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.

CADASIL in Arabs: clinical and genetic findings.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs. METHODS: We studied three families from Saudi Arabia (Family A), Kuwait (Family B) and Yemen (Family C) with 19 individuals affected by CADASIL. RESULTS: The mean age of onset was 31 +/- 6 and the clinical presentation included stroke in 68%, subcortical dementia in 17% and asymptomatic leukoariosis detected by MRI in 15%. Migraine and depression were frequently associated, 38% and 68% respectively. The mean age of death was 56 +/- 11. All NOTCH3 exons were screened for mutations, which revealed the presence of previously reported mutations c.406C>T (p.Arg110>Cys) in two families (family A&B) and c.475C>T (p.Arg133>Cys) mutation in family C. CONCLUSION: CADASIL occurs in Arabs, with clinical phenotype and genotype similar to that in other ethnic groups.

Primary angiitis of the central nervous system at conventional angiography.

PURPOSE: To retrospectively determine the sensitivity and specificity of cerebral angiography for the diagnosis of primary angiitis of the central nervous system (CNS). MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was not required. Thirty-eight patients (13 men, 25 women; mean age, 55 years) had undergone cerebral angiography followed by cortical and leptomeningeal biopsy for possible primary angiitis of the CNS during an 8-year period. Angiography reports were reviewed by investigators blinded to the results of biopsy. Angiographic findings were categorized as typical for vasculitis, normal, or other. Sensitivity and specificity of cerebral angiography for the diagnosis of primary angiitis of the CNS were calculated. RESULTS: Fourteen patients had typical angiographic findings of vasculitis. None had primary angiitis of the CNS at brain biopsy (60% specificity). Specific pathologic diagnoses other than primary angiitis of the CNS were made in six patients. Findings of brain biopsy in the remaining eight patients were nondiagnostic. Repeat angiograms were obtained in three of the eight patients. One patient demonstrated interval improvement in multiple focal intracranial arterial stenoses and two demonstrated worsening. Primary angiitis of the CNS was found at biopsy in two of the remaining 24 patients (0% sensitivity). One of the two patients had slow filling of a single distal cortical artery, and the other patient had multiple regions of abnormally prolonged capillary blush. CONCLUSION: In this series, patients suspected of having primary angiitis of the CNS on the basis of clinical and angiographic findings did not have primary angiitis of the CNS at biopsy. Typical angiographic findings of primary angiitis of the CNS are often associated with other specific pathologic diagnoses, which emphasizes the importance of brain biopsy.

Prognosis of patients with suspected primary CNS angiitis and negative brain biopsy.

The authors retrospectively analyzed 25 patients who had a nondiagnostic brain biopsy for clinically suspected primary CNS angiitis to determine the effect of immunosuppressive therapy on 1-year outcome. Good outcome was seen in 6 of 10 treated patients and in 8 of 15 untreated patients (p= 0.93). These findings do not indicate that the addition of immunosuppressive therapy significantly enhances outcome of patients with clinically suspected primary angiitis of the CNS and a nondiagnostic brain biopsy.