Panagiotis Kostopoulos

Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial.

BACKGROUND Only 2-5% of patients who have a stroke receive thrombolytic treatment, mainly because of delay in reaching the hospital. We aimed to assess the efficacy of a new approach of diagnosis and treatment starting at the emergency site, rather than after hospital arrival, in reducing delay in stroke therapy. METHODS We did a randomised single-centre controlled trial to compare the time from alarm (emergency call) to therapy decision between mobile stroke unit (MSU) and hospital intervention. For inclusion in our study patients needed to be aged 18-80 years and have one or more stroke symptoms that started within the previous 2·5 h. In accordance with our week-wise randomisation plan, patients received either prehospital stroke treatment in a specialised ambulance (equipped with a CT scanner, point-of-care laboratory, and telemedicine connection) or optimised conventional hospital-based stroke treatment (control group) with a 7 day follow-up. Allocation was not masked from patients and investigators. Our primary endpoint was time from alarm to therapy decision, which was analysed with the Mann-Whitney U test. Our secondary endpoints included times from alarm to end of CT and to end of laboratory analysis, number of patients receiving intravenous thrombolysis, time from alarm to intravenous thrombolysis, and neurological outcome. We also assessed safety endpoints. This study is registered with ClinicalTrials.gov, number NCT00153036. FINDINGS We stopped the trial after our planned interim analysis at 100 of 200 planned patients (53 in the prehospital stroke treatment group, 47 in the control group), because we had met our prespecified criteria for study termination. Prehospital stroke treatment reduced the median time from alarm to therapy decision substantially: 35 min (IQR 31-39) versus 76 min (63-94), p<0·0001; median difference 41 min (95% CI 36-48 min). We also detected similar gains regarding times from alarm to end of CT, and alarm to end of laboratory analysis, and to intravenous thrombolysis for eligible ischaemic stroke patients, although there was no substantial difference in number of patients who received intravenous thrombolysis or in neurological outcome. Safety endpoints seemed similar across the groups. INTERPRETATION For patients with suspected stroke, treatment by the MSU substantially reduced median time from alarm to therapy decision. The MSU strategy offers a potential solution to the medical problem of the arrival of most stroke patients at the hospital too late for treatment. FUNDING Ministry of Health of the Saarland, Germany, the Werner-Jackstädt Foundation, the Else-Kröner-Fresenius Foundation, and the Rettungsstiftung Saar.

Carotid Artery Stenting in Acute Stroke

OBJECTIVES The purpose of this study is to demonstrate the technical success of carotid artery stenting in acute extracranial internal carotid artery (ICA) occlusion as well as the benefit in clinical outcome. BACKGROUND Stroke caused by acute occlusion of the ICA is associated with a significant level of morbidity and mortality. For this type of lesion, treatment with standard intravenous thrombolysis alone leads to a good clinical outcome in only 17% of the cases, with a death rate as high as 55%. Recanalization of the occluded ICA can lead to an improvement in acute symptoms of stroke, prevent possible deterioration, and reduce long-term stroke risk. At present, there is no consensus treatment for patients with acute ischemic stroke presenting with severe clinical symptoms due to atherosclerotic occlusion of the extracranial ICA. METHODS Carotid artery stenting was performed in 22 patients with acute atherosclerotic extracranial ICA occlusion within 6 h of stroke symptom onset. In 18 patients, there was an additional intracranial occlusion at the level of the terminal segment of the ICA (n = 4) and at the level of the middle cerebral artery (n = 14). Intracranial occlusions were either treated with the Penumbra system or the Solitaire stent-based recanalization system, or a combination of mechanical recanalization and intra-arterial thrombolysis. Recanalization results were assessed by angiography immediately after the procedure. The neurologic status was evaluated before and after the treatment with a follow-up as long as 90 days using the National Institutes of Health Stroke Scale and the modified Rankin Scale. RESULTS Successful revascularization of extracranial ICA with acute stent implantation was achieved in 21 patients (95%). There was no acute stent thrombosis. After successful recanalization of the origin of the ICA, the intracranial recanalization with Thrombolysis In Myocardial Infarction flow grade 2/3 was achieved in 11 of the 18 patients (61%). The overall recanalization rate (extracranial and intracranial) was 14 of 22 patients (63%). Nine patients (41%) had a modified Rankin Scale score of ≤2 at 90 days. The mortality rate was 13.6% at 90 days. CONCLUSIONS Carotid artery stenting in acute atherosclerotic extracranial ICA occlusion with severe stroke symptoms is feasible, safe, and useful within the first 6 h after symptom onset.

Point‐of‐care laboratory halves door‐to‐therapy‐decision time in acute stroke

Currently, stroke laboratory examinations are usually performed in the centralized hospital laboratory, but often planned thrombolysis is given before all results are available, to minimize delay. In this study, we examined the feasibility of gaining valuable time by transferring the complete stroke laboratory workup required by stroke guidelines to a point‐of‐care laboratory system, that is, placed at a stroke treatment room contiguous to the computed tomography, where the patients are admitted and where they obtain neurological, laboratory, and imaging examinations and treatment by the same dedicated team. Our results showed that reconfiguration of the entire stroke laboratory analysis to a point‐of‐care system was feasible for 200 consecutively admitted patients. This strategy reduced the door‐to‐therapy‐decision times from 84 ± 26 to 40 ± 24 min (p < 0.001). Results of most laboratory tests (except activated partial thromboplastin time and international normalized ratio) revealed close agreement with results from a standard centralized hospital laboratory. These findings may offer a new solution for the integration of laboratory workup into routine hyperacute stroke management. Ann Neurol 2011;

Methylation Status and Neurodegenerative Markers in Parkinson Disease

BACKGROUND Increased concentrations of plasma total homocysteine (tHcy) have been associated with age-related diseases, including dementia, stroke, and Parkinson disease (PD). Methylation status might link Hcy metabolism to neurodegenerative proteins in patients with PD. METHODS We tested blood samples from 87 patients with PD (median age 68 years; 35 men) for tHcy, methylmalonic acid (MMA), vitamin B(12), vitamin B(6), folate, S-adenosyl methionine (SAM), S-adenosyl homocysteine (SAH), and amyloid-beta(1-42). We collected citrate blood from a subset of 45 patients to prepare platelet-rich plasma, and we used washed platelets to prepare cell extracts for amyloid precursor protein (APP) and alpha-synuclein assays. We used brain parenchyma sonography to estimate the substantia nigra echogenic area in a subset of 59 patients. RESULTS Serum concentrations of tHcy were increased in PD patients (median 14.8 micromol/L). tHcy (beta coefficient = -0.276) and serum creatinine (beta = -0.422) were significant predictors of the ratio of SAM/SAH in plasma (P < 0.01). The plasma SAM/SAH ratio was a significant determinant for DemTect scores (beta = 0.612, P = 0.004). Significant negative correlations were found between concentrations of SAH in plasma and platelet APP and between SAM and platelet alpha-synuclein. A larger echogenic area of the substantia nigra was related to higher serum concentrations of MMA (P = 0.016). CONCLUSIONS Markers of neurodegeneration (APP, alpha-synuclein) are related to markers of methylation (SAM, SAH) in patients with PD. Better cognitive function was related to higher methylation potential (SAM/SAH ratio).

Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke : The ReFlow (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke) Study

OBJECTIVES This study sought to assess the feasibility and safety of a recently described technique of mechanical recanalization with the help of a stent-like device. BACKGROUND In the special group of acute stroke patients with an intracranial large vessel occlusion, intravenous tissue-type plasminogen activator on its own leads to a good clinical outcome (mRS ≤ 2) in only 15% to 25% of cases. The aforementioned technique of mechanical recanalization showed very promising clinical results. METHODS Forty patients presenting within 6 h from stroke symptom onset were enrolled. Mechanical recanalization was performed using a Solitaire FR revascularization device. The primary endpoint of the study was the clinical outcome rated with the help of the modified Rankin Scale (mRS) after 90 days. RESULTS Twenty-four patients (60%) showed a good clinical outcome (mRS ≤ 2) at 90 days. One symptomatic hemorrhage was detected on follow-up computed tomography. The death rate was 12.5% (5 patients). Successful recanalization (Thrombolysis In Cerebral Infarction score ≥ 2b) of the target vessel was achieved in 95% of the patients with a mean of 1.8 runs with the device. CONCLUSIONS The ReFlow (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke) study shows that mechanical recanalization with flow restoration is highly effective in stroke patients with a large intracranial vessel occlusion presenting within 4.5 h after symptom onset. (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke [ReFlow]; NCT01210729).