Peter U. Heuschmann

Lifestyle Risk Factors for Ischemic Stroke and Transient Ischemic Attack in Young Adults in the Stroke in Young Fabry Patients Study

Background and Purpose— Although many stroke patients are young or middle-aged, risk factor profiles in these age groups are poorly understood. Methods— The Stroke in Young Fabry Patients (sifap1) study prospectively recruited a large multinational European cohort of patients with cerebrovascular events aged 18 to 55 years to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke or transient ischemic attack, we studied age- and sex-specific prevalences of various risk factors. Results— Among 4467 patients (median age, 47 years; interquartile range, 40–51), the most frequent well-documented and modifiable risk factors were smoking (55.5%), physical inactivity (48.2%), arterial hypertension (46.6%), dyslipidemia (34.9%), and obesity (22.3%). Modifiable less well-documented or potentially modifiable risk factors like high-risk alcohol consumption (33.0%) and short sleep duration (20.6%) were more frequent in men, and migraine (26.5%) was more frequent in women. Women were more often physically inactive, most pronouncedly at ages <35 years (18–24: 38.2%; 25–34: 51.7%), and had high proportions of abdominal obesity at age 25 years or older (74%). Physical inactivity, arterial hypertension, dyslipidemia, obesity, and diabetes mellitus increased with age. Conclusions— In this large European cohort of young patients with acute ischemic cerebrovascular events, modifiable risk factors were highly prevalent, particularly in men and older patients. These data emphasize the need for vigorous primary and secondary prevention measures already in young populations targeting modifiable lifestyle vascular risk factors. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00414583.

Incidence and predictors of post‐stroke epilepsy

Stroke is the leading cause of seizures and epilepsy in the elderly. The aim of this study was to assess the incidence of post‐stroke epilepsy (PSE) based on the revised epilepsy definition of the International League Against Epilepsy (ILAE) in a population‐based study and to describe possible predictors.

DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke (DEPTH-SOS): a protocol of a multicenter randomized controlled clinical trial and a literature review.

Rationale Although decompressive hemicraniectomy clearly reduces mortality in severe space-occupying middle cerebral artery infarction (so-called malignant middle cerebral artery infarction), every fifth patient still dies in the acute phase and every third patient is left with moderate to severe disability. Therapeutic hypothermia is a neuroprotective and antiedematous treatment option that has shown promising effects in severe stroke. A combination of both treatment strategies may have the potential to further reduce mortality and morbidity in malignant middle cerebral artery infarction, but needs evaluation of its efficacy within the setting of a randomized clinical trial. Aims The DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke (DEPTH-SOS) trial aims to investigate safety and feasibility of moderate therapeutic hypothermia (33°C ± 1) over at least 72 h in addition to early decompressive hemicraniectomy (≤48 hours after symptom onset) in patients with malignant middle cerebral artery infarction. Design The DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke is a prospective, multicenter, open, two-arm (1:1) comparative, randomized, controlled trial. Study outcomes The primary end-point is mortality at day 14. The secondary end-points include functional outcome at day 14 and at 12 months follow-up, and complications related to hypothermia. Discussion The results of this trial will provide data on safety and feasibility of moderate hypothermia in addition to decompressive hemicraniectomy in malignant middle cerebral artery infarction. Furthermore, efficacy data on early mortality and long-term functional outcome will be obtained, forming the basis of subsequent trials.

MRI in acute cerebral ischemia of the young: The Stroke in Young Fabry Patients (sifap1) Study

Objective: We focused on cerebral imaging findings in a large cohort of young patients with a symptomatic ischemic cerebrovascular event (CVE) to extract relevant pathophysiologic and clinical information. Methods: We analyzed the scans of 2,979 patients (aged 18–55 years) enrolled in the sifap1 project with clinical evidence of ischemic stroke (IS) or clinically defined TIA in whom MRI, including diffusion-weighted imaging, was obtained within 10 days of the CVE. Age groups were categorized as 18–34, 35–44, and 45–55 years. We compared age- and sex-specific proportions of infarct features, white matter hyperintensities, and old microbleeds. Results: Acute infarcts were identified in 1,914 of 2,264 patients (84.5%) with IS and 101 of 715 patients (14.1%) with TIA. Among patients with IS, younger age was significantly associated with acute infarcts in the posterior circulation, while anterior circulation infarcts and acute lacunar infarcts were more frequent in older age groups. One or more old infarcts were present in 26.8% of IS and 17.1% of TIA patients. This rate remained high even after excluding patients with a prior CVE (IS, 21.7%; TIA, 9.9%). The prevailing type of old infarction was territorial in patients younger than 45 years and lacunar in those aged 45 years or older. The frequency of white matter hyperintensities (46.4%) and their severity was positively associated with age. Old microbleeds were infrequent (7.2%). Conclusions: Young adults show a high frequency of preexisting and clinically silent infarcts and a relative preference for acute ischemia in the posterior circulation. Findings suggesting small-vessel disease become apparent at age 45 years and older.

Breastfeeding is associated with lower risk for multiple sclerosis.

Background: Multiple sclerosis (MS) is an autoimmune disease with known genetic and environmental susceptibility factors. Breastfeeding has been shown to be protective in other autoimmune diseases. Objective: This case-control study analyzed the association of breastfeeding in infancy on the risk of developing MS. Methods: A case-control study was performed in Berlin of 245 MS patients and 296 population-based controls, who completed a standardized questionnaire on their history and duration of breastfeeding in infancy and demographic characteristics. Univariable and multivariable logistic regression analysis was performed to investigate the association between breastfeeding and MS. The multivariate model was adjusted for age, gender, number of older siblings, number of inhabitants in place of domicile between ages 0 and 6 (categorized in each case), and daycare attendance between ages 0 and 3. Results: In multivariable analysis, breastfeeding showed an independent association with MS (adjusted OR 0.58; p = 0.028). However, with no breastfeeding as reference, the protective effect only emerges after four months of breastfeeding (multivariable analysis for ≤ four months adjusted OR 0.87; p = 0.614 and for > four months OR 0.51; p = 0.016). Conclusion: The results of this case-control study support the hypothesis that breastfeeding is associated with a lower risk of MS. These results are in line with findings of previous studies on other autoimmune diseases, in which breastfeeding was shown to have protective effects.

Glycosylated Hemoglobin A1 Predicts Risk for Symptomatic Hemorrhage After Thrombolysis for Acute Stroke

Background and Purpose— Symptomatic intracerebral hemorrhage (sICH) is the most feared acute complication after intravenous thrombolysis. The aim of this study was to determine the predictive value of parameters of glycosylated hemoglobin A1 (HbA1c) on sICH. Methods— In a retrospective single center series, 1112 consecutive patients treated with thrombolysis were studied. Baseline blood glucose was obtained at admission. HbA1c was determined within hospital stay. A second head computed tomography was obtained after 24 hours or when neurological worsening occurred. Modified Rankin Scale was used to assess outcome at 90 days. Results— A total of 222 patients (19.9%) had any hemorrhage; 43 of those had sICH (3.9%) per Safe Implementation of Treatments in Stroke definition and 95 (8.5%) per National Institute of Neurological Disorders and Stroke definition; 33.2% of patients had a dependent outcome (modified Rankin Scale score 3–5). In univariate analysis history of diabetes mellitus, HbA1c, blood glucose, and National Institute of Health Stroke Scale score on admission were associated with any hemorrhage and sICH. In multivariate analysis National Institute of Health Stroke Scale score, a history of diabetes mellitus, and HbA1c were predictors of sICH per National Institute of Neurological Disorders and Stroke, and only HbA1c when Safe Implementation of Treatments in Stroke criteria were used. Conclusions— In our study, HbA1c turns out to be an important predictor of sICH after thrombolysis for acute stroke. These results suggest that hemorrhage after thrombolysis may be a consequence of long-term vascular injury rather than of acute hyperglycemia, and that HbA1c may be a better predictor than acute blood glucose or a history of diabetes mellitus.

Influence of Acute Complications on Outcome 3 Months after Ischemic Stroke

Background Early medical complications are potentially modifiable factors influencing in-hospital outcome. We investigated the influence of acute complications on mortality and poor outcome 3 months after ischemic stroke. Methods Data were obtained from patients admitted to one of 13 stroke units of the Berlin Stroke Registry (BSR) who participated in a 3-months-follow up between June 2010 and September 2012. We examined the influence of the cumulative number of early in-hospital complications on mortality and poor outcome (death, disability or institutionalization) 3 months after stroke using multivariable logistic regression analyses and calculated attributable fractions to determine the impact of early complications on mortality and poor outcome. Results A total of 2349 ischemic stroke patients alive at discharge from acute care were included in the analysis. Older age, stroke severity, pre-stroke dependency and early complications were independent predictors of mortality 3 months after stroke. Poor outcome was independently associated with older age, stroke severity, pre-stroke dependency, previous stroke and early complications. More than 60% of deaths and poor outcomes were attributed to age, pre-stroke dependency and stroke severity and in-hospital complications contributed to 12.3% of deaths and 9.1% of poor outcomes 3 months after stroke. Conclusion The majority of deaths and poor outcomes after stroke were attributed to non-modifiable factors. However, early in-hospital complications significantly affect outcome in patients who survived the acute phase after stroke, underlining the need to improve prevention and treatment of complications in hospital.

Should transesophageal echocardiography be performed in acute stroke patients with atrial fibrillation

The diagnostic need for echocardiography in acute stroke patients with documented atrial fibrillation (AF) is controversial because the index stroke per se is an indication for therapeutic anticoagulation according to guidelines. We retrospectively analyzed medical records of 2390 stroke patients consecutively admitted over a 2-year period to three different stroke units at university hospitals in Berlin, Germany. AF was diagnosed in 21.2% (n=506) of 2185 patients with acute ischemic stroke or transient ischemic attack. Overall, 36.6% (n=185) of all AF patients underwent transesophageal echocardiography (TEE) or transthoracic echocardiography within days of hospital admission. According to multivariate analysis, age and in-hospital conventions determined the diagnostic use of TEE in stroke patients with known AF, while the existing cardiovascular risk profile had no impact. Major cardiac sources of embolism were identified by echocardiography in 9.7% (n=18) of all AF patients with acute stroke, including non-AF-related sources of embolism in 3.8% (n=7). However, echocardiographic findings did not result in any therapeutic intervention other than immediate anticoagulation. Furthermore, echocardiographic findings had no impact on the prescription of anticoagulants at hospital discharge or long-term survival. Taken together, our data indicate that diagnostic echocardiography offers only a little additional information and does not impact clinical management and outcome in acute stroke patients with known AF.

Prediction of vascular risk after stroke - protocol and pilot data of the Prospective Cohort with Incident Stroke (PROSCIS).

Rationale Long-term risk of vascular disease is substantially increased after stroke with several models proposed to predict subsequent stroke and other vascular events after an index event. However, recent validation studies demonstrate limited predictive properties of available prognostic models. Aims We aim to determine prediction models of different complexity for the combined vascular end-point of stroke, myocardial infarction, and vascular death at three-years after first-ever stroke. An independent external validation of the developed models will be performed. Design Prospective observational hospital-based cohort study of patients after first-ever stroke. Methods The new predictive models will be developed using the following steps: (1) Development of a basic score based on clinical history data (e.g. hypertension, myocardial infarction, and atrial fibrillation); (2) Development of an advanced score including additional factors such as blood-based biomarkers and results of vascular imaging; (3) Comparing the models fit using different methods (discrimination, calibration); (4) Assessment of clinical utility of an advanced score using methods based on reclassification tables (e.g. net reclassification improvement, integrated discrimination improvement, decision curve analysis); and (5) Investigation of external validity. Outcomes Primary outcome is a combined vascular end-point composed of stroke, myocardial infarction, and vascular death at three-years after stroke. Furthermore, each component of the composite end-point will be investigated individually and the patterns and time points of risk transitions between vascular end-points and stroke sub-types will be determined.

Prevalence dependent calibration of a predictive model for nasal carriage of methicillin-resistant Staphylococcus aureus

BackgroundPublished models predicting nasal colonization with Methicillin-resistant Staphylococcus aureus among hospital admissions predominantly focus on separation of carriers from non-carriers and are frequently evaluated using measures of discrimination. In contrast, accurate estimation of carriage probability, which may inform decisions regarding treatment and infection control, is rarely assessed. Furthermore, no published models adjust for MRSA prevalence.MethodsUsing logistic regression, a scoring system (values from 0 to 200) predicting nasal carriage of MRSA was created using a derivation cohort of 3091 individuals admitted to a European tertiary referral center between July 2007 and March 2008. The expected positive predictive value of a rapid diagnostic test (GeneOhm, Becton & Dickinson Co.) was modeled using non-linear regression according to score. Models were validated on a second cohort from the same hospital consisting of 2043 patients admitted between August 2008 and January 2012. Our suggested correction score for prevalence was proportional to the log-transformed odds ratio between cohorts. Calibration before and after correction, i.e. accurate classification into arbitrary strata, was assessed with the Hosmer-Lemeshow-Test.ResultsTreating culture as reference, the rapid diagnostic test had positive predictive values of 64.8% and 54.0% in derivation and internal validation corhorts with prevalences of 2.3% and 1.7%, respectively. In addition to low prevalence, low positive predictive values were due to high proportion (> 66%) of mecA-negative Staphylococcus aureus among false positive results. Age, nursing home residence, admission through the medical emergency department, and ICD-10-GM admission diagnoses starting with “A” or “J” were associated with MRSA carriage and were thus included in the scoring system, which showed good calibration in predicting probability of carriage and the rapid diagnostic test’s expected positive predictive value. Calibration for both probability of carriage and expected positive predictive value in the internal validation cohort was improved by applying the correction score.ConclusionsGiven a set of patient parameters, the presented models accurately predict a) probability of nasal carriage of MRSA and b) a rapid diagnostic test’s expected positive predictive value. While the former can inform decisions regarding empiric antibiotic treatment and infection control, the latter can influence choice of screening method.