Brain Iron Content in Egyptian Patients with Sickle Cell Disease: Impact on Neurocognitive Functions

Background:Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment which may be due to iron overload in brain tissue or hemoglobin polymerization and endothelial dysfunction.Primary objectivewas measuring brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI in Egyptian adolescents and young adults with multi-transfused SCD in comparison to beta thalassemia major (BTM) and age- and sex-matched healthy controls.Secondary objectiveswere evaluating the impact of brain iron content on neurocognitive functions of SCD patients and its association with MRI assessment of liver iron concentration (LIC) and cardiac iron (myocardial T2*).Methods: 32 children and young adults with SCD (mean age: 15.3 ± 3.7, 19 males and 13 females), 15 BTM (mean age: 19.4 ± 4.3, 7 males and 8 females) and 11 healthy control age- and gender-matched were recruited. Thorough clinical assessment, hematological and serum ferritin were performed. Brain MRI study using multi-echo fast gradient echo sequence was performed only for 15 patients with SCD, 15 patients with BTM and 11 controls and brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. LIC and myocardial T2 were performed for; 15 with SCD and 15 with BTM. 32 SCD patients were examined for the neurocognitive functions; Wechsler IV Intelligence scale (verbal, perceptual, memory, processing and total IQ), Benton Visual Retention Test and Brief Psychiatric Rating Scale (BPRS).Results:For SCD patients their mean transfusion index was 174.70±63.98ml/kg/year and mean iron overload/day 0.30±0.12 mg/kg. 30 (93.8%) all SCD patients were on regular chelation therapy; 16 were on deferiprone and 16 were on combined chelation over last 5 years. Of those 32 SCD patients; 20 received concomitantly hydroxyurea therapy. Mean total IQ for SCD patients was 86.9±10.7; 68.9% had under- threshold <90 IQ and 27.5% had average (90-109) IQ. 12.5% of SCD patients had moderate to severe anxiety and 60.8% had of SCD patients had depression. No significant differences were found between SCD, BTM as regards LIC (p=0.102) No significant differences were found between SCD, BTM and control group in all regions of interests in brain MRI except that left thalamus R2* higher in BTM patients than both SCD and controls (p=0.032). R2* values of different regions of brain in relation with the studied parameters of SCD patients was not significant except that mean right caudate R2* was higher in female 17.4±0.8 than male 15.6±1.7 (p=0.044). The correlation coefficients showed no significant association between brain R2* and LIC or heart R2* values of SCD patients. There were positive correlation between left caudate R2* and both age and HbS%, negative correlation between transfusion index and right thalamus R2*, negative correlation between HbA% and left caudate R2* among SCD patients.Conclusion:Brain iron content in adolescents and young adults with SCD was not significantly different from either controls or BTM; SCD had high prevalence of neurocognitive dysfunction, which could not be explained by brain iron content or distribution. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Hidden Brain iron content in Sickle cell disease: Impact on Neurocognitive Functions

10.21203/rs.3.rs-399346/v1 ◽

2021 ◽

Author(s):

Mohsen Saleh ElAlfy ◽

Ahmed Samir Ibrahim ◽

Ghada Samir Ibrahim ◽

Hanaa Midhat Abdel Gader Hussein ◽

Hend Galal Eldeen Mohammed ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Brain Mri ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Brain Iron ◽

Cell Disease ◽

Neurocognitive Dysfunction ◽

Neurocognitive Functions

Abstract Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment. We aim to quantitatively measure cerebral tissue R2* to investigate the brain iron deposition in children and young adults with SCD in comparison to beta thalassemia major (BTM) and healthy controls and evaluate its impact on neurocognitive functions in patients with SCD. Thirty-two SCD, fifteen BTM and eleven controls were recruited. Multi-echo fast-gradient echo sequence brain MRI was performed and brain R2* values of both caudate and thalamic regions were calculated. SCD patients were examined for the neurocognitive functions. SCD had high iron overload 0.30±0.12 mg/kg/day. 68.9% of SCD had under- threshold IQ, 12.5% had moderate to severe anxiety and 60.8% had depression. There was no differences between SCD, BTM and controls in brain MRI except that left thalamus R2* higher in BTM than both SCD and controls (p=0.032). Mean right caudate R2* was higher in female than male (p=0.044). No significant association between brain R2* and LIC or heart R2* values in SCD. Left caudate R2* directly correlate with age and HbS%, negative correlate with HbA% while right thalamus R2* negatively correlate with transfusion index and among SCD patients. Conclusion: Neurocognitive dysfunction in SCD could not be explained solely by brain iron overload.

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Hidden brain iron content in sickle cell disease: impact on neurocognitive functions

European Journal of Pediatrics ◽

10.1007/s00431-021-04189-7 ◽

2021 ◽

Author(s):

Mohsen Saleh Elalfy ◽

Ahmed Samir Ibrahim ◽

Ghada Samir Ibrahim ◽

Hanaa Midhat Abdel Gader Hussein ◽

Hend Galal Eldeen Mohammed ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Iron Content ◽

Brain Iron ◽

Cell Disease ◽

Neurocognitive Functions ◽

Disease Impact

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Evaluation of brain iron content in Egyptian Patients with Sickle cell disease and its impact on Neurocognitive functions

QJM ◽

10.1093/qjmed/hcab113.026 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Mohsen Saleh Elalfy ◽

Fatma Soliman Elsayed Ebeid ◽

Mohammed Ahmed Samir Ibrahim ◽

Hanaa Midhat Abdel Gader Hussein

Keyword(s):

Iron Overload ◽

Brain Mri ◽

Healthy Controls ◽

Brain Iron ◽

Cell Disease ◽

Neurocognitive Functions ◽

The Difference ◽

Mri Study ◽

The Brain ◽

Age And Sex

Abstract Background Sickle cell disease (SCD) is considered the most prevalent monogenic diseases worldwide. Iron overload is one of the major complications in those patients, especially who in need for frequent transfusion, affecting many organs including the brain. MRI is a valuable, reliable and non-invasive method for quantifying iron concentration in many organs as the liver and heart and it is now used for monitoring of the chelation therapy in SCD patients. Several studies began reporting differences in global cognitive function, particularly for children with SCD, they are at a high risk for neurocognitive impairment they often scored lower on general IQ measures than healthy children which is due to iron overload in brain tissue from the chronic transfusions which can lead to strokes and may be a silent stroke. Objective The current study assessed brain iron content (using R2* values) in the caudate and thalamic regions through quantitative brain MRI study in SCD patients in comparison to age and sex-matched healthy controls. Methods A case-control study recruited 32 patients with SCD and 11 healthy controls. Brain MRI study using multi-echo fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated for only 15 SCD patients and the 11 controls. All recruited SCD patients and controls were examined for the neurocognitive functions by these tests: Wechsler IV Intelligence Scale for Adult shows (Verbal, Perceptual, Memory, Processing and Total IQ), their all normal values between 90 – 110. Benton Visual Retention Test have cut of point at (> 4 or = 4). Those values are the same for the difference between the obtained correct and the expected correct, and the difference between the obtained error and expected error. Results The fifteen patient with SCD who underwent brain MRI were age and sex matched with the eleven healthy control (15 SCD patients: mean-age: 16.93 ± 3.41 years, 40.6% females and 11healthy controls: mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. As regards the brain MRI, there was no statistically significant differences between SCD and control group in all regions of interests (p > 0.05). Our study showed that 72.7% of our SCD patients had under threshold TIQ scores. Also18% of the patients showed moderate anxiety, 9% mild anxiety and 9% showed severe anxiety. Conclusion The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur.

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Non-invasive Quantitative MRI assessment of brain iron overload in patients with BThalassemia and Sickle cell disease

QJM ◽

10.1093/qjmed/hcab106.023 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Ghada Samir Ibrahim ◽

Fatma Soliman Elsayed Ebeid ◽

Hend Galal Eldeen Mohammed Ahmed Samir Ibrahim

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Chelation Therapy ◽

Brain Mri ◽

Control Group ◽

Healthy Controls ◽

Brain Iron ◽

Cell Disease ◽

Mri Study ◽

Age And Sex

Abstract Background B-Thalassemia, sickle cell disease (SCD) and other inherited hemoglobin disorders are considered the most prevalent monogenic diseases worldwide. Secondary iron overload is one of the major complications in such groups of patients affecting many organs (e.g. liver, heart and endocrinal glands). Objective The current study will assess brain iron content ( using R2* values ) in the caudate and thalamic regions through quantitative brain MRI study in B-Thalassemia and SCD patients in comparison to age and sex-matched healthy controls. Also evaluation of the association with LIC (liver iron concentrations) and MIC (myocardial iron concentrations) was done. Methods A case control study on 30 patients (15 with B-thalassemia major and 15 with SCD) and 11 age and sex-matched healthy controls was carried out in the period between August 2018 till August 2019. Brain MRI study using multiecho fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. Also brain R2* values were correlated with the LIC and HIC in B-thalassemia and SCD groups. Results 15 transfusion dependent B-thalassemia (mean-age: 19.40 ± 4.31 years, 53.3% females), 15 SCD patients (SCD; mean-age: 16.93 ± 3.41 years, 40.6% females) and 11 age and sex matched healthy controls (HC; mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. No statistically significant differences were found between SCD and control group in all regions of interests No statistically significant differences were found between the three subgroups (p > 0.05) in right thalamus, left and right caudate regions. However, in B-thalassemia subgroup, patients had moderately significantly higher R2* values compared to the controls and SCD patients as regards the left thalamic region with mean R2* values (16.69 ± 1.34) Hz compared to (15.65 ± 1.10) Hz in the control group (p = 0.021) and (15.79 ± 0.77) Hz in the SCD group (p = 0.029). There were no significant correlations between LIC and HIC with brain R2* values of all regions of interests in both B-thalassemia and SCD subgroups. Conclusion MRI is a valuable, reliable, safe and noninvasive method for quantifying iron concentration (in cases of iron overload) in many organs as the liver and heart and it is now used internationally for regular follow up of LIC and HIC for monitoring of the chelation therapy in B-thalassemia and SCD patients. The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur. This may be explained by heavy chelation therapy regimens given to our patients due to their poor compliance so as to keep the pre-transfusion hemoglobin level above 10mg/dl to prevent detrimental cardiac affection as cardiac siderosis, arrhythmias including heart block, or even heart failure.

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Mortality in Sickle Cell Patient Transitioning from Pediatric to Adult Program: 10 Years Grady Comprehensive Sickle Cell Center Experience.

Blood ◽

10.1182/blood.v112.11.1426.1426 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1426-1426 ◽

Cited By ~ 6

Author(s):

Si mbo O Aduloju ◽

Sheila Palmer ◽

James R. Eckman

Keyword(s):

Young Adults ◽

Sickle Cell Disease ◽

Mortality Rate ◽

Sudden Death ◽

Iron Overload ◽

Organ Failure ◽

Cause Of Death ◽

Sickle Cell ◽

Cell Disease ◽

Adult Care

Abstract Over the last three decades there has been improvement in survival in children with sickle cell disease. Overall survival from birth to age 18 of 86% and 95% has been reported in children with sickle cell anemia (HbSS) and sickle hemoglobin C (Hb SC) disease respectively. These encouraging results are secondary to initiation of preventive measures like newborn screening, penicillin prophylaxis, immunization and stroke prevention and other supportive therapies. Ballas (Blood2004;104 supl:Abstr 3743) reported high death rate for young adults with the disease. To determine the death rates and cause of death in our population, we did a retrospective review of our patients who had recently transitioned into adult care. Mortality rate and circumstances of death in a 10 year period of transition from pediatric to adult program in Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital between 1996 and 2006 were determined. Total number of deaths was obtained from the clinical database. Death, autopsy and medical records were reviewed to determine the cause and circumstances of death. Between 1996 and 2006, 387 young adults with sickle cell disease (HbSS, HbSC, HbS beta thalassemia) transitioned to the adult program at age 18. Twenty two (5.8%) patients died during their first 10 years of transition. Mean age at death was 23.4 (range 21.6–26) and male to female ratio was 1.2 to 1. Ten patients (45%) died due to chronic organ failure all due to chronic iron overload (end stage liver disease in 8 and congestive heart failure in 2). Eight patients (36%) died due to complications of acute vaso-occlusive crisis (sudden death in 4, acute chest/multi-organ failure in 4) while 4 patients (18%) died of non-sickle related causes. Three of four who died of sudden death has documented pulmonary hypertension. Our mortality rate is lower than those reported by Ballas with the most common cause of death being complications of iron overload in chronically transfused patients. Specific interventions targeted at improving management of iron overload need to be developed for the increasing numbers of patients on chronic transfusion transitioning into adult care.

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Pancreatic Iron Deposition Following the Role of Iron Loading Among Transfusion Dependent Sickle Cell Disease Egyptian Children and Young Adults

Blood ◽

10.1182/blood-2019-123683 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4828-4828

Author(s):

Mohsen Saleh Elalfy ◽

Khalid Allam ◽

Ahmed Ibrahim ◽

Basant Mosaad ◽

Fatma Soliman Elsayed Ebeid

Keyword(s):

Young Adults ◽

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Iron Loading ◽

Cell Disease ◽

Liver Iron ◽

Cardiac Iron ◽

Iron Load

Background: Transfusion in sickle cell disease (SCD) is uncommon but a well-defined practice; either as a replacement in severe anemia or as a prophylactic therapy for its major complications mainly stroke. Differential iron loading in SCD especially the extrahepatic organs is not fully studied. Primary objective is to measure pancreatic iron load among Egyptian transfusion-dependant SCD patients by using MRI T2* relaxometry method. Secondaryobjective is to correlate pancreatic iron load to transfusion iron input, both hepatic and cardiac iron load, trend of serum ferritin. Subjects and Methods: Sixty-six transfusion-dependant SCD child and young adults 8-25 years with more than twenty transfusions before enrollment, non was on regular exchange transfusion; they underwent clinical and laboratory assessments; complete hemogram, serum ferritin and serum amylase. All patients performed MRI examination on a 1.5- Tesla super conductive MR Philips scanner in MRI unit in Ain Shams University Hospital; the study takes about 10 -15 minutes. Radiological quantification of iron overload was performed via simple mathematical models using Microsoft Excel Spread Sheet for heart, pancreas, and kidneys. Results: The mean age of the studied SCD patients were 15.68 ± 7.02 years, they were 35 male (53.0%), 43 of them (65.2%) had positive family history of SCD. All were multiple transfusion; 22 for cardiopulmonary complication and acute chest syndrome (ASC), nine for stroke prevention and 35 for frequent sickling crisis and symptomatic anemia. Most of patients (80.3%) were on chelation therapies that were mainly (92.5%) oral mono-therapy. High frequencies of comorbidities were recorded in the studied cohort; delayed puberty (65.2%), hepatitis C infection (23.1%) and stroke (14.1%). The studied SCD patients had median transfusion index of 120ml/kg/year with mean iron overload per day 0.23 ± 0.15 mg/kg and half of them had serum ferritin > 2500ug/L. Almost two-thirds had moderate to severe liver iron overload with median LIC 11.63 mg/g liver dry weight, none had cardiac iron overload with median cardiac T2* 31 msec and nearly half of them (42.2%) showed marked decrease in signal intensity of renal cortex with relative sparing of the renal medulla and pelvis. Most of them (86%) had normal to mild pancreatic iron overload with median pancreatic R2* 53.8 msec. Pancreatic R2 level was not significantly correlated to either transfused iron, liver iron or serum ferritin and amylase. Patients with moderate to severe pancreatic iron overload had lower pre-transfusion hemoglobin level (p=0.004), higher level of marker of hemolysis (total bilirubin (p=0.012) and indirect bilirubin (p=0.048) than those with normal pancreatic MRI. Radiological quantification of iron overload was performed via a simple cheap and quick method for analysis of data. Conclusion: Moderately heavy transfused patients with SCD had no iron overload in the heart; pancreas follow same pattern as heart with minimal or no pancreatic iron loading, however moderate to severe hepatic iron loading. Whether iron loading might be related only to frequency of transfusion or also to frequency of vaso-occlusive will be discussed. Disclosures No relevant conflicts of interest to declare.

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