Retinal microvascular analysis using Fundus Fluorescein Angiography in Egyptian sickle cell disease patients

Background Sickle cell disease can affect retina of eye via vaso-occulsive changes that occur in micro-vessels of retina which could be analysed by using Fundus Fluorescein Angiography. Aim To analyze macular microvascular alternation in patients with SCD by Fundus Fluorescein Angiography (FFA) and to assess the role of potentially contributory Clinico-pathological factors including Trans-Cranial Doppler, genotypes, hydroxyurea, transfusion therapy and finally iron overload state on the development of macular alterations. Method This was across-sectional study which included 30 Sickle cell disease patients randomly recruited from the Paediatric Haematology clinic, children Hospital, Ain Shams University, Cairo, Egypt. Complete blood count (CBC), Trans-Cranial Doppler (TCD) and Fundus Fluorescein Angiography. Results In our study, there were 30 patients with mean age (14.1± 4.02), 5 patients had abnormal/conditional Trans-Cranial, 15 patients had Vaso-occlusive crises, 11 patients were on regular simple blood transfusion; all 30 studied sickle cell disease patients had normal Fundus Fluorescein Angiography and eye examination and only one patient hadabnormal visual acuity;A 29 years oldgirl who had five attacks of cerebral strokes last year, on regular simple blood transfusion and Hydroxyurea treatment with abnormal TCD and recurrent Vaso-occlusive crises in last two years, Although her vision is hand movement yet Fundus Fluorescein Angiography was normal. Conclusion we didn’t find any Retinal microvascular alternation in our studied SCD patients using Fundus Fluorescein Angiography, we related our results to the fact that our studied SCD patients were young and all our studied patients were on hydroxyurea therapy with fair compliance, further studies using large sample size are warranted in order to illustrate the utility of Fundus Fluorescein Angiography (FFA) as a tool for better detection of sickle retinopathy.

Effect of Progesterone Therapy In Traumatic Subarachinoid Haemorrhage On Clinical Outcome, Resistive Vascular Indices of Middle Cerebral Artery Transcranial Doppler And Thromboelastometry. A Promising Layout.

Rationale . Recent evidence questions for a safe approach to resuscitate population with traumatic sub-arachinoid hemorrhage (tSAH). Progesterone neuro-protective actions are a matter of debate among literatures. This was the epitome of the current research. Primary outcome was to investigate progesterone actions on cerebral blood flow velocimetry using trans-cranial doppler and on visco-elastic properties of the coagulation and fibrinolytic system by rotational thrombo-elastometry (ROTEM) scanning. Secondary outcome were tracking mortality rate and length of ICU stay. Methods. The current research was a prospective, randomized, double-blind, placebo controlled mono-centeric study. Three hundred thirty two (332) adult patients of both sexes aged 25–60 years, recruited with solo tSAH (no other intra- axial lesions) admitted to Minia university hospital, neuro-critical care floor one. Exclusion criteria included poly-trauma patients (accompanying bone fractures or surgical abdomen), Glasgow coma scale less than 8, red blood cell transfusion during the first 6 hours after admission, hematochrit value > 50%, history of deep venous thrombosis. Two groups were designed, Control group and Progesterone (PR) group. PR group received 100 mg (2ml) intramuscular seven days once daily from hospital admission, while Control group received intramuscular isotonic saline (2ml) daily for seven days as a placebo. Trans-cranial doppler was performed on admission, two days and seven days post-admission. ROTEM exploited on admission and seven days after admission.ResultsProgesterone ameliorated hyperfibrinolysis ( prolong LYS 30 min.) of ROTEM scanning but no other impact on other parameters. Progesterone statistically dampened resistive vascular indices namely pulsatality index (P value =0.001, 0.003) and resistive index (P value=0.001,0.003) but no effect on mean flow velocity of bilateral middle cerebral artery scanning, Progesterone also shortened ICU stay. Conclusions.Progesterone can offer neuronal protection in patients with tSAH by impeding over-fibrinolytic activation .Registration number. (NCT04426487) on clinical trial.gov.Date of registration. Eight of June 2020. Institutional review board. (625/4-2020).

The correlation between the preoperative measurement of estimated cerebral perfusion pressure and estimated intracranial pressure as obtained by trans cranial doppler with modified fisher grade as seen in computed tomography scan head in patients with acute sub arachnoid hemorrahage undergoing surgical clipping

Background: In Aneurysmal Sub Arachnoid haemorrhage, precise Cerebral Perfusion Pressure (CPP) and Intracranial Pressure (ICP) measurement can only be achieved by an invasive monitoring device. The study aimed at non-invasively estimating the preoperative values of CPP and ICP by use of validated formulae. These estimated flow velocities (estimated CPP or eCPP and estimated ICP or eICP) of the Middle Cerebral Artery were obtained by Trans Cranial Doppler ultrasound and comparing it with the preoperative CT Head Fisher Scale. In the Institute Rimed Digi-Lite Trans Cranial Doppler machine was used for research and Siemens (Somatom) 64 CT Scanner from GE (Signa) was used to perform CT scan of patients.Methods: It is a prospective, observational study which was studied between July 2017 and December 2018 in Post Graduate Institute of Medical Education and Research, Chandigarh, India. This study is a secondary analysis of a prospective observational study which was primarily designed to evaluate the neurological outcome related to the effect of estimated Intracranial Pressure and estimated Cerebral Perfusion Pressure as measured by Trans Cranial Doppler in patients with a SAH. A total of 100 patients were recruited in this study.Results: There was significant correlation between estimated CPP and Fisher Grading. There was no strong correlation between the modified Fisher Grade and estimated ICP.Conclusions: This study was able to give a statistically significant correlation between eCPP and Fisher Grading (p value- 0.047), as the Modified Fisher grading increased, so did the eCPP, this observation was unique, and it went against the hypothesis. However, no statistically significant co-relation was seen during comparison of eICP and Fisher Grading (p value- 0.069).

Plasma BDNF Levels Are Associated with Stroke in Children with SCD

Background: Cerebrovascular disease, particularly overt stroke, is one of the most critical clinical complications of sickle cell disease (SCD). Individual stroke risk for patients with SCD is assessed by measuring trans-cranial Doppler ultrasound (TCD) velocity. While TCD screening and resulting use of chronic blood transfusion therapy in patients with abnormal TCDs has reduced stroke incidence in patients with SCD from 11% to 1%, the test has significant limitations. It can only be performed on children old enough to remain still for the assessment, or young enough to have open bony windows; typically 2-16 years of age. Additionally the test has poor positive predictive value, causing patients to be placed on chronic transfusion therapy who would not have gone on to have a stroke. Hydroxyurea (HU) is replacing chronic transfusion therapy in many institutions for primary stroke prevention, but many sites initiate a "cooling off" period of transfusions prior to initiating HU, and transfusion therapy may be indicated for abnormal TCD velocities in patients already on HU. The pathophysiology of stroke in SCD patients is not completely understood, but vascular remodeling, abnormal cerebral blood flow, and vaso-occlusion all play a role. Plasma levels of Brain derived neurotrophic factor (BDNF), myeloperoxidase (MPO), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) have been shown to be associated with high trans-cranial Doppler ultrasound (TCD) velocity in children with SCD; but there is limited data on their potential association with stroke in this population. BDNF is a neurotropin that is responsive to hypoxia and promotes neurogenesis as well as playing a key role in the regulation of the cell survival pathway; myeloperoxidase (MPO) promotes vascular injury by oxygen radical generation, leukocyte/neutrophil recruitment, and oxidative stress; vascular cell adhesion molecule 1 (VCAM-1) is and endothelial adhesion molecule involved in the pathophysiology of vaso-occlusion in SCD through promoting RBC adhesion; and intercellular adhesion molecule 1 (ICAM-1) is expressed on endothelial and immune system cells and is thought to be a ligand for leukocyte adhesion. We hypothesized that BDNF, MPO, VCAM-1 and ICAM-1 may be involved in stroke in SCD, and may be potential biomarkers to be used to assess an individual with SCD's stroke risk in addition to TCD. Methods: We collected plasma samples from the peripheral blood of fifteen SCD patients (HbSS) at the time of either silent cerebral infarct (SCI) or stroke. Stroke (n=8) or SI was confirmed by MRI using diffusion imaging and T2 FLAIR. The cohort included 6 females and 9 males between the ages of 3 and 20 years. Plasma from fifteen age and gender matched control patients with HbSS but had normal MRIs and TCD velocities less than 170 m/s. We measured plasma levels of BDNF, MPO, VCAM-1 and ICAM-1 using antibody immobilized fluorescent beads (Millipore, Billerica, MA) and Luminex xMAP technology (Bio-Rad, Hercules, CA). Student's t-test was used to analyze the difference in plasma levels between the stroke and control groups. Results and Conclusions: BDNF levels were significantly higher in the stroke group than in the control group; 2978.2 ± 960.3 pg/ml compared to 2200.8 ± 758.4 pg/ml, p=0.005. Difference in MPO levels between the two groups approached significance; 36617.2 ± 14828.9 pg/ml compared to 29521.9 ± 7889.6 pg/ml, p=0.07. Difference in VCAM-1 levels also approached significance; 143997.0 ± 9963.8 pg/ml compared to 138126.9 ± 11902.0 pg/ml, p=0.08, but there was no significant difference in ICAM-1 levels. Only BDNF plasma levels positively correlated with the area and volume of the infarct, p=0.009. These results further support the assertion that BDNF is involved in the pathophysiology of cerebrovascular disease in SCD. It is possible that MPO and VCAM-1 may also play a role, and that a significant difference was not found due to sample size limitations. Plasma BDNF levels, and possibly MPO and VCAM-1 plasma levels, have potential as biomarkers for stroke risk to improve the positive predictive value of TCD velocities in patients with SCD, or to assess risk in patients unable to receive TCDs. Disclosures No relevant conflicts of interest to declare.

Hydroxyurea Therapy Prevents High Risk Trans-Cranial Doppler Development in Children with Sickle Cell Disorders

Annual evaluation by Trans-Cranial Doppler (TCD) of cerebral artery blood flow is useful for determining stroke risk in children with sickle cell disease. Since the publication of the Stroke Prevention Trial in Sickle Cell Anaemia (STOP) results in 2006 it has been standard practice at our centre to perform annual TCD imaging scans on all children with sickle cell disease to identify individuals with high risk features. Data from the STOP trial demonstrated that the incidence of stroke was reduced by 90% in children with high risk TCDs when they were managed on a regular transfusion programme. In more recent years, the use of hydroxyurea as a disease modifying therapy has increasingly become our practice, particularly so since the publication of the BABY-HUG trial data in 2014. Hydroxyurea has significantly altered the clinical course of sickle cell disease in children and prior to this era, 11% of patients would experience a stroke before the age of 20 years. In light of the changing management strategies for children with sickle cell disease, we reviewed the past 10 years TCD results from our patients. Annual TCD evaluation of cerebral artery blood flow was performed by radiologists and radiographers accredited to the Kings College national training programme. Scans were performed using Philips iU22 scanners with dedicated F5-1 transducers as per the UK National Screening protocol. Velocities were measured in the middle (MCA), anterior (ACA) and posterior cerebral arteries (PCA), internal carotid artery (ICA) and bifurcation on right and left sides (10 measurements per scan). The TCD service at our centre has had a positive external peer review. Over the past 10 years, 303 TCD imaging scans have been performed on 53 children aged 2-18 years. The number of abnormal, high-risk results (cerebral blood flow velocity (CBF-V) >200 cm/s) has been zero. 137 scans were performed in children prior to those individuals commencing hydroxyurea therapy, and the results of 3 scans were conditional, based on an increased CBF-V (171-200 cm/s) detected in 1 or more arteries. The other 168 scans were performed on children who were receiving hydroxyurea, of which 4 results were conditional. 49 of the 53 children have continuously had a normal TCD with no conditional or abnormal results. 4 children developed transient conditional TCD. The 3 conditional results recorded prior to commencing hydroxyurea therapy relate to 2 patients. One case in which a child with severe phenotype already on regular blood transfusions developed a conditional TCD which subsequently normalised without adjustment to their regular transfusion programme. Transfusions were then stopped and hydroxyurea commenced and this patient has since maintained normal TCD features (8 years follow up). The other 2 conditional scans relate to one patient where a conditional TCD developed in a young child not receiving any therapy. This feature normalised without treatment by the time of the following annual scan but subsequently reoccurred the following year. Hydroxyurea was commenced because of the second conditional TCD result, which then normalised and has remained normal (7 years follow up). The 4 conditional results that occurred in individuals receiving hydroxyurea relate to 2 patients. Both children developed conditional TCDs and the increased CBF-V persisted until their next annual scan. In both cases hydroxyurea was escalated to maximum tolerated dose following the second conditional TCD result. TCDs in both patients normalised by the time of their next annual scan and have remained normal since (6 years and 2 years follow up). Our hydroxyurea practice has resulted in not a single child being started on transfusion therapy from our TCD programme. Importantly, at the end of this observation period all 53 children have normal TCD features and no child is managed on a transfusion programme. In the era of high dose hydroxyurea therapy, our experience is that we have not seen any abnormal TCD results. We need to consider whether TCD remains relevant or whether alternative strategies to predict and prevent stroke need to be developed. Disclosures No relevant conflicts of interest to declare.