Frederik Geisler

Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study

BACKGROUND Specialised CT-equipped mobile stroke treatment units shorten time to intravenous thrombolysis in acute ischaemic stroke by starting treatment before hospital admission; however, direct effects of pre-hospital thrombolysis on clinical outcomes have not been shown. We aimed to compare 3-month functional outcomes after intravenous thrombolysis in patients with acute ischaemic who had received emergency mobile care or and conventional care. METHODS In this observational registry study, patients with ischaemic stroke received intravenous thrombolysis (alteplase) either within a stroke emergency mobile (STEMO) vehicle (pre-hospital care covering 1·3 million inhabitants of Berlin) or within conventional care (normal ambulances and in-hospital care at the Charité Campus Benjamin Franklin in Berlin). Patient data on treatment, outcome, and demographics were documented in STEMO (pre-hospital) or conventional care (in-hospital) registries. The primary outcome was the proportion of patients who had lived at home without assistance before stroke and had a 3-month modified Rankin Scale (mRS) score of 1 or lower. Our multivariable logistic regression was adjusted for demographics, comorbidities, and stroke severity. This study is registered with ClinicalTrials.gov, number NCT02358772. FINDINGS Between Feb 5, 2011, and March 5, 2015, 427 patients were treated within the STEMO vehicle and their data were entered into a pre-hospital registry. 505 patients received conventional care and their data were entered into an in-hospital thrombolysis registry. Of these, 305 patients in the STEMO group and 353 in the conventional care group met inclusion criteria and were included in the analysis. 161 (53%) patients in the STEMO group versus 166 (47%) in the conventional care group had an mRS score of 1 or lower (p=0·14). Compared with conventional care, adjusted odds ratios (ORs) for STEMO care for the primary outcome (OR 1·40, 95% CI 1·00-1·97; p=0·052) were not significant. Intracranial haemorrhage (p=0·27) and 7-day mortality (p=0·23) did not differ significantly between treatment groups. INTERPRETATION We found no significant difference between the proportion of patients with a mRS score of 1 or lower receiving STEMO care compared with conventional care. However, our results suggest that pre-hospital start of intravenous thrombolysis might lead to improved functional outcome in patients. This evidence requires substantiation in future large-scale trials. FUNDING Zukunftsfonds Berlin, the Technology Foundation Berlin with EU co-financing by the European Regional Development Fund via Investitionsbank Berlin, and the German Federal Ministry for Education and Research via the Center for Stroke Research Berlin.

Characterization of motor and somatosensory function for stroke patients

In a pilot study, stroke patients with a lesion related to the motor system were studied using magnetoencephalography (MEG) and electromyography (EMG). The patients performed sustained finger movements for 30 s followed by 30 s of rest and 20 repetitions of this sequence in total. Task-related cortical signals derived from MEG were observed here at very different frequency scales. Slow signals below 0.1 Hz were extracted by independent component analysis and are associated with the sustained activation of the motor cortex, the dcMEG motor activation. MEG-EMG coupling phenomena in the 10-30 Hz range were analyzed using the imaginary part of coherency and are attributed to cortico-muscular coupling driving the muscles. Additionally a signal from the somatosensory cortex due to an electrical stimulation at the wrist, the N20m, was recorded as a physiological marker. Field maps and time series associated with the three types of signals are presented for one patient and one control subject as the signal quality of the patient data was not sufficient to achieve a group result. The feasibility of a comprehensive electrophysiological measuring and analysis procedure of the motor function for stroke research is demonstrated by the results.

Influence of Distance to Scene on Time to Thrombolysis in a Specialized Stroke Ambulance

Background and Purpose— Specialized computed tomography–equipped stroke ambulances shorten time to intravenous thrombolysis in acute ischemic stroke by starting treatment before hospital arrival. Because of longer travel-time-to-scene, time benefits of this concept are expected to diminish with longer distances from base station to scene. Methods— We used data from the Prehospital Acute Neurological Treatment and Optimization of Medical Cares in Stroke (PHANTOM-S) trial comparing time intervals between patients for whom a specialized stroke ambulance (stroke emergency mobile) was deployed and patients with conventional emergency medical service. Expected times from base station to scene had been calculated beforehand using computer algorithms informed by emergency medical service routine data. Four different deployment zones with–75% probability–expected arrival within 4, 8, 12, and 16 minutes and total population coverage of ≈1.3 million inhabitants were categorized for stroke emergency mobile deployment. We analyzed times from alarm-to-arrival at scene, to start of intravenous thrombolysis and from onset-to-intravenous thrombolysis. Results— Corresponding to the size of the respective catchment zone, the number of patients cared increased with distance (zone 1: n=30, zone 2: n=127, zone 3: n=156, and zone 4: n=217). Although time to stroke emergency mobile arrival increased with distance (mean: 8.0, 12.5, 15.4, and 18.4 minutes in zones 1–4), time from alarm-to-intravenous thrombolysis (mean: 41.8 versus 76.5; 50.2 versus 79.1; 54.5 versus 76.6; and 59.3 versus 78.0 minutes, respectively; all P<0.01) remained shorter in the stroke emergency mobile group across all zones. Conclusions— In a metropolitan area such as Berlin, time benefits justify a specialized stroke ambulance service up to a mean travel time of 18 minutes from base station. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01382862.

Effects of Ultraearly Intravenous Thrombolysis on Outcomes in Ischemic Stroke

The effects of intravenous thrombolysis (IVT) in ischemic stroke are time dependent.1,2 Because of delays in conventional stroke workup, previous randomized IVT trials were unable to include patients with onset-to-treatment time (OTT) ≤60 minutes of symptom onset. With the invention of computed tomography–equipped mobile stroke units (MSUs), a relevant proportion of patients treated on such ambulances receive IVT within this ultraearly time window.3 In this study, we assessed the effects of IVT on 3-month functional outcome and mortality in different OTT intervals, including the first hour after onset, using a pooled analysis of 2 prospective prehospital and in-hospital registries in Berlin/Germany.4 Methods of patient inclusion and documentation in the 2 registries were described elsewhere4 (URL: http://www.clinicaltrials.gov. Unique identifier: NCT02358772). Briefly, all patients admitted through emergency medical services who received IVT between February 5, 2011, and March 5, 2015, were included in the registries. The prehospital registry included patients thrombolysed in an MSU and admitted to the nearest stroke unit thereafter. Intra-arterial treatment was optional in patients with occlusion of proximal intracranial arteries in both cohorts. The in-hospital registry comprised patients receiving IVT at Charite-Universitatsmedizin, Campus Benjamin Franklin. We excluded patients with nonstroke diagnosis, IVT without known exact (witnessed) time of onset, denial/withdrawal of informed consent for follow-up, missing 3-month follow-up, or incomplete documentation of data used in the multivariable analyses. For the pooled analyses of time-to-treatment effects, we included …

Chronic sensory stroke with and without central pain is associated with bilaterally distributed sensory abnormalities as detected by quantitative sensory testing

Abstract Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. As compared with reference data from healthy controls, patients with CPSP showed alterations of thermal and mechanical thresholds on the body area contralateral to their stroke (P < 0.01). Patients with sensory stroke but without CPSP (non–pain sensory stroke [NPSS] patients) exhibited similar albeit less pronounced contralesional changes. Paradoxical heat sensation (PHS) and dynamic mechanical allodynia (DMA) showed higher values in CPSP, and an elevated cold detection threshold (CDT) was seen more often in CPSP than in patients with NPSS (P < 0.05). In patients with CPSP, changes in CDT, PHS, dynamic mechanical allodynia, and temporal pain summation (wind-up ratio) each correlated with the presence of pain (P < 0.05). On the homologous ipsilesional body area, both patient groups showed additional significant abnormalities as compared with the reference data, which strongly resembled the contralesional changes. In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.

Auto-antibody-negative limbic-like encephalitis as the first manifestation of Neurosyphilis

Syphilis is caused by the spirochete Treponema pallidum.When nvasion of the central nervous system (CNS) occurs, Neurosyphilis an develop and is able to imitate a wide variety of diseases with any clinical symptoms, including photophobia, headache, nausea nd cranial nerve palsies [1]. For instance Neurosyphilis can be the ause of simultaneous infarction in the territories of the posterior nferior cerebellar arteries [2]. Here we present a patient with an epileptic seizure on the asis of mesiotemporal encephalitis as the first manifestation of he disease and show that auto-antibodies typical of phenotypially similar CNS diseases were absent in this condition. This is of mportance, because in many patients it is usually not ruled out, hat encephalitis might be caused by auto-antibodies and Syphilis s only diagnosed by coincidence. This clinical course highlights the variety of clinical symptoms hatNeurosyphilis can causeand the importanceof considering this

Effects of Prehospital Thrombolysis in Stroke Patients With Prestroke Dependency

Background and Purpose— Data on effects of intravenous thrombolysis on outcome of patients with ischemic stroke who are dependent on assistance in activities of daily living prestroke are scarce. Recent registry based analyses in activities of daily –independent patients suggest that earlier start of intravenous thrombolysis in the prehospital setting leads to better outcomes when compared with the treatment start in hospital. We evaluated whether these observations can be corroborated in patients with prestroke dependency. Methods— This observational, retrospective analysis included all patients with acute ischemic stroke depending on assistance before stroke who received intravenous thrombolysis either on the Stroke Emergency Mobile (STEMO) or through conventional in-hospital care (CC) in a tertiary stroke center (Charité, Campus Benjamin Franklin, Berlin) during routine care. Prespecified outcomes were modified Rankin Scale scores of 0 to 3 and survival at 3 months, as well as symptomatic intracranial hemorrhage. Outcomes were adjusted in multivariable logistic regression. Results— Between February 2011 and March 2015, 122 of 427 patients (28%) treated on STEMO and 142 of 505 patients (28%) treated via CC needed assistance before stroke. Median onset-to-treatment times were 97 (interquartile range, 69–159; STEMO) and 135 (interquartile range, 98–184; CC; P<0.001) minutes. After 3 months, modified Rankin Scale scores of 0 to 3 was observed in 48 STEMO patients (39%) versus 35 CC patients (25%; P=0.01) and 86 (70%, STEMO) versus 85 (60%, CC) patients were alive (P=0.07). After adjustment, STEMO care was favorable with respect to modified Rankin Scale scores of 0 to 3 (odds ratio, 1.99; 95% confidence interval, 1.02–3.87; P=0.042) with a nonsignificant result for survival (odds ratio, 1.73; 95% confidence interval, 0.95–3.16; P=0.07). Symptomatic intracranial hemorrhage occurred in 5 STEMO versus 12 CC patients (4.2% versus 8.5%; P=0.167). Conclusions— The results of this study suggest that earlier, prehospital (as compared with in-hospital) start of intravenous thrombolysis in acute ischemic stroke may translate into better clinical outcome in patients with prestroke dependency. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02358772.

Evaluation of a score for the prehospital distinction between cerebrovascular disease and stroke mimic patients

Background Patients with a sudden onset of focal neurological deficits consistent with stroke, who turn out to have alternative conditions, have been labeled stroke mimics. Aims We assessed a recently validated telemedicine-based stroke mimic score (TeleStroke mimic score; TM-score) and individual patient characteristics with regard to its discriminative value between cerebrovascular disease and stroke mimic patients in the in-person, pre-hospital setting. Methods We evaluated patients cared for in a mobile stroke unit in Berlin, Germany. We investigated whether the TM-score (comprising six parameters), Face Arm Speech Time test, and individual patient characteristics were able to differentiate cerebrovascular disease from stroke mimic patients. Results We included 423 patients (299 (70.7%) cerebrovascular disease and 124 (29.3%) stroke mimic) in the final analysis. A TM-score > 30 indicated a high probability of a cerebrovascular disease and a score ≤15 of a stroke mimic. The TM-score performed well to identify stroke mimics (area under the curve of 0.74 under receiver-operating characteristic curve analysis). The cerebrovascular disease patients were older (74.8 vs. 69.8 years, p = 0.001), had more often severe strokes (NIHSS > 14 25.8% vs. 11.3%, p = 0.001), presented more often with weakness of the face (70.9% vs. 42.7%, p = 0.001) or arm (60.9% vs. 33.9%, p = 0.001), dysarthria (59.5% vs. 40.3%, p < 0.001), history of atrial fibrillation (38.1% vs. 21.0%, p = 0.001), arterial hypertension (78.9% vs. 53.2%, p < 0.001), and less often with seizure (0.7% vs. 21.0%, p < 0.001). Conclusions The TM-score and certain patient characteristics can help paramedics and emergency physicians in the field to identify stroke mimic patients and select the most appropriate hospital destination.

GLM analysis of time resolved NIRS data of motor activation during different motor tasks

The hemodynamic response to motor activation was investigated by time-resolved NIRS in healthy subjects and patients with unilateral impairment in motor ability. Healthy subjects performed a simple and a complex finger movement task, patients a handgrip task. A General Linear Model approach (GLM) was applied during NIRS data processing. In general, compared to the integral (continuous wave signal), higher significance of activation was found for the variance signal that selectively represents changes in the deep compartment. A discussion of GLM results with respect to task complexity and difficulty is provided.

Primär- und Sekundärprävention des Schlaganfalls bei Diabetes

ZusammenfassungSchlaganfälle sind weltweit eine der wichtigsten Ursachen für dauerhafte Behinderung und Tod im Erwachsenenalter. Neben der arteriellen Hypertonie, Rauchen, Bewegungsmangel und kardialen Erkrankungen ist Diabetes mellitus ein unabhängiger und beeinflussbarer Risikofaktor für ischämische Schlaganfälle. Es gibt bisher keine eindeutige Evidenz für eine Reduktion der Inzidenz von Schlaganfällen durch medikamentöse oder nichtmedikamentöse Normalisierung und Senkung des langfristigen Glukosespiegels. In der täglichen Praxis wird dennoch zumeist die Normalisierung der Blutzuckerkonzentration angestrebt. Dies gilt auch für die Akutphase nach einem Schlaganfall. Eine zu starke Reduzierung des kurz- und langfristigen Glukosespiegels kann aber nicht empfohlen werden, da hier das Risiko für unerwünschte Nebenwirkungen (Hypoglykämien) mögliche Vorteile überwiegt. Der besondere Fokus der Prävention von Schlaganfällen bei Diabetespatienten liegt auf der leitliniengerechten Behandlung beeinflussbarer vaskulärer Risikofaktoren wie arterieller Hypertonie, Hypercholesterinämie, Übergewicht oder Rauchen.AbstractStroke is one of the most important causes of permanent disability and death in adults worldwide. In addition to hypertension, smoking, lack of physical activity and cardiac diseases, diabetes mellitus is an independent and modifiable risk factor for ischemic stroke. To date no unambiguous evidence exists for a reduction of the incidence of stroke by normalizing and lowering of long-term glucose levels with or without drugs. Nevertheless, normalization of blood glucose is an important goal in daily clinical practice. This also applies to the acute phase after stroke. Excessive lowering of short-term and long-term glucose levels is not recommended due to the increased risk of adverse events (hypoglycemia) which outweighs possible benefits. The focus in the prevention of stroke in patients with diabetes consists of guideline-conform treatment of modifiable vascular risk factors, such as hypertension, hyperlipoproteinemia, obesity and smoking.