Access, timing and frequency of very early stroke rehabilitation - insights from the Baden-Wuerttemberg stroke registry.

BACKGROUND: While the precise timing and intensity of very early rehabilitation (VER) after stroke onset is still under discussion, its beneficial effect on functional disability is generally accepted. The recently published randomized controlled AVERT trial indicated that patients with severe stroke might be more susceptible to harmful side effects of VER, which we hypothesized is contrary to current clinical practice. We analyzed the Baden-Wuerttemberg stroke registry to gain insight into the application of VER in acute ischemic stroke (IS) and intracerebral hemorrhage (ICH) in clinical practice. METHODS: 99,753 IS patients and 8824 patients with ICH hospitalized from January 2008 to December 2012 were analyzed. Data on the access to physical therapy (PT), occupational therapy (OT), and speech therapy (ST), the time from admission to first contact with a therapist and the average number of therapy sessions during the first 7 days of admission are reported. Multiple logistic regression models adjusted for patient and treatment characteristics were carried out to investigate the influence of VER on clinical outcome. RESULTS: PT was applied in 90/87% (IS/ICH), OT in 63/57%, and ST in 70/65% of the study population. Therapy was mostly initiated within 24 h (PT 87/82%) or 48 h after admission (OT 91/89% and ST 93/90%). Percentages of patients under therapy and also the average number of therapy sessions were highest in those with a discharge modified Rankin Scale score of 2 to 5 and lowest in patients with complete recovery or death during hospitalization. The outcome analyses were fundamentally hindered due to biases by individual decision making regarding the application and frequency of VER. CONCLUSIONS: While most patients had access to PT we noticed an undersupply of OT and ST. Only little differences were observed between patients with IS and ICH. The staff decisions for treatment seem to reflect attempts to optimize resources. Patients with either excellent or very unfavorable prognosis were less frequently assigned to VER and, if treated, received a lower average number of therapy sessions. On the contrary, severely disabled patients received VER at high frequency, although potentially harmful according to recent indications from the randomized controlled AVERT trial.

Vertebral Artery Hypoplasia Does Not Influence Lesion Size and Clinical Severity in Acute Ischemic Stroke.

BACKGROUND: Vertebral artery hypoplasia (VAH) is common, but its role in acute ischemic stroke (AIS) is uncertain. We aimed to evaluate the frequency, characteristics, and role of VAH in a large typical cohort of patients with AIS. METHODS: Up to 815 AIS patients (52.8% men, mean age 70 ± 14 years) were included in the study. All patients received a stroke work-up including brain imaging and duplex ultrasound. VAH was defined by a vessel diameter of less than or equal to 2.5 mm or a difference to the contralateral side of greater than 1:1.7. Vascular risk factors and stroke features were recorded. The subgroup of patients with posterior circulation AIS and magnetic resonance imaging was analyzed additionally, including the parameter of stroke extent. RESULTS: Up to 111 patients (13.6%) had VAH, with a mean diameter of 2.4 ± .4 mm. Patients with VAH were significantly younger (P = .037) and more often male (P = .033). There was no difference considering the National Institutes of Health Stroke Scale and modified Rankin Scale scores on admission or history of stroke. The distribution of patients without VAH was significantly different among the groups with anterior, posterior, and both circulations ischemia (P = .009). In the group with posterior circulation stroke, 36 patients (20.9%) had VAH. There were no differences in age, sex, history of stroke, risk factors, vascular territory, stroke size, or etiology. VAH patients had less often embolic stroke patterns (P = .009). CONCLUSIONS: VAH is more common in patients with posterior circulation stroke and in younger patients. Apart from that, we found no clear evidence that VAH would be a predisposing factor for stroke or that it increased the risk for larger ischemic lesions in the posterior circulation.

Predictors and early outcome of hemorrhagic transformation after acute ischemic stroke.

BACKGROUND: Hemorrhagic transformation (HT) after acute ischemic stroke is frequently detected using magnetic resonance imaging (MRI), in particular in patients treated with tissue plasminogen activator (tPA). Knowledge about causes and early clinical consequences of HT mostly arises from computed tomography-based studies. We analyzed potential predictors and early outcome of HT after stroke detected by MRI with T(2)*-weighted gradient echo sequences (T(2)*-MRI). METHODS: 122 consecutive stroke patients (mean age 65.5 years, 41% women) who underwent T(2)*-MRI within 6-60 h after stroke onset were included. 25.4% of patients were treated with tPA; the overall detection rate of HT on T(2)*-MRI was 20.5%. Potential predictors of HT, such as age, sex, blood pressure, stroke etiology, prior antithrombotic medication, neurological deficit on admission, tPA treatment, and specific MRI findings, were analyzed. In addition, we evaluated the effect of HT on early outcome: a decrease of >4 points on the National Institute of Health Stroke Scale (NIHSS) on day 5 was considered early improvement, and an increase of >4 points was considered early deterioration. RESULTS: The main predictor for occurrence of HT was tPA treatment (48.4 vs. 11.1%; odds ratio 7.50; 95% confidence interval 2.9-19.7; p < 0.001). Furthermore, the development of HT was associated with a severer neurological deficit on admission (mean NIHSS score 9.9 vs. 5.9; p = 0.003), and territorial infarction (88 vs. 58.8%; p = 0.007). 19 patients (15.6%) showed early improvement which was associated with the occurrence of HT (p = 0.011) and tPA treatment (p < 0.001). CONCLUSIONS: HT is a frequent finding on T(2)*-MRI in patients with acute ischemic stroke associated with tPA treatment, territorial infarction and severer neurological deficits on admission. However, HT does not cause clinical deterioration; it is rather related to a favorable early outcome likely reflecting early recanalization and better reperfusion in these patients.

Comparison of long-term prognostic value of N-terminal-proBNP and midregional-pro-adrenomedullin in patients with acute myocardial infarction.

BACKGROUND: N-terminal-proBNP (NT-proBNP) and Midregional-pro-Adrenomedullin (MR-proADM) predict mortality of patients with acute myocardial infarction (AMI). Comparison of the prognostic values of NT-proBNP and MR-proADM to predict long-term adverse clinical events (AE) after AMI has not been evaluated yet. METHODS: 30 patients with AMI were enrolled into this prospective study. Measurements of NT-proBNP and MR-proADM were performed at initial presentation, two or three days and four months after AMI. Long-term AE defined as recurrent AMI, need for repeated percutaneous transluminal angioplasty or coronary bypass graft surgery, congestive heart failure, cardiopulmonary resuscitation, cardiogenic shock, syncope, and death were documented during a follow-up period of ten months. RESULTS: At initial presentation, NT-proBNP values were significantly higher in patients with AE compared to patients without AE (p < 0.05). The area under the ROC curve (AUC) indicated good predictive performance of NT-proBNP (AUC 0.78, 95% CI 0.59-0.91, p = 0.003) and MR-proADM (AUC 0.71, 95% CI 0.51-0.86, p = 0.046) regarding AE. Comparing both AUC revealed no differences between NT-proBNP and MR-proADM as predictors of AE (p = 0.59). Patients with NT-proBNP levels > or = 370 pg/mL were more likely to suffer from AE than patients with lower levels (relative risk 6.7, 95% CI 1.0-46, p = 0.018). With this cutoff, NT-proBNP could exclude AE with a negative predictive value of 92% being similar to MR-proADM (negative predictive value 76%, relative risk 2.8, 95% CI 1.2-6.9, p = 0.042). CONCLUSIONS: Early measurements of NT-proBNP or MR-proADM during the acute phase of AMI may allow the risk of a long-term AE to be excluded, based on the comparable test characteristics,.

Diurnal Variation of Intravenous Thrombolysis Rates for Acute Ischemic Stroke and Associated Quality Performance Parameters.

INTRODUCTION: Based on data from the Baden-Wuerttemberg stroke registry, we aimed to explore the diurnal variation of acute ischemic stroke (IS) care delivery. MATERIALS AND METHODS: 92,530 IS patients were included, of whom 37,471 (40%) presented within an onset-to-door time ≤4.5 h. Daytime was stratified in 3-h time intervals and working vs. non-working hours. Stroke onset and hospital admission time, rate of door-to-neurological examination time ≤30 min, onset-/door-to-imaging time IV thrombolysis (IVT) rates, and onset-/door-to-needle time were determined. Multivariable regression models were used stratified by stroke onset and hospital admission time to assess the relationship between IVT rates, quality performance parameters, and daytime. The time interval 0:00 h to 3:00 h and working hours, respectively, were taken as reference. RESULTS: The IVT rate of the whole study population was strongly associated with the sleep-wake cycle. In patients presenting within the 4.5-h time window and potentially eligible for IVT stratification by hospital admission time identified two time intervals with lower IVT rates. First, between 3:01 h and 6:00 h (IVT rate 18%) and likely attributed to in-hospital delays with the lowest diurnal rate of door-to-neurological examination time ≤30 min and the longest door-to-needle time Second, between 6:01 h and 15:00 h (IVT rate 23-25%) compared to the late afternoon and evening hours (IVT rate 27-29%) due to a longer onset-to-imaging time and door-to-imaging time. No evidence for a compromised stroke service during non-working hours was observed. CONCLUSION: The analysis provides evidence that acute IS care is subject to diurnal variation which may affect stroke outcome. An optimization of IS care aiming at constantly high IVT rates over the course of the day therefore appears desirable.

Long-term follow-up of chronic spinal cord stimulation for medically intractable orthostatic tremor.

Orthostatic tremor (OT) is a rare form of tremor occurring in the legs when standing upright. Medical treatment frequently is unsatisfactory, thus in selected cases, surgical treatment, such as spinal cord stimulation (SCS) or thalamic deep brain stimulation has been proposed. We report the long-term results (follow-up (FU) 34-133 months) of SCS in four patients with medically intractable OT. Outcome was assessed by recording the time tolerated to stand still pre- and post-operatively and by a patient self-rating (PSR) scale (0 = poor to 6 = excellent). Furthermore, surface electromyography (EMG) recordings of different leg muscles were performed to estimate tremor activity with and without SCS post-operatively. With chronic SCS, all four patients showed an improvement of unsteadiness occurring in the presence of stimulation-induced paraesthesia of the legs. The mean standing time improved from 51 s (SD 47 s, range 4-120 s) pre-operatively to 220 s (SD 184 s, range 10-480 s) with SCS at last available FU. Tremor activity in the EMG of the anterior tibial muscle was reduced by 30-60 % with SCS compared with off SCS. PSR score was 4 or 5 in three patients and 3 in the other. In conclusion, SCS is an effective long-term treatment option in patients with otherwise intractable OT.

Restriction of therapy mainly explains lower thrombolysis rates in reduced stroke service levels.

OBJECTIVE: To assess the influence of preexisting disabilities, age, and stroke service level on standardized IV thrombolysis (IVT) rates in acute ischemic stroke (AIS). METHODS: We investigated standardized IVT rates in a retrospective registry-based study in 36,901 patients with AIS from the federal German state Baden-Wuerttemberg over a 5-year period. Patients admitted within 4.5 hours after stroke onset were selected. Factors associated with IVT rates (patient-level factors and stroke service level) were assessed using robust Poisson regression modeling. Interactions between factors were considered to estimate risk-adjusted mortality rates and potential IVT rates by service level (with stroke centers as benchmark). RESULTS: Overall, 10,499 patients (28.5%) received IVT. The IVT rate declined with service level from 44.0% (stroke center) to 13.1% (hospitals without stroke unit [SU]). Especially patients >80 years of age and with preexisting disabilities had a lower chance of being treated with IVT at lower stroke service levels. Interactions between stroke service level and age group, preexisting disabilities, and stroke severity (all p < 0.0001) were observed. High IVT rates seemed not to increase mortality. Estimated potential IVT rates ranged between 41.9% and 44.6% depending on stroke service level. CONCLUSIONS: Differences in IVT rates among stroke service levels were mainly explained by differences administering IVT to older patients and patients with preexisting disabilities. This indicates considerable further potential to increase IVT rates. Our findings support guideline recommendations to admit acute stroke patients to SUs.

Intravenous Thrombolysis is Effective in Young Adults: Results from the Baden-Wuerttemberg Stroke Registry.

BACKGROUND: The efficacy of intravenous thrombolysis (IVT) is sufficiently proven in ischemic stroke patients of middle and older age by means of randomized controlled trials and large observational studies. However, data in young stroke patients ≤50 years are still scarce. In this study, we aimed to evaluate the effectiveness and safety of IVT in young adults aged 18-50 years. Data from a consecutive and prospective stroke registry was analyzed that covers a federal state with 10.8 million inhabitants in southwest Germany. METHODS: Our analysis comprises 51,735 ischemic stroke patients aged 18-80 years and hospitalized from January 2008 to December 2012. Of these, 4,140 (8%) were aged 18-50 years and 7,529 (15%) underwent IVT. Data on 8,439 patients (16% of the study population) were missing for National Institutes of Health stroke severity score at admission and/or modified Rankin Scale (mRS) at discharge and were excluded from outcome analysis. In sensitivity analysis, patients with incomplete data were also examined. Binary logistic regression models were used adjusted for patient, hospital, and procedural parameters and stratified by age group (18-50 and 51-80 years, subgroup analyses 18-30, 31-40, and 41-50 years) to assess the relationship between IVT and mRS at discharge. RESULTS: IVT appears equally effective in young adults 18-50 years (adjusted odds ratio 1.40, 95% confidence interval 1.12-1.75; p = 0.003), compared to patients 51-80 years of age (1.33, 1.23-1.43; p < 0.001). Age-stratified analyses suggest an inverse relation of age and effectiveness, which appears to be highest in very young patients 18-30 years of age (2.78, 1.10-7.05; p = 0.03). DISCUSSION: Ischemic stroke etiology, vascular dynamics, and recovery in young patients differ from those of middle and older age. The evidence from routine hospital care in Germany indicates that IVT in young stroke patients appears to be at least equally effective as in the elderly.

Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials.

OBJECTIVE: To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice. DESIGN: A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany. SETTING: All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants. PARTICIPANTS: Data from 84,439 patients with acute ischaemic stroke were analysed, 10,263 (12%) were treated with thrombolytic therapy and 74,176 (88%) were not treated. MAIN OUTCOME MEASURES: Primary endpoint was the dichotomised score on a modified Rankin scale at discharge ("favourable outcome" score 0 or 1 or "unfavourable outcome" score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis). RESULTS: After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92). CONCLUSION: The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy.

Loss of callosal fibre integrity in healthy elderly with age-related white matter changes.

Age-related white matter changes (ARWMC) appear to correspond to a continuum from normal functioning to clinically overt neurological syndromes. Disturbance of the structural integrity of cerebral fibre tracts-the so-called cerebral network-by ARWMC might be one explanation for this development. From 3 T magnetic resonance imaging (MRI) data of 34 healthy elderly subjects (60-82 years) we calculated the lesion volume of ARWMC and the area of the corpus callosum (CC). Gait, balance and cognition were assessed. We compared these findings in those with mild (n = 22) and advanced (n = 12) ARWMC and performed tract-based spatial statistics (TBSS) to analyze white matter structural integrity. In subjects with advanced ARWMC, TBSS showed a significant decrease of fractional anisotropy (FA) in several large tracts of the white matter including the CC; total CC, CC2 and CC5 areas were significantly smaller. Despite these morphological changes, tests of gait, balance and cognition as measured by the Mini-Mental State Examination (MMSE) were in the normal range for both groups; only the Montreal Cognitive Assessment (MoCA) detected executive and language dysfunction in those with advanced ARWMC. Loss of tissue integrity and atrophy of the CC secondary to spatially remote lesions in the peri- and paraventricular white matter in ARWMC appear to be already detectable in healthy elderly individuals.

Long-term prognostic value of mid-regional pro-adrenomedullin and C-terminal pro-endothelin-1 in patients with acute myocardial infarction.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) and endothelin-1 have been shown to predict mortality of patients with acute myocardial infarction. However, the prognostic value of both biomarkers in predicting long-term clinical events after acute myocardial infarction remains unclear. METHODS: In a prospective study, 30 patients suffering from acute ST elevation myocardial infarction or non-ST elevation myocardial infarction were enrolled. Measurements of MR-proADM and CT-pro-endothelin-1 (CT-proET-1) were performed at initial presentation, 2 or 3 days and 4 months after acute myocardial infarction. Long-term clinical events (e.g., recurrent myocardial infarction, percutaneous transluminal coronary angioplasty, aorto-coronary venous bypass or cardiogenic shock) were documented over a period from the 4th until the 10th month. RESULTS: Both MR-proADM and CT-proET-1 were able to differentiate patients with subsequent long-term clinical events (n=11) from those without (n=19). At the time of acute myocardial infarction, median MR-proADM level of the event group was 0.69 nmol/L as compared to 0.59 nmol/L of the no-event group (p=0.036). A difference was still observed after 3 days (event group median 0.66 nmol/L; no-event group median 0.57 nmol/L; p=0.022). Accordingly, median CT-proET-1 level was 72.9 pmol/L in the event group as compared to a median of 54.4 pmol/L in patients in the no-event group (p=0.009) 3 days after acute myocardial infarction. Within the acute phase, patients with MR-proADM levels > or =0.67 nmol/L were 3 times more likely (relative risk 2.8; 95% confidence interval 1.2-6.9; p=0.042) to suffer from a future clinical event. The area under the curve (AUC) was 0.71 (95% confidence interval 0.51-0.86; p=0.046). After 3 days, patients with CT-proET-1 levels > or =57 pmol/L were 6 times more likely (relative risk 5.9; 95% confidence interval 0.9-40.4; p=0.036) to suffer from a future clinical event. The AUC was 0.76 (95% confidence interval 0.55-0.90; p=0.015). CONCLUSIONS: Elevated levels of MR-proADM and CT-proET-1 during the acute phase of myocardial infarction may predict an adverse long-term clinical outcome.