Why now? Moving from stroke risk factors to stroke triggers

PURPOSE OF REVIEW: While chronic risk factors for stroke are reasonably well understood, the acute precipitants, or triggers, of stroke, remain relatively understudied. RECENT FINDINGS: Several converging lines of evidence indicate that transient perturbations in systemic metabolism may provoke the onset of cardiovascular events, including stroke. Epidemiologic data, including studies utilizing novel designs that consider intraindividual differences across different time periods, have been used to clarify triggers for myocardial ischemia, and these methods are beginning to be employed in stroke research. Acute infections, particularly upper respiratory infections, and other inflammatory stimuli have emerged as important triggers of acute ischemic stroke. The mechanisms involved include immunologically mediated activation of platelets and endothelial dysfunction. There also appears to be a period of time, or 'stroke-prone state', characterized by diffuse activation of the vasculature during which patients may be at increased risk of initial and recurrent ischemic events. SUMMARY: Confirmation of these findings in further studies may help elucidate the mechanisms behind this short-term increase in stroke risk. Improved methods of assessment of this period of heightened susceptibility could lead to more temporally focused preventive interventions.     

„Childhood stroke“

Childhood arterial ischemic stroke differs in essential aspects from adult stroke. It is rare, often relatively unknown among laypersons and physicians and the wide variety of age-specific differential diagnoses (stroke mimics) as well as less established care structures often lead to a considerable delay in the diagnosis of stroke. The possible treatment options in childhood are mostly off-label. Experiences in well-established acute treatment modalities in adult stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in children and only based on case reports and case series. The etiological clarification is time-consuming due to the multitude of risk factors which must be considered. Identifying each child’s individual risk profile is mandatory for acute treatment and secondary prevention strategies and has an influence on the individual outcome. In addition to the clinical neurological outcome the residual neurological effects of stroke on cognition and behavior are decisive for the integration of the child into its educational, later professional and social environment.     

Acute brain MRI–DWI patterns and stroke recurrence after mild-moderate stroke

Brain ischemic lesions identified by diffusion-weighted imaging (DWI) have been shown to predict high risk of early future ischemic events in patients with transient ischemic attacks and minor stroke. The aim of this study is to analyze different brain MRI–DWI patterns in patients with mild-moderate stroke to define acute patterns related with a higher risk of stroke recurrence in long-term follow-up (from 6 to 36 months). Retrospective review of case series from a prospective stroke record including 253 patients with mild-moderate stroke (NIHSS from 1 to 7) and acute MRI–DWI lesions. MRI–DWI lesions were analyzed to determine clinically relevant lesions, based on the number, location, age and affected arterial territories. We defined three patterns: (1) multiple versus single lesions; (2) single deep versus single cortical lesions; and (3) single lesions versus multiple lesions affecting different arterial territories and/or of different age. The impact of these patterns on recurrence was analyzed by Cox regression analysis. 38 patients (15.0%) suffered a recurrence. Univariate analysis showed the risk of recurrence for each pattern. Pattern 1: patients with multiple lesions had greater risk of recurrence than those with single lesions (28.2 vs. 9.9%; OR: 3.75 (95% CI: 1.76–7.27), p < 0.0001). Pattern 2: patients with single cortical lesions had higher risk than those with deep lesions (14.3 vs. 6.7% OR: 2.33 (95% CI: 0.86–6.33), p < 0.089). Pattern 3: patients with multiple DWI in different territories or different age had the highest recurrence rate (30.6%), OR: 4.01 (95% CI: 1.70–9.47), p < 0.001, compared to patients with single lesions. Cox regression analysis adjusted by possible confounders, showed that for pattern 1 the OR for recurrence was 2.49 (95% CI: 1.27–4.89), p = 0.008; for pattern 2, OR:1.99 (95% CI: 0.74–5.37), p = 0.17; for pattern 3, OR: 2.85 (95% CI: 1.31–6.15), p = 0.008. Brain MRI–DWI patterns assessed in the acute phase of mild-moderate stroke are useful to identify those patients at high risk of recurrence.     

Acute care in stroke: do stroke units make the difference?

The consideration of stroke as a medical emergency and the development of new specific treatments to be applied in a narrow therapeutic window have shown the need to establish an adequate organization system for the management of stroke. It should be considered as an integral process both outside and inside the hospital. General care is essential and must already start outside the hospital, and comprises respiratory and cardiac care, fluid and metabolic management, especially blood glucose control, avoiding the administration of glucose solutions, blood pressure control, early treatment of hyperthermia and prevention and treatment of neurologic and systemic complications. In the early 70s, the first stroke units (SU) were established as intensive-care SU, but failed to show improvement in terms of reduction of mortality-morbidity. Nowadays, the concept has changed to a non-intensive-care SU. The benefit of these SU has been amply demonstrated in terms of reduction in mortality and in long institutionalization, as well as better functional outcome compared with general wards, and the efficacy of a neurology ward compared to a general medicine department has also been shown, but at the moment there are no studies analyzing the differences between a stroke team (ST) in a department of neurology and a SU. In this regard, we have performed a sequential analysis comparing both SU and ST and demonstrated a reduction in length of stay, complications and acute care costs with an improvement in functional state at hospital discharge, a reduction in the discharge to nursing homes with an increase in patients translated into rehabilitation wards. With these data, we can conclude that SU, not ST are the most effective organizational model for acute stroke management. Definitely, the SU make the difference.     

Should all patients with mild ischemic stroke be excluded from therapeutic stroke trials?

We aimed to investigate stroke etiology in our cohort of patients with mild ischemic stroke (MIS) and to study the effect of stroke etiology on patient outcome. We also studied the effect of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in this cohort. We analyzed patients with MIS who were eligible for IV rt-PA presenting within 3 hours of symptom onset with a National Institutes of Health Stroke Scale (NIHSS) score ?5 admitted from March 2006 through June 2009. Stroke etiology was determined using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Primary outcome was the discharge NIHSS score. We identified 110 patients with MIS with a male-to-female ratio of: 1.4:1 and a mean age of 69 ± 13 years. The mean admission NIHSS score was 2 ± 3. The stroke risk factors were identified as: hypertension, 82 patients (75%); previous stroke/transient ischemic attack, 36 patients (33%); and atrial fibrillation, 28 patients (26%). Stroke etiology was identified as: large vessel atherosclerosis (31 patients, 28%), cardioembolism (29, 26%), small vessel occlusion (seven, 6%) and those with other or undetermined conditions (43, 39%). IV rt-PA was administered to 25 patients (23%). Despite the use of IV rt-PA in only one patient with small vessel occlusion, patients in our study with this stroke etiology tended to have better outcomes compared to those with other stroke subtypes, although the difference was not statistically significant. The discharge NIHSS score did not show any statistically significant difference between the treated and untreated patients with MIS. Our study shows that MIS may be caused by non small vessel occlusion in more patients than previously reported and this subgroup of patients with MIS should not be excluded from trials of intravenous and endovascular therapies.     

Ischemic stroke of the cortical “hand knob” area: stroke mechanisms and prognosis

Cortical ischemic stroke affecting the precentral “hand knob” area is a rare but well known stroke entity. To date, little is known about the underlying stroke mechanisms and the prognosis. Twenty-nine patients admitted to our service between 2003 and 2007 were included in the study on the basis of an acute ischemic infarct of the cortical “hand knob” area confirmed by diffusion-weighted magnetic resonance imaging with contralateral hand paresis. For all patients clinical, epidemiological as well as imaging data at the time point of admission were analysed retrospectively and follow-up data on all patients was obtained. The majority (n = 21/72%) had an isolated infarct of the cortical “hand knob” area. In 23 (79%) patients it was a first ever stroke. Ten patients (34%) had ipsilateral extracranial stenosis of the internal carotid artery (ICA), whereas potential cardiac embolic sources were less frequent (n = 4/14%). No patient exhibited ipsilateral MCA stenosis. All but two patients (93%) had marked atherosclerotic alterations of the ICA. Hypertension was the most prevalent vascular risk factor (n = 23/79%). At follow-up (mean 25.0 months, range 0.4–47.4 months) no patient had died and only one (3%) experienced a recurrent stroke. The majority of patients (79%) reported improvement of hand paresis, 17 (59%) were asymptomatic (modified Rankin score = 0). Only one patient was significantly disabled due to a recurrent stroke. In conclusion, ischemic infarcts affecting the cortical “hand knob” area are frequently associated with atherosclerotic changes of the carotid artery, suggesting an arterio-arterial thrombembolic stroke mechanism. It mostly reflects first ever ischemic stroke, and follow-up data suggest a rather benign course.     

Can stroke cause neurodegenerative dementia?

Stroke and dementia have typically been housed in different taxonomies. They are considered to be exemplars of very different forms of brain injury: stroke as an acute vascular injury and dementia as a progressive degenerative disease. Yet there is definite overlap between the two conditions: stroke increases the likelihood of developing dementia. Recent work has confirmed that vascular risk factors such as diabetes and hypertension predispose to dementia. However, in the absence of any clear findings of a direct pathway from stroke to degenerative dementia, the separation has persisted. In this review, we summarize the evidence relating to whether stroke can initiate or promote degenerative dementia and, in particular, Alzheimer's disease. The evidence comes from autopsy studies, from brain imaging studies, from studies of patients with symptomatic stroke and from studies in CADASIL. A number of studies have demonstrated that stroke can lead to changes in brain volume and cognitive performance, although generally of a different profile to the atrophy and cognitive decline seen in Alzheimer's disease. Much of the evidence is circumstantial, and does little to support a claim that stroke triggers neurodegenerative dementia. The question, then, remains open. None of the studies reviewed included the necessary longitudinal follow-up of stroke patients incorporating cognitive assessment, imaging and pathology. Given the high prevalence and substantial burden of dementia, there is much to be gained from identifying prognostic markers and it remains an exciting idea that we might be able to identify a subgroup of stroke patients who are at high risk.     

Deteriorating patients with large hemispheric stroke

C Clinical deterioration following acute ischemic stroke is common. It may be due to both systemic and neurological factors. Systemic factors that may contribute to clinical deterioration include fever, infection, hypotension, hypoxia, and hypercarbia. The primary neurological causes of deterioration are cerebral edema and, rarely, recurrent stroke. Edema in patients with small strokes, often has no or minimal impact on clinical status. Should deterioration occur in patients with small strokes it is usually transient, with the important exception of cerebellar strokes. On the other hand, edema following large hemispheric strokes can have lethal consequences. Considerable effort has recently been directed toward determining the best management of massive hemispheric swelling following ischemic stroke.     

Do common infections cause stroke?

Infections have long been recognized as a potential, if uncommon, cause of cerebrovascular disease. In recent years, with the growing recognition of the importance of inflammation in atherosclerosis, there has been renewed interest in the possibility that common infections may participate in the atherosclerotic process or lead to stroke through other mechanisms. Specific organisms that have been implicated include Chlamydia pneumoniae, herpes viruses, human immunodeficiency virus, Helicobacter pylori, and organisms associated with periodontal infections. This article outlines the epidemiological, pathological, and laboratory evidence that these infections may be associated with atherosclerosis and stroke. Although definitive proof of an association between a specific infection and stroke is generally lacking, the accumulating evidence does indicate that several types of infections may be among the modifiable risk factors that contribute to the risk of stroke.     

Risk factors between intracranial–extracranial atherosclerosis and anterior–posterior circulation stroke in ischaemic stroke

Objectives: Atherosclerosis is an important cause of stroke and remains a challenge for stroke prevention. Risk factors involved in atherosclerotic stroke and anterior and posterior circulation strokes (ACS and PCS, respectively) are different. The purpose of this study is to investigate differences in risk factors between intracranial and extracranial atherosclerosis (ICAS and ECAS), ACS and PCS, and ICAS/ECAS with ACS/PCS in a Chinese acute ischaemic stroke population.

Methods: We analysed 551 ischaemic stroke patients who had been enrolled between August 2005 and July 2008. First, risk factors were compared between non-atherosclerosis, ICAS, ECAS, and combined ICAS and ECAS groups. ICAS and ECAS were assessed with transcranial Doppler and carotid colour Doppler ultrasound, respectively. Second, risk factors were compared between ACS and PCS groups. Stroke lesion was assessed with magnetic resonance imaging. Third, risk factors were compared in ICAS/ECAS associated with ACS/PCS.

Results: The risk factor for ICAS was high diastolic blood pressure (OR, 1.075; 95% CI, 1.016–1.138; p = 0.013), and the risk factors for ECAS were age (OR, 1.113; 95% CI, 1.046–1.183; p = 0.001) and low density lipoprotein (OR, 1.450; 95% CI, 1.087–1.935; p = 0.012). Hypertension (OR, 1.090; 95% CI, 1.001–1.109; p = 0.027) was associated with PCS. Age (OR, 1.026; 95% CI, 1.011–1.128; p = 0.003), male gender (OR, 2.278; 95% CI, 1.481–3.258; p = 0.003) and age (OR, 1.067; 95% CI, 1.013–1.123; p = 0.014), scores of NIHSS (OR, 1.069; 95% CI, 1.012–1.130; p = 0.018) were risk factors for ICAS and ECAS with ACS, respectively.

Conclusion: Risk factors are different between ICAS and ECAS, ACS and PCS, and ICAS/ECAS with ACS/PCS. Thus, targeted strategies are needed to consider these differences to prevent, treat and manage these diseases.