Posterior reversible encephalopathy syndrome post stem cell transplantation in sickle cell disease: case series and literature review.

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression. Methods: This is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances. Results: During ten years follow-up (2011-2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions (p = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence (p = 0.006), size (p = 0.016) and number (p = 0.005) of CMBs. Conclusion: PRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.

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.

Diagnostic accuracy of large and medium vessel occlusions in acute stroke imaging by neurology residents and stroke fellows: A comparison of CT angiography alone and CT angiography with CT perfusion.

INTRODUCTION: Neurology senior residents and stroke fellows are first to clinically assess and interpret imaging studies of patients presenting to the emergency department with acute stroke. The aim of this study was to compare the diagnostic accuracy of brain CT angiography (CTA) with and without CT perfusion (CTP) between neurology senior residents and stroke fellows. METHODS: In this neuroimaging study, nine practitioners (four senior neurology residents (SNRs) and five stroke fellows (SFs)) clinically assessed and interpreted the imaging data of 50 cases (15 normal images, 21 large vessel occlusions (LVOs) and 14 medium vessel occlusions (MeVOs) in two sessions, 1 week apart in comparison to final diagnosis of experienced neuroradiologist and experienced stroke neurologist consensus. Interrater agreement of CTA alone and CTA with CTP was quantified using kappa statistics, sensitivity, specificity and overall accuracy. RESULTS: Overall, arterial occlusions were correctly identified in 221/315 (70.1%) with CTA alone and in 266/315 (84.4%) with CTA and CTP (p < 0.001). The sensitivity of overall arterial occlusions detection with CTA alone was 94.2% (95% CI: 90.8%-96.6%) while with addition of CTP was 98% (95% CI: 95.6%-99.3%), The specificity of CTA alone was 74.7% (95% CI: 67.2%-81.3%) which increased with CTP to 84.4% (95% CI: 77.7%-89.8%). The likelihood of correct identification with CTA alone was 156/189 (82.54%) for LVOs and 65/126 (51.59%) for MeVOs. This increased to 169/189 (89.42%; p = 0.054) for LVOs and 97/126 (76.98%; p < 0.001) for MeVOs when the CTA images with CTP were viewed. There was good overall interrater agreement between readers when using CTA alone (k 0.71, 95% CI, 0.62-0.80) and almost perfect (k 0.85, 95% CI, 0.76-0.94) when CTP was added to the image for interpretation. CTA and CTP had a significantly lower median interquartile range (IQR) interpretation time than CTA alone (114 [IQR, 103-120] s vs 156 [IQR, 133-160] s, p < 0.001). DISCUSSION: In cerebral arterial occlusions, the rate of LVO and MeVOs detections increases when adding CTP to CTA. The accuracy and time for diagnosing arterial occlusion can be significantly improved if CTP is added to CTA. As MeVOs are commonly missed by front-line neurology senior residents or stroke fellows, cases with significant deficits and no apparent arterial occlusions need to be reviewed with neuroradiological expertise.

Institutional review boards in Saudi Arabia: the first survey-based report on their functions and operations.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Recurrence of methotrexate-induced leukoencephalopathy after methotrexate rechallenge: A case report and literature review.

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.

Conjoint glutamic acid decarboxylase 65 and P/Q voltage gated calcium channel antibodies in autoimmune epilepsy: A case report.

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.

Novel mutation in DOCK8-HIES with severe phenotype and successful transplantation.

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 immunological features in the third patient by HSCT.

Advances in thrombolytics for treatment of acute ischemic stroke.

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.

Does mild deficit for patients with stroke justify the use of intravenous 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.

Cerebral vasospasm in intracerebral hemorrhage-case report.

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.

Covered stent graft for treatment of a pseudoaneurysm and carotid blowout syndrome.

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.

Feasibility of IA thrombolysis for acute ischemic stroke among anticoagulated patients.

BACKGROUND AND PURPOSE: Limited information exists regarding thrombolysis among anticoagulated acute stroke patients. We present data from three consecutive patients, on active warfarin therapy, treated with intra-arterial reteplase. CASES: All patients were screened for the presence of intracranial hemorrhage. Warfarin was reversed with fresh frozen plasma in all patients and cerebral angiography and intra-arterial administration of reteplase was performed. Computed tomographic scans were performed to detect any subsequent intracranial hemorrhage. Ages ranged from 58 to 79 years with initial National Institutes of Health Stroke Scale scores ranging from 12 to 17. Baseline international normalized ratios (INRs) were 1.99-2.25. None of the patients suffered from intracranial hemorrhage following thrombolysis, and two of the patients experienced early neurological improvement. CONCLUSION: Low dose, intra-arterial reteplase following acute reversal of elevated INR is feasible and may offer a potential treatment for patients suffering with acute ischemic stroke while receiving active warfarin treatment.

Angiographic analysis of intravascular thrombus volume in patients with acute ischemic stroke.

PURPOSE: To investigate the role that intravascular thrombus volume plays in mechanical thrombectomy and dose-titrated algorithms using pharmaceutical thrombolytic therapies. METHODS: The angiographic studies of 33 consecutive patients (19 women; mean age 66+/-11 years) who underwent endovascular treatment for acute ischemic stroke were reviewed. A double-injection technique was utilized that involved 2 catheters for simultaneous injection of contrast proximal and distal to the thrombus to delineate its boundaries. The thrombus volume was calculated using the formula for cylindrical objects after measuring its length and diameter. RESULTS: The volume of the 36 thrombi measured in the study group was 46+/-59 mm3. The mean length and diameter were 10+/-6 and 2+/-1 mm, respectively. The time between symptom onset and acquisition of angiographic images ranged from 167 to 589 minutes (mean 336+/-109). In a multivariate analysis, thrombus volume was not associated with any recanalization (odds ratio 2.4, 95% CI 0.02-191) after adjusting for initial occlusion grade, time between symptom onset and angiography, and previous intravenous use of thrombolytic agents. Volume capacities for retrieval devices to retain 50% and 75% of the thrombi were estimated as 29.2 mm3 and 55.3 mm3, respectively. CONCLUSION: The large variation in thrombi volume must be considered in designing retrieval devices to optimize their performance.

Management of recurrent cerebral arterial occlusion in a patient with cardiac decompensation.

We describe a woman with congestive heart failure who presented with acute cardiac decompensation followed by ischemic stroke. The management of the patient posed unique challenges for thrombolytic treatment (due to existing coagulopathy) and subsequent optimization of hemodynamic status. Issues related to rethrombosis and use of platelet glycoprotein IIB/IIIA inhibitors are also discussed.

Unusual causes of cerebral venous thrombosis.

Cerebral venous thrombosis is a relatively uncommon condition afflicting mostly young adults. Thrombosis of cerebral veins or sinuses results in variable and nonspecific clinical features, including headache, lethargy, motor or sensory deficits, seizures, neck stiffness and sometimes fever. A multitude of conditions have been attributed as risk factors for CVT. The more common conditions include hereditary thrombophilia, pregnancy and purperium, postoperative state, intracranial and local infections and the use of oral contraceptives. Frequently, the cause of CVT is multifactorial, and in less than twenty percent of cases no clear risk factor is identified. In this review, we have focused on relatively rare and unusual causes of cerebral venous thrombosis. Many of the conditions described have very few reported cases and the causal relationship is not well established.

Early and intermediate-term outcomes with drug-eluting stents in high-risk patients with symptomatic intracranial stenosis.

OBJECTIVE: To report the 1-month and intermediate-term results of treatment of symptomatic intracranial stenosis using drug-eluting stents. BACKGROUND: Patients with intracranial stenosis who are at high risk because of either high-grade stenosis or medication failure may have an annual risk of recurrent ischemic events in excess of 40%. Drug-eluting stents may reduce the rate of ischemic events in patients with a low restenosis rate. METHODS: We determined rates of technical success (defined as reduction of target lesion to stenosis <30%) and 1-month major stroke or death in patients with symptomatic intracranial stenosis (> or =70% and/or medication failure). Patients' clinical and follow-up information during a mean period of 14.3 +/- 7 months were obtained. Kaplan-Meier analysis was performed to determine the rate of major stroke-free survival during 12 months. RESULTS: There were 18 patients (mean age, 58 +/- 16 yr; 12 were men) treated with either a sirolimus-eluting stent (n = 14) or a paclitaxel-eluting stent (n = 4) for stenosis located in the: intracranial internal carotid artery (n = 6), proximal middle cerebral artery (n = 4), intracranial vertebral artery (n = 4), vertebrobasilar junction (n = 2), or basilar artery (n = 2). There was one major stroke and no death observed in the 1-month follow-up. At the 6-month follow-up examination, no major stroke or death was observed. Major stroke-free survival was 86% (+/-standard error of 9%) at 12 months after the procedure. One symptomatic angiographic restenosis was observed during the follow-up period. CONCLUSION: A low rate of major stroke or death was observed after treatment of symptomatic intracranial stenosis using drug-eluting stents in high-risk patients.

Carotid stent-supported angioplasty via radiobrachial route.

Endovascular stent-supported angioplasty is a treatment option for atherosclerotic disease of the cervical internal carotid artery in high-risk patients. The traditional transfemoral approach is not suitable for patients who suffer from common femoral artery or abdominal aorta atheropathy. We report a case of carotid stent deployment using the radial route in a 68-year-old man with type B aortic dissection, having severe right internal carotid artery origin stenosis, presenting with ipsilateral retinal ischemic events. Technical aspects of carotid stenting via the radial approach are described and the related literature is discussed.

Advances in thrombolytics and mechanical devices for treatment of acute ischemic stroke.

Stroke is a leading cause of death and disability. Recently, there have been advances in the treatment of acute ischemic stroke aimed at re-establishing blood flow to the affected area in an effort to save the ischemic penumbra surrounding the area of infarction. This is achieved by the use of thrombolytics intravenously or intra-arterially. The use of mechanical devices facilitates the function of pharmacological agents used in addition to minimizing the associated risks. In this review, we first discuss the therapeutic potentials and strategies employed in using different thrombolytics in management of acute ischemic stroke. Subsequently, we discuss the recent advances and therapeutic applications of mechanical devices in this field.

Endovascular treatment of subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a common and devastating form of stroke. A large number of patients with aSAH develop angiographic or clinical vasospasm responsible for high morbidity and mortality. Rapid advances in the field of interventional neurology and the development of minimally invasive techniques have resulted in expansion of potential therapeutic applications. Treatment of aSAH has benefited from this rapid advance in the field of endovascular therapies. In the first section of the review, we discuss the therapeutic options and techniques for embolizations of intracranial aneurysms. In the second section, we discuss evolving endovascular treatment methods employed to intervene in delayed complications of cerebral vasospasm in patients with aSAH.

Catheter-based aortography fails to identify aortic atherosclerotic lesions detected on transesophageal echocardiography.

BACKGROUND AND PURPOSE: Transesophageal echocardiography is used to detect the aortic arch pathology during diagnostic workup of ischemic stroke events. Conventional angiography is increasingly used in diagnosing and treating atherosclerotic vascular lesions in patients with ischemic stroke. Although catheter-based aortography can be performed with cerebral angiography, there is limited information about the utility of aortography in identifying atherosclerotic abnormalities of the aortic arch. METHODS: A retrospective chart review was performed to identify patients who underwent aortography as part of their angio-graphic study and transesophageal echocardiography. Both studies were reviewed independently in the absence of knowledge of the results of the other study. The findings of these aortograms were correlated with the findings of transesophageal echocardiography. RESULTS: A total of 34 patients underwent both aortography and echocardiography. Of a total of 34 trans esophageal echocardiograms, 29 showed abnormal findings in the aorta (85%) and 5 appeared normal (15%). These aortic abnormalities included mild to moderate atherosclerosis in 18 cases (52%), moderate to severe atherosclerosis in 4 cases (12%), and severe atherosclerosis in 7 cases (21%). None of these abnormalities were detected by aortography. No disease was visualized in the origin of the supraaortic arteries. CONCLUSIONS: Aortic arch atherosclerosis is common in patients with ischemic stroke; however, aortograms acquired during conventional angiography fail to identify abnormalities detected on transesophageal echocardiogram.