned more than two weeks after the last symptomatic event. METHODS: Consecutive patients underwent magnetic resonance imaging (T2, DWI, ADC). The presence of clinically appropriate lesions was assessed by two independent observers, and related to the type of presenting event, the NIH score, persistence of symptoms and signs, and the time since the presenting event. RESULTS: 101 patients (53 men) were scanned at a median time of 21 days (IQR=17-28) after symptom onset. Reproducibility of the assessment of DWI abnormalities was high: interobserver agreement =97% (kappa=0.94, p<0.0001); intraobserver agreement =94% (kappa=0.88, p<0.0001). DWI showed a clinically appropriate ischaemic lesion in 29 of 51 (57%) minor stroke patients, and in 7 of 50 (14%) TIA patients. The independent predictors of a positive DWI scan were presentation with minor stroke versus TIA (p=0.009) and increasing NIH score (p=0.009), but there was no difference between patients presenting 2-4 weeks compared with >4 weeks after symptom onset. In minor stroke patients, the presence of a clinically appropriate lesion was associated with persistent symptoms (63% versus 36%; p=0.12) and signs (64% versus 33%, p=0.06) at the time of scanning. CONCLUSIONS: DWI shows a clinically appropriate ischaemic lesion in more than half of minor stroke patients presenting more than two weeks after the symptomatic event, but only in a small proportion of patients with TIA. The persistence of lesions on DWI is closely related to markers of severity of the ischaemic event. These results justify larger studies of the clinical usefulness of DWI in subacute minor stroke.

Transient ischaemic attacks mimicking focal motor seizures.

Limb shaking is an under-recognised form of transient ischaemic attack (TIA), which can easily be confused with focal motor seizures. However, it is important to distinguish limb shaking TIAs and focal seizures, as patients with this form of TIA almost invariably have severe carotid occlusive disease and are at high risk of stroke. A patient with limb shaking TIAs is presented in whom the diagnosis was missed.

Major variation in carotid bifurcation anatomy: a possible risk factor for plaque development?

BACKGROUND AND PURPOSE: Why is carotid plaque often so strikingly asymmetrical within individuals, and why does the extent of disease vary so considerably between individuals with similar systemic risk factors? Variability of carotid bifurcation anatomy is a possible explanation. Flow models suggest that vessel anatomy, in particular vessel diameter and area ratios, affects plaque formation at arterial bifurcations. However, carotid bifurcation anatomy could only be a major risk factor for plaque formation if it was sufficiently variable. Since very few data exist on the extent of interindividual and intraindividual variability of bifurcation anatomy, we studied 5395 angiograms from the European Carotid Surgery Trial. METHODS: To minimize changes in bifurcation anatomy secondary to atherosclerosis, we excluded vessels with >/=30% stenosis. We measured arterial diameters at disease-free points and calculated the following ratios: internal to common carotid (ICA/CCA), external to common carotid (ECA/CCA), external to internal carotid (ECA/ICA), and outflow/inflow area. For intraindividual asymmetry, we compared the ratios on both sides. RESULTS: Each ratio varied markedly between individuals. The 95% ranges were as follows: ICA/CCA, 0.44 to 0.86; ECA/CCA, 0.34 to 0.80; ECA/ICA, 0.55 to 1.33; and outflow/inflow area, 0.38 to 1.28. The results were very similar in 407 bifurcations with no disease. Among the 755 patients with <30% stenosis bilaterally, side differences of >/=25% were present in 17% (95% CI, 15% to 20%) for the ICA/CCA ratio, 27% (95% CI, 24% to 30%) for the ECA/CCA ratio, 32% (95% CI, 28% to 35%) for the ECA/ICA ratio, and 42% (95% CI, 38% to 45%) for the outflow/inflow area ratio. CONCLUSIONS: We found large interindividual differences in carotid bifurcation anatomy. For example, there was 4-fold variation of the ratio of outflow to inflow area. Intraindividual variation was also considerable. These data highlight the potential importance of anatomic variation as a risk factor for atheroma and provide a firm basis for flow modeling studies.

Sex differences in carotid bifurcation anatomy and the distribution of atherosclerotic plaque.

BACKGROUND AND PURPOSE: Plaque formation at arterial bifurcations depends on vessel anatomy, particularly the relative sizes of the branches, and the ratio of the outflow to inflow area. The facts that carotid plaque is more common in men and that carotid bruits in the absence of stenosis are more frequent in women raise the possibility that there are sex differences in carotid bifurcation anatomy. We studied 5395 angiograms from the European Carotid Surgery Trial. METHODS: To minimize secondary changes we excluded angiograms with >/=50% stenosis and also studied vessels with no disease. We measured arterial diameters at disease-free points and calculated the following ratios: internal/common (ICA/CCA); external/common (ECA/CCA); internal/external (ICA/ECA) carotid arteries; carotid bulb/CCA; and outflow/inflow area. We related these to sex and also studied the distribution of plaque in the whole trial population. RESULTS: Among 2930 angiograms with <50% stenosis, the mean ICA/CCA ratio, ICA/ECA ratio, and outflow/inflow area ratio were larger in women than in men (all P<0.0001). The findings were similar in 622 bifurcations without atheroma. There were also differences in the distribution of plaque, with men more likely to have the maximum stenosis distal to the carotid bulb (odds ratio, 2.29; 95% CI, 1.33 to 4.01; P=0.001) and women more likely to have stenosis of the ECA (odds ratio, 1.54; 95% CI, 1.30 to 1.85; P<0.0001). CONCLUSIONS: Sex differences in carotid bifurcation anatomy are not limited to absolute vessel size. In addition, the outflow to inflow area ratio is bigger in women, and relative to the CCA and ECA, women have larger ICAs than men. Irrespective of whether these differences are congenital or acquired, they may partly explain the sex differences that we found in the distribution of plaque and the sex differences in the prevalence of carotid atheroma in the general population.