Predictors of symptomatic intracranial haemorrhage in off-label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. METHODS: This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. RESULTS: Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. CONCLUSIONS: Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.

[Mission (im)possible : Setting up a neurological center 12,000 km away with telemedicine]. / "Mission (im)possible" : Aufbau eines neurologischen Zentrums 12.000 km entfernt mittels Telemedizin.

BACKGROUND: Specialized neurological treatment decreases the mortality and morbidity of stroke patients. In many regions of the world an extensive coverage is not available. The cooperation between the Krankenhaus Nordwest (KHNW, Frankfurt, Germany) and the Government of Brunei Darussalam describes the set-up process of a specialized neurological center, including stroke unit, science and rehabilitation center. AIM: The aim of this project called to teach to treat - to treat to teach was to set up a center of excellence in neurology in Brunei Darussalam over a distance of 12,000 km. Treatment options were elucidated by teaching and taught by case examples. MATERIAL AND METHODS: The construction of the Brunei Neuroscience Stroke and Rehabilitation Center (BNSRC) began in July 2010. To overcome the large distance between the department of neurology and neuroradiology at the KHNW and the BNSRC, a telemedical network was established. We provided daily teleteaching for all professions involved in patient care as well as 24/7 availability of teleneurological services from Germany to support the local team on site. RESULTS: In the BNSRC unit over 1000 patients with ischemic and hemorrhagic stroke and all the various acute neurological conditions were treated from July 2010 until July 2016 as inpatients and over 5000 were treated as outpatients. Since 2010, a total of 52 patients with stroke were treated by thrombolysis within the thrombolytic window and 81 hemicraniectomies were performed. CONCLUSION: The project has shown that it is possible to convey specialized neurological knowledge over large distances to provide significant benefits for patients and caregivers.

Intravenous thrombolysis for acute ischaemic stroke in the elderly: data from the Baden-Wuerttemberg stroke registry.

BACKGROUND AND PURPOSE: In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed. METHODS: The data registry collected 101,349 patients with ischaemic stroke hospitalized from January 2008 to December 2012. Of these, 38,575 (38%) were aged 80 years and older and 10 286 (10.1%) underwent IVT. Favourable outcome at discharge was defined as modified Rankin Scale (mRS) ≤1 or not worse than prior to stroke. Multiple logistic regression models stratified by 10-year age groups were used to assess the relationship between IVT and mRS at discharge, adjusted for patient characteristics, admitting facility and length of hospital stay. RESULTS: The highest IVT rate was 15% in patients aged <50 years, with a continuous decline down to 8% in patients aged ≥90 years. Adjusted odds ratios and 95% confidence intervals for patients 80-89 years of age were 2.20 (1.95-2.47) (P < 0.0001) and 1.25 (0.88-1.78) (P = 0.21) for patients >90 years of age, compared to patients of the same age decade not treated with IVT. CONCLUSIONS: The evidence from routine hospital care in southwest Germany indicates that IVT is an effective treatment also for aged patients with ischaemic stroke in an age range between 80 and 89 years. Although no clear evidence for the effectiveness of IVT beyond 90 years was found, treatment should also be carefully considered in these patients. High age should not discourage from treatment.

SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses.

BACKGROUND: Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis. METHODS: SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT). RESULTS: The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT (n = 203); CAS vs. BMT (n = 197), and BMT alone (n = 113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come "mentally prepared" that an intervention was necessary) to accept BMT, and other economic constraints. CONCLUSIONS: Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid Stenosis Trialists Collaboration.

Volatile sedation with sevoflurane in intensive care patients with acute stroke or subarachnoid haemorrhage using AnaConDa®: an observational study.

BACKGROUND: The anaesthetic conserving device, AnaConDa(®), allows use of inhaled anaesthetics for sedation in the intensive care unit. We prospectively measured cerebral and cardiopulmonary parameters in patients with acute stroke or subarachnoid haemorrhage during a switch from i.v. to inhalative sedation. METHODS: 25 patients were switched from i.v. to an indefinite period of inhaled sedation with sevoflurane. Mean arterial (MAP), intracranial (ICP), and cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (MFV) and fractional tissue oxygen extraction (FTOE), systemic cardiopulmonary parameters, and administered drugs were assessed before and after the change (-6 to +12 h). RESULTS: In 8 patients, critically reduced MAP or ICP crisis led to premature termination of sevoflurane sedation. In the other 17 patients, after the first hour, mean ICP increased [2.4 (4.5) mm Hg; P=0.046], MAP decreased [7.8 (14.1) mm Hg; P=0.036] and thus CPP decreased also [-10.2 (15.1) mm Hg; P=0.014]. MFV and FTOE did not change. Over a 12 hour post switch observational period, [Formula: see text] increased slightly [0.3 (0.8) kPa; P=0.104], ICP did not change [0.2 (3.9) mm Hg; P=0.865], but MAP [-6 (6.9) mm Hg; P=0.002] and thus CPP decreased [-6 (8.5) mm Hg; P=0.010]. CONCLUSION: Sevoflurane led to sufficient sedation, but decreased MAP and CPP in a selected cerebrovascular neurocritical care population. In about a third of these patients, severe adverse reactions, including intolerable ICP increases, were observed.

[Mechanical thrombectomy in acute ischemic stroke. What is the position after the latest study results?]. / Mechanische Thrombektomie bei akutem ischämischem Schlaganfall : Wo stehen wir nach den jüngsten Studienergebnissen?

Mechanical devices for the recanalization of vessel occlusions in severe acute ischemic stroke have been developed for more than a decade. Several devices have been approved for clinical use on the basis of uncontrolled case series. Many neurologists have asked for randomized clinical trials comparing the new devices with standard treatment, e.g. thrombolytic therapy within a 4.5 h time window. The first 3 investigator initiated randomized trials published in 2013 failed to show superiority of mechanical thrombectomy over standard treatment. In the aftermath of these negative results several new trials with changes in design (e.g. shorter time window and only proximal vessel occlusions) and the use of modern devices with proven higher recanalization rates, so called stent retrievers, have been launched. In October 2014 the first of these new trials was presented and showed a clear superiority of thrombectomy. Based on this result interim analyses of five other studies were performed and most were prematurely terminated because of overwhelming efficacy. Only one trial testing another type of recanalization device failed to reach a statistically significant result. Currently five studies have already been published and two more studies have been presented at scientific conferences. This article provides an overview of the study protocols and the results of the individual studies, their common features and the characteristics of patients who benefit from this treatment. Finally, the consequences that these results may have for the treatment of patients with severe stroke caused by proximal vessel occlusion are discussed.

[Intensive care therapy of space-occupying large hemispheric infarction. Summary of the NCS/DGNI guidelines]. / Intensivtherapie des raumfordernden ischämischen Hemisphäreninfarkts. Zusammenfassung der NCS/DGNI-Leitlinie.

Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference.

Prevalence of atrial fibrillation in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Oral anticoagulation (OAC) is an effective preventive therapy for ischemic stroke in atrial fibrillation (AF). The management of anticoagulation in AF patients with previous intracerebral hemorrhage (ICH) is challenging. The aim of this study was to determine the prevalence of AF after acute ICH in a consecutive monocenter cohort, and to document the subsequent management with respect to OAC. METHODS: Consecutive patients with spontaneous ICH were prospectively included within 19 months. Diagnosis of AF was based on medical history, 12-lead electrocardiogram (ECG), 24-h and continuous ECG monitoring. CHADS2 scores and patient medication were recorded at admission and after 3 months. Additionally, after 3 months mortality, the management of anticoagulation and a newly detected AF were assessed. RESULTS: In total, 206 ICH patients were eligible for data analysis. After 3 months, AF had been diagnosed in 64/206 ICH patients (31.1%). Mortality after 3 months was higher in patients with AF in univariate analysis (45.3% vs. 31.0%). After adjusting for comorbidities and OAC use, AF did not remain an independent predictor for mortality. In total, 35 patients with AF survived 3 months. Of these, CHADS2 score was 2 (2/3, median, interquartile range (IQR)) and 27/35 patients had an indication for OAC with respect to the CHADS2 score, but only 25.7% had been (re-)started on OAC. No consistent factors for deciding whether to initiate OAC treatment could be identified. CONCLUSIONS: Atrial fibrillation is a frequent comorbidity in patients suffering an ICH. Our findings underline the prevailing uncertainty regarding the anticoagulation management of AF after ICH.

Statins reduce peri-procedural complications in carotid stenting.

BACKGROUND: In primary and secondary prevention, statins significantly reduce cardiovascular and cerebrovascular events. Pre-interventional statin medication shows a benefit in carotid artery stenosis patients treated with endarterectomy; however, there are few data available for patients treated with stent-angioplasty. The aim of this study was to investigate whether pre-interventional statin therapy is associated with decreased peri-interventional risk of stroke, myocardial infarction, and mortality in patients undergoing stent-angioplasty for internal carotid stenosis. METHODS: Data for 344 consecutively documented patients with internal carotid artery stenosis treated with stent-angioplasty in the years 2002-2012 at the same stroke center were collected in a prospectively defined database. Risk factors, medication, and indication for therapy were documented. Univariate and multivariate analysis was performed to investigate independent reduction of peri-interventional stroke, myocardial infarction, or death by statin medication prior to stent-angioplasty. RESULTS: The median age was 70 years (p25: 63, p75: 76), 75.5% of patients were male, and the median stenosis was 85% according to ECST criteria (p25: 80%, p75: 90%). 20.1% of patients had asymptomatic stenoses, and 60.2% had statin medication before stenting. As per multivariate analysis, pre-interventional statin medication was a predictor for significant peri-interventional risk reduction regarding primary endpoint ischemic stroke, myocardial infarction (MI), or death (odds ratio (OR) 0.31, p = .006). Statins also had a significant protective effect in secondary endpoint ischemic stroke, intracranial bleeding or death (OR 0.39, p = .014), and ischemic stroke or myocardial infarction (OR 0.20; p = .002). CONCLUSIONS: This study shows that pre-interventional statin medication has a protective effect against peri-interventional stroke, MI, or death in patients with internal carotid artery stenosis treated with stent-angioplasty. Accordingly, statins could be considered as a standard pre-interventional medical therapy in carotid stenting.

Prolonged low-dose thrombolysis in posterior circulation stroke.

BACKGROUND: We aimed to investigate the feasibility, preliminary safety, and efficacy of prolonged low-dose intravenous thrombolysis in posterior circulation stroke patients with a thrombus lodged in the basilar artery who were ineligible for standard rtPA administration. METHODS: We retrospectively analyzed consecutively collected patients in our stroke database who suffered from a basilar artery thrombosis and were treated with prolonged (>1 h), intravenous, low-dose (≤20 mg) rtPA between 01/2005 and 11/2012. RESULTS: Patients included in this study (n = 14) were 68.5 years (IQR 55.5; 72.75) of age and presented with a median NIHSS of 2 (1; 5.25). Median time from symptom onset to treatment was 63 h (33; 141). A median dose of 5.21 µg/kg h (4.46; 6.25) rtPA was administered over 24 h (min 10; max 48). No patient experienced symptomatic intracerebral hemorrhage, one patient developed a spinal epidural hematoma, and two elderly patients were switched to comfort care and died. In eight patients (57%) a decrease in thrombus size or no thrombus at all was detected on control imaging. Nine patients (64%) had a favorable outcome (mRS 0-2) at day 90. CONCLUSIONS: Prolonged low-dose thrombolysis with rtPA may be considered as individual treatment option in selected high-risk patients with basilar artery thrombosis. Presented data may lay the groundwork to further investigate safety and efficacy in a prospective trial.

[Clinical course of cerebral sinus venous thrombosis. Data from a monocentric cohort study over 15 years]. / Verlauf der zerebralen Sinus-/Venenthrombose. Daten einer monozentrischen Kohortenstudie über 15 Jahre.

INTRODUCTION: Thrombosis of cerebral veins or sinuses (CVST) is a rare condition. In a monocentric retrospective cohort study the clinical characteristics, risk factors, radiological findings as well as course and prognosis of patients over the past 15 years were examined. METHODS: Between January 1998 and March 2013 all patients who were treated as inpatients for CVST at the department of neurology of the University of Heidelberg were systematically registered in a database. Along with all relevant clinical data the modified Rankin scale (MRS) was used to measure the clinical severity. A follow-up visit was performed at three time points. The odds ratios (OR) were calculated to establish predictors of good outcome (MRS 0-2), mortality at discharge and at follow-up. Significant variables after univariate analysis were tested for independency in a multivariate logistic regression model. RESULTS: A total of 143 patients were included in the study. The median age was 43 years (range 17-74 years) and 67.4 % of patients were female. The most common symptoms were headache (70.6 %), seizures (50.4 %) and paresis (37.8 %). The most prominent clinical risk factor was oral contraception (40.4 %). The two most common localizations of thrombosis were the transversal sinus with the sigmoid sinus (66.4 %) and the sagittal superior sinus (47.6 %). On admission 42.7 % of patients suffered additionally from intracerebral hemorrhage and 12.6 % from congestive infarction. Of the patients 9.5 % (10 out of 105) showed a pathologically reduced activated protein C (APC) resistance and 8.4 % (6 out of 94) a prothrombin mutation. All patients were initially treated with heparin and 88.7 % were switched to cumarin during the course of the disease. The median duration of anticoagulation was 15.75 months (range 1-121 months). On discharge 77.7 % had a good outcome and the in-hospital mortality was 4.7 %. The median time to follow-up in 108 patients was 36 months (range 3-132 months), 74.1 % of patients had a good outcome (MRS 0-2) and 18.5 % died. Independent predictors of in-hospital mortality were MRS on admission (OR 2.2, 95 % CI 1.03-4.7) and of mortality at follow-up the presence of a malignant disease (OR 50.2, 6-423) and intracerebral hemorrhage on admission (OR 10.3, 1.7-62.6). DISCUSSION: The results of this study are in line with previously published data on CVST. The most prominent clinical risk factors for CVST were female gender and oral contraception. At discharge from hospital and 3 years after CVST approximately 75 % of patients achieved a good clinical outcome. A severe clinical syndrome and the presence of an intracerebral hemorrhage on admission were independent predictors of mortality.

[Therapeutic options in malignant cerebral venous and sinus thrombosis]. / Therapiemöglichkeiten bei schweren, intensivpflichtigen Sinus- und Venenthrombosen.

BACKGROUND: Cerebral venous and sinus thrombosis (CVST) constitutes less than 0.5-1 % of all strokes and occurs predominantly in young female adults. In general the clinical outcome is favorable but 3-15 % of patients die in the acute phase and in the majority of cases due to cerebral herniation. Intensive care treatment analogous to that of severe ischemic infarct leads to an aggressive interdisciplinary therapy concept that can achieve good clinical outcome. Based on five cases of severe CVST treatment options will be presented. RESULTS: All five patients were affected by impending or incipient cerebral herniation and severe focal neurological deficits which resulted in the decision to implement thrombectomy, thrombolysis or hemicraniectomy. Despite the severe course and many intensive care complications which suggested a poor prognosis, all five patients could be transferred to rehabilitation after having survived the acute phase and achieved an amazingly good overall clinical outcome. CONCLUSION: Considering the life-threatening course of severe CVST, aggressive interdisciplinary management by endovascular thrombectomy and hemicraniectomy can lead to a scarcely expected clinical outcome without disability or severe dependency. This treatment should be performed early and in an escalatory manner in patients with severe CVST who have an increased risk of an unfavorable outcome due to edema, infarction and hemorrhage.

A consecutive and prospective stroke database covers the state of Baden-Wuerttemberg with 10.8 million inhabitants in Germany.

BACKGROUND: In 1998 Baden-Wuerttemberg (BW), a federal state in southwest Germany with 10.8 million inhabitants, implemented a structured medical concept for the treatment of acute stroke. METHODS: Since 2004 participation in the BW stroke database is mandatory for all hospitals in BW involved in acute stroke care. The stroke database includes all inpatients ≥18 years of age who have suffered an ischemic or hemorrhagic stroke within 7 days before hospitalization. This article presents methodological aspects and first results of the BW stroke database in the time period from 2007 to 2011. RESULTS: Annual inclusion numbers increased continuously (29,422 vs. 35,724, p < 0.001). Median age of stroke onset was stable over time. The proportion of stroke patients ≥80 years increased from 36.9 to 38.8% (p < 0.001). Rates of patients treated in neurology departments rose from 50.7 to 60.9% (p < 0.001) and numbers of patients treated in stroke units rose from 59.1 to 68.4% (p < 0.001). Admission via emergency medical systems increased from 42.8 to 49.7% (p < 0.001) and arrival within 3 h increased from 29.8 to 34.4% (p < 0.001). CONCLUSION: We present results from a large, prospective and consecutive stroke patient database. This first analysis demonstrates a continuous increase of absolute and relative numbers of stroke patients who arrive within 3 h after onset, are hospitalized in neurology departments and treated in stroke units, and are aged ≥80 years.

[Treatment of asymptomatic carotid artery stenosis: improvement of evidence with new SPACE-2 design necessary]. / Therapie asymptomatischer Karotisstenosen: Notwendige Klärung der Evidenz mit neuem SPACE-2-Design.

Asymptomatic carotid artery stenosis may be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS) or with best medical treatment (BMT) only. Definitive and evidence-based treatment recommendations for one of these options are currently not possible. Studies showing an advantage of CEA over BMT alone do not meet current standards from a pharmacological point of view. On the other hand, more recent data point to a further stroke risk reduction using BMT according to current standards. Studies on carotid artery stenting as a third alternative treatment are partially insufficient, especially when comparing CAS with BMT. Initiated in 2009, the randomized, controlled, multicenter SPACE-2 trial is intended to answer the question about the best treatment option of asymptomatic carotid artery stenosis; however, to increase recruitment rates as a condition for the successful completion of this important study, the trial design had to be modified.

Key design elements of successful acute ischemic stroke treatment trials.

PURPOSE: We review key design elements of positive randomized controlled trials (RCTs) in acute ischemic stroke (AIS) treatment and summarize their main characteristics. METHOD: We searched Medline, Pubmed and Cochrane databases for positive RCTs in AIS treatment. Trials were included if (1) they had a randomized controlled design, with (at least partial) blinding for endpoints, (2) they tested against placebo (or on top of standard therapy in a superiority design) or against approved therapy; (3) the protocol was registered and/or published before trial termination and unblinding (if required at study commencement); (4) the primary endpoint was positive in the intention to treat analysis; and (5) the study findings led to approval of the investigational product and/or high ranked recommendations. A topical approach was used, therefore the findings were summarized as a narrative review. FINDINGS: Seventeen positive RCTs met the inclusion criteria. The majority of trials included less than 1000 patients (n = 15), had highly selective inclusion criteria (n = 16), used the modified Rankin score as a primary endpoint (n = 15) and had a frequentist design (n = 16). Trials tended to be national (n = 12), investigator-initiated and performed with public funding (n = 11). DISCUSSION: Smaller but selective trials are useful to identify efficacy in a particular subgroup of stroke patients. It may also be of advantage to limit the number of participating countries and centers to avoid heterogeneity in stroke management and bureaucratic burden. CONCLUSION: The key characteristics of positive RCTs in AIS treatment described here may assist in the design of further trials investigating a single intervention with a potentially high effect size.

Continuous monitoring versus HOLTER ECG for detection of atrial fibrillation in patients with stroke.

BACKGROUND AND PURPOSE: Detection of atrial fibrillation is of vital importance because oral anticoagulation decreases the risk of a stroke by 64%. Current standards for stroke unit treatment require continuous electrocardiogram (ECG) monitoring for at least 24 h. Additionally, a 24-h HOLTER ECG (HOLTER) should be performed in selected patients. It remains unclear whether continuous monitoring at the bedside is equivalent to HOLTER for the detection of atrial fibrillation. Furthermore, we investigate how many additional patients with paroxysmal atrial fibrillation can be identified as a result of a longer duration of continuous monitoring. METHODS: In this study, we prospectively compared the detection rates of HOLTER and 24-h monitoring at the Stroke Unit at the University of Heidelberg over a period of 9 months. Continuous monitoring was analyzed by trained nurses, HOLTER by cardiologists. RESULTS: We included 370 patients with ischemic stroke or transient ischemic attack (TIA) in our study. Of these, 192 patients underwent HOLTER. Previously unknown atrial fibrillation was detected in 44 patients, 13 patients had no atrial fibrillation in baseline ECG, but atrial fibrillation was detected by continuous monitoring. In two patients, the HOLTER showed atrial fibrillation; both patients had also been detected by continuous monitoring. Median time to detection of the atrial fibrillation during continuous monitoring was 43 h after hospitalization. CONCLUSION: In this study, use of HOLTER does not give any additional benefit in comparison with continuous monitoring with intermittent analysis by trained staff alone. The median detection time of 43 h emphasizes the importance of longer continuous monitoring.

[HTLV-1-associated myelopathy/tropical spastic paraparesis: a differential diagnosis in multiple sclerosis]. / HTLV-1-assoziierte Myelopathie/tropische spastische Paraparese : Eine Differenzialdiagnose der Multiplen Sklerose.

Human T-cell lymphotropic virus 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease caused by infection with HTLV-1. The disorder is very rare in Europe but endemic in many parts of the world. The pathogenesis is not clearly characterized but is based on a possibly immune-mediated injury of the cervicothoracic spinal cord. Clinically, HAM/TSP constitutes a slowly progressive spastic paraparesis associated with bladder dysfunction and often mimics the course of autoimmune and neurodegenerative diseases. The diagnosis is based on typical symptoms as well as detection of HTLV-1 specific antibodies and proviral HTLV-1 DNA or HTLV-1 RNA. The therapy is limited to symptomatic treatment. Transmission of HTLV-1 can occur vertically by breast feeding, through sexual contact or via infected blood products. Based on a clinical case report, we present here a current review on the pathophysiology, epidemiology, clinical manifestations, diagnosis and treatment of HAM/TSP.

Paroxysmal atrial fibrillation is more prevalent than persistent atrial fibrillation in acute stroke and transient ischemic attack patients.

BACKGROUND: Atrial fibrillation (AF) is a common cause of ischemic stroke and transient ischemic attack (TIA). More extensive diagnostic effort is required to detect paroxysmal AF (pxAF) than persistent AF (pAF); the prevalence of pxAF in stroke patients is unknown. We evaluated the prevalence of pAF and pxAF in ischemic stroke and TIA patients. METHODS: Consecutive patients with acute ischemic stroke/TIA were enrolled prospectively. We aimed to detect patients with a history of AF, with AF newly diagnosed in the emergency room (ER), or with newly diagnosed AF during a 3-month period following the event. Differences in the frequency of AF diagnosis with respect to the disposition of patients after ER work-up were assessed. RESULTS: A total of 692 patients were enrolled (male: 52.2%; ischemic stroke: 69.1%; TIA: 30.9%). A previously documented history of AF was present in 19.7% (pAF: 47.1%, pxAF: 52.9%). In 3.8% of patients, AF was newly diagnosed in the ER (pxAF: 61.5%) and in 5.2% during the 3-month follow-up period. The overall prevalence of AF was 28.6% (pxAF: 62.6%). Previously documented pxAF evaded diagnosis at ER presentation in 48.6%. The prevalence of AF increased with age (p < 0.001). Patients with pxAF were younger than those with pAF (p = 0.004) and more often female (p = 0.05). The presence of any AF was associated with higher initial NIHSS scores (p < 0.001) and higher modified Rankin scores after 3 months (p < 0.001). CONCLUSION: pxAF occurs more often than pAF in stroke/TIA patients. As effective stroke prevention is available for AF, it is important to develop and evaluate sensitive methods for detecting pxAF.

[New oral anticoagulants in atrial fibrillation]. / Neue orale Antikoagulanzien beim Vorhofflimmern.

Atrial fibrillation (AF) causes at least 20% of all ischemic strokes. In large randomized trials of primary and secondary stroke prevention, anticoagulation with vitamin K antagonists (VKA) protected much more efficiently than antiplatelet agents against stroke. Because of the problematic pharmacological properties of VKA only part of the AF patients are currently being treated with oral anticoagulants (OAK). The targeted development of specific oral inhibitors of the central coagulation factors thrombin and factor Xa allows reliable anticoagulation without regular coagulation monitoring. In the present review, pharmacological properties of the different agents are compared. Of the four large randomized phase 3 studies in AF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) with the primary efficacy endpoint stroke and systemic embolism, the published data from the RELY trial indicate a superior efficacy of dabigatran etexilate (2 × 150 mg/day) and a lower risk of intracranial hemorrhage compared to warfarin. Favorable preliminary results have been demonstrated for the factor Xa inhibitor rivaroxaban. Apixaban was more efficacious than ASA and had a similar risk of hemorrhage in the AVERROES study. Thus, the available data suggest a favorable benefit-risk ratio for the new substances in addition to improved patient comfort. Currently unresolved issues relate to the verification of patient adherence by suitable coagulation tests and to the emergency coagulation diagnostics and therapy in acute ischemic or hemorrhagic strokes under the new OAC.