Elena Haapaniemi

Analysis of 1008 Consecutive Patients Aged 15 to 49 With First-Ever Ischemic Stroke The Helsinki Young Stroke Registry

Background and Purpose— To analyze trends in occurrence, risk factors, etiology, and neuroimaging features of ischemic stroke in young adults in a large cohort. Methods— We evaluated all 1008 consecutive ischemic stroke patients aged 15 to 49 admitted to Helsinki University Central Hospital, 1994 to 2007. Etiology was classified by Trial of Org 10172 in Acute Stroke Treatment criteria. Comparisons were done between groups stratified by gender and age. Results— Estimated annual occurrence was 10.8/100 000 (range 8.4 to 13.0), increasing exponentially with aging. Of our 628 male and 380 female (ratio 1.7:1) patients, females were preponderant among those <30, whereas male dominance rapidly increased around age of 44. The most frequent risk factors were dyslipidemia (60%), smoking (44%), and hypertension (39%). Males and patients >44 clearly had more risk factors. Cardioembolism (20%) and cervicocerebral artery dissection (15%) were the most frequent etiologic subgroups. Proportions of large-artery atherosclerosis (8%) and small-vessel disease (14%) began to enlarge at age 35, whereas frequency of undetermined etiology (33%) decreased along aging. Posterior circulation infarcts were more common among patients <45 years of age. Left hemisphere infarcts were more frequent in general. There were 235 (23%) patients with multiple and 126 (13%) with silent infarcts, and 55 (5%) patients had leukoaraiosis. Conclusions— The frequency of ischemic stroke increases sharply at age 40. Etiology and risk factors start resembling those seen in the elderly in early midlife but causes defined in younger patients still are frequent in those aged 45 to 49. Subclinical infarcts were surprisingly common in the young.

Gut microbiota are related to Parkinson's disease and clinical phenotype

In the course of Parkinsons disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha‐synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non‐motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1–V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker.

Recurrent ischemic events in young adults after first-ever ischemic stroke

Data on recurrence of vascular events and their prognostic factors in young (<50 years of age) stroke patients are not well defined.

Safety of Thrombolysis in Stroke Mimics Results From a Multicenter Cohort Study

Background and Purpose— Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. Methods— In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. Results— One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5–2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0–5.0) compared with 7.9% (95% confidence interval, 7.2–8.7) in ischemic strokes. Conclusions— In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

SMASH-U: A Proposal for Etiologic Classification of Intracerebral Hemorrhage

Background and Purpose— The purpose of this study was to provide a simple and practical clinical classification for the etiology of intracerebral hemorrhage (ICH). Methods— We performed a retrospective chart review of consecutive patients with ICH treated at the Helsinki University Central Hospital, January 2005 to March 2010 (n=1013). We classified ICH etiology by predefined criteria as structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic disease (S), hypertension (H), or undetermined (U). Clinical and radiological features and mortality by SMASH-U (Structural lesion, Medication, Amyloid angiopathy, Systemic/other disease, Hypertension, Undetermined) etiology were analyzed. Results— Structural lesions, namely cavernomas and arteriovenous malformations, caused 5% of the ICH, anticoagulation 14%, and systemic disease 5% (23 liver cirrhosis, 8 thrombocytopenia, and 17 various rare conditions). Amyloid angiopathy (20%) and hypertensive angiopathy (35%) were common, but etiology remained undetermined in 21%. Interrater agreement in classifying cases was high (&kgr;, 0.89; 95% CI, 0.82–0.96). Patients with structural lesions had the smallest hemorrhages (median volume, 2.8 mL) and best prognosis (3-month mortality 4%), whereas anticoagulation-related ICHs were largest (13.4 mL) and most often fatal (54%). Overall, median ICH survival was 5½ years, varying strongly by etiology (P<0.001). After adjustment for baseline characteristics, patients with structural lesions had the lowest 3-month mortality rates (OR, 0.06; 95% CI, 0.01–0.37) and those with anticoagulation (OR, 1.9; 1.0–3.6) or other systemic cause (OR, 4.0; 1.6–10.1) the highest. Conclusions— In our patients, performing the SMASH-U classification was feasible and interrater agreement excellent. A plausible etiology was determined in most patients but remained elusive in one in 5. In this series, SMASH-U based etiology was strongly associated with survival.

Community-Based Thrombolytic Therapy of Acute Ischemic Stroke in Helsinki

Background and Purpose— Thrombolysis with alteplase is used in acute ischemic stroke within 3 hours after symptom onset in many stroke centers, but experience remains limited in Europe. Methods— Using eligibility and management criteria similar to those published by the American Heart Association, we treated 75 consecutive patients aged 21 to 83 years (mean age, 63.6 years; median Scandinavian Stroke Scale score, 32/58) with hemispheric infarction with alteplase in 1998–2001. Their neuroradiological findings (ischemic and hemorrhagic changes) and functional outcome at 3 months were evaluated. Results— Sixty-one percent of the patients had recovered functional independence (Barthel Index 95 to 100) at the 3-month follow-up. On the modified Rankin Scale (mRS), 37% (28/75) of patients had no or minimal symptoms (mRS 0 to 1), while 17% (13/75) remained dependent (mRS 4 to 5) and 5% (4/75) died. Cerebral parenchymal hematomas occurred in 8% (6/75) and hemorrhagic transformation in 8% (6/75) of the patients. Low initial diastolic blood pressure and administration of intravenous antihypertensive medication were associated with unfavorable outcome (mRS 3 to 6). Conclusions— We conclude that our management protocol for thrombolytic therapy is safe. These rates of functional outcome, case fatality, and hemorrhagic cerebral events compare favorably with those of other published series of stroke thrombolysis with similar time windows and management guidelines. Associations between blood pressure and its treatment during thrombolysis with functional outcome deserve further analysis.

Etiology of first‐ever ischaemic stroke in European young adults: the 15 cities young stroke study

Risk factors for IS in young adults differ between genders and evolve with age, but data on the age‐ and gender‐specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers.

Demographic and geographic vascular risk factor differences in european young adults with ischemic stroke: The 15 cities young stroke study

Background and Purpose— We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. Methods— We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. Results— In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. Conclusions— Primary preventive strategies for ischemic stroke in young adults—having high rate of modifiable risk factors—should be targeted according to sex and age at continental level.

Is D-dimer helpful in evaluating stroke patients? A systematic review

D‐dimer (DD) is a fibrin degradation product present in negligible amounts in healthy individuals, but in thrombotic/fibrinolytic conditions substantially increases in plasma. Over the last two decades numerous studies have explored whether DD measurements would help stroke clinicians. An easy, reliable, and inexpensive test for stroke diagnosis, determination of stroke subtype, severity, prognosis, and recurrence risk is being sought. We searched the database, of studies indexed in English on MEDLINE, using the keywords ‘cerebral venous thrombosis, D‐dimer, deep vein thrombosis, intracerebral hemorrhage, ischemic stroke, outcome, prognosis, and subarachnoid hemorrhage’ for relevant studies. Here, we systematically review current evidence on plasma DD levels in patients with ischemic and hemorrhagic strokes, transient ischemic attacks, and cerebral venous thrombosis. Numerous studies showed that patients with various strokes and stroke‐related diseases had acutely increased plasma DD levels. Plasma DD levels, however, are neither sensitive nor specific enough to be utilized in stroke diagnostics and cannot replace either clinical or radiological evaluation. Regarding prediction of patient outcome, good clinical evaluation is clearly superior to DD testing.

How Does Number of Risk Factors Affect Prognosis in Young Patients With Ischemic Stroke

Background and Purpose— We aimed to explore clinical features of young patients with ischemic stroke with no traditional vascular risk factors and to assess the impact of risk factor counts on outcomes. Methods— We included 990 patients aged 15 to 49 years with first-ever ischemic stroke followed for a mean of 9.0±3.8 years (survivors). Risk factors were categorized as well-documented and less well-documented. Outcome measures were unfavorable functional outcome (3-month modified Rankin Scale 2–6); recurrent ischemic stroke; myocardial infarction or other arterial noncerebrovascular event; and death from any cause. Results— Compared with those with at least 1 well-documented risk factor, the 127 (12.8%) patients without risk factors were younger (median age, 37 versus 44 years; P<0.001), likely to be females (54.3% versus 34.9%; P<0.001), and they had more frequently a low-risk source of cardioembolism (21.3% versus 8.1%; P<0.001), internal carotid artery dissection (12.6% versus 6.4%; P=0.011), or vertebral artery dissection (17.3% versus 7.2%; P<0.001). The groups had similar 3-month functional outcomes. Patients without well-documented risk factors had less frequently recurrent ischemic strokes (4.7% versus 13.6%; log rank P=0.014), noncerebrovascular arterial events (0% versus 6.1%; P=0.008), and lower long-term mortality (3.4% versus 14.3%; P=0.003) than did those with at least 1 risk factor. Adjusted for demographics and stroke etiology, the number of well-documented risk factors was associated with higher risk for noncerebrovascular events. Increasing count of less well-documented risk factors was, in turn, independently associated with higher long-term mortality. Conclusions— In young adults with first-ever ischemic stroke, risk factor counts added independent prognostic information regarding noncerebrovascular events and mortality.