Pierre Amarenco

Underlying pathologies of stroke of unknown cause include atherosclerosis in brain arteries, either intracranial (e.g. moderate middle cerebral artery stenosis), extracranial (e.g. vertebral artery origin stenosis) or proximal (e.g. thick plaques in the aortic arch), thought to be unrelated to the stroke; cardiac findings of undetermined causal link (e.g. patent foramen ovale); incomplete or late workup responsible for true, undiagnosed cause (e.g. arterial dissection, mobile intracardiac/luminal thrombus disappeared at the time of examination). In the next years, new diagnostic tools may hopefully determine which of these pathologies are or are not causally related to stroke.

Background and Purpose— Clinical and imaging studies have reported an independent and intriguing association between intracranial arterial dolichoectasia (IADE) and markers of small-vessel disease (SVD) such as lacune(s). We used a large brain-autopsy collection to investigate the relation between IADE and pathologically assessed cerebral SVD. Methods— The entire arterial tree from the heart to the intracranial small intracerebral arteries was investigated in 381 consecutive autopsies from patients with stroke. Vascular risk factors, heart status (weight, coronary atherosclerosis, and myocardial infarction), prevalence and severity of atherosclerosis from heart to brain (aortic arch, carotid, vertebral, and intracranial arteries), dolichoectasia, cerebral SVD, and brain tissue lesions (lacune(s), é tat cribl é) were evaluated. Analyses were adjusted for age, sex, and heart weight. Results— Twenty-three (6%) of 381 patients had IADE, affecting mainly the basilar artery, with a median basilar artery diameter of 6 mm (range, 4 to 9 mm). Patients with IADE had a >2-fold increase in the prevalence of basilar artery plaques and ulcerated plaques in the aortic arch (both P =0.006), but there were no associations with coronary or cervical artery plaques. SVD was more frequent in IADE-positive than in IADE-negative patients (45% vs 18%; P =0.004). The adjusted odds ratio was 3.85 (95% confidence interval, 1.56 to 9.52). Cerebral amyloid angiopathy was not observed in IADE-positive patients. Conclusions— Compared with stroke patients without IADE, those with IADE were more likely to have pathologic evidence of cerebral SVD and its consequences, independent of age, arterial hypertension, or diabetes mellitus. IADE and cerebral SVD may have unidentified biologic processes in common.

Thirty years of clinical trials have demonstrated that stroke can be prevented by reducing blood pressure to less than 140/90 mm Hg or by a further decrease of 10/5 mm Hg when blood pressure is controlled, by reducing LDL cholesterol by at least 1 mmol/l (39 mg/dl), and by inhibiting platelet aggregation. The (too simplistic) concept of the polypill strategy combining pharmacologic agents to achieve these goals is supposed to reduce the risk by 80% overall. However, reducing general salt and sugar intake, giving up smoking, developing prevention clinics with prevention nurses to improve adherence to preventive treatments, as well as decreasing poverty and malnutrition, increasing the level of hygiene, fighting against infectious diseases and financially helping developing countries are all combined necessary approaches to decrease the worldwide burden of stroke and other vascular diseases.

This editorial refers to ‘Plasma lipids predict myocardial infarction, but not stroke, in patients with established cerebrovascular disease’^† by A. Patel et al., on page 1910

Background and Purpose— The Framingham stroke risk score (FSRS) and Framingham cardiovascular risk score (FCRS) estimate the individual absolute cardiovascular and stroke risks. Common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CPs) are markers of subclinical atherosclerosis and help in the early identification of presymptomatic individuals. The purpose of this study was to correlate Framingham risk score (FRS) with CCA-IMT and CPs and evaluate their respective contribution to stroke risk. Methods— In 510 consecutive patients with brain infarction and 510 matched controls, we calculated the FSRS and FCRS for each individual and performed carotid ultrasonography. Mean CCA-IMT was measured off-line at a central core laboratory, and presence of CPs was assessed. Results— FRS progressively increased according to tertiles of CCA-IMT ( P for trend P for interaction P =0.0006), 2.16 (1.57 to 2.98; P P Conclusions— CCA-IMT, CPs, and FRSs correlated well. The CCA-IMT value may help discriminate between subjects at low or high 10-year risk.

Two studies found that stroke patients with intracranial arterial dolichoectasia (IADE) had lacunar infarction more often than the control subjects. The relation between IADE and other manifestations of small‐vessel disease (multilacunar state, leukoaraiosis, and état criblé) was not investigated. The magnetic resonance images of 510 patients with brain infarction in the Etude du Profil Genetique de l'Infarctus Cerebral (GENIC) study were evaluated for the diagnosis of multilacunar infarction (>1 lacunar infarct), leukoaraiosis (assessed in periventricular and subcortical regions according to Scheltens and colleagues' scale, with severe leukoaraiosis defined as a score > 8), état criblé (using a semiquantitative score ranging from 0–8, with severe EC > 4), and IADE (using the consensus method). By comparison with stroke patients without IADE (n = 447), IADE(+) stroke patients (n = 63) had significantly more frequent multilacunar state (51 vs 33%), severe leukoaraiosis (34 vs 19%), and severe état criblé (32 vs 12%). After adjustment for potential confounding factors, the odds ratios (95% confidence interval) for the presence of IADE were 2.05 (1.08–3.87) for multilacunar state, 2.40 (1.11–5.20) for severe leukoaraiosis, and 3.60 (1.43–9.08) for severe état criblé. The factors significantly associated with état criblé were older age and a familial history of stroke. IADE in stroke patients was independently associated with parenchymal manifestations of small‐vessel disease. These conditions may have in common underlying pathophysiological processes. Ann Neurol 2005

In this group, transoesophageal echocardiography (TOE) shows inter-atrial septal abnormalities in 55–60% of cases. The same abnormal septum is observed in 20% of the normal population. However, when present in a patient with a stroke of unknown cause, is this abnormality responsible for the stroke or the marker for the true cause of stroke? For example, having yellow nails is statistically associated with lung cancer, but does not mean that yellow nails cause lung cancer.

Stroke is the leading cause of adult disability and dependency in western society. Despite the determined efforts of basic science and clinical investigators, neuroprotective therapies for acute stroke have yet to be realised. Stroke prevention, therefore, remains the key route for reducing morbidity and mortality. Hypertension and hypercholesterolaemia are the most important modifiable risk factors for stroke. Several recent landmark studies have shown that lipid lowering with statins can reduce the risk of ischaemic stroke, as well as coronary heart disease. In addition, clinical trials evaluating the effects of blood pressure lowering have shown that antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs) and angiotensin II receptor antagonists can reduce stroke risk. Accumulating evidence suggests certain antihypertensive agents such as CCBs might also prevent the formation and progression of carotid atheroma, independently of their blood-pressure-lowering effects. It follows that rigorous identification and targeting of high- risk or stroke-prone individuals for blood pressure and lipid-lowering interventions should be of practical importance to all physicians involved in the management of stroke.