Background:Reperfusion treatments with intravenous thrombolysis and endovascular thrombectomy after acute ischemic stroke (AIS) can improve patients' outcomes significantly. Yet, a substantial portion of patients miss the opportunity to receive reperfusion treatments. In this study, we aimed to assess the role of intravenous tirofiban in this specific population. Methods:A search was performed in Embase, Cochrane Central Register of Controlled Trials, Medline, and Web of Science databases from inception until August 2024. The random-effects model was used to calculate odds ratios (ORs) with their corresponding 95% confidence intervals (CIs). Efficacy endpoints included excellent (modified Rankin scale of 0-1) and good (modified Rankin scale of 0-2) functional outcomes at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH), any ICH, and 90-day mortality. Results:Four randomized clinical trials, including a total of 1,199 patients, were included. Of these, 599 patients (50%) received tirofiban. The meta-analysis demonstrated that tirofiban was associated with significantly higher rates of both excellent (OR 1.63 [95% CI, 1.24-2.13]; I2 = 0) and good (OR 1.65 [95% CI, 1.19-2.29]; I2 = 0) functional outcomes at 90 days. No significant differences were observed in sICH, any ICH, or 90-days mortality. Conclusion:Treatment with intravenous tirofiban can be beneficial without increased risk in patients with AIS who are not eligible for reperfusion treatment. Further studies are still needed to validate the generalizability of these findings. Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/view/CRD42024590097, CRD42024590097.

BACKGROUND:The ethics committee has the responsibility to comply with the rules and guidelines regarding oversight of all human research activities, particularly when the research study involves vulnerable people. It also has the role of educating researchers on ethical issues, scientific truthfulness, preventing misconduct and conflicts of interest. In our study we evaluate and benchmark the function of the local ethical committees across the country from the researchers point-of-view. METHODS:We employed an online IRB-RAT survey to measure perspectives of investigators towards IRB functions dealing with fairness issues, services, bias, and competences and upholding the rights of the human participants. Two responses were recorded: first shows how important an IRB function is for the investigator in his work, second shows how researchers rate their IRBs in being descriptive in that specific function. The difference of these two scores represent the outcome. RESULTS:We had 179 participants, 166(94%) researchers/research coordinators, and 13(7.2%) IRB members, 94 (53%) participants had been working in the research field for more than 11 years, and the majority 163(90%) revealed that they had IRB contact. The largest gap between actual rating and ideal was observed for the item "An IRB that requires that its chair be an experienced investigator" with a score difference of 1.53. In contrast, the smallest score difference was for the item "Considering the protection of human participants," which had a score of 0.51. CONCLUSION:According's to researchers point of view; IRBs respect researchers, view human protections as a primary role, do not allow personal bias, maintain accurate records and take timely action whenever misconduct is reported. Further collaborations are needed to enhance IRB performance and to engage researchers in more productive communication with their IRBs.

Methotrexate (MTX) is potent chemotherapeutic agent, often administered intrathecally to treat or prevent central nervous system involvement in lymphomas and leukemias, particularly T-cell lymphoblastic leukemia (T-LBL). MTX has been linked to adverse neurologic effects that mimic acute stroke, including facial drooping, hemiplegia, impaired consciousness, and seizures, as well as changes on imaging-known as MTX-induced leukoencephalopathy (LE). We report a case of a 17-year-old male diagnosed with T-LBL, who had been receiving MTX chemotherapy for 4 months. After receiving his fourth dose of MTX, he presented to the emergency department with fever, facial drooping, and acute left-sided weakness. Brain magnetic resonance imaging (MRI) revealed bilateral deep white matter T2 hyperintense foci, increased on the right, with associated diffusion restriction in the right centrum semiovale-consistent with MTX-induced LE. After his symptoms resolved, he was discharged on leucovorin. Six months afterward, he was rechallenged with MTX and developed recurrence of symptoms. Repeat MRI showed well-defined T2/FLAIR hyperintensities in the right centrum semiovale without corresponding diffusion restriction. The left centrum semiovale hyperintensity became less conspicuous in comparison to the previous MRI study. We report a rare case of recurrence of LE after MTX rechallenge and discuss mechanisms, best imaging modalities, and possible treatment options for MTX-induced LE. Given the ominous presentation of MTX-induced LE, we urge clinicians to maintain a high index of suspicion for this condition. Further research is necessary to understand why only certain patients develop recurrence of LE after subsequent doses of MTX.

Institutional review boards (IRBs) are formally designated to review, approve, and monitor biomedical research. They are responsible for ensuring that researchers comply with the ethical guidelines concerning human research participants. Given that IRBs might face different obstacles that cause delays in their processes or conflicts with investigators, this study aims to report the functions, roles, resources, and review process of IRBs in Saudi Arabia. This was a cross-sectional self-reported survey conducted from March 2021 to March 2022. The survey was sent to 53 IRB chairpersons and the administration directors (or secretary) across the country through email after receiving verbal consent. The validated survey consisted of eight aspects: (a) organizational aspects, (b) membership and educational training, (c) submission arrangements and materials, (d) minutes, (e) review procedures, (f) communicating a decision, (g) continuing review, and (h) research ethics committee (REC) resources. A total of 200 points indicated optimal IRB functions. Twenty-six IRBs across Saudi Arabia responded to the survey. Overall, the IRBs in this study scored a total of 150/200 of the points on the self-assessment tool. Relatively newer IRBs (established less than ten years ago) conducted meetings at least once in a month, had annual funding, had more balanced gender representation, tended to score higher than older IRBs. The organizational aspect score was the lowest among all items in the survey (14.3 score difference, p-value < 0.01). The average turnaround time for expedited research from proposal submission to final decision was 7 days, while it was 20.5 days for the full committee review. Saudi IRBs performed generally well. However, there is room for focused improvement with respect to extra resources and organizational issues that require closer evaluation and guidance from the regulatory bodies.

Numerous autoantibodies are implicated in the pathogenesis of autoimmune epilepsy. In the past decade, many case series reported the association of glutamic acid decarboxylase 65 (GAD 65) antibodies with epilepsy. Conjoint presence of GAD 65 antibodies with antinuclear, anti-thyroid, and anti-parietal cell antibodies has often been demonstrated. However, concomitant elevated levels of GAD 65 and P/Q voltage gated calcium channel (VGCC) antibodies is rare. We report a case of autoimmune epilepsy with conjoint GAD 65 and P/Q VGCC antibodies in the absence of malignancy. This report highlights a possible role of P/Q VGCC antibodies in the pathogenesis of autoimmune epilepsy.

Background: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease.Objective: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution.Method: We examined the clinical manifestations and immunological workup of these patients. Their DNA was also screened for causative mutation. Post transplantation, clinical and immunological data for the transplanted patient was also collected.Results: All patients had a severe course of the disease with rarely reported severe complications in HIES. One patient died with lymphoma while another died with progressive multifocal leukoencephalopathy (PML) due to a slow virus. All our patients had two novel mutations in the DOCK8 gene. One of these mutations was a novel pathogenic mutation and explains the severity of the disease (homozygous splice site mutation at position 5 after the end of exon 45), while the other mutation was mostly non-pathogenic. Hematopoietic stem cell transplantation (HSCT) was performed in the youngest patient with excellent engraftment and full reversibility of the clinical manifestations.Conclusion: We report 3 patients from a consanguineous family diagnosed with AR-HIES due to a novel pathogenic mutation in DOCK8 gene leading to fatal outcome in 2 patients and complete resolution of the clinical and immuno-logical features in the third patient by HSCT. (C) 2016 Elsevier Inc. All rights reserved.

Over the past 50 years, thrombolytic agents have been devised with the aim of recanalizing occluded coronary vessels, and later on, applied in the setting of acute ischemic stroke. Pharmacologic agents have generally targeted the plasminogen-plasmin transformation, facilitating the natural process of fibrinolysis. Newer agents with varying degrees of fibrin selectivity and pharmacologic half-life have influenced both recanalization rates and hemorrhagic complications, inside and outside the CNS. Intra-arterial (IA) administration of fibrinolytic agents increases delivery of the drug to the thrombus at a higher concentration with smaller quantities and therefore lowers systemic exposure. Mechanical thrombus disruption or extraction allows for drug delivery to a greater surface area of the thrombus. Delays associated with IA therapy may worsen the risk/benefit ratio of thrombolysis; therefore, combinations of IA-IV treatments have been studied. To date, there are no direct comparative trials to show that endovascular administration is more efficacious or carries a lower risk of hemorrhagic complications than IV tissue plasminogen activator.

Intravenous (IV) tissue plasminogen activator (t-PA) is an effective medication currently used to treat acute ischemic stroke within 3 hours of symptom onset in patients with an identifiable clinical deficit measured using the National Institutes of Health Stroke Scale (NIHSS). Some reports suggest that patients with milder acute ischemic stroke may improve spontaneously and may not benefit additionally from IV thrombolysis. The objective of this retrospective study was to assess the outcomes of patients at our stroke center who received IV t-PA treatment for acute ischemic stroke, within 3 hours of symptom onset, outside the setting of a clinical trial and had a NIHSS score of less than or equal to 10 compared with historic control subjects. There were 52 patients who received IV t-PA for acute ischemic stroke. Of those, 31 (male 44% [n = 14]) had a NIHSS score of 10 or less (mean NIHSS score 6 +/- 2). The mean age was 61 +/- 14 years, the mean NIHSS score was 6 +/- 2, and the mean modified Rankin scale (mRS) score was 1.4 +/- 1.5. We identified 98 patients (male 74% [n = 73]) in the National Institute of Neurological Disorders and Stroke IV recombinant t-PA study placebo group. The mean age was 65 +/- 13 years, the mean NIHSS score was 7 +/- 2, and the mean mRS score was 2.5 +/- 1.7. Assuming equal variances, the mRS score at discharge, for the IV t-PA-treated group, demonstrated a better clinical outcome that was statistically significant (P < .009). This retrospective study demonstrates that administering IV t-PA to patients with a mild stroke, measuring 10 or less by the NIHSS, can lead to improved clinical outcome when compared with patients with similar NIHSS score who have not received similar treatment.

BACKGROUND:Cerebral vasospasm is commonly seen in subarachnoid hemorrhage. However the vasospasm in spontaneous intracerebral hemorrhage without subarachnoid extension has not been described.REPORT:We report a patient who developed intracerebral hemorrhage associated with cerebral vasospasm demonstrated by conventional angiography. The vasospasm involved the superior and inferior divisions of the middle cerebral artery on the side of intracerebral hemorrhage. The vasospasm resolved in six days as documented by a repeat angiography.CONCLUSION:Cerebral vasospasm can be rarely seen in patients with intracerebral hemorrhage. Further elaboration is required to understand the pathophysiology and subsequent impact on outcome in such patients.

BACKGROUND:Carotid blowout syndrome with pseudoaneurysm, a rapidly progressive pathology, may present emergently with massive oral hemorrhage. Use of an endograft prosthesis offers a treatment strategy with salvation of the carotid artery.CASE HISTORY:A 55 year old man with advanced squamous cell carcinoma of the head and neck presented with recurrent transoral hemorrhage, requiring endovascular treatment.TECHNICAL REPORT:Coil embolization was initially performed with little impact on the hemorrhage. A 7 x 40 mm Fluency® Plus covered stent (Bard Peripheral Vascular, Tempe, Arizona, USA) was placed and was supplemented by a second 8 x 40 mm Fluency Plus stent, with resulting cessation of active contrast extravasation.DISCUSSION:The risks and benefits of various treatment options of carotid pseudoaneurysm with blowout are discussed including the use or omission of antiplatelet and anticoagulant regimens, with reference to previously reported cases.CONCLUSION:Tandem, overlapping covered stent placement in the common carotid artery is feasible and offers a treatment option for carotid blowout syndrome. Risks of aggravation of hemorrhage versus long-term thromboembolic events without antiplatelet therapy must be considered in cases of active ongoing hemorrhage.

BACKGROUND AND PURPOSE: Arterial reocclusion and distal embolization are known complications of ischemic stroke intervention, impacting treatment strategies and device design. We sought to determine their rates of occurrence and effects on long-term outcomes during endovascular treatment of patients with acute ischemic stroke.MATERIALS AND METHODS: Retrospective analysis of data from 4 prospective acute stroke protocols was performed. Patients underwent the standard technique for parent vessel angiography followed by pharmacologic thrombolysis and/or sonographic thrombolysis and/or mechanical thrombus disruption. Certain patients also received systemic heparin or abciximab therapy. Demographic, clinical, and angiographic variables were assessed at onset, 24 hours, 1 week, and 1-3 months after the event. "Distal embolization" was defined qualitatively as appearance of an occlusion on a downstream vessel. "Arterial reocclusion" was defined as subsequent reocclusion of the target vessel after initial recanalization had been achieved.RESULTS: Arterial reocclusion occurred in 18% of these patients, whereas distal embolization occurred in 16% of the 91 patients treated in these protocols. Arterial reocclusion, but not distal embolization, was associated with a lower likelihood of favorable outcome at 1-3 months (P=.05; odds ratio, 3.9; 95% confidence interval, 0.01-0.98) after adjusting forage, initial National Institutes of Health Stroke Scale scores, sex, time to treatment, initial angiographic grade, symptomatic intracranial hemorrhage, and final recanalization.CONCLUSIONS: Arterial reocclusion and distal embolization occur in 16%-18% of patients with stroke undergoing endovascular intervention. Only arterial reocclusion is associated with poor long-term outcome. Prospective studies are needed to identify risk factors for their occurrence and possible preventive therapies.