Ischemic Stroke-A Scientometric Analysis.

Background: Stroke is the second leading cause of death world-wide. A comprehensive scientometric study regarding ischemic stroke research has not been performed yet. This study aims at investigating the global research output on ischemic stroke research. Methods: All 21,115 articles regarding ischemic stroke were retrieved from the Web-of-Science-Core-Collection and analyzed regarding regional differences, the authors' sex, subtopics of stroke, as well as international research collaborations. Results: A total of 132 different countries participated, with the USA contributing most publications with 4,614 (21.9%), followed by China with 3,872 (18.3%), and Germany with 1,120 (5.3%). Analyzing the scientific quality of different countries by H-index, the USA ranked first with an H-index of 202, followed by Germany (H-index 135) and the United Kingdom (UK;H-index 129). The most frequently used topic was "Clinical Neurology" with 9,028 publications. Among all first authors attributed to their sex, 32.3% of all first authors were female and 67.7% were male (4,335 vs. 9,097). The proportion of female last authors was comparatively lower at 22.4% (3,083 publications) compared with 77.6% male authors (10,658 publications). There was a broad network of international collaborations. Conclusions: Research in ischemic stroke has substantially increased over time. Scientists from the USA have the highest number of publications, followed by China and Germany. Measured by the H-index, the USA held the highest publication quality, followed by Germany and the UK. The scientific landscape was male-dominated with 67.7% of all first authors being male. Worldwide international collaborations play a major role in ischemic stroke research.

Effects of state-wide implementation of the Los Angeles Motor Scale for triage of stroke patients in clinical practice.

BACKGROUND: The prehospital identification of stroke patients with large-vessel occlusion (LVO), that should be immediately transported to a thrombectomy capable centre is an unsolved problem. Our aim was to determine whether implementation of a state-wide standard operating procedure (SOP) using the Los Angeles Motor Scale (LAMS) is feasible and enables correct triage of stroke patients to hospitals offering (comprehensive stroke centres, CSCs) or not offering (primary stroke centres, PSCs) thrombectomy. METHODS: Prospective study involving all patients with suspected acute stroke treated in a 4-month period in a state-wide network of all stroke-treating hospitals (eight PSCs and two CSCs). Primary endpoint was accuracy of the triage SOP in correctly transferring patients to CSCs or PSCs. Additional endpoints included the number of secondary transfers, the accuracy of the LAMS for detection of LVO, apart from stroke management metrics. RESULTS: In 1123 patients, use of a triage SOP based on the LAMS allowed triage decisions according to LVO status with a sensitivity of 69.2% (95% confidence interval (95%-CI): 59.0-79.5%) and a specificity of 84.9% (95%-CI: 82.6-87.3%). This was more favourable than the conventional approach of transferring every patient to the nearest stroke-treating hospital, as determined by geocoding for each patient (sensitivity, 17.9% (95%-CI: 9.4-26.5%); specificity, 100% (95%-CI: 100-100%)). Secondary transfers were required for 14 of the 78 (17.9%) LVO patients. Regarding the score itself, LAMS detected LVO with a sensitivity of 67.5% (95%-CI: 57.1-78.0%) and a specificity of 83.5% (95%-CI: 81.0-86.0%). CONCLUSIONS: State-wide implementation of a triage SOP requesting use of the LAMS tool is feasible and improves triage decision-making in acute stroke regarding the most appropriate target hospital.

Impact of mobile stroke units.

Since its first introduction in clinical practice in 2008, the concept of mobile stroke unit enabling prehospital stroke treatment has rapidly expanded worldwide. This review summarises current knowledge in this young field of stroke research, discussing topics such as benefits in reduction of delay before treatment, vascular imaging-based triage of patients with large-vessel occlusion in the field, differential blood pressure management or prehospital antagonisation of anticoagulants. However, before mobile stroke units can become routine, several questions remain to be answered. Current research, therefore, focuses on safety, long-term medical benefit, best setting and cost-efficiency as crucial determinants for the sustainability of this novel strategy of acute stroke management.

Can ultrasound attenuation measurement be used to characterise grain statistics in castings?

Industrial inspection protocols are qualified using mock-ups manufactured according to the same procedure as the plant part. For coarse-grained castings, known for their low inspectability, relying on mock-ups becomes particularly challenging owing to the variability of grain properties among components. Consequently, there is a keen interest in the capability to verify whether the grain size of the component under test matches the qualification specification in-situ. This paper investigates the potential of an attenuation measurement for assessing the ultrasonic inspectability of coarse-grained components using qualified procedures in a practical setting. The experimental part of the study focuses on an industrial Inconel 600 mock-up with spatially varying attenuation, measured across the entire sample in an immersion tank. Three zones with distinctly different attenuations were examined using metallography, which allowed for calculating classical grain size histograms and two-point correlation functions. For one of the zones, we synthesised the microstructure with the same statistical properties numerically and simulated the propagation of ultrasound using a grain-scale finite element model. The results showed good agreement with the experiment, and lead to several suggestions for the reasons for the discrepancy, the varying grain size statistics being the most likely. A parametric study, which followed, depicted the effect of the mean and standard deviation-to-mean ratio of the log-normal grain size distribution on the attenuation of ultrasound and its frequency dependence. Most notably, we demonstrated the known non-uniqueness of the relationship between the log-normal grain size distribution parameters and the attenuation. We suggested that the correlation length calculated from a single exponential fit to the two-point correlation function is a more robust metric describing grain statistics for this context, which can be obtained from attenuation. The correlation lengths estimated from measured attenuation using the second-order approximation model for the three zones of the studied mock-up yielded results of acceptable accuracy. We concluded that this metric could replace the average grain size in practical settings, as it retains more statistical information than the mean grain size and allows for linking measurements to the established theoretical attenuation models which this paper demonstrates.

Normal brain aging and Alzheimer's disease are associated with lower cerebral pH: an in vivo histidine 1H-MR spectroscopy study.

It is unclear whether alterations in cerebral pH underlie Alzheimer's disease (AD) and other dementias. We performed proton spectroscopy after oral administration of histidine in healthy young and elderly persons and in patients with mild cognitive impairment and dementia (total N = 147). We measured cerebral tissue pH and ratios of common brain metabolites in relation to phosphocreatine and creatine (Cr) in spectra acquired from the hippocampus, the white matter (WM) of the centrum semiovale, and the cerebellum. Hippocampal pH was inversely associated with age in healthy participants but did not differ between patients and controls. WM pH was low in AD and, to a lesser extent, mild cognitive impairment but not in frontotemporal dementia spectrum disorders and pure vascular dementia. Furthermore, WM pH provided incremental diagnostic value in addition to N-acetylaspartate to Cr ratio. Our study suggests that in vivo assessment of pH may be a useful marker for the differentiation between AD and other types of dementia.

Intravenous thrombolysis with tPA and cortical involvement increase the risk of early poststroke seizures: Results of a case-control study.

The aim of this study was to identify the risk factors for early poststroke seizures (PSS) in patients with acute ischemic stroke. We undertook a case-control study at a single stroke center. Patients with seizure occurring during the first 7 days following ischemic stroke admitted between 2010 and 2016 were retrospectively identified and matched with controls (patients with stroke without early PSS) for age and sex. We included 79 cases and 158 controls. Blood sugar levels on admission, stroke localization, National Institutes of Health Stroke Scale (NIHSS) and Rankin score, and intravenous (i.v.) thrombolysis with recombinant tissue plasminogen activator (rtPA) were statistically associated with early PSS in univariate analysis. Multiple logistic regression after forward and backward variable selection identified cortical stroke localization (odds ratio (OR): 2.49; 95% confidence intervals (CI): 1.35 to 4.59; p = 0.003) and i.v. thrombolysis (OR: 2.26; 95% CI: 1.16 to 4.43; p = 0.008) as variables independently associated with early PSS. Cortical involvement and i.v. thrombolysis are independent risk factors associated with the occurrence of early PSS. This association is not explained by age or sex, concomitant drugs, diabetes or alcoholism, sodium and cholesterol levels, blood pressure on admission, stroke etiology or severity, and hemorrhage following i.v. thrombolysis. Further studies are required to fully elucidate the association between different reperfusion therapies and early PSS. This article is part of the Special Issue "Seizures & Stroke".

Realistic Film Noise Generation Based on Experimental Noise Spectra.

Generating 2D noise with local, space-varying spectral characteristics is vital where random noise fields with spatially heterogeneous statistical proper-ties are observed and need to be simulated. A realistic, non-stationary noise generator relying on experimental data is presented. That generator is desired in areas such as photography and radiography. For example, before performing actual X-ray imaging in practice, output imag-es are simulated to assess and improve setups. For that purpose, realistic film noise modelling is crucial because noise downgrades the detectability of visual signals. The presented film noise synthesiser improves the realism and value of radiographic simulations significantly, allowing more realistic assessments of radiographic test setups. The method respects space-varying spectral characteristics and probability distributions, locally simulating noise with re-alistic granularity and contrast. The benefits of this ap-proach are to respect the correlation between noise and image as well as internal correlation, the fast generation of any number of unique noise samples, the exploitation of real experimental data, and its statistical non-stationarity. The combination of these benefits is not available in exist-ing work. Validation of the new technique was undertaken in the field of industrial radiography. While applied to that field here, the technique is general and can also be utilised in any other field where the generation of 2D noise with local, space-varying statistical properties is necessary.

Prehospital Stroke Management Optimized by Use of Clinical Scoring vs Mobile Stroke Unit for Triage of Patients With Stroke: A Randomized Clinical Trial.

Importance: Transferring patients with large-vessel occlusion (LVO) or intracranial hemorrhage (ICH) to hospitals not providing interventional treatment options is an unresolved medical problem. Objective: To determine how optimized prehospital management (OPM) based on use of the Los Angeles Motor Scale (LAMS) compares with management in a Mobile Stroke Unit (MSU) in accurately triaging patients to the appropriate hospital with (comprehensive stroke center [CSC]) or without (primary stroke center [PSC]) interventional treatment. Design, Setting, and Participants: In this randomized multicenter trial with 3-month follow-up, patients were assigned week-wise to one of the pathways between June 15, 2015, and November 15, 2017, in 2 regions of Saarland, Germany; 708 of 824 suspected stroke patients did not meet inclusion criteria, resulting in a study population of 116 adult patients. Interventions: Patients received either OPM based on a standard operating procedure that included the use of the LAMS (cut point ≥4) or management in an MSU (an ambulance with vascular imaging, point-of-care laboratory, and telecommunication capabilities). Main Outcomes and Measures: The primary end point was the proportion of patients accurately triaged to either CSCs (LVO, ICH) or PSCs (others). Results: A predefined interim analysis was performed after 116 patients of the planned 232 patients had been enrolled. Of these, 53 were included in the OPM group (67.9% women; mean [SD] age, 74 [11] years) and 63 in the MSU group (57.1% women; mean [SD] age, 75 [11] years). The primary end point, an accurate triage decision, was reached for 37 of 53 patients (69.8%) in the OPM group and for 63 of 63 patients (100%) in the MSU group (difference, 30.2%; 95% CI, 17.8%-42.5%; P < .001). Whereas 7 of 17 OPM patients (41.2%) with LVO or ICH required secondary transfers from a PSC to a CSC, none of the 11 MSU patients (0%) required such transfers (difference, 41.2%; 95% CI, 17.8%-64.6%; P = .02). The LAMS at a cut point of 4 or higher led to an accurate diagnosis of LVO or ICH for 13 of 17 patients (76.5%; 6 triaged to a CSC) and of LVO selectively for 7 of 9 patients (77.8%; 2 triaged to a CSC). Stroke management metrics were better in the MSU group, although patient outcomes were not significantly different. Conclusions and Relevance: Whereas prehospital management optimized by LAMS allows accurate triage decisions for approximately 70% of patients, MSU-based management enables accurate triage decisions for 100%. Depending on the specific health care environment considered, both approaches are potentially valuable in triaging stroke patients. Trial Registration: ClinicalTrials.gov identifier: NCT02465346.

Mobile Stroke Units - Cost-Effective or Just an Expensive Hype?

PURPOSE OF REVIEW: Acute stroke is a treatable disease. Nevertheless, only a minority of patients obtain guideline-adjusted therapy. One major reason is the small time window in which therapies have to be administered in order to reverse or mitigate brain injury and prevent disability. The Mobile Stroke Unit (MSU) concept, available for a decade now, is spreading worldwide, comprising ambulances, fully equipped with computed tomography, laboratory unit and telemedicine connection to the stroke centre and staffed with a specialised stroke team. Besides its benefits, this concept adds a relevant amount of costs to health services. RECENT FINDINGS: The feasibility of the MSU and its impact on reducing treatment times have been proven by several research trials. In addition, pre-hospital stroke diagnosis including computed tomographic angiography analysis facilitates correct triage of patients, needing mechanical recanalization, thereby reducing the number of secondary or inter-hospital transfers. Even so, the concept is not yet fully implemented on a broad scale. One reason is the still open question of cost-effectiveness. There are assumptions based on the randomised trials of MSUs hinting towards an acceptable amount of money per quality-adjusted life years and overall cost-effectiveness. Up to now, neither a prospective analysis nor a consideration of secondary transfer avoidance is available. The MSU concept is an innovative and impactful strategy to improve stroke management, especially in times of constraints in healthcare economics and health care professionals. Prospective information is needed to answer the cost-effectiveness question satisfactorily.

Prehospital Computed Tomography Angiography in Acute Stroke Management.

BACKGROUND: An ambulance equipped with a computed tomography (CT) scanner, a point-of-care laboratory, and telemedicine capabilities (mobile stroke unit [MSU]) has been shown to enable the delivery of thrombolysis to stroke patients directly at the emergency site, thereby significantly decreasing time to treatment. However, work-up in an MSU that includes CT angiography (CTA) may also potentially facilitate triage of patients directly to the appropriate target hospital and specialized treatment, according to their individual vascular pathology. METHODS: Our institution manages a program investigating the prehospital management of patients with suspicion of acute stroke. Here, we report a range of scenarios in which prehospital CTA could be relevant in triaging patients to the appropriate target hospital and to the individually required treatment. RESULTS: Prehospital CTA by use of an MSU allowed to detect large vessel occlusion of the middle cerebral artery in one patient with ischemic stroke and occlusion of the basilar artery in another, thereby allowing rational triage to comprehensive stroke centers for immediate intra-arterial treatment. In complementary cases, prehospital imaging not only allowed diagnosis of parenchymal hemorrhage with a spot sign indicating ongoing bleeding in one patient and of subarachnoid hemorrhage in another but also clarified the underlying vascular pathology, which was relevant for subsequent triage decisions. CONCLUSION: Defining the vascular pathology by CTA directly at the emergency site may be beneficial in triaging patients with various cerebrovascular diseases to the most appropriate target hospital and specialized treatment.

Optimized care in Patients with Rare Diseases: TSC at the Center for Rare Diseases (ZSEUKS) at Saarland University Medical Center, Germany.

Providing comprehensive medical care for patients with rare diseases is both challenging and rewarding. We will give a short summary of the most relevant medical issues pertinent to this subject, and will illustrate some of these issues by sharing our experience in the care of patients with TSC disease.

Standard operating procedures improve acute neurologic care in a sub-Saharan African setting.

OBJECTIVE: Quality of neurologic emergency management in an under-resourced country may be improved by standard operating procedures (SOPs). METHODS: Neurologic SOPs were implemented in a large urban (Banjul) and a small rural (Brikama) hospital in the Gambia. As quality indicators of neurologic emergency management, performance of key procedures was assessed at baseline and in the first and second implementation years. RESULTS: At Banjul, 100 patients of the first-year intervention group exhibited higher rates of general procedures of emergency management than 105 control patients, such as neurologic examination (99.0% vs 91.4%; p < 0.05) and assessments of respiratory rate (98.0% vs 81.9%, p < 0.001), temperature (60.0% vs 36.2%; p < 0.001), and glucose levels (73.0% vs 58.1%; p < 0.05), in addition to written directives by physicians (96.0% vs 88.6%, p < 0.05), whereas assessments of other vital signs remained unchanged. In stroke patients, rates of stroke-related procedures increased: early CT scanning (24.3% vs 9.9%; p < 0.05), blood count (73.0% vs 49.3%; p < 0.01), renal and liver function tests (50.0% vs 5.6%, p < 0.001), aspirin prophylaxis (47.3% vs 9.9%; p < 0.001), and physiotherapy (41.9% vs 4.2%; p < 0.001). Most effects persisted until the second-year evaluation. SOP implementation was similarly feasible and beneficial at the Brikama hospital. However, outcomes did not significantly differ in the hospitals. CONCLUSIONS: Implementing SOPs is a realistic, low-cost option for improving process quality of neurologic emergency management in under-resourced settings. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for patients with suspected neurologic emergencies in sub-Saharan Africa, neurologic SOPs increase the rate of performance of guideline-recommended procedures.

Dosage Calculation for Intravenous Thrombolysis of Ischemic Stroke: To Weigh or to Estimate.

BACKGROUND: Estimation is a widely used method of assessing the weight of patients with acute stroke. Because the dosage of tissue plasminogen activator (tPA) is weight-dependent, errors in estimation lead to incorrect dosing. METHODS: We installed a ground-level scale in the computed tomography (CT) suite of our hospital and also integrated a scale into the CT table of our Mobile Stroke Unit in order to prospectively assess the differences between reported, estimated, and measured weights of acute stroke patients. An independent rater asked patients to report their weight. The patients' weights were also estimated by the treating physician and measured with a scale. Differences between reported, estimated, and measured weights were analyzed statistically. RESULTS: For 100 consecutive patients, weighing was possible without treatment delays. Weights estimated by the physician diverged from measured weights by 10% or more for 27 patients and by 20% or more for 6 patients. Weights reported by the patient diverged from measured weights by 10% or more for 12 patients. Weights reported by the patients differed significantly less from measured weights (mean, 4.1 ± 3.1 kg) than did weights estimated by the physician (5.7 ± 4.4 kg; p = 0.003). CONCLUSION: This first prospective study of weight assessment in acute stroke shows that the use of an easily accessible scale makes it feasible to weigh patients with acute stroke without the treatment delay associated with additional patient transfers. Physicians' estimates of patients' weights demonstrated substantial aberrations from measured weights. Avoiding these deviations would improve the accuracy of tPA dosage.

Mobile stroke units for prehospital thrombolysis, triage, and beyond: benefits and challenges.

In acute stroke management, time is brain. Bringing swift treatment to the patient, instead of the conventional approach of awaiting the patient's arrival at the hospital for treatment, is a potential strategy to improve clinical outcomes after stroke. This strategy is based on the use of an ambulance (mobile stroke unit) equipped with an imaging system, a point-of-care laboratory, a telemedicine connection to the hospital, and appropriate medication. Studies of prehospital stroke treatment consistently report a reduction in delays before thrombolysis and cause-based triage in regard to the appropriate target hospital (eg, primary vs comprehensive stroke centre). Moreover, novel medical options for the treatment of stroke patients are also under investigation, such as prehospital differential blood pressure management, reversal of warfarin effects in haemorrhagic stroke, and management of cerebral emergencies other than stroke. However, crucial concerns regarding safety, clinical efficacy, best setting, and cost-effectiveness remain to be addressed in further studies. In the future, mobile stroke units might allow the investigation of novel diagnostic (eg, biomarkers and automated imaging evaluation) and therapeutic (eg, neuroprotective drugs and treatments for haemorrhagic stroke) options in the prehospital setting, thus functioning as a tool for research on prehospital stroke management.

First Automated Stroke Imaging Evaluation via Electronic Alberta Stroke Program Early CT Score in a Mobile Stroke Unit.

BACKGROUND: Recently, a mobile stroke unit (MSU) was shown to facilitate acute stroke treatment directly at the emergency site. The neuroradiological expertise of the MSU is improved by its ability to detect early ischemic damage via automatic electronic (e) evaluation of CT scans using a novel software program that calculates the electronic Alberta Stroke Program Early CT Score (e-ASPECTS). METHODS: The feasibility of integrating e-ASPECTS into an ambulance was examined, and the clinical integration and utility of the software in 15 consecutive cases evaluated. RESULTS: Implementation of e-ASPECTS onto the MSU and into the prehospital stroke management was feasible. The values of e-ASPECTS matched with the results of conventional neuroradiologic analysis by the MSU team. The potential benefits of e-ASPECTS were illustrated by three cases. In case 1, excluding early infarct signs supported the decision to directly perform prehospital thrombolysis. In case 2, in which stroke was caused by large-vessel occlusion, the high e-ASPECTS value supported the decision to initiate intra-arterial treatment and triage the patient to a comprehensive stroke center. In case 3, the e-ASPECTS value was 10, indicating the absence of early infarct signs despite pre-existing cerebral microangiopathy and macroangiopathy, a finding indicating the program's robustness against artefacts. CONCLUSIONS: This study on the integration of e-ASPECTS into the prehospital stroke management via a MSU showed for the first time that such integration is feasible, and aids both decision regarding the treatment option and the triage regarding the most appropriate target hospital.

Retrospective Consent to Hemicraniectomy after Malignant Stroke among the Elderly, Despite Impaired Functional Outcome.

BACKGROUND: Decompressive hemicraniectomy (DHC) after space-occupying strokes among patients older than 60 years has been shown to reduce mortality rates but at the cost of severe disability. There is an ongoing debate about what could be considered an acceptable outcome for these patients. Data about retrospective consent to the procedure after lengthy time periods are lacking. METHODS: This study included 79 consecutive patients who underwent DHC during a 7.75-year period. Surviving patients were assessed for functional and psychological outcome, quality of life (QoL) and retrospective consent for the procedure. Patients younger than 60 years were compared with older patients. RESULTS: Of our 79 patients, 44 were younger than 60 years (median 50 years, interquartile range (IQR) 19-59 years) and 35 were older (median 68 years, interquartile range 60-87 years). The 30-day mortality rate was higher for the older group, but the difference was not statistically significant. Functional outcome was significantly better in the younger group: 31% of the patients in this group vs. 10% in the older group had a modified Rankin Scale score of 0-3 (p = 0.046). The mean National Institutes of Health Stroke Scale score was 17 ± 14 for the younger group and 29 ± 15 for the older group (p = 0.002). On the 36-Item Short Form Health Survey, with the exception of the item 'General health', the older group reported higher values for all items, with statistically significant differences between the 2 groups on the items 'Role limitation emotional' (p = 0.0007) and 'Vitality' (p = 0.02). In the younger group, 29% of patients retrospectively declined consent for DHC opposed to 0% of patients in the older group (p = 0.07). CONCLUSIONS: Despite impaired functional outcome after DHC, indicators of QoL and retrospective consent are higher for patients older than 60 years over the long term. This finding should be taken into account by those who counsel patients and caregivers with regard to this serious procedure.

'Stroke Room': Diagnosis and Treatment at a Single Location for Rapid Intraarterial Stroke Treatment.

BACKGROUND: For patients with acute ischemic stroke, intra-arterial treatment (IAT) is considered to be an effective strategy for removing the obstructing clot. Because outcome crucially depends on time to treatment ('time-is-brain' concept), we assessed the effects of an intervention based on performing all the time-sensitive diagnostic and therapeutic procedures at a single location on the delay before intra-arterial stroke treatment. METHODS: Consecutive acute stroke patients with large vessel occlusion who obtained IAT were evaluated before and after implementation (April 26, 2010) of an intervention focused on performing all the diagnostic and therapeutic measures at a single site ('stroke room'). RESULT: After implementation of the intervention, the median intervals between admission and first angiography series were significantly shorter for 174 intervention patients (102 min, interquartile range (IQR) 85-120 min) than for 81 control patients (117 min, IQR 89-150 min; p < 0.05), as were the intervals between admission and clot removal or end of angiography (152 min, IQR 123-185 min vs. 190 min, IQR 163-227 min; p < 0.001). However, no significant differences in clinical outcome were observed. CONCLUSION: This study shows for the, to our knowledge, first time that for patients with acute ischemic stroke, stroke diagnosis and treatment at a single location ('stroke room') saves crucial time until IAT.

Is prehospital treatment of acute stroke too expensive? An economic evaluation based on the first trial.

BACKGROUND: Recently, a strategy for treating stroke directly at the emergency site was developed. It was based on the use of an ambulance equipped with a scanner, a point-of-care laboratory, and telemedicine capabilities (Mobile Stroke Unit). Despite demonstrating a marked reduction in the delay to thrombolysis, this strategy is criticized because of potentially unacceptable costs. METHODS: We related the incremental direct costs of prehospital stroke treatment based on data of the first trial on this concept to one year direct cost savings taken from published research results. Key parameters were configuration of emergency medical service personnel, operating distance, and population density. Model parameters were varied to cover 5 different relevant emergency medical service scenarios. Additionally, the effects of operating distance and population density on benefit-cost ratios were analyzed. RESULTS: Benefits of the concept of prehospital stroke treatment outweighed its costs with a benefit-cost ratio of 1.96 in the baseline experimental setting. The benefit-cost ratio markedly increased with the reduction of the staff and with higher population density. Maximum benefit-cost ratios between 2.16 and 6.85 were identified at optimum operating distances in a range between 43.01 and 64.88 km (26.88 and 40.55 miles). Our model implies that in different scenarios the Mobile Stroke Unit strategy is cost-efficient starting from an operating distance of 15.98 km (9.99 miles) or from a population density of 79 inhabitants per km2 (202 inhabitants per square mile). CONCLUSION: This study indicates that based on a one-year benefit-cost analysis that prehospital treatment of acute stroke is highly cost-effective across a wide range of possible scenarios. It is the highest when the staff size of the Mobile Stroke Unit can be reduced, for example, by the use of telemedical support from hospital experts. Although efficiency is positively related to population density, benefit-cost ratios can be greater than 1 even in rural settings.

Isolated central nervous system relapse of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system. CASE PRESENTATION: We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML) during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF) with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable. CONCLUSIONS: In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.