Effects of a team Quality Improvement method in a national clinical audit programme of four clinical specialties in Ministry of Health hospitals in Saudi Arabia.

In 2018, the Ministry of Health (MoH) in Saudi Arabia developed a clinical excellence strategy. An objective was to reduce variation in clinical practices in MoH hospitals, particularly for conditions with high mortality in Saudi Arabia, by applying best practice clinical standards and using the clinical audit process to measure clinical practice. The strategy included working with multiprofessional teams in hospitals to implement improvements needed in clinical practice. To test the feasibility of carrying out national clinical audits in MoH hospitals, audits were carried out in 16 MoH hospitals on four clinical subjects-acute myocardial infarction, major trauma, sepsis, and stroke. Clinical expert groups, including Saudi clinicians and an international clinical expert, developed clinical care standards for the four conditions from analyses of international and Saudi clinical guidelines. The audits were designed with the expert groups. Multiprofessional teams were appointed to carry out the audits in designated MoH hospitals. Data collectors in each hospital were trained to collect data. Workshops were held with the teams on the clinical care standards and how data would be collected for the audits, and later, on the findings of data collection and how to use the improvement process to implement changes to improve compliance with the standards. After 4 months, data collection was repeated to determine if compliance with the clinical care standards had improved. Data collected from each hospital for both cycles of data collection were independently reliably tested. All designated hospitals participated in the audits, collecting and submitting data for two rounds of data collection and implementing improvement plans after the first round of data collection. All hospitals made substantial improvements in clinical practices. Of a total of 84 measures used to assess compliance with a total of 52 clinical care standards for the four clinical conditions, improvements were made by hospital teams in 58 (69.1%) measures. Improvements were statistically significant for 34 (40.5%) measures. The project demonstrated that well-designed and executed audits using evidence-based clinical care standards can result in substantial improvements in clinical practices in MoH hospitals in Saudi Arabia. Keys to success were the improvement methodology built into the audit process and the requirement for hospitals to appoint multiprofessional teams to carry out the audits. The approach adds to evidence on the effectiveness of clinical audits in achieving improvements in clinical quality and can be replicated in national audit programmes.

Endovascular thrombectomy for acute ischemic stroke in Saudi Arabia: A single-center experience.

PURPOSE: This study aimed to investigate the outcomes of endovascular thrombectomy-treated patients in King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: A retrospective cohort study of acute ischemic stroke patients treated with endovascular thrombectomy. Patients were included in the study between January 2015 and December 2022. Good outcomes were defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Multivariate logistic regression analysis was performed to identify the independent factors associated with good outcomes. RESULTS: During the study period, 369 patients with acute ischemic stroke (mean ± SD age, 61/- 15.1 yrs; 55.4 % male) underwent mechanical thrombectomy. Median National Institute of Health Stroke Scale (NIHSS) 15. Intravenous thrombolysis was administered to 34.5 % of the patients. Successful recanalization in the anterior circulation was achieved in 84.8 % of patients. Data from mRS performed after 90 days in the anterior circulation were available for 71.2 % of the patients. Of these, 41 % showed a good outcome, and the mortality rate was 22.4 %. The significant factors associated with good outcomes were age, NIHSS score, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and short arterial puncture to recanalization. CONCLUSION: The number of patients who underwent endovascular thrombectomy has increased over time. The treatment outcomes and mortality were comparable with those of previous endovascular thrombectomy registries despite the high prevalence of DM, lower ASPECT score, and prolonged onset-to-recanalization time.

Assessing the readiness of hospitals in Riyadh Province for efficient and timely stroke management: A pilot study.

OBJECTIVES: To assess the readiness of hospitals in Riyadh to establish acute stroke centers by following the Australian Clinical Guidelines for Stroke Management. METHODS: This study was a quantitative cross-sectional observational study conducted among hospitals in the central region of Saudi Arabia (Jan 2018 - April 2018). A self-administered questionnaire/survey tool was adapted from an Australian survey developed by the Stroke Foundation in Melbourne, Australia.The data were analyzed using SPSS version 21.0. Appropriate statistical tests (chi-square and Fisher's exact test) were used for bivariate analyses. RESULTS: A total of 3932 stroke patient visits were recorded in 37 hospitals in the central region of Saudi Arabia. The most common limitations of acute stroke services were that 25 (67.57%) of the hospitals had no stroke unit and 21 (56.76%) had inadequate clinical staff. Magnetic resonance imaging and computed tomography were available in 32 (86.49%) and 36 (97.30%) hospitals, respectively. Only two-thirds of hospitals 25 (67.57%) followed protocols for rapid Emergency Department (ED) triage. CONCLUSION: We found that most of our hospitals were not fully prepared to address acute stroke management in a manner that was reasonably consistent with international guidelines. We recommend raising the hospital's requirements a higher level to be in line with the stroke guidelines.

Management of acute ischemic stroke in patients with COVID-19 infection: Insights from an international panel.

OBJECTIVE: To present guidance for clinicians caring for adult patients with acuteischemic stroke with confirmed or suspected COVID-19 infection. METHODS: The summary was prepared after review of systematic literature reviews,reference to previously published stroke guidelines, personal files, and expert opinionby members from 18 countries. RESULTS: The document includes practice implications for evaluation of stroke patientswith caution for stroke team members to avoid COVID-19 exposure, during clinicalevaluation and conduction of imaging and laboratory procedures with specialconsiderations of intravenous thrombolysis and mechanical thrombectomy in strokepatients with suspected or confirmed COVID-19 infection. RESULTS: Conclusions-The summary is expected to guide clinicians caring for adult patientswith acute ischemic stroke who are suspected of, or confirmed, with COVID-19infection.

An Epidemiological Model for First Stroke in Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia has a young but ageing population, leading to concerns for planning for future growth in the number of strokes to provide necessary care. An understanding of the expected evolution of stroke incidence is therefore necessary to plan infrastructure changes. Our aim was to predict the number of first strokes occurring in Saudi Arabia over a 10-year period. METHODS: An epidemiological model was developed, using local mortality and population data to model changes in the population. Gender- and age-specific stroke rates were then applied to the population projections to estimate the number of first strokes occurring over a 10-year period. Stroke incidence data from a range of sources were applied to obtain a plausible range for the change in expected number of first strokes. RESULTS: The model predicted population growth of 12.8% over the 10-year period. Depending on the stroke incidence data applied, the number of first strokes occurring during this time was predicted to increase within the range 57%-67%. CONCLUSIONS: A growing and ageing population is expected to lead to a substantial increase in the number of first strokes occurring in Saudi Arabia in the coming decade. Our results suggest that stroke care services will need to be expanded to continue to ensure high quality care, and that strategies for stroke prevention will play an important role in reducing the overall burden. This type of analysis can be applied to other countries' stroke policy planning.

Workforce requirements for comprehensive ischaemic stroke care in a developing country: the case of Saudi Arabia.

BACKGROUND: Ischaemic stroke care requires a co-ordinated multi-disciplinary approach to optimise patient outcomes. Current care provision in Saudi Arabia is below international recommendations, and with increasing patient numbers, variable access to new therapies, and sub-optimal co-ordination of staff, the Kingdom's Ministry of Health has prioritised strategies to develop stroke care. Our objective was to use local epidemiological data to predict stroke incidence and to combine this with international staffing recommendations to estimate future staff requirements and their costs over a 10-year period. METHODS: We researched existing stroke services and staff availability within Saudi Arabia to establish current provision, undertook epidemiological modelling to predict stroke incidence, and used international staffing recommendations for acute and rehabilitation services to develop a care pathway to provide state-of-the-art stroke services. This information was used to determine the additional staff requirements, and their costs, across the Kingdom. RESULTS: Our research concluded that current staff numbers and services are inadequate to cope with the projected increase in the number of stroke cases. In order to provide acute and rehabilitation services which use the latest technologies, re-organisation of existing staff and services would be required, together with significant investment in new staff across several disciplines. An estimated additional 43.8 full-time equivalent stroke neurologists would be required, plus 53.5 full-time equivalent interventional neuroradiologists in addition to expansion of occupational therapy and psychology services. The total cost of additional staff over 10 years was estimated to be 862 390 778 Saudi Riyals ($229 970 874). CONCLUSIONS: Providing high-quality care for ischaemic stroke patients would involve significant investment in new staff in Saudi Arabia. Further research is required on the applicability of international staffing ratios to countries where there is a significant workforce gap. Nevertheless, this analysis provides a framework to inform stroke care planning and can be adapted to other regions or countries.

Medical teachers' perception towards simulation-based medical education: A multicenter study in Saudi Arabia.

OBJECTIVE: This study aims to evaluate the perception of medical teachers toward the integration of simulation-based medical education (SBME) in undergraduate curriculum and also identify contextual barriers faced by medical teachers. METHODS: This cross-sectional observational study included medical teachers from three universities. A questionnaire was used to report teachers' perception. RESULTS: SBME was perceived by medical teachers (basic sciences/clinical, respectively) as enjoyable (71.1%/75.4%), effective assessment tool to evaluate students' learning (60%/73.9%) and can improve learning outcome (88.8%/79.7%). Similarly, (91.1%/71%) of teachers think that simulation should be part of the curriculum and not stand alone one time activity. Teachers' training for SBME has created a significant difference in perception (p < 0.05). Lack of teachers' training, time, resources and the need to integrate in medical curriculum are major perceived barriers for effective SBME. CONCLUSION: Results highlight the positive perception and attitude of medical teachers toward the integration of SBME in undergraduate curriculum. Prior formal training of teachers created a different perception. Top perceived barriers for effective SBME include teachers' formal training supported with time and resources and the early integration into the curriculum. These critical challenges need to be addressed by medical schools in order to enhance the integration SBME in undergraduate curricula.

Stroke and high-risk TIA outcomes with reduction of treatment duration when treatment initiated in emergency rooms (SHORTER-study).

BACKGROUND: Following transient ischemic attack (TIA) and minor stroke, the risk of recurrent stroke can be significantly reduced with short-duration dual antiplatelet therapy (DAPT). We wish to investigate whether 10 days of DAPT is as effective as 21 days' treatment. STUDY DESIGN: This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA + clopidogrel) is non-inferior to 21 days of DAPT in patients with acute ischemic stroke (AIS) or high-risk TIA. In both groups, DAPT is started within 24 hours of symptom onset. This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size is 1932. OUTCOMES: Non-inferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intra-cranial and systemic hemorrhage. STUDY PERIOD: Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025. DISCUSSION: The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes.

Cerebral Venous Thrombosis With Topical Estrogen-Progesterone Use in a Young Heterosexual Male: A Case Report.

INTRODUCTION: Our report sheds light on the risk of topical hormonal use in relation to cerebral venous sinus thrombosis. We diagnosed our patient with cerebral venous thrombosis (CVT) using computed tomography venogram, then detailed history and examination were obtained, and thorough blood tests and imaging were done to exclude other causes of CVT like thrombophilias, infections, and malignancies. CASE REPORT: Our patient is a 37-year-old heterosexual male, presented with headache only. The computed tomography venogram showed extensive CVT in the right internal jugular vein, sigmoid, transverse, and straight cerebral venous; detailed history and investigations suggest that his use of crushed oral contraceptive pills mixed with water topically on the scalp is the most important predisposing factor. This patient was managed with anticoagulants and is being followed in the clinic. CONCLUSION: Oral hormonal use in contraceptives is a known risk factor for CVT. This case sheds light on the importance of topical hormonal use concerning CVT in females and males; it stresses the need for more studies in that area, as it is poorly studied.

Exploring the path less traveled: Distal radial access for diagnostic and interventional neuroradiology procedures.

BACKGROUND: Recently there is a trend for radial first which advocates radial artery access as the first choice to perform diagnostic and interventional neurovascular procedures. Although safer than the conventional common femoral artery access, it is associated with a high rate of radial artery occlusion. Distal radial artery access is recently proposed to avoid this complication. This study aims to assess the feasibility and safety of distal radial artery access across a wide range of interventional neurovascular procedures. MATERIALS AND METHODS: All Interventional neurovascular cases attempted via distal radial artery access from September 2019 till March 2021 were included in the study. Data regarding patient demographics, distal radial artery diameter, access site cannulation, size of the sheath, procedural details including success rate and complications were collected. RESULTS: During the study period, 102 patients underwent 114 procedures via the distal radial artery approach. The mean age of patients was 41.9 ± 15.2 years. Overall procedure success rate via DRA was 94.7% (108/114). 72 diagnostic cerebral angiograms and 36 interventional procedures were successfully completed while six procedures required switching to alternate access. CONCLUSION: Distal radial artery access is a safe and feasible option for diagnostic cerebral angiography and a wide range of neurovascular procedures.

The use of flat panel angioCT (DynaCT) for navigation through a deformed and fractured carotid stent.

Navigation through a previously deployed and deformed stent is a difficult interventional task. Inadvertent navigation through the struts of a stent can potentially lead to incomplete secondary stent extension and vessel occlusion. Better visualisation of the pathway through the stent can reduce the risks of the procedural complications and reduce the reluctance of the interventionalist to navigate through a previously deployed stent. We describe a technique of visualisation of the pathway navigated by a guidewire through a previously deployed deformed and fractured carotid stent by the use of DynaCT. Three-dimensional reconstruction of the stent/microwire allows excellent visualisation of the correct pathway of the microwire within the stent.

Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel.

BACKGROUND AND PURPOSE: On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection. METHODS: The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document. RESULTS: This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection. CONCLUSIONS: These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.

Cerebral venous thrombosis in Saudi Arabia. Clinical variables, response to treatment, and outcome.

OBJECTIVE: To investigate cerebral venous thrombosis (CVT) clinical presentations, risk factors, and response to treatment in Saudi Arabia. METHODS: Retrospective analysis of the King Fahad Medical City, Riyadh, acute stroke database from April 2005 through February 2008 revealed 22 patients with CVT. Hypercoagulable work-up and neuroimaging were performed. RESULTS: Sixteen patients were female (72.7%), and the median age was 35 years. Clinical presentations included: headache (77.3%), seizures (54.5%), focal neurological signs (54.5%), and decreased level of consciousness (50%). Over two-thirds (n=11; 69%) of female patients had a history of oral contraceptive use, which was the most common risk factor. Protein S deficiency (n=3), antiphospholipid antibody syndrome secondary to systemic lupus erythematosus (SLE) (n=1), rhinocerebral mucormycosis (n=1), leukemia (n=1), non-Hodgkin`s lymphoma (n=1), sepsis (n=1), and unknown (n=6) were causes. Affected areas included superior sagittal (n=13), transverse (n=16), sigmoid (n=14), straight (n=6), and cavernous sinus (n=1); internal cerebral vein (n=2); vein of Galen (n=3); cortical veins (n=10); and internal jugular vein (n=12). Two patients had quadriparesis, and 2 patients died. The remainder (n=18, 81.8%) improved. Bilateral hemorrhagic presentation or venous infarction, deep venous system thrombosis, and underlying malignancy had less favorable results. CONCLUSION: Presentations in our series were similar to those in other reports, although altered consciousness and seizures were more common. Cortical vein involvement was also higher than commonly reported. Oral contraceptive use was a primary risk factor in female patients. Outcomes were favorable in 81.8% of patients.

A national economic and clinical model for ischemic stroke care development in Saudi Arabia: A call for change.

BACKGROUND: Stroke is a significant burden in Saudi Arabia and the Saudi Ministry of Health's stroke committee has identified an urgent need to improve care. AIM: The purpose of this study was to undertake a health-economic analysis to quantify the impact of developing stroke care in the country. METHODS: An economic model was developed to assess the costs and clinical outcomes associated with an ischemic stroke care development program compared with current stroke care. Based on Saudi epidemiological data, cohorts of ischemic stroke patients enter the model each year for the first 10 years based on increasing incidence. Four treatment options were modeled including reperfusion and non-reperfusion treatments. The development scenario estimates the impact of gradually increasing uptake of more effective treatments over 10 years. Changes in the stroke care organization are considered along with resources required to increase capacity, allowing more patients to be admitted to stroke hospitals and access effective treatments. RESULTS: The stroke care development program is associated with an increase in functionally independent patients and a decrease in disabling strokes compared with current stroke care. Additionally, the development program is associated with estimated cost savings of $602 million over 15 years ($255 million direct costs, $348 million indirect costs). CONCLUSIONS: The model predicts that the stroke care development program is associated with improved patient outcomes and lower overall costs compared with the current stroke care program.

Stroke burden in Mexican Americans: the impact of mortality following stroke.

PURPOSE: To estimate ethnic-specific all-cause mortality risk following ischemic stroke and to compare mortality risk by ethnicity. METHODS: DATA from the Brain Attack Surveillance in Corpus Christi Project, a population-based stroke surveillance study, were used. Stroke cases between January 1, 2000 and December 31, 2002 were identified from emergency department (ED) and hospital sources (n = 1,234). Deaths for the same period were identified from the surveillance of stroke cases, the Texas Department of Health, the coroner, and the Social Security Death Index. Ethnic-specific all-cause cumulative mortality risk was estimated at 28 days and 36 months using Kaplan Meier analysis. Cox proportional hazards regression was used to compare mortality risk by ethnicity. RESULTS: Cumulative 28-day all-cause mortality risk for Mexican Americans (MAs) was 7.8% and for non-Hispanic whites (NHWs) was 13.5%. Cumulative 36-month all-cause mortality risk was 31.3% in MAs and 47.2% in NHWs. MAs had lower 28-day (RR = 0.58; 95% CI: 0.41, 0.84) and 36-month all-cause mortality risk (RR = 0.79, 95% CI: 0.64, 0.98) compared with NHWs, adjusted for confounders. CONCLUSIONS: Better survival after stroke in MAs is surprising considering their similar stroke subtype and severity compared with NHWs. Social or psychological factors, which may explain this difference, should be explored.

Is the benefit of early recanalization sustained at 3 months? A prospective cohort study.

BACKGROUND AND PURPOSE: Early arterial recanalization can lead to dramatic recovery (DR) during intravenous tissue plasminogen activator (tPA) therapy. However, it remains unclear whether this clinical recovery is sustained 3 months after stroke. METHODS: We studied consecutive patients treated with intravenous tPA (0.9 mg/kg within 3 hours) who had M1 or proximal M2 middle cerebral artery occlusion on pretreatment transcranial Doppler according to previously validated criteria. Patients were continuously monitored for 2 hours after tPA bolus to determine complete, partial, or no early recanalization with the Thrombolysis in Brain Ischemia (TIBI) flow grading system. A neurologist obtained the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores independently of transcranial Doppler results. DR was defined as a total NIHSS score of 0 to 3 points, and early recovery (ER) was defined improvement by > or =10 points at 2 hours after tPA bolus. Good long-term outcome was defined as an NIHSS score of 0 to 2 or an mRS score of 0 to 1 at 3 months. RESULTS: Fifty-four patients with proximal middle cerebral artery occlusion had a median prebolus NIHSS score of 16 (range, 6 to 28; 90% with > or =10 points). The tPA bolus was given at 130+/-32 minutes (median, 120 minutes; 57% treated within the first 2 hours). DR+ER was observed in 50% of patients with early complete recanalization (n=18), 17% with partial recanalization (n=18), and 0% with no early recanalization (n=18) (P=0.025). Overall, DR+ER was observed in 12 patients (22%), and 9 (75%) had good outcome at 3 months in terms of NIHSS (P=0.009) and mRS (P=0.006) scores compared with non-DR and non-ER patients. If early recanalization was complete, 50% of these patients had good outcome at 3 months, and 78% with DR+ER sustained early clinical benefit. If recanalization was partial, 44% had good long-term outcome, and 66% of patients with DR+ER sustained the benefit. If no early recanalization occurred, 22% had good long-term outcome despite the lack of DR within 2 hours of tPA bolus (P=0.046). Mortality was 11%, 11%, and 39% in patients with complete, partial, and no early recanalization, respectively (P=0.025). Reasons for not sustaining DR in patients with early recanalization were subsequent symptomatic intracranial hemorrhage and recurrent ischemic stroke. CONCLUSIONS: DR or ER after recanalization within 2 hours after tPA bolus was sustained at 3 months in most patients (75%) in our study. Complete or partial early recanalization leads to better outcome at 3 months after stroke. Fewer patients achieve good long-term outcome without early recanalization.

A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest.

BACKGROUND: Cardiac arrest causes devastating neurological morbidity and mortality. Mild/moderate hypothermia is neuroprotective after global cerebral ischemia. More rapid controlled attainment of the target temperature may increase efficacy. METHODS: We assessed the safety and feasibility of endovascular cooling in a single arm study of comatose patients who had been successfully resuscitated after cardiac arrest. Core temperature was reduced to a target of 33 degrees C for 24 h using a closed loop endovascular system placed in the inferior vena cava, followed by controlled rewarming. Primary outcomes were speed and accuracy of cooling, survival and GOS after 30 days. RESULTS: Thirteen patients were enrolled, six male, age 60 +/- 19 years. Time from cardiac arrest to return of spontaneous circulation was 14.3 min (range 5-32.5). It took 3h and 39 min (median 210 min, IQ 80-315) to reach 33 degrees C; cooling averaged 0.8 +/- 0.3 degrees C/h (range 0.22-1.12 degrees C/h). Temperature was tightly maintained for all patients averaging 32.7 +/- 0.5 degrees C. Rewarming lasted 18.3 +/- 5.9 h. Five patients (38%) had 30-day Glasgow Outcome Scores of 1-2. Four patients died, none related to the hypothermia procedure. No unanticipated or procedure-related adverse events occurred. CONCLUSION: In comatose survivors of cardiac arrest, hypothermia via endovascular methods is safe and feasible, and target temperatures can be achieved and controlled rapidly and precisely. More studies are needed to assess the efficacy of rapid endovascular hypothermia after cardiac arrest.

Proteasome Inhibitor Reduces Astrocytic iNOS Expression and Functional Deficit after Experimental Intracerebral Hemorrhage in Rats.

Intracerebral hemorrhage (ICH) is associated with perihematoma inflammation and edema. We have recently shown cell death and a robust activation of the proinflammatory transcription factor, nuclear factor-κB (NF-κB) in brain areas adjacent to the hematoma. Proteasome represents a key component necessary for the activation of NF-κB. The aim of our present study was to examine if selective proteasome inhibition with a clinically relevant agent, PS-519, might influence the ICH pathogenesis, and improve functional outcome. ICH was induced in Sprague-Dawley rats by the double blood injection method. PS-519 was administered intravenously 4 h and 15 min after induction of ICH. Behavioral testing was performed 3, 5, and 7 days later. The animals were sacrificed on day 7, and their brains were evaluated for hemorrhage size and inflammation using immunohistochemistry with antibody to various inflammatory markers. Treatment with PS-519 significantly (p < 0.05) reduced behavioral impairment post-ICH as determined by the footfault test. This effect was not due to difference in ICH volume. The improved functional status of PS-519 treated animals correlated positively (p < 0.01) with reduced expression of astroglial iNOS in areas adjacent to the hemorrhage 7 days post-ICH. No delayed changes in expression of OX-42 and ED-1 (microglia/macrophages marker), or vimentin (intermediate filament; marker of astroglia activation) were detected in animals treated with PS-519. This data suggests that modulation of proteasome-activated processes may represent a strategic target for treatment of ICH in humans.

Intracranial angioplasty and stent placement after stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis (SAMMPRIS) trial: present state and future considerations.

OBJECTIVE: The results of prematurely terminated stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis (SAMMPRIS) due to excessively high rate of stroke and death in patients randomized to intracranial stent placement is expected to affect the practice of endovascular therapy for intracranial atherosclerotic disease. The purpose of this report is to review the components of the designs and methods SAMMPRIS trial and to describe the influence of those components on the interpretation of trial results. METHODS: A critical review of the patient population included in SAMMPRIS is conducted with emphasis on "generalizability of results" and "bias due to cherry picking phenomenon." The technical aspects of endovascular treatment protocol consisting of intracranial angioplasty and stent placement using the Gateway balloon and Wingspan self-expanding nitinol stent and credentialing criteria of trial interventionalists are reviewed. The influence of each component is estimated based on previous literature including multicenter clinical trials reporting on intracranial angioplasty and stent placement. RESULTS: The inclusion criteria used in the trial ensured that patients with adverse clinical or angiographic characteristics were excluded. Self-expanding stent as the sole stent, technique of prestent angioplasty, periprocedural antiplatelet treatment, and intraprocedural anticoagulation are unlikely to adversely influence the results of intracranial stent placement. A more permissive policy toward primary angioplasty as an acceptable treatment option may have reduced the overall periprocedural complication rates by providing a safer option in technically challenging lesions. The expected impact of a more rigorous credentialing process on periprocedural stroke and/or death rate following intracranial stent placement in SAMMPRIS such as the one used in carotid revascularization endarterectomy versus stenting trial remains unknown. CONCLUSION: The need for developing new and effective treatments for patients with symptomatic intracranial stenosis cannot be undermined. The data support modification but not discontinuation of our approach to intracranial angioplasty and/or stent placement for intracranial stenosis. There are potential patients in whom angioplasty and/or stent placement might be the best approach, and a new trial with appropriate modifications in patient selection and design may be warranted.