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Introduction: Despite global progress in stroke care, challenges persist, especially in Low- and Middle-Income countries (LMIC). The Middle East and North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO) Stroke Program Accreditation Initiative aims to improve stroke care regionally., Material & Method: A 2022 survey assessed stroke unit readiness in the Middle East and North Africa (MENA) + region, revealing significant regional disparities in stroke care between high-income and low-income countries. Additionally, it demonstrated interest in the accreditation procedure and suggested that regional stroke program accreditation will improve stroke care for the involved centers., Conclusion: An accreditation program that is specifically tailored to the regional needs in the MENA + countries might be the solution. In this brief review, we will discuss potential challenges faced by such a program and we will put forward a well-defined 5-step accreditation process, beginning with a letter of intent, through processing the request and appointment of reviewers, the actual audit, the certification decisions, and culminating in granting a MIENA-SINO tier-specific certificate with recertification every 5 years., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objective/aim: To investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO)., Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios., Results: Four studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma., Conclusions: The presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact., Competing Interests: Declaration of Competing Interest The Authors declare that they did not receive any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Endovascular thrombectomy (EVT) is the standard treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Although > 70% of patients in the trials assessing EVT for AIS-LVO had successful recanalization, only a third ultimately achieved favorable outcomes. A "no-reflow" phenomenon due to distal microcirculation disruption might contribute to such suboptimal outcomes. Combining intra-arterial (IA) tissue plasminogen activator (tPA) and EVT to reduce the distal microthrombi burden was investigated in a few studies. We present a pooled-data meta-analysis of the existing evidence of this combinatorial treatment., Methods: We followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) recommendations. We aimed to include all original studies investigating EVT plus IA tPA in AIS-LVO patients. Using R software, we calculated pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI). A fixed-effects model was adopted to evaluate pooled data., Results: Five studies satisfied the inclusion criteria. Successful recanalization was comparable between the IA tPA and control groups at 82.9% and 82.32% respectively. The 90-day functional independence was similar between both groups (OR= 1.25; 95% CI= 0.92-1.70; P= 0.154). Symptomatic intracranial hemorrhage (sICH) was also comparable between both groups (OR= 0.66; 95% CI= 0.34-1.26; P= 0.304)., Conclusion: Our current meta-analysis does not show significant differences between EVT alone and EVT plus IA tPA in terms of functional independence or sICH. However, with the limited number of studies and included patients, more randomized controlled trials (RCTs) are needed to further investigate the benefits and safety of combined EVT and IA tPA., Competing Interests: Declaration of Competing Interest The Authors declare that they did not receive any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2023. Published by Elsevier Inc.)

Background and Purpose: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors., Methods: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted., Results: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates., (© 2022 European Academy of Neurology.)

Background: Acute stroke care is complex and requires multidisciplinary networking. There are insufficient data on stroke care in the Middle East and adjacent regions in Asia and Africa., Objective: Evaluate the state of readiness of stroke programs in the Middle East North Africa and surrounding regions (MENA+) to treat acute stroke., Method: Online questionnaire survey on the evaluation of stroke care across hospitals of MENA+ region between April 2021 and January 2022., Results: The survey was completed by 34/50 (68%) hospitals. The median population serviced by participating hospitals was 2 million. The median admission of patients with stroke/year was 600 (250-1,100). The median length of stay at the stroke units was 5 days. 34/34 (100%) of these hospitals have 24/7 CT head available. 17/34 (50%) have emergency guidelines for prehospital acute stroke care. Mechanical thrombectomy with/without IVT was available in 24/34 (70.6%). 51% was the median (IQR; 15-75%) of patients treated with IVT within 60 min from arrival. Thirty-five minutes were the median time to reverse warfarin-associated ICH., Conclusion: This is the first large study on the availability of resources for the management of acute stroke in the MENA+ region. We noted the disparity in stroke care between high-income and low-income countries. Concerted efforts are required to improve stroke care in low-income countries. Accreditation of stroke programs in the region will be helpful., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al Hashmi, Shuaib, Imam, Amr, Humaidan, Al Nidawi, Sarhan, Mustafa, Khalefa, Ramadan, Usman, Hokmabadi, Ghorbani, Nassir, Aladham, Salmeen, Kikano, Muda, Jose, Bulushi, Sajwani, Wasay, Bashir, Al Hazzani, Khoja, Alkadere, Osman, Hussein, Churojana, Hammami, Ozdemir, Giray, Gurkas, Hussain, Sallam and Mansour.)

Background: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke., Objective: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort., Methods: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020., Results: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Distal vessel occlusions represent about 25-40% of acute ischemic stroke (AIS), either as primary occlusion or secondary occlusion complicating mechanical thrombectomy (MT) for large vessel occlusion., Objective: Our aim was to evaluate safety and effectiveness of MT associated with the best medical treatment (BMT) in the management of AIS patients with distal vessel occlusion in comparison with the BMT alone., Methods: Retrospective analysis was conducted on AIS patients treated by MT+BMT for primary distal vessel occlusion between 2015 and 2020, and were compared with a historic cohort managed by BMT alone between 2006 and 2015 selected based on the same inclusion criteria. A secondary analysis was conducted using propensity score matching (PSM) including the following: NIHSS, age and treatment with intravenous thrombolysis (IVT) as covariates., Results: Of 650 patients screened, 44 patients with distal vessel occlusions treated by MT+BMT were selected and compared with 36 patients who received BMT alone. After PSM, 28 patients in each group were matched without significant difference. Good clinical outcome defined as mRS≤2 was achieved by 53.6% of the MT+BMT group and 57% of the BMT group (OR, 0.87; 95%CI, 0.3-2.4; p = 1.00). The mortality rate was comparable in both groups (7% vs. 10.7% in MT+BMT and BMT patients, respectively; OR=0.64; 95%CI, 0.1-4; p = 1.00). Symptomatic intracranial hemorrhage (ICH) was seen in only one patient treated by MT+BMT (3.6%)., Conclusion: Mechanical thrombectomy seems to be comparable with the best medical treatment regarding the effectiveness and safety in the management of patients with distal vessel occlusions., Competing Interests: Conflict of interest The other authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year., Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020)., Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths., Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Background: COVID-19 pandemic has negatively impacted stroke care services at multiple levels. There was a decline in acute stroke admissions. Fewer interventions have been performed. Increased "door-to-needle times and "door-to-groin puncture" during this pandemic. These factors combined have led to declining in the favoured outcomes of stroke patients' globally. Yet this pandemic permits an opportunity for higher preparedness for future pandemics., Objectives and Methods: This paper aims to shed light on the main lessons learned in the field of stroke care during the first wave of COVID-19 pandemic. Here we are presenting proposals and initiatives for better preparedness in future similar emergencies. These proposals are based primarily on literature review of COVID-19 publications, as well as the first-hand experience gained during the first wave at the regional level. In addition to the consensus and collective ride of stroke experts in the Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA+-SINO) and interaction and collaboration with international stroke specialists from the Stroke World Organization (WSO), European Stroke Organization (ESO) and stroke and COVID-19 papers authors., Conclusion: Stroke care is very complex, particularly in the initial hours after onset of symptoms. A successful outcome requires very close collaboration between clinical personnel from multiple specialties. Preparedness for future pandemics requires the improvement of care plans that allow for rapid assessment of stroke patients and ensuring that regular 'mock exercises' familiarize quintessential services that care for the stroke patients., (Copyright © 2021. Published by Elsevier B.V.)

Background: While mechanical thrombectomy (MT) is the standard of care for large vessel occlusion strokes, the optimal management of tandem occlusions (TO) remains uncertain. We aimed to determine the current practice patterns among stroke physicians involved in the treatment of TO during MT., Methods: We distributed an online survey to neurovascular practitioners (stroke neurologists, neurointerventionalists, neurosurgeons, and radiologists), members of professional societies. After 2 months the site was closed and data were extracted and analyzed. We divided respondents into acute stenting and delayed treatment groups and responses were compared between the two groups., Results: We received 220 responses from North America (48%), Latin America (28%), Asia (15%), Europe (5%), and Africa (4%). Preferred timing for cervical revascularization varied among respondents; 51% preferred treatment in a subsequent procedure during the same hospitalization whereas 39% preferred to treat during MT. Angioplasty and stenting (41%) was the preferred technique, followed by balloon angioplasty and local aspiration (38%). The risk of intracerebral hemorrhage was the most compelling reason for not stenting acutely (68%). There were no significant differences among practice characteristics and timing groups. Most practitioners (70%) agreed that there is equipoise regarding the optimal endovascular treatment of cervical lesions in TO; hence, 77% would participate in a randomized controlled trial., Conclusions: The PICASSO survey demonstrates multiple areas of uncertainty regarding the medical and endovascular management of TOs. Experts acknowledged the need for further evidence and their willingness to participate in a randomized controlled trial to evaluate the best treatment for the cervical TO lesion., Competing Interests: Competing interests: SO-G: Consultant for Medtronic and Stryker Neurovascular. OOZ: Consultant and speaker for Cerenovus, Stryker, Penumbra, and Medtronic. TNN: Research support from Medtronic. SOM: Consultant for Bayer, Medtronic, Pfizer, and Boehringer Ingelheim. FMA: Consultant for Balt USA, Medtronic, MicroVention, Penumbra, and Stryker. AHS: Consultant for Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA, Cerebrotech Medical Systems, Cerenovus, Corindus, Endostream Medical, Imperative Care, Integra LifeSciences Corp, Medtronic, MicroVention, Minnetronix Neuro, Northwest University–DSMB Chair for HEAT Trial, Penumbra, Q’Apel Medical, Rapid Medical, Rebound Therapeutics Corp (purchased by Integra LifeSciences Corp), Serenity Medical, Silk Road Medical, StimMed, Stryker, Three Rivers Medical, VasSol, W L Gore & Associates. JFF: Consultant for Stream Biomedical, Penumbra and Medtronic Neurovascular., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines., Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation., Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile., Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction., Competing Interests: Competing interests: TNN: PI CLEAR study (Medtronic). DCH: Stryker, Vesalio, Cerenovus consultant. AEH: consultant and speaker for Medtronic, Stryker, Microvention, Penumbra, Balt, Scientia, Genentech and GE Healthcare. PJ: Medtronic, Microvention, Balt, Cerenovus consultant. SO-G: Medtronic, Stryker consultant. DSL: Cerenovus, Genentech, Stryker, Medtronic consultant. TGJ: advisor/investor for Anaconda, Route92, FreeOx, and Blockade Medical; Medtronic grants, DAWN, AURORA PI (Stryker). WJM: consultant: Rebound Therapeutics, Viseon Imperative Care, Q’Apel, Stryker, Stream Biomedical, Spartan Micro; Investor: Cerebrotech, Endostream, Q’Apel, Viseon, Rebound, and Spartan Micro. RGN: Stryker; Cerenovus/Neuravi; Anaconda, Cerebrotech, Ceretrieve, Vesalio (Advisory Board); Imperative Care., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide., Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior)., Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers., Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions., Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Background: COVID-19 infection has been known to predispose patients to both arterial and venous thromboembolic events such as deep venous thrombosis, pulmonary embolism, myocardial infarction, and stroke. A few reports from the literature suggest that Cerebral Venous Sinus Thrombosis (CVSTs) may be a direct complication of COVID-19., Objective: To review the clinical and radiological presentation of COVID-19 positive patients diagnosed with CVST., Methods: This was a multicenter, cross-sectional, retrospective study of patients diagnosed with CVST and COVID-19 reviewed from March 1, 2020 to November 8, 2020. We evaluated their clinical presentations, risk factors, clinical management, and outcome. We reviewed all published cases of CVST in patients with COVID-19 infection from January 1, 2020 to November 13, 2020., Results: There were 8 patients diagnosed with CVST and COVID-19 during the study period at 7 out of 31 participating centers. Patients in our case series were mostly female (7/8, 87.5%). Most patients presented with non-specific symptoms such as headache (50%), fever (50%), and gastrointestinal symptoms (75%). Several patients presented with focal neurologic deficits (2/8, 25%) or decreased consciousness (2/8, 25%). D-dimer and inflammatory biomarkers were significantly elevated relative to reference ranges in patients with available laboratory data. The superior sagittal and transverse sinuses were the most common sites for acute CVST formation (6/8, 75%). Median time to onset of focal neurologic deficit from initial COVID-19 diagnosis was 3 days (interquartile range 0.75-3 days). Median time from onset of COVID-19 symptoms to CVST radiologic diagnosis was 11 days (interquartile range 6-16.75 days). Mortality was low in this cohort (1/8 or 12.5%)., Conclusions: Clinicians should consider the risk of acute CVST in patients positive for COVID-19, especially if neurological symptoms develop., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients., Aim: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease., Methods: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST)., Results: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19., Conclusions: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

Background and Purpose: There is little information on the acute cerebrovascular complications of coronavirus disease 2019 (COVID-19) in Egypt. The aim of this study was to estimate the proportion of acute cerebrovascular disease (CVD) among COVID-19 patients and evaluate their clinical and radiological characteristics in comparison with non-COVID-19 CVD. Materials and Methods: In a retrospective study, COVID-19 patients whom presented with CVD in Assiut and Aswan University Hospitals were compared with non-COVID-19, CVD patients, admitted to Qena University Hospital, prior to the pandemic. The following data were collected: clinical history and presentation, risk factors, comorbidities, brain imaging (MRI or CT), chest CT, and some laboratory investigations. Results: Fifty-five (12.5%) of the 439 patients with COVID-19 had acute CVD. Of them, 42 (9.6%) had ischemic stroke while 13 patients (2.9%) had hemorrhagic CVD. In the 250 cases of the non-COVID-19 group, 180 had ischemic stroke and 70 had hemorrhagic stroke. A large proportion of patients with COVID-19 who presented with ischemic stroke had large vessel occlusion (LVO), which was significantly higher than in non-COVID-19 patients with CVD (40 vs. 7.2%, P < 0.001). Comorbidities were recorded in 44 (80%) cases. In COVID-19 ischemic stroke patients, risk factors [hypertension and ischemic heart disease (IHD)] and comorbidities (hepatic and renal) were significantly higher than those in non-COVID-19 patients. In addition, 23.5% had hemorrhagic CVD, and six patients with LVO developed hemorrhagic transformation. Conclusion: Acute CVD among patients with COVID-19 was common in our study. LVO was the commonest. Hypertension, IHD, and anemia are the most common risk factors and could contribute to the worsening of clinical presentation. Comorbidities were common among patients with CVD, although a large number had elevated liver enzymes and creatinine that were partially due to COVID-19 infection itself. The current results begin to characterize the spectrum of CVD associated with COVID-19 in patients in Upper Egypt. Registration ID: The ID number of this study is IRB no: 17300470., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khedr, Soliman, Abo-Elfetof, Amin, Mansour, Aly, Zaki and Saber.)

Background: In developing countries like Egypt, the clinical workflow of stroke management is poorly established due to the lack of awareness of the stroke patients concerning their need of therapeutic intervention and the poor identification of facilities equipped to treat stroke. Hence, establishing a stroke system of care in developing countries that can efficiently and rapidly triage patients to the appropriate reperfusion therapy center is imperative to improving stroke management and outcomes. Aims: To evaluate a pilot experience in stroke hospital identification and expediting decision-making in AIS treatment through the Alexandria stroke network and Egyptian Stroke Network (ESN)-app. Methods: Between 2017 and 2019, seven hospitals registered themselves on the AS-Network as pilot hospitals. The ESN-application was used to detect stroke type, tele-connect stroke teams and hospitals, track triage of patients to equipped facility in real time, and streamline stroke workflow. The quality of and time required for stroke management were compared between 84 patients with acute ischemic stroke (AIS) whose treatment involved the ESN-app and 276 patients whose treatment did not. Results: During this pilot study, 360 AIS cases received reperfusion therapy, 84 of which were indicated by the ESN-app. The use of the application was associated with the significant drop in time metrics for the reperfusion AIS-patients (door-in-door-out time; 56 ± 34 min vs. 96 ± 45 min, door-to-groin puncture time; 50 ± 7 min vs. 120 ± 25 min, door-to-needle time; 55 ± 12 min vs. 78 ± 16 min with p < 0.0001). Its use was also associated with higher rates of excellent outcomes at the 90-day follow-up (without ESN-app vs. with ESN-app, 67.9 vs. 47.1%, p = 0.001) but no difference in 90-day mortality or symptomatic intracerebral hemorrhage (without ESN-app vs. with ESN-app, 9.5 vs. 11.2% and 4.8 vs. 5.1%, p > 0.05). Conclusion: Our pilot experience demonstrated that the use of the ESN-app expedited the stroke treatment workflow and facilitated tele-connection between registered stroke facilities. Additionally, its use might be associated with achieving higher rates of excellent outcomes at 90 days, where a larger scale study is needed for more confirmation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mansour, Ramadan, Elfatatry, Hamdi, Abudu, Hassan, Eldeeb, Marouf, Mogahed, Farouk, Abas, Hamed, Afify, Abdallah and Zaidat.)

Background and Purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology., Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20-6/16/20)., Results: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p

Background and Purpose: The effect of coronavirus disease 2019 (COVID-19) pandemic on performance of neuroendovascular procedures has not been quantified., Methods: We performed an audit of performance of neuroendovascular procedures at 18 institutions (seven countries) for two periods; January-April 2019 and 2020, to identify changes in various core procedures. We divided the region where the hospital was located based on the median value of total number of COVID-19 cases per 100,00 population-into high and low prevalent regions., Results: Between 2019 and 2020, there was a reduction in number of cerebral angiograms (30.9% reduction), mechanical thrombectomy (8% reduction), carotid artery stent placement for symptomatic (22.7% reduction) and asymptomatic (43.4% reduction) stenoses, intracranial angioplasty and/or stent placement (45% reduction), and endovascular treatment of unruptured intracranial aneurysms (44.6% reduction) and ruptured (22.9% reduction) and unruptured brain arteriovenous malformations (66.4% reduction). There was an increase in the treatment of ruptured intracranial aneurysms (10% increase) and other neuroendovascular procedures (34.9% increase). There was no relationship between procedural volume change and intuitional location in high or low COVID-19 prevalent regions. The procedural volume reduction was mainly observed in March-April 2020., Conclusions: We provided an international multicenter view of changes in neuroendovascular practices to better understand the gaps in provision of care and identify individual procedures, which are susceptible to change., (© 2020 American Society of Neuroimaging.)

COVID-19 pandemic has led to a change in the way we manage acute medical illnesses. This pandemic had a negative impact on stroke care worldwide. The World Stroke Organization (WSO) has raised concerns due to the lack of available care and compromised acute stroke services globally. The numbers of thrombolysis and thrombectomy therapies are declining. As well as, the rates and door-to treatment times for thrombolysis and thrombectomy therapies are increasing. The stroke units are being reallocated to serve COVID-19 patients, and stroke teams are being redeployed to COVID-19 centers. Covid 19 confirmed cases and deaths are rising day by day. This pandemic clearly threatened and threatening all stroke care achievements regionally. Managing stroke patients during this pandemic is even more challenging at our region. The Middle East and North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO) is the main stroke organization regionally. MENA-SINO urges the need to developing new strategies and recommendations for stroke care during this pandemic. This will require multiple channels of interventions and create a protective code stroke with fast triaging path. Developing and expanding the tele-stroke programs are urgently required. There is an urgent need for enhancing collaboration and cooperation between stroke expertise regionally and internationally. Integrating such measures will inevitably lead to an improvement and upgrading of the services to a satisfactory level., (Copyright © 2020. Published by Elsevier Inc.)

Background: Tandem basilar artery occlusions (tBAO) are defined as concomitant basilar artery and extracranial dominant vertebral artery occlusions. The prognosis of such tBAO treated by mechanical thrombectomy (MT) has been scantly reported. The purpose of our study was to compare the safety and effectiveness of MT for patients with tBAO compared to those with non-tandem basilar artery occlusions (ntBAO)., Patients and Methods: Retrospective analysis of a database of patients who underwent MT at two academic centres. All patients treated for BAO were retrieved. Patients with tBAO, defined as a concomitant BAO and extracranial vertebral artery (VA) occlusion or severe stenosis ≥70% (V1 or proximal V2 segment) were compared with patients with ntBAO., Results: A total of 15 patients with tBAO and 74 patients with ntBAO were enrolled. Successful reperfusion (modified thrombolysis in cerebral infarction score ≥2b) was obtained in 73.3% versus 90.5% (OR = 0.29, 95%CI: 0.07-1.15), good clinical outcome (3-months modified Rankin scale ≤2) was reached by 26.7% versus 32.4% (OR = 0.76; 95% CI: 0.24-2.63) and mortality at 3-months was 46.7% versus 31% (OR = 1.94; 95%CI: 0.63-6) of patients with tBAO versus ntBAO, respectively. Two patients (13.3%) with tBAO and three (4%) with ntBAO had symptomatic intracranial haemorrhage (OR = 3.64; 95% CI: 0.55-24)., Conclusion: Mechanical thrombectomy for patients with tandem basilar artery occlusion tends to be associated with lower rates of successful reperfusion and good clinical outcome, and higher rate of mortality. Larger multicentre studies are warranted to better precise the proper selection and management of such patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The novel coronavirus (COVID-19) global pandemic is associated with an increased incidence of acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO). The treatment of these patients poses unique and significant challenges to health care providers requiring changes in existing protocols., Case Presentation: A 54-year-old COVID-19 positive patient developed sudden onset left hemiparesis secondary to an acute right middle cerebral artery occlusion (National Institutes of Health Stroke Scale (NIHSS) score = 11). Mechanical thrombectomy (MT) was performed under a new protocol specifically designed to maximize protective measures for the team involved in the care of the patient. Mechanical Thrombectomy was performed successfully under general anesthesia resulting in TICI 3 recanalization. With regards to time metrics, time from door to reperfusion was 60 mins. The 24-h NIHSS score decreased to 2. Patient was discharged after 19 days after improvement of her pulmonary status with modified Rankin Scale = 1., Conclusion: Patients infected by COVID-19 can develop LVO that is multifactorial in etiology. Mechanical thrombectomy in a COVID-19 confirmed patient presenting with AIS due to LVO is feasible with current mechanical thrombectomy devices. A change in stroke workflow and protocols is now necessary in order to deliver the appropriate life-saving therapy for COVID-19 positive patients while protecting medical providers.

Background: Automated ASPECTS has the potential of reducing interobserver variability in the determination of early ischemic changes. We aimed to assess the performance of an automated ASPECTS vs. ASPECTS interpreted for sent CT images on WhatsApp and to correlate these results with the outcome. Materials and Methods: Patients with anterior circulation stroke who had baseline NCCT and underwent successful IV-thrombolysis were included. NCCT-ASPECTS was assessed by two neuroradiologists, and discrepancies were resolved by agreement. Two groups of patients were included; group 1, where treatment was decided after an automated ASPECTS interpretation that was provided by RAPID software, and group 2, where patients received IV-tPA after an assessment of CT images sent on WhatsApp. Results: A total of 122 patients were included: 36 in group 1 and 86 in group 2. In group 2, the interobserver agreement for NCCT ASPECTS was moderate (κ = 0.36), as was the dichotomized data (κ = 0.44). IOA, however, improved (to κ = 0.57 and κ = 0.64) when the same CT images were interpreted on a workstation. In group 1, Automated ASPECTS showed excellent agreement (κ = 0.80) with agreement reads for workstation images. There were significantly ( P < 0.001) increased odds of functional independence and fewer hemorrhagic complications with thrombolyzed patients in group 1. Conclusions: Automated ASPECTS provided by the RAPID@IschemaView ASPECTS performs at a level equal to the agreement read of expert neuroradiologists, and this performance was severely degraded when WhatsApp captured CT images used for ASPECTS assessment. In our study, we found that automated ASPECTS might predict outcomes after IV thrombolysis., (Copyright © 2020 Mansour, Ramadan, Abdo, Hamdi, Eldeeb, Marouf, Elsalamawy, Elfatatry, Elnekidy and Reda.)

Background: Several patient and disease characteristics are thought to influence DBS outcomes; however, most previous studies have focused on long-term outcomes with only a few addressing immediate postoperative course., Objective: To evaluate predictors of immediate outcomes (postoperative confusion and length of postoperative hospitalization) following deep brain stimulation surgery (DBS) in Parkinson disease (PD) patients., Methods: We conducted a retrospective study of PD patients who underwent DBS at our institution from 2006 to 2011. We computed the proportion of patients with postoperative confusion and those with postoperative hospitalization longer than 2 d. To look for associations, Fisher's exact tests were used for categorical predictors and logistic regression for continuous predictors., Results: We identified 130 patients [71% male, mean age: 63 ± 9.1, mean PD duration: 10.7 ± 5.1]. There were 7 cases of postoperative confusion and 19 of prolonged postoperative hospitalization. Of the 48 patients with tremors, none had postoperative confusion, whereas 10.1% of patients without tremors had confusion (P = .0425). Also, 10.2% of patients with preoperative falls/balance-dysfunction had postoperative confusion, whereas only 1.6% of patients without falls/balance-dysfunction had postoperative confusion (P = .0575). For every one-unit increase in score on the preoperative on-UPDRS III/MDS-UPDRS III score, the odds of having postoperative confusion increased by 10% (P = .0420). The following factors were noninfluential: age, disease duration, dyskinesia, gait freezing, preoperative levodopa-equivalent dose, number of intraoperative microelectrode passes, and laterality/side of surgery., Conclusion: Absence of tremors and higher preoperative UPDRS III predicted postoperative confusion after DBS in PD patients. Clinicians' awareness of these predictors can guide their decision making regarding patient selection and surgical planning., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: Several mechanical thrombectomy (MT) devices have been designed with the goal of improving the recanalization rates of major intracranial artery occlusions., Objective: In this single-center experience, we analyzed the acute ischemic stroke (AIS) treatment with Primary MT; safety and efficacy and clinical results in our patients with large vessel occlusion (LVO)., Methods: During a five-year period (from September 2011 to July 2016), out of 996 patients who presented to our center with a diagnosis of AIS, 113 (11.4%) patients (55 men and 58 women) underwent primary mechanical recanalization within three hours from onset of signs and symptoms for anterior and 12 hours for posterior circulation (with computer tomography angiography/perfusion ELVO). Successful recanalization (thrombolysis in cerebral infarction 2b-3), good outcome (modified Rankin scale score 0-2) and overall mortality rate, and symptomatic intracranial hemorrhage [sICH: parenchymal hematoma Type 1 or Type 2; National Institutes of Health Stroke Scale (NIHSS) score increment ≥4 points] were prospectively assessed., Results: The mean age of the patients was 62 ± 11.73 years, with a baseline mean admission NIHSS score of 16.7 ± 3.2. The mean time from onset to puncture (time to treatment) was 208.55 ± 53.49. Successful recanalization was achieved in 104 (92%) cases. Good outcome was observed in 89 (78.8%) patients, and mortality was 11.5% ( n = 13). sICH occurred in five (4.4%) patients., Conclusion: MT, within the first 4.5 hours, as primary treatment of acute LVO stroke provides high rate of recanalization and favorable clinical outcomes with low procedural complications.

Background: This article reports our experience regarding in-stent restenosis in the carotid arteries with special focus was given to angiographic morphology and clinical predictors of in-stent restenosis., Methods: Between July 2008 and August 2011, 245 carotid angioplasty and stenting procedures were performed in 243 patients (172 men and 71 women). Stenting for de novo stenoses was performed in 214 (87.3%) carotid arteries, and 31 (12.7%) vessels were treated because of postsurgical restenosis. Symptomatic lesions were detected in 187 patients (76.3%). Angiography confirmed any significant recurrent lesion detected on the ultrasound scan. Symptomatic or significant (70%) recurrent lesions detected on the ultrasound scan were an indication for retreatment., Results: During the follow-up period of 821 days (range: 62-1750 days), there were 10 deaths, all non-procedure related. Stent restenosis was defined as greater than 30% narrowing of the vessel lumen diameter and could be detected in 35 (14.3%) patients. Retreatment was indicated in 16 (6.5%) patients. Three types of restenosis were differentiated: tandem type restenosis (n = 5 of 35); "in-stent" restenosis (n = 18 of 35); and "end-stent" restenosis (n = 12 of 35). Interventions, either dilation alone (n = 12) or dilation with restenting (n = 4) for restenosis, were performed with 1 procedure-related dysphasia that resolved in 30 days. Female gender, hypercholesterolemia, peripheral vascular disease (PVD), initial stenosis, and surgical graft were predictors of target lesion revascularization., Conclusions: In our cohort, history of surgical endarterectomy, female gender, hypercholesterolemia, PVD, and initial stenosis were predictors of in-stent restenosis. Three types of restenosis were identified in our cohort., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: The primary objective was to evaluate predictors of quality of life (QOL) and functional outcomes following deep brain stimulation (DBS) in Parkinson's disease (PD) patients. The secondary objective was to identify predictors of global improvement., Methods: PD patients who underwent DBS at our Center from 2006 to 2011 were evaluated by chart review and email/phone survey. Postoperative UPDRS II and EQ-5D were analyzed using simple linear regression adjusting for preoperative score. For global outcomes, we utilized the Patient Global Impression of Change Scale (PGIS) and the Clinician Global Impression of Change Scale (CGIS)., Results: There were 130 patients in the dataset. Preoperative and postoperative UPDRS II and EQ-5D were available for 45 patients, PGIS for 67 patients, and CGIS for 116 patients. Patients with falls/postural instability had 6-month functional scores and 1-year QOL scores that were significantly worse than patients without falls/postural instability. For every 1-point increase in preoperative UPDRS III and for every 1-unit increase in body mass index (BMI), the 6-month functional scores significantly worsened. Patients with tremors, without dyskinesia, and without gait-freezing were more likely to have "much" or "very much" improved CGIS., Conclusions: Presence of postural instability, high BMI, and worse baseline motor scores were the greatest predictors of poorer functional and QOL outcomes after DBS.

Background: After the initial subarachnoid hemorrhage (SAH), rebleeding is the major cause of morbidity and poor outcome, which is maximal in the first 24 h. We supposed that the coiling of ruptured intracranial aneurysms within 24 h of SAH is related to the improved clinical outcome compared with coiling 24 h after aneurysmal SAH., Objective: We examined whether coiling ruptured aneurysms within 24 h of aneurysmal SAH is associated with better early 24 h and late 30 days outcome., Method: This prospective study was carried on 30 patients with aneurysmal SAH presenting to the Alexandria University Hospital and Insurance Main Hospital during the period from February 2013 to May 2014. They were divided into two groups: Group I (10 patients treated within 24 h of presentation) and Group II (20 patients treated after 24 h of presentation). Time interval from presentation to treatment were 78.60 and 10.60 h for subacute and hyperacute group, respectively. All patients were treated with endovascular coiling. Change between admission and immediate postoperative World Federation of Neurosurgeons classification Scale was measured for early outcome, while remote outcome was measured by modified Rankin Scale at 30 days follow-up., Results: There was a clinical improvement regarding early 24 h outcome (weighted by postoperative WFNS grade) and on late 30 days outcome (weighted by Modified Rankin Scale Score) in the group managed within 24 h versus who were treated after 24 h (P = 0.049 and P = 0.024, respectively). There was a significant decrease in the incidence of clinical rebleeding detected by postoperative computed tomography (CT) of the brain in patients undergoing aneurysm treatment within 24 h (P = 0.029)., Conclusion: The study affirms evidence that the management of ruptured intracranial aneurysms within 24 h of SAH is associated with better immediate and short-term clinical outcome.

Purpose: Against the background of the increasing dilemma in the scientific community regarding protected versus unprotected carotid artery stent (CAS) placement and the disputed points in interpreting the results of scientific studies as well as the difficulty in conducting such randomized controlled studies, this article gives a review of experiences with carotid stent placement without the use of protection devices., Methods: This series comprised 133 consecutive patients with 136 carotid stenoses of which 128 carotid arteries (94%) were either symptomatic (93 out of 136 = 68.4%) or had a greater than 70% stenosis (35 out of 136 = 25.7%) and 8 out of 136 were asymptomatic and had stenoses between 50% and 70%. Patients underwent neurologic and sonographic evaluation before the procedure and during follow-up (mean 18 months)., Results: Primary stent placement was carried out in 110 out of 136 lesions and predilatation was necessary before stent deployment in 26 lesions,. Neurologic periprocedural complications included 3 disabling and 1 non-disabling strokes. During the follow-up period there were 6 deaths all unrelated to the carotid disease and no major strokes. The degree of stenosis decreased from a mean of 81% to a mean of 12.3% immediately after the procedure, 22 patients were defined as restenosis of which 9 were symptomatic., Conclusions: Carotid stent placement without the use of distal protection devices was found to be a safe and effective procedure with a relatively low incidence of periprocedural complications.

Efforts have been done to recover proteins from waste liquors rich in protein in a soluble form. Cheese whey and animal bloods are by-products from the manufacture of cheese and meat. It contains a variety of proteins which can be reclaimed. The efficiency of protein precipitation from the sweet-cheese whey by the use of hydroxyethyl cellulose (HEC) was similar to that precipitated by the use of carboxymethyl cellulose (CMC). Both are greater than that precipitated by trichloro acetic acid. The same results of the efficiency of precipitation were attained when the plasma was precipitated. It was found that cheese-whey protein-HEC-complex and plasma protein-HEC-complex contain a large amount of essential amino acids. Electrophoretic separation of whey protein complex showed that beta-Lactoglobulin forms the major fraction while in case of plasma protein complex albumin forms the major fraction. The fractionation patterns of different complexes with HEC, CMC or TCA gave the same components and about the same ratio. It appears from these results that HEC-protein complexes are preferable than CMC-protein complexes or proteins precipitated by TCA. Chemical analysis of whey protein complexes revealed that lactose content of whey protein-HEC-complex was higher than that of CMC-complex or protein precipitated by TCA. Elemental analysis of protein complexes showed that the level of sodium, phosphorus, and potassium was increased while that of copper or zinc decreased. Cellulose derivative protein complexes showed no significant effects on the liver or kidney function of albino rat and these results indicted that no toxic effect was observed from the uses of these protein complexes in feeding.