Anton Haass

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.

Stent-Assisted Mechanical Recanalization for Treatment of Acute Intracerebral Artery Occlusions

Background and Purpose— The purpose of this study was to demonstrate a new approach to the use of a self-expanding stent in the treatment of acute ischemic stroke. Methods— Twenty-two consecutive patients with acute intracerebral artery occlusions were treated with a self-expandable intracranial stent, which was withdrawn in its unfolded state. For this technique, we used the Solitaire AB/FR, which is the only intracranial stent that is fully recoverable. Eight patients had an occlusion of the basilar artery, 12 had a middle cerebral artery occlusion, and 2 had terminal carotid artery occlusions; 6 of these had to be treated first for an acute occlusion originating in the internal carotid artery. Recanalization results were assessed by follow-up angiography immediately after the procedure. Neurologic status was evaluated before and after treatment (90-day follow-up) according to the National Institutes of Health Stroke Scale and modified Rankin scale. Results— Successful revascularization was achieved in 20 of 22 (90.9%) patients (thrombolysis in cerebral infarction [TICI] 2a/b and 3), a TICI 3 state was accomplished in 12 patients, and partial recanalization or slow distal branch filling with filling of more than two-thirds of the vessel territory was achieved in 8 patients (TICI 2b). There was immediate flow restoration in 21 of 22 (95.4%) cases after deployment of the device. The stent was removed in its unfolded state in all patients. The mean time from stroke symptom onset to recanalization was 277 minutes, with a standard deviation of 118 minutes. Mean National Institutes of Health Stroke Scale score on admission was 19.4, with a standard deviation of 5.7. Almost two-thirds of the patients (63.6%) improved by >10 points on the National Institutes of Health Stroke Scale at discharge, and 50% showed a modified Rankin scale score of ≤2 at 90 days (59% with a modified Rankin scale ≤3). Mortality was 18.1%. In 1 case, an asymptomatic intracranial hemorrhage was detected on control computed tomography, and 2 patients had a symptomatic intracranial hemorrhage. Conclusion— Withdrawal of an unfolded, fully recoverable, intracranial stent yielded very promising angiographic and clinical results. It combines the advantages of prompt flow restoration and mechanical thrombectomy.

Streamlining of prehospital stroke management: the golden hour.

Thrombolysis with alteplase administered within a narrow therapeutic window provides an effective therapy for acute ischaemic stroke. However, mainly because of prehospital delay, patients often arrive too late for treatment, and no more than 1-8% of patients with stroke obtain this treatment. We recommend that all links in the prehospital stroke rescue chain must be optimised so that in the future more than a small minority of patients can profit from time-sensitive acute stroke therapy. Measures for improvement include continuous public awareness campaigns, education of emergency medical service personnel, the use of standardised, validated scales for recognition of stroke symptoms and for triaging to the appropriate institution, and advance notification to the receiving hospital. In the future, use of telemedicine technologies for interaction between the emergency site and hospital, and the strategy of treatment directly at the emergency site (mobile stroke unit concept), could contribute to more efficient use of resources and reduce the time taken to instigate treatment to within 60 min--the golden hour--of the onset of the symptoms of stroke.

The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe

Background and purpose The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. Methods A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. Results A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. Conclusion Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.

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.

Revascularization in acute ischaemic stroke using the penumbra system: the first single center experience

Background and purpose:  This is the first single center experience illustrating the effectiveness of the penumbra system (PS) in the treatment of large vessel occlusive disease in the arena of acute ischaemic stroke. The PS is an innovative mechanical thrombectomy device, employed in the revascularization of large cerebral vessel occlusions in patients via the utilization of an aspiration platform.

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;

Highly Substituted Hydroxyethyl Starch (HES 200/0.62) Leads to Type-l von Willebrand Syndrome after Repeated Administration

Hydroxyethyl starch (HES) is a frequently used plasma substitute that is popular due to a high degree of therapeutic safety. However, the administration of large volumes of highly substituted, high-molecular-weight starch often leads to iatrogenic von Willebrand syndrome (vWS) with hemorrhagic complications. In patients with cerebral circulatory disturbances we carried out hemodilution therapy during 9-10 days, infusing HES 200/0.62. A von Willebrand factor (vWF) multimeric analysis was carried out in 6 patients using a modified western blot according to the sodium dodecyl sulfate agarose gel electrophoresis method. The vWF multimeric analysis showed that all multimers decreased to the same degree, corresponding to type-I vWS.

Toscana virus infection in german travellers returning from the mediterranean

Toscana virus is a member of the sandfly fever group, genus Phlebovirus of the family Bunyaviridae [1]. It is a well-known cause of meningitis in humans in several regions of the Mediterranean (the Tuscany region of Italy [2], Portugal [3]. In recent years increasing numbers of Toscana virus infections have been observed in tourists returning from Italy and Portugal. We report on two human cases of acute Toscana virus infection in tourists returning from southern France and Greece, respectively. The cases were detected during a retrospective serological study on the prevalence of arbovirus antibodies in 140 patients with central nervous system (CNS) disorders in the Saarland in Germany. Indirect immunofluorescence was used for detection of antibodies. In this test system IgM-titers > 1:10 and IgG-titers > 1:40 indicate an acute infection with Toscana virus. Case 1: On August 12, 1994, a 19-year-old man was admitted to a neurological department with typical symptoms of meningitis (fever, weakness, severe headache, nausea, vomiting, and neck stiffness) with increasing intensity for about 1 day. Neurological examination including electroencephalography and computed tomography revealed no abnormalities, with the exception of symptoms of meningeal irritation. Cerebrospinal fluid showed signs of aseptic meningitis with 82/3 cells, predominantly lymphocytes. Microbiological and serological testing did not reveal any positive results. The symptoms improved during the next days and the patient was discharged from the hospital 7 days after admission with all symptoms resolved and without any neurological sequelae. Our retrospective serological testing using indirect immunofluorescence found positive IgM (1: 40) and IgG (1: 80) against Toscana virus. On retrospective contact the patient remembered a stay of 2 weeks near Marseille, southern France, and returning to Germany 12 days before the onset of symptoms. On his return trip he did not enter any known endemic area of Toscana virus. Case 2: A 73-year-old woman was admitted to a neurological department on June 30, 1993. The patient complained of fever, severe headache, nausea, and vomiting for about 1 day. Neurological examination (including electroencephalography and computed tomography) revealed no abnormal results with the exception of meningeal symptoms. In CSF 73/3 cells (predominantly lymphocytic cells) were found, which led to the diagnosis of aseptic meningitis. The intensity of symptoms decreased slowly during the following days without any therapy and the patient could be discharged from the hospital 11 days after admission without any neurological sequelae. Our retrospective serological testing revealed IgM (1:20) and IgG (1:80) antibodies against Toscana virus. When contacting the patient, she reported that she had been visiting Lavrion (60 km south of Athens, Greece) from May 30 to June 18, 1993. Anamnestically she remembered many insect bites during her stay. On her return journey she did not enter any other known endemic area of Toscana virus. These two cases of acute Toscana virus infection in travellers to the Mediterranean, detected only by chance, indicate, that Toscana virus infection in travellers is not a rare event. E.g. Schwarz [4] reported on 13 cases of Toscana virus meningitis in travellers mainly to Italy. The two cases also show the importance of asking patients about their travel history, possibly connected with the acute symptoms. The two cases in southern France and Greece also indicate that Toscana virus is not restricted to the known endemic areas (Italy, Portugal), but probably has larger areas of occurrence, at least in the European part of the Mediterranean. Acute Toscana virus infection mostly presents as mild disease with meningeal irritation or aseptic meningitis. The symptoms last about 4 to 7 days and resolve without any neurological sequelae. The diagnosis can be made by detection of antibodies in the blood. Invasive diagnostic procedures are unnecessary. The two cases presented above show that Toscana virus infections are not rare in travellers. Physicians and neurologists should be aware of these sandtly-transmitted infections causing neurological symptoms. It also shows the importance of asking the patient for his putative travel history and to think of imported infections in those patients. G. Dobler, J. Treib, A. Haass, G. FrOsner, R. Woesner, K. Schimrigk

Mobile stroke unit for diagnosis-based triage of persons with suspected stroke

Background: In this feasibility study, we tested whether prehospital diagnostic stroke workup enables rational decision-making regarding treatment and the target hospital in persons with suspected stroke. Methods: A mobile stroke unit that delivers imaging (including multimodal brain imaging with CT angiography and CT perfusion), point-of-care-laboratory analysis, and neurologic expertise directly at the emergency site was analyzed for its use in prehospital diagnosis-based triage of suspected stroke patients. Results: We present 4 complementary cases with suspected stroke who underwent prehospital diagnostic workup that enabled direct diagnosis-based treatment decisions and reliable triage regarding the most appropriate medical facility for that individual, e.g., a primary hospital vs specialized centers of a tertiary hospital. Conclusions: This preliminary report demonstrates the feasibility of prehospital diagnostic stroke workup for immediate etiology-specific decision-making regarding the necessary time-sensitive stroke treatment and the most appropriate target hospital.