An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England

Objective Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. Study design and setting A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. Results Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. Conclusion Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations

Symptomatic hemorrhage after alteplase therapy not due to silent ischemia

BACKGROUND: Stroke thrombolysis-related intracerebral hemorrhage may occur remotely from the anatomical site of ischemia. One postulated mechanism for this is simultaneous multiple embolization with hemorrhage into a "silent" area of ischemia. RESULTS: A patient suffered a disabling stroke affecting the right cerebral hemisphere. He was treated with intravenous alteplase and underwent extensive early imaging with multimodal MRI. Several hours after treatment he developed a brainstem hemorrhage despite having no evidence of ischemia on DWI MRI in the brainstem. CONCLUSION: Not all occurrences of remote ICH after stroke thrombolysis are secondary to multiple emboli with silent ischemia

New MR sequences in daily practice: susceptibility weighted imaging. A pictorial essay

Background Susceptibility-weighted imaging (SWI) is a relatively new magnetic resonance (MR) technique that exploits the magnetic susceptibility differences of various tissues, such as blood, iron and calcification, as a new source of contrast enhancement. This pictorial review is aimed at illustrating and discussing its main clinical applications. Methods SWI is based on high-resolution, threedimensional (3D), fully velocity-compensated gradientecho sequences using both magnitude and phase images. A phase mask obtained from the MR phase images is multiplied with magnitude images in order to increase the visualisation of the smaller veins and other sources of susceptibility effects, which are displayed at best after postprocessing of the 3D dataset with the minimal intensity projection (minIP) algorithm. Results SWI is very useful in detecting cerebral microbleeds in ageing and occult low-flow vascular malformations, in characterising brain tumours and degenerative diseases of the brain, and in recognizing calcifications in various pathological conditions. The phase images are especially useful in differentiating between paramagnetic susceptibility effects of blood and diamagnetic effects of calcium. SWI can also be used to evaluate changes in iron content in different neurodegenerative disorders. Conclusion SWI is useful in differentiating and characterising diverse brain disorders

Prospective study on the mismatch concept in acute stroke patients within the first 24 h after symptom onset - 1000Plus study

<p>Abstract</p> <p>Background</p> <p>The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months.</p> <p>Methods and design</p> <p>1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up.</p> <p>Discussions</p> <p>The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task.</p> <p>Trial Registration</p> <p>clinicaltrials.gov NCT00715533</p

Microvessel changes after post-ischemic benign and malignant hyperemia: experimental study in rats

<p>Abstract</p> <p>Background</p> <p>The present investigation was designed to elucidate the use of dynamic contrast enhanced perfusion MR imaging (DCE pMRI) in characterizing hyperemia, including microvessel changes, and to examine whether DCE pMRI can predict benign or malignant hyperemia.</p> <p>Methods</p> <p>Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) by intraluminal suture placement. All rats were randomized to 4 groups: MCAO for 0.5 hours followed by saline treatment (10 ml/kg; group 1); MCAO for 3 hours followed by treatment with saline (group 2) or urokinase (25000 IU/kg; group 3); and MCAO for 6 hours followed by urokinase treatment (group 4). Relative cerebral blood volume (rCBV) and relative maximum slope of increase of the signal intensity time curve (rMSI) were quantitatively analyzed from MRI. Microvessel diameter and blood-brain barrier disruption obtained by laser scanning confocal microscopy (LSCM) as well as transmission electron microscopy (TEM) were obtained for correlative study.</p> <p>Results</p> <p>Benign hyperemia was noticed only in group 1; malignant hyperemia was seen in group 3. Although the rCBV of malignant hyperemia was slightly higher than in benign hyperemia (<it>P </it>> 0.05), the rMSI, on the other hand, was significantly lower (<it>P </it>< 0.05). Fluoro-isothiocyanate dextran (FITC-dextran) extravasations, marked glial end-foot process swelling, and significant vasodilatation were seen in malignant hyperemia, while no or mild leakage of FITC-dextran and slight glial end-foot process swelling occurred in benign hyperemia.</p> <p>Conclusion</p> <p>Our findings indicate that DCE pMRI can characterize post-ischemic hyperemia and correlates well with microvascular damage.</p

The fading of reported effectiveness. A meta-analysis of randomised controlled trials

BACKGROUND: The "real" effect size of a medical therapy is constant over time. In contrast, the effect size reported in randomised controlled trials (RCTs) may change over time because the sum of all kinds of bias influencing the reported effectiveness is not necessarily constant. As this would affect the validity of meta-analyses, we tested the hypothesis that the reported effect size decreases over time. Furthermore, we tested three hypotheses that would explain a possible change. METHODS: Because of well established outcome measures, the lipid-lowering drugs Pravastatin and Atorvastatin (serum low-density lipoprotein cholesterol, LDL-C) and the anti-glaucoma drugs Timolol and Latanoprost (intraocular pressure, IOP) were chosen for this investigation. Studies were identified by a standardized MEDLINE search. RCTs investigating the above identified medications administered as monotherapy, and in defined dosages, were included. Publication year, baseline (= pre-treatment value in the treatment group of interest) and post intervention means, number of patients and the assignment to experimental or control group were extracted for each study. RESULTS: A total of 625 citations were screened; 206 met the inclusion criteria. The reported effect size of Pravastatin (change of reported effect size in five years: -3.22% LDL-C, P < .0001), Timolol (-0.56 mmHg, P < .0001) and Latanoprost (-1.78 mmHg, P = .0074) decreased over time, while there was no significant change for Atorvastatin (+0.31% LDL-C, P = .8618). Multiple regression analysis showed that baseline values were the most important influencing factor; study size or treatment group did not play a significant role. CONCLUSION: The effectiveness of medical therapies reported in RCTs decreases over time in three of the four investigated pharmaceuticals, caused mainly by baseline differences. We call this phenomenon "fading of reported effectiveness". Under this condition the validity of a meta-analysis may be impaired. Therefore we propose to observe this phenomenon in future meta-analyses in order to guarantee a maximum of transparency

An emergency clinical pathway for stroke patients – results of a cluster randomised trial (isrctn41456865)

BACKGROUND: Emergency Clinical Pathways (ECP) for stroke have never been tested in randomized controlled trials (RCTs). OBJECTIVE: To evaluate the effectiveness of an ECP for stroke patients in Latium (Italy) emergency system. METHODS: cluster-RCT designed to compare stroke patient referrals by Emergency Medical Service (EMS) and Emergency Room (ER) health professionals trained in the ECP, with those of non-trained EMS and ER controls. Primary outcome measure was the proportion of eligible (aged /= 80 and symptom onset /= 6 hours) stroke patients referred to a stroke unit (SU). Intention to treat (ITT) and per-protocol (PP) analyses were performed, and risk ratios (RR) adjusted by age, gender and area, were calculated. RESULTS: 2656 patients in the intervention arm and 2239 in the control arm required assistance; 78.3% of the former and 80.6% of the latter were admitted to hospitals, and respectively 74.8% and 78.3% were confirmed strokes. Of the eligible confirmed strokes, 106/434 (24.4%) in the intervention arm and 43/328 (13.1%) in the control arm were referred to the SU in the ITT analysis (RR = 2.01; 95% CI: 0.79-4.00), and respectively 105/243 (43.2%) and 43/311 (13.8%) in the PP analysis (RR = 3.21; 95%CI: 1.62-4.98). Of patients suitable for i.v. thrombolysis, 15/175 (8.6%) in the intervention arm and 2/115 (1.7%) in the control arm received thrombolysis (p = 0.02) in the ITT analysis, and respectively 15/99 (15.1%) and 2/107 (1.9%)(p = 0.001) in the PP analysis. CONCLUSION: Our data suggest potenti efficiency and feasibility of an ECP. The integration of EMS and ERs with SU networks for organised acute stroke care is feasible and may ameliorate the quality of care for stroke patients. TRIAL REGISTRATION: Current Controlled Trials (ISRCTN41456865)