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BackgroundRapid revascularisation in acute ischaemic stroke is crucial to reduce its total burden including societal costs. A quality improvement (QI) project that included streamlining the stroke care pathway and simulation-based training was followed by a significant reduction in median door-to-needle time (27 to 13 min) and improved patient outcomes after stroke thrombolysis at our centre. Here, we present a retrospective cost-effectiveness analysis of the QI project.MethodsCosts for implementing and sustaining QI were assessed using recognised frameworks for economic evaluations. Effectiveness was calculated from previously published outcome measures. Cost-effectiveness was presented as incremental cost-effectiveness ratios including costs per minute door-to-needle time reduction per patient, and costs per averted death in the 13-month post-intervention period. We also estimated incremental cost-effectiveness ratios for a projected 5-year post-intervention period and for varying numbers of patients treated with thrombolysis. Furthermore, we performed a sensitivity analysis including and excluding costs of unpaid time.ResultsAll costs including fixed costs for implementing the QI project totalled US$44 802, while monthly costs were US$2141. We calculated a mean reduction in door-to-needle time of 13.1 min per patient and 6.36 annual averted deaths. Across different scenarios, the estimated costs per minute reduction in door-to-needle time per patient ranged from US$13 to US$29, and the estimated costs per averted death ranged from US$4679 to US$10 543.ConclusionsWe have shown that a QI project aiming to improve stroke thrombolysis treatment at our centre can be implemented and sustained at a relatively low cost with increasing cost-effectiveness over time. Our work builds on the emerging theory and practice for economic evaluations in QI projects and simulation-based training. The presented cost-effectiveness data might help guide healthcare leaders planning similar interventions.

Background Tenecteplase has probably pharmacological and clinical advantages in the treatment of acute ischemic stroke. There are lacking data about safety and efficacy of tenecteplase in wake-up stroke (WUPS). Aims To investigate safety and efficacy of tenecteplase compared to alteplase in WUPS patients included in NOR-TEST. Methods WUPS patients in NOR-TEST were included in the study based on DWI-FLAIR mismatch. Included patients randomly assigned (1:1) to receive intravenous tenecteplase 0.4 mg/kg (to a maximum of 40 mg) or alteplase 0.9 mg/kg (to a maximum of 90 mg). Neurological improvement was defined as 1) favorable functional outcome at 90 days modified Rankin Scale (mRS) of 0 or 1 and 2) neurological improvement measured with the National Institutes of Health Stroke Scale (NIHSS) of 4 points within 24 hours as compared to admission NIHSS or NIHSS 0 at 24 hours. Results Of 1100 patients from 13 stroke centers included in NOR-TEST, 45 were WUPS patients. Of these, 5 patients were stroke mimics and excluded. Of the remaining 40 patients (3.6%), 24 were treated with alteplase (60%). There was no difference in the number of patients achieving a good clinical outcome (mRS 0-1) in either treatment group. Patients treated with tenecteplase showed a better early neurological improvement (87.5% vs 54.2%, P = 0.027). No ICH was detected on MRI/CT 24-28 hours after thrombolysis. Conclusions In WUPS patients treated in NOR-TEST, there was no difference in clinical outcomes at 90 days and no ICH events or deaths were observed in either alteplase- or tenecteplase-treated patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01949948.

Purpose Endovascular treatment (EVT) is traditionally performed by neurointerventional radiologists at tertiary medical centres imposing long transport ways to large vessel occlusion (LVO) stroke patients in rural areas. The purpose of this study is to evaluate the technical and clinical results over time at Stavanger University Hospital, a hospital without neurointerventional expertise, where trained general interventional radiologist performs EVT. Methods All patients with LVO stroke treated with EVT from May 2009 to December 2018 were included in the analysis. Technical outcome was measured by the modified treatment in cerebral ischaemia (mTICI) score, functional outcome by the modified Rankin Scale (mRS), complications registered. Results A total of 235 patients were treated with EVT. An angiographically good result (mTICI 2b or 3) could be seen in 66.7% of the patients treated the first year. In 2011, the year EVT with stent retrievers was introduced, the recanalization rate rose to 81.8%, and from 2014 onwards, it was stable around 80%. After introduction of aspiration together with stent retrievers in 2012, a good functional outcome (mRS 0-2) was obtained in >40% of the treated patients. In 2018, 61.1% of the patients got a good functional outcome. Conclusions Endovascular treatment of LVO stroke performed by general vascular interventional radiologist in close collaboration with diagnostic neuroradiologists and stroke neurologists can achieve technical revascularization results and clinical patient outcomes in line with international recommendations, and the randomized controlled studies performed. This approach may help to introduce EVT in geographical areas where this service is lacking due to the absence of neurointerventional specialists.

Objectives Endovascular treatment (EVT) is the gold standard treatment for emergent large vessel occlusion (LVO). The benefit of EVT for emergent LVO in elderly patients (>80 years old) is still debated as they have been under-represented in randomized controlled trials. Elderly patients with an emergent LVO are a growing population warranting further study. Materials & Methods We included 225 consecutive patients treated with EVT for LVO either in the anterior or posterior circulation. The clinical outcome was assessed using the National Institute of Health Stroke Scale (NIHSS). Long-term functional outcome was assessed using 90-day modified ranking scale (mRS). Results Neurological improvement: A five-year higher age predicted a 0.43 higher mean NIHSS score after EVT (p = .027). After adjusting for confounders (influencing variables), the association between age and post-interventional NIHSS was reduced and non-significant (p = .17). At discharge, a five-year higher age predicted a 0.74 higher mean NIHSS (p = .003). After adjusting for confounders this association was reduced and non-significant (p = .06). Long-term functional outcome: A five-year higher age predicted a 0.20 higher mRS at three months (p

Background In acute ischemic stroke (AIS), rapid treatment with intravenous thrombolysis (IVT) is crucial for good clinical outcome. Weekly simulation-based team-training of the stroke treatment team was implemented, resulting in faster treatment times. The aim of this study was to assess whether this time reduction led to a higher proportion of stroke mimics (SMs) among patients who received IVT for presumed AIS, and whether these SM patients were harmed by intracranial hemorrhage (ICH). Methods All suspected AIS patients treated with IVT between January 1, 2015 and December 31, 2020 were prospectively registered. In 2017, weekly in situ simulation-based team-training involving the whole stroke treatment team was introduced. To analyze possible unintended effects of simulation training, the proportion of SMs among patients who received IVT for presumed AIS were identified by clinical and radiological evaluation. Additionally, we identified the extent of symptomatic ICH (sICH) in IVT-treated SM patients. Results From 2015 to 2020, 959 patients were treated with IVT for symptoms of AIS. After introduction of simulation training, the proportion of patients treated with IVT who were later diagnosed as SMs increased significantly (15.9% vs. 24.4%, p = .003). There were no ICH complications in the SM patients treated before, whereas two SM patients suffered from asymptomatic ICH after introduction of simulation training (p = 1.0). When subgrouping SMs into prespecified categories, only the group diagnosed with peripheral vertigo increased significantly (2.5% vs. 8.6%, p < .001). Conclusions Simulation training of the acute stroke treatment team was associated with an increase in the proportion of patients treated with IVT for a suspected AIS who were later diagnosed with peripheral vertigo. The proportion of other SM groups among IVT-treated patients did not change significantly. No sICH was detected in IVT-treated SM patients. publishedVersion

Objective Metric based virtual reality simulation training may enhance the capability of interventional neuroradiologists (INR) to perform endovascular thrombectomy. As pilot for a national simulation study we examined the feasibility and utility of simulated endovascular thrombectomy procedures on a virtual reality (VR) simulator. Methods Six INR and four residents participated in the thrombectomy skill training on a VR simulator (Mentice VIST 5G). Two different case-scenarios were defined as benchmark-cases, performed before and after VR simulator training. INR performing endovascular thrombectomy clinically were also asked to fill out a questionnaire analyzing their degree of expectation and general attitude towards VR simulator training. Results All participants improved in mean total procedure time for both benchmark-cases. Experts showed significant improvements in handling errors (case 2), a reduction in contrast volume used (case 1 and 2), and fluoroscopy time (case 1 and 2). Novices showed a significant improvement in steps finished (case 2), a reduction in fluoroscopy time (case 1), and radiation used (case 1). Both, before and after having performed simulation training the participating INR had a positive attitude towards VR simulation training. Conclusion VR simulation training enhances the capability of INR to perform endovascular thrombectomy on the VR simulator. INR have generally a positive attitude towards VR simulation training. Whether the VR simulation training translates to enhanced clinical performance will be evaluated in the ongoing Norwegian national simulation study.

The benefit of acute ischemic stroke (AIS) treatment is highly time dependent. Although studies on workflow improvement in AIS are increasingly gaining attention, there is a lack of consensus and consistency regarding the definition, measurement, and reporting of AIS workflow times. We discuss the challenges related to defining and measuring workflow times in AIS and propose a basic set of time intervals that should be reported in AIS workflow studies. We particularly focus on patients undergoing mechanical thrombectomy. Importantly, endovascular treatment workflow times should always be reported in conjunction with reperfusion quality because one is not informative without the other. We further suggest standardized reporting of workflow times that includes the 90th percentile in addition to medians and interquartile ranges, means, and SDs. The proposed methodology serves as a framework for AIS studies and aids further discussion on workflow‐related AIS research.

During the coronavirus disease 2019 (COVID-19) pandemic, infectious disease control is of utmost importance in acute stroke treatment. This is a new situation for most stroke teams that often leads to uncertainty among physicians, nurses, and technicians who are in immediate contact with patients. The situation is made even more complicated by numerous new regulations and protocols that are released in rapid succession. Herein, we are describing our experience with simulation training for COVID-19 stroke treatment protocols. One week of simulation training allowed us to identify numerous latent safety threats and to adjust our institution-specific protocols to mitigate them. It also helped our physicians and nurses to practice relevant tasks and behavioral patterns (eg, proper donning and doffing PPE, where to dispose potentially contaminated equipment) to minimize their infectious exposure and to adapt to the new situation. We therefore strongly encourage other hospitals to adopt simulation training to prepare their medical teams for code strokes during the COVID-19 pandemic.

BackgroundIn eligible patients with acute ischaemic stroke, rapid revascularisation is crucial for good outcome. At our treatment centre, we had achieved and sustained a median door-to-needle time of under 30 min. We hypothesised that further improvement could be achieved through implementing a revised treatment protocol and in situ simulation-based team training sessions. This report describes a quality improvement project aiming to reduce door-to-needle times in stroke thrombolysis.MethodsAll members of the acute stroke treatment team were surveyed to tailor the interventions to local conditions. Through a review of responses and available literature, the improvement team suggested changes to streamline the protocol and designed in situ simulation-based team training sessions. Implementation of interventions started in February 2017. We completed 14 simulation sessions from February to June 2017 and an additional 12 sessions from November 2017 to March 2018. Applying Kirkpatrick’s four-level training evaluation model, participant reactions, clinical behaviour and patient outcomes were measured. Statistical process control charts were used to demonstrate changes in treatment times and patient outcomes.ResultsA total of 650 consecutive patients, including a 3-year baseline, treated with intravenous thrombolysis were assessed. Median door to needle times were significantly reduced from 27 to 13 min and remained consistent after 13 months. Risk-adjusted cumulative sum charts indicate a reduced proportion of patients deceased or bedridden after 90 days. There was no significant change in balancing measures (stroke mimics, fatal intracranial haemorrhage and prehospital times).ConclusionsImplementing a revised treatment protocol in combination with in situ simulation-based team training sessions for stroke thrombolysis was followed by a considerable reduction in door-to-needle times and improved patient outcomes. Additional work is needed to assess sustainability and generalisability of the interventions.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Background Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient. Aim To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients. Methods Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain of survival for Emergency Stroke Care by assembling international expertise in Stroke and Emergency Medical Services (EMS). Ten programs were identified for Acute Stroke Care to improve survival and outcomes, with recommendations for implementation of best practice. Conclusions Efficient prehospital systems for acute stroke will be improved through public awareness, optimized prehospital triage and timely diagnostics, and quick and equitable access to acute treatments. Documentation, use of metrics and transparency will help to build a culture of excellence and accountability.

Background and Purpose— Tenecteplase represents a promising alternative to alteplase as thrombolytic treatment in acute ischemic stroke. There are limited data on tenecteplase 0.4 mg/kg in patients with increased stroke severity. We aimed to assess safety and efficacy of tenecteplase 0.4 mg/kg in patients with moderate and severe ischemic stroke. Methods— NOR-TEST (Norwegian Tenecteplase Stroke Trial) was a phase III trial designed to investigate the safety and efficacy of tenecteplase 0.4 mg/kg versus alteplase 0.9 mg/kg in ischemic stroke. In this post hoc analysis, moderate stroke was defined as admission National Institutes of Health Stroke Scale; 6 to 14 and severe stroke as National Institutes of Health Stroke Scale; ≥15. Rates of favorable outcome at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality after 7 and 90 days were assessed. Results— In patients with moderate stroke (n=261), there were no differences in rates of favorable outcome, sICH, or mortality between tenecteplase and alteplase. In patients with severe stroke (n=87), there were no differences in outcome, frequency of sICH, or mortality at 7 days, but all-cause mortality at 90 days was increased in patients treated with tenecteplase (10 [26.3%] versus 4 [9.1%]; P =0.045). One patient died of sICH in the tenecteplase group, and 2 patients died of sICH in the alteplase group. Conclusions— Rates of favorable outcome and sICH were similar between treatment groups in patients with moderate and severe stroke. Mortality after 90 days was increased in patients with severe stroke receiving tenecteplase. Future studies assessing tenecteplase 0.4 mg/kg should monitor safety parameters closely in patients with severe stroke. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

Purpose: Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous long-term ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors which can help selecting patients with the highest possibility of detecting atrial fibrillation with prolonged rhythm monitoring. The clinical relevance of short-term atrial fibrillation, the need for medical intervention and the evaluation as to whether intervention results in improved clinical outcomes should be assessed. Method: The Nordic Atrial Fibrillation and Stroke Study is an international, multicentre, prospective, observational trial evaluating the occurrence of occult atrial fibrillation in cryptogenic stroke and transient ischaemic attack. Patients with cryptogenic stroke or transient ischaemic attack from the Nordic countries are included and will have the Reveal LINQ® Insertable cardiac monitor system implanted for 12 months for atrial fibrillation detection. Biomarkers which can be used as predictors for atrial fibrillation and may identify patients, who could derive the most clinical benefit from the detection of atrial fibrillation by prolonged monitoring, are being studied. Conclusion: The primary endpoint is atrial fibrillation burden within 12 months of continuous rhythm monitoring. Secondary endpoints are atrial fibrillation burden within six months, levels of biomarkers predicting atrial fibrillation, CHA2DS2-VASc score, incidence of recurrent stroke or transient ischaemic attack, use of anticoagulation and antiarrhythmic drugs, and quality of life measurements. The clinical follow-up period is 12 months. The study started in 2017 and the completion is expected at the end of 2020. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NOR-FIB is an investigator driven academic study. Of the 500 devices, 400 are supported by Medtronic. The study is supported by the research infrastructure of the European Cerebrovascular Research Infrastructure (ECRI).

Background. The main complications after endovascular therapy of intracranial aneurysms are aneurysm rupture and thromboembolic events. Yet, the widespread use of magnetic resonance imaging (MRI) in follow-up of these patients also demonstrates other, rarely known complications such as aseptic meningitis and foreign body reaction. Case Presentation. A small aneurysm in the right posterior communicating artery was treated with endovascular therapy in a 65 year old woman. Two weeks after successful interventional treatment, the patient developed a headache. On MRI performed five months after intervention, vasogenic edema was seen in the vascular territory of the right internal carotid artery. The edema and the symptoms diminished without specific treatment within a year. Interpretation. The clinical and radiological presentation of this case are suggestive of a foreign body reaction, a treatable condition that radiologists and clinicians should be aware of.

This study evaluates the effect of a mass media intervention (MMI) on the number of admissions to the emergency room (ER) with a suspected acute-onset stroke and on the number of patients treated with intravenous thrombolysis (IVT). The MMI was run for 1 month, with a precampaign month, priming the treatment chain and raising in-hospital awareness.This study conducted a prospective analysis of all patients admitted to the ER before, during, and after the MMI to assess changes in admission rate and IVT treatment rate. The primary end point was to assess any change in the IVT treatment rate, and the secondary end point was to determine the number of acute stroke admissions to the ER within 4.5 hours of symptom onset.The MMI resulted in an increased IVT treatment rate from 7.3 to 11.3 patients per month, an increment of 54% (P = .002). This also resulted in IVT treatment percentages as high as 42%. The number of suspected acute stroke admissions to the ER increased from 37.3 to 72.8 patients per month, a 97% increase (P .0001). The Epinion interviews showed that stroke symptom recognition increased from 66% to 75%.The MMI produced a significant increase in IVT treatment rate. This increased treatment rate is largely due to the increase in the number of acute stroke admissions to the ER. Targeting the treatment chain before the MMI led to unprecedented IVT treatment percentages. The effect of our MMI lasted for approximately 6 months before tapering off; repeated campaigns are a prerequisite for sustained IVT treatment rates.

Stroke is one of the leading causes of mortality worldwide. Understanding the risk factors associated with stroke mortality is important to improve patient management. Few studies have examined long-term mortality and its associated predictive risk factors.We examined long-term mortality in 1137 patients with acute stroke and compared it to a geographically age- and sex-matched, stroke-free control group. We followed the stroke patients for as long as 16.4 years. In 1018 of these patients we assessed the effect of demographic, clinical, and hematological factors on mortality.At the end of the study period, 51.7% of the patients and 32.7% of the stroke-free control individuals had died (hazard ratio 2.2, confidence interval 1.9-2.5, P .001). A total of 72.5% of the patients and 53% of the controls with 12 years' follow-up (n = 570) had died (P .001). Regression analyses indicate that, in addition to known risk factors such as age, diabetes, and stroke severity, both low cholesterol (P .001) and hemoglobin (P .002), hyperhomocysteinemia (P = .005), and elevated serum creatinine (P .001) at index stroke are associated with increased long-term mortality.Stroke patients surviving the first year after stroke have a markedly increased mortality rate as seen in long-term follow-up. Furthermore, the results from this study indicate that changes in creatinine, homocysteine, and hemoglobin should be followed more carefully as standard practice after acute stroke.

Objectives: Endovascular treatment (EVT) has emerged as the gold standard therapy for stroke due to large vessel occlusion (LVO). There is however limited evidence to suggest that similar efficacy can be expected in elderly patients. We aimed to assess the efficacy and safety of EVT in elderly patients (aged > 80), comparing outcomes to younger patients (aged < 80). Material and Methods: A total of 195 patients with LVO stroke treated with EVT were included and dichotomized by age. We compared neurological improvement, clinical 90 day outcome, technical recanalization rates, procedure-related complications, and mortality in between the groups. Results: Both groups showed equally marked neurological improvement. A favorable outcome modified Rankin Scale (mRS < 2) was seen in 28% of the elderly patients compared to 46% of the younger patients (p = 0.01). mRS 0–3 was seen in 46% of the elderly patients and 58% of the younger patients (p = 0.09). The rates of successful technical recanalization did not differ between the groups and there were no differences in procedural complication rates or incidence of symptomatic intracranial bleeding. Three-month mortality rates were however higher in the elderly group. Conclusions: EVT in the elderly resulted in equally notable neurological improvement as compared to younger patients. Although the elderly had a higher mortality rate and fewer favorable clinical outcomes at 3 month follow-up, a strict upper age limit for EVT seems unjustified.

Additional file 1. Additional materials.

Patients who suffer acute ischaemic stroke can be treated with thrombolysis if therapy is initiated early. Radiological evaluation of the intracranial tissue before such therapy can be given is mandatory. In this review current radiological diagnostic strategies are discussed for this patient group. Beyond non-enhanced computed tomography (CT), the standard imaging method for many years, more sophisticated CT stroke protocols including CT angiography and CT perfusion have been developed, and additionally an increasing number of patients are examined with magnetic resonance imaging as the first imaging method used. Advantages and challenges of the different methods are discussed.

In open continuous culture, a continuous feed of medium flowing into a constant volume of growing culture and a constant withdrawal of an equal amount of culture produces a steady-state condition for growth. Continuous cultures could also render industrial exploitation of plant cell cultures more economical. The large scale propagation of various plants and glycosides by means of cultured plant cells demonstrates the relevance of the cell culture method to agriculture and industry. The establishment of open continuous cultures, in particular synchronous cultures greatly enhances possibilities for better understanding induction processes. The inoculum for continuous cultures generally is batch cultures of cell suspensions. The genetic stability of cell suspension cultures is of great concern. Semicontinuous culture has been mainly employed for maintaining stock cultures in an exponential growth phase over longer periods of time by avoiding nutrient limitation through frequent subculture.

Background Acute Ischemic Stroke (AIS) treatment has been revolutionised in the last two decades with the increasing use of Intravenous Thrombolysis (IVT) and with the advent of Endovascular therapy (EVT). AIS treatment and outcome are time dependant and time saving measures are being implemented at every step of the treatment chain. These changes have resulted in lower treatment times in-hospital, but it is unclear if this translates into more patients being treated within 60 min of symptom onset – the Golden Hour. The clinical outcome of IVT therapy in this patient group was our secondary outcome. Methods From 2009 onwards, systematic changes were made to the AIS treatment chain leading to a dramatic decrease in Door-to-Needle (DTN) time. Analyses were performed on the number of these treatments year on year and their clinical outcomes within the Golden Hour at Stavanger University Hospital (SUS). Results Six-hundred and thirteen patients were included; seventy-three were treated within the Golden Hour. The percentage of total IVT treatments occurring in the Golden Hour rose from 2.2% in 2009 to 14.5% in 2015 (p = 0.006) with a high of 18.3% in 2012 (p < 0.001). All of these patients had a Median NIHSS of 0 at discharge, irrespective of age and pre-existing comorbidity. There was no incidence of any ICH and in-hospital mortality was only 2.7% in this group. Discussion The time from AIS symptom onset to treatment is filled with delays. Despite the inherence of some delays,significant efforts on the part of the pre- and in- hospital treatment chain have made IVT therapy within 60 min a possibility. The allocation and use of resources in the setting of rapid AIS treatment is warrantedand yields unprecedented results. Conclusions Our study shows that improved treatment routines led to an increase in the number of patients treated within the Golden Hour. Treatment in the Golden Hour leads to excellent outcomes in all patients, irrespective of age and pre-existing comorbidity.

Objectives Stroke is one of the leading causes for nursing home placement (NHP). We have studied the prognosis and risk factors regarding NHP for stroke patients initially discharged to their homes. Materials and methods All stroke patients in the municipality of Stavanger, Norway, between January 1, 1996, and March 31, 2004, were included and followed until death or May 31, 2012. Time intervals for NHP and death were compared to an age- and sex-matched, stroke-free control cohort. Logistic regression analysis was used to assess risk factors for NHP. Results A total of 452 patients were included. A total of 48 patients (10.6%) were directly placed in a nursing home, while 401 patients (88.7%) were discharged to their homes; 180 patients (44.7%) directly and 221 patients (55.3%) after temporary rehabilitation. Of the patients discharged to their homes, 29.7% needed NHP at a later time point as compared to 19.9% of the controls (P

Aims: This study aims to evaluate the implementation of a rapid response treatment protocol for patients presenting with acute onset ischemic stroke. Improvements of routines surrounding the admission and treatment of patients with intravenous thrombolysis (IVT), such as door-to-needle (DTN) times, and increasing the numbers of patients treated are discussed. Methods: We conducted a retrospective analysis of all patients (n = 320) treated with IVT for acute onset ischemic stroke at the Stavanger University Hospital, Norway, between 2003 and 2012. In 2009, a succession of changes to pre- and intra-hospital routines were made as well as an improvement in the education of primary health care physicians, nurses and paramedics involved in the treatment of acute onset stroke patients (rapid response treatment protocol). Analyses of DTN times, onset-to-needle times and the number of patients treated per year were carried out to ascertain the effect of the changes made. The primary aim was to analyze DTN times to look for any changes, and the secondary aim was to analyze changes in the number of patients treated per year. Results: In the years after the implementation of the rapid treatment protocol, we saw an improvement in the median DTN time with a decrease from 73 to 50 min in the first year (p = 0.03), a decrease of 45 min in the second year (p = 0.01) and a decrease of 31 min in the third year (p < 0.001). Similarly, an improvement in the number of patients treated per year was seen after enhancements in the treatment chain were made. A significant, 27-fold increase was shown when the number of patients treated in 2012 was compared with all patients treated in all years prior to the implementation of the rapid treatment protocol. Conclusions: The implementation of the rapid treatment protocol for acute onset ischemic stroke patients led to a significant decrease in the DTN time at our center. These improvements also produced an increase in the number of patients treated per year. The extension of the therapeutic window from 3 to 4.5 h for the use of intravenous recombinant tissue plasminogen activator also played a role in the increased treatment numbers.

Background. Metabolic syndromes such as Wernicke’s encephalopathy may present with a sudden neurological deficit, thus mimicking acute onset stroke. Due to current emphasis on rapid admission and treatment of acute stroke patients, there is a significant risk that these stroke mimics may end up being treated with thrombolysis. Rigorous clinical and radiological skills are necessary to correctly identify such metabolic stroke mimics, in order to avoid doing any harm to these patients due to the unnecessary use of thrombolysis.Patient. A 51-year-old Caucasian male was admitted to our hospital with suspicion of an acute stroke due to sudden onset dysarthria and unilateral facial nerve paresis. Clinical examination revealed confusion and dysconjugate gaze. Computed tomography (CT) including a CT perfusion (CTP) scan revealed bilateral thalamic hyperperfusion. The use of both clinical and radiological findings led to correctly diagnosing Wernicke’s encephalopathy.Conclusion. The application of CTP as a standard diagnostic tool in acute stroke patients can improve the detection of stroke mimics caused by metabolic syndromes as shown in our case report.

ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naive subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (Aβ)38 , Aβ40 , Aβ42 , total tau (t-tau), and phosphorylated tau (p-tau). We performed three-dimensional radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. We found significant associations between levels of all three CSF Aβ analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample, all three amyloid analytes showed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF Aβ38 and Aβ42 showed negative associations, with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. CSF Aβ levels in early PD correlate with ventricular enlargement, previously associated with PD dementia. Therefore, CSF and MRI markers may help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer's disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy.

Objectives The understanding of stroke has changed in the recent years from rehabilitation to an emergency approach. We review existing data from symptom recognition to thrombolysis and identify challenges in the different phases of patient treatment. Results Implementation of treatment in dedicated stroke units with a multidisciplinary team exclusively treating stroke patients has led to significant reduction of stroke morbidity and mortality. Yet, first the introduction of treatment with intravenous rtPA (IVT) has led to the ‘time is brain’ concept where stroke is conceived as an emergency. As neuronal death in stroke is time dependent, all effort should be laid on immediate symptom recognition, rapid transport to the nearest hospital with a stroke treatment facility and diagnosis and treatment as soon as possible. The main cause of prehospital delay is that patients do not recognize that they suffered a stroke or out of other reasons do not call the Emergeny Medical Services immediately. Educational stroke awareness campaigns may have an impact in increasing the number of patients eligible for rtPA treatment and can decrease the prehospital times if they are directed both to the public and to the medical divisions treating stroke. Stroke transport times can be shortened by the use of helicopter and a stroke mobile – an ambulance equipped with a CT scanner – may be helpful to decrease time from onset to treatment start in the future. Yet, IVT has several limitations such as a narrow time window and a weak effect in ischemic strokes caused by large vessel occlusions. In these cases, interventional procedures and the concept of bridging therapy, a combined approach of IVT and intraarterial thrombolysis or mechanical thrombectomy, might improve recanalization rates and patient outcome. Conclusions As neuronal death in stroke patients occurs in a time-dependent fashion, all effort should be made to decrease time from symptom onset to treatment start with rtPA: major challenges are stroke recognition in the public, transport times to hospital and an efficient stroke triage in the hospital.

Farbu E, Kurz KD, Kurz MW. Ischemic stroke – novel therapeutic strategies. Acta Neurol Scand: 2011: 124 (Suppl. 191): 28–37. © 2011 John Wiley & Sons A/S. Objectives – Treatment of acute, ischemic stroke has changed markedly during the last two decades. We review existing data for optimizing modern stroke care. Results – Implementation of stroke units, giving systematic treatment and observation to stroke patients, has lead to a significant reduction in death and dependency. Introduction of intravenous rt-PA (IVT) within 3 h for selected stroke patients and recent extension of the time window to 4.5 h improved the outcome even further. Still, one must consider that IVT has several limitations, such as a narrow time window and several contraindications, and the effect is modest, particularly in strokes with a large vessel occlusion. Recanalization of the occluded vessel is a major predictor for good outcome and should be set as a goal. Intra-arterial rt-PA (IAT) and the concept of bridging therapy (IVT prior to IAT or thrombectomy with a mechanical device) may improve recanalization rates and outcome. Randomized controlled trials (RCT) are available for IAT, but not for thrombectomy with devices, and we mostly have retrospective non-controlled data. The Merci- and Penumbra system are the most studied devices, for which recent studies report acceptable safety and efficacy. Conclusions – Sufficiently powered RCTs to evaluate the effect of thrombectomy with mechanical devices are warranted, but as the natural course of a large vessel stroke carries a devastating prognosis, a proactive recanalization approach is justified based on today’s knowledge.

Background Depression is common in dementia, with important clinical implications. Few studies of depression in dementia with Lewy bodies are available, and the results are inconsistent. Objective To examine the frequency of depression and its characteristics and correlates, in people with mild dementia. Methods All referrals for patients with a first time diagnosis of dementia to geriatric and older psychiatry outpatient clinics in the counties of Rogaland and Hordaland in Western Norway from March 2005 to March 2007 were screened for the study. Participants and their caregivers underwent a comprehensive and standardised diagnostic and assessment procedure. The depression subitem of the neuropsychiatric inventory (NPId) and Montgomery and Asberg depression rating scale (MADRS) were used to estimate depression. Cut-off scores for any depression were 0/1 (NPId) and 6/7 (MADRS), and for clinically significant depression 3/4 and 14/15, respectively. Results Two hundered and twenty-three subjects with dementia participated, of whom 59 and 50% showed symptoms of depression assessed by NPI or MADRS, respectively, and 25 and 16% had clinically significant depression as measured by NPI and MADRS, respectively. Depression was more frequent in dementia with Lewy bodies (DLB) than in Alzheimer's disease (AD; p

Vefring H, Haugarvoll K, Tysnes O-B, Larsen JP, Kurz MW, for the Norwegian ParkWest Study group. The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study. Acta Neurol Scand: 2010: 122: 438–441. © 2010 John Wiley & Sons A/S. Objectives – Apolipoprotein E (APOE) gene alleles have been associated with various neurodegenerative disorders. However, there have been conflicting reports on associations between APOE alleles and Parkinson’s disease (PD) and age at onset in PD. There exist no data on APOE alleles in an unselected cohort of patients with incident PD. Patients and methods – To determine the role of APOE alleles in PD and age of onset in PD at time of diagnosis, 203 patients with incident PD and 187 healthy control subjects from Western and Southern Norway were investigated according to their APOE allele status. Results – No association was observed between any APOE alleles and susceptibility to PD or age at onset in PD. Conclusion – In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long-term follow-up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD.

Alzheimer's disease (AD) pathology is found in a considerable portion of patients with Parkinson's disease (PD), particularly those with early dementia (PDD). Altered cerebrospinal fluid (CSF) levels of amyloid-β (Aβ) and tau proteins have been found in PDD, with intermediate changes for Aβ42 in non-demented PD. The authors investigated whether AD-related CSF protein levels are altered and relate to neuropsychological performance in early, untreated PD.CSF concentrations of Aβ42, Aβ40 and Aβ38 were measured by electrochemiluminiscene and levels of total tau (T-tau) and phosphorylated tau (P-tau) by ELISA in 109 newly diagnosed, unmedicated, non-demented, community-based PD patients who had undergone comprehensive neuropsychological testing, and were compared with those of 36 age-matched normal controls and 20 subjects with mild AD.PD patients displayed significant reductions in Aβ42 (19%; p=0.009), Aβ40 (15.5%; p=0.008) and Aβ38 (23%; p=0.004) but not T-tau (p=0.816) or P-tau (p=0.531) compared with controls. CSF Aβ42 reductions in PD were less marked than in AD (53%; p=0.002). Sequential regression analyses demonstrated significant associations between CSF levels of Aβ42 (β=0.205; p=0.019), Aβ40 (β=0.378; p0.001) and Aβ38 (β=0.288; p=0.001) and memory impairment, but not executive-attentional or visuospatial dysfunction. Tau protein levels did not correlate with cognitive measures.CSF Aβ levels are altered in a subset of patients with early PD and relate to memory impairment. Our study suggests that alterations in Aβ protein metabolism may contribute to the heterogeneity in pattern and course of cognitive decline associated with PD. Longitudinal studies are needed to clarify the clinical significance of CSF Aβ peptides as prognostic biomarkers in PD.

Parkinson's disease (PD) is the second most common neurodegenerative illness after Alzheimer's disease (AD). Cognitive impairment and dementia are common features in PD and characterized by a wide range of cognitive deficits distinct from those seen in AD. Mild cognitive impairment occurs even early in PD and is associated with shorter time to dementia. The purpose of this review is to present recent findings on clinical aspects of dementia in PD and to elucidate underlying clinical and neurobiological risk factors.

Objectives – To examine the effect of early statin treatment on progression of arteriosclerosis in internal carotid arteries (ICA); to compare the progression of arteriosclerosis in ICA of patients treated with a statin to the progression seen in drug-naive patients. Patients and methods – We performed repetitive Doppler scans of 363 carotid arteries with ICA stenosis ≥40% in 254 patients over time. Information on statin therapy and other risk factors for stroke were correlated with the annual change in degree of ICA stenosis. Results – In statin-treated patients, 19% of ICA stenosis showed a progression while 74% showed a regression of stenosis. In statin-naive patients, 63% of stenotic arteries showed a progression, while a reduction could be observed in 28%. Decrease of ICA stenosis was most accentuated in patients with a mild stenosis and was independent of serum cholesterol levels. Conclusion – Treatment with statins already in early stages of ICA stenosis might delay the progression and even reverse the degree of stenosis.

Russian-Iranian satellite and missile cooperation has grown substantially over the past ten to fifteen years, and there are sufficient grounds to suggest that the scale of the two countries' collaboration in this field is much higher and more focused than many in the West are aware. At a time when both Moscow and Tehran are taking bolder measures to counter US and Western interests, growing trends of Russian support to Iran's satellite and missile program development can not be ignored. The following article correlates Russian direct and indirect assistance to the progressive development of Iran's satellite and missile program, addressing Iranian assets including the Mesbah, Sina-1, and Zohreh platforms as well as the Shahab-3,-4 and -5 missiles.