scholarly journals Volume of white matter hyperintensities is an independent predictor of intelligence quotient and processing speed in children with sickle cell disease

2014 ◽  
Vol 168 (4) ◽  
pp. 553-556 ◽  
Author(s):  
Veronica van der Land ◽  
Channa T. Hijmans ◽  
Marieke de Ruiter ◽  
Henri J. M. M. Mutsaerts ◽  
Marjon H. Cnossen ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Processing Speed ◽  
Intelligence Quotient ◽  
White Matter Hyperintensities ◽  
Independent Predictor ◽  
Cell Disease

scholarly journals Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease

2015 ◽  
Vol 172 (2) ◽  
pp. 274-284 ◽  
Author(s):  
Veronica van der Land ◽  
Henri J. M. M. Mutsaerts ◽  
Marc Engelen ◽  
Harriët Heijboer ◽  
Mark Roest ◽  
...  
Keyword(s):  
Factor Analysis ◽  
Risk Factor ◽  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
White Matter Hyperintensities ◽  
Risk Factor Analysis ◽  
Cerebral White Matter ◽  
Cell Disease

scholarly journals Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anna M. Hood ◽  
Hanne Stotesbury ◽  
Melanie Kölbel ◽  
Michelle DeHaan ◽  
Michelle Downes ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Sickle Cell Disease ◽  
Young Children ◽  
Sickle Cell ◽  
Processing Speed ◽  
Post Treatment ◽  
Cell Disease ◽  
Double Blind ◽  
Randomised Controlled

Abstract Background Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA. Methods The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3–7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry. Discussion Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA. Trial registration ClinicalTrials.govNCT04351698. Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020

scholarly journals Longitudinal evaluation of cerebral white matter hyperintensities lesion volume in children with sickle cell disease

2016 ◽  
Vol 176 (3) ◽  
pp. 485-487 ◽  
Author(s):  
Renzo Manara ◽  
Giacomo Talenti ◽  
Patrizia Rampazzo ◽  
Mario Ermani ◽  
Maria Montanaro ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
White Matter Hyperintensities ◽  
Cerebral White Matter ◽  
Lesion Volume ◽  
Cell Disease ◽  
Longitudinal Evaluation

scholarly journals Reduced Cerebrovascular Reserve Capacity in Adults with Sickle Cell Disease

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 972-972
Author(s):  
Lena Vaclavu ◽  
Lena Vaclavu ◽  
Henri JMM Mutsaerts ◽  
Esben Thade Petersen ◽  
Ed T VanBavel ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Risk ◽  
Adult Patients ◽  
Healthy Controls ◽  
Cell Disease ◽  
Cerebrovascular Reserve ◽  
Cerebral Vasodilation ◽  
O2 Delivery

Abstract Introduction: Sickle Cell Disease (SCD) is frequently complicated by stroke. Although transcranial Doppler effectively identifies children at risk for stroke, adult patients do not benefit from this test. In SCD, chronic hemolytic anemia leads to cerebral vasodilation, elevated cerebral blood flow (CBF) and subsequently, impaired cerebrovascular reserve (CVR) capacity. CVR represents the maximum increase in CBF in response to metabolic stressors. CVR mapping is a promising imaging biomarker for stroke risk assessment, potentially identifying patients with preclinical hemodynamic impairment. Our laboratory performs CVR mapping by measuring CBF prior to and following maximum cerebral vasodilation with acetazolamide (ACZ). The primary aim of this study was to quantitatively assess CVR in adult patients with SCD compared to healthy controls. Methods: Adult SCD patients (HbSS/HbSβ0) were recruited for this IRB-approved study with ACZ-induced vasodilation and venous blood sampling. Patients with a history of clinically overt stroke were excluded. Controls were selected from patients' friends and family members without SCD and matched on age, sex, and race. The following MRI images were acquired at 3T (Philips Healthcare, Best, NL): time of flight MRA for visualization of major cerebral vessels, T2 FLAIR for manual segmentation of white matter hyperintensities (WMHs), and pseudo-continuous arterial spin labeling (ASL) for CBF assessment. CBF was measured at baseline and 10min post ACZ (16mg/kg intravenous infusion over 3min). MRI images were processed with the ExploreASL toolbox, to obtain registered maps of quantified CBF and CVR (% change in CBF). We measured T1blood in each subject to improve quantification accuracy as these values can differ in SCD. Group comparisons were performed using non-parametric two-sample tests. Correlations were characterized by Spearman's rho (ρ). P<0.05 was considered significant. Median values with interquartile range (IQR) are reported for non-normally distributed variables, otherwise mean and standard deviation are reported. Results: 30 patients with SCD (mean age 33±12y,19M) and 11 controls (mean age 37±15y, 6M) were included in this cross-sectional controlled cohort study. Mean hemoglobin levels in patients with SCD were 8.8±1.4 g/dL and in healthy controls were 13.7±1.3 g/dL. Patients with SCD had higher baseline CBF compared to healthy controls (median 73(IQR:25) vs 42(IQR:6) mL/100g/min, p<0.001, F1a). CBF was inversely related to hemoglobin (ρ=-0.84, p<0.001, F1b). ACZ elicited an increase in CBF(p<0.001) which was similar in magnitude in both groups (patients 29±16, controls 35±11, mL/100g/min, F1c), resulting in a lower mean CVR in patients compared to controls (41±24% vs 81±27%, p<0.001, F1d). Baseline CBF predicted CVR (ρ=-0.68, p<0.001, F1e). WMHs were present in both groups, and WMH volume correlated with age (ρ = 0.54, p<0.001). There were no statistical associations between WMH volume and CVR (ρ = -0.15, p=0.4) or CBF(ρ = 0.02, p=0.9), however, two patients with the largest WMH volume (>6 mL) had the lowest CVR (<20%). Discussion: This study shows that regional CVR can be measured using ASL-MRI with ACZ challenge. ACZ was well-tolerated and elicited a robust cerebrovasodilatory response in both groups. However, the relative increase in oxygen delivery (CVR) was much lower in SCD patients, which suggests that patients with SCD have nearly maximal cerebrovascular dilation at baseline. Our data suggest that chronic vasodilation due to anaemia has let to outward remodelling of vessels in adult patients, permitting a larger vascular bed to compensate their anemia. Our premise is that resting O2 delivery is normal in SCD patients; we showed that increasing CBF overcomes severe anemia. However, high resting CBF limits the brain's ability to recruit additional O2 under times of stress. SCD patients have many transient interruptions in O2 delivery including aplastic crisis, splenic sequestration and sleep apnea, as well as metabolic stressors such as fever, sickle cell crisis, infection, and seizure. While baseline CBF predicted global CVR, ASL provides information regarding regional O2 delivery that may offer insight into distribution of ischemic white matter damage. Further study is needed to determine the impact of blood transfusions and hydroxyurea on CVR and whether there is a critical CVR threshold that predicts stroke risk. Disclosures No relevant conflicts of interest to declare.

Cognitive Function Of Nigerian Children With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1008-1008
Author(s):  
Olubusola Oluwole ◽  
Robert Noll ◽  
Julie Makani ◽  
Enrico M Novelli
Keyword(s):  
Working Memory ◽  
Cognitive Function ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Teaching Hospital ◽  
Cognitive Deficits ◽  
Processing Speed ◽  
University Teaching ◽  
Cell Disease ◽  
Intelligence Scale

Abstract Background Sickle cell disease (SCD) -related neurological complications include overt stroke, silent infarctions and cognitive impairment (CI). CI significantly impacts developmental growth and quality of life. Despite the high prevalence of SCD in sub-Saharan Africa, there is limited information on the burden of neurological dysfunction. To address this gap, we conducted a study to elucidate the prevalence and correlates of CI in SCD-children in an urban tertiary care setting in Nigeria. Method This case-control, cross-sectional study was approved by the University of Pittsburgh IRB, Lagos University Teaching Hospital (LUTH) and Lagos State University Teaching Hospital (LASUTH) in Nigeria. Participants were recruited from the LUTH sickle cell clinic and the Sickle Cell Foundation-associated clinics, which included a transcranial Doppler (TCD) clinic. Participants were English-speaking children between the ages 6-16 with laboratory-diagnosed homozygous SCD (HbSS, sickle cell anemia). Children who had an on-going sickle cell crisis or who received a blood transfusion within 3 months were excluded from the study. HbAA siblings of the patients and unaffected age-matched children from the LASUTH pediatric primary care clinic were recruited as control subjects. For a comprehensive assessment of cognitive function, subtests of the Wechsler Intelligence Scale for Children (WISC IV) were administered to assess processing speed (Symbol Search, Coding subtests) and Working Memory (Digit Span, Symbol search subtests) indices. Baseline hemoglobin levels were obtained via a Stat-site hemoglobin analyzer, and oxygen saturation levels were obtained using a pulse oximeter. Baseline demographic data was obtained by surveying the parents/guardians. Lastly, children recruited from the Sickle Cell Foundation TCD clinic (n=24) were stratified by stroke risk levels (standard, conditional, high and indeterminate) based on the TCD velocity values. Results A total of 56 children diagnosed with sickle cell disease (M=29, mean age=9.2, SD: 2.76) and 42 unaffected children (M=24, mean age= 9.41, SD: 2.75) participated in this study. We found a higher prevalence of cognitive deficits, especially in areas of processing speed (p=0.013) and short-term auditory memory (p=0.002) in SCD patients as compared to controls. There was also a close association with working memory deficits (p=0.07). Surprisingly, we did not find an association between the cognitive performance of SCD children and their levels of anemia, oxygen levels or body mass index. TCD high risk level was marginally associated with a lower hemoglobin and severe anemia (p=0.05) although there was no significant correlation with working memory and processing speed indices. Conclusion Children with SCD in Nigeria suffer from cognitive deficits in the areas of memory and attention when evaluated with subtests of the Wechsler Intelligence Scale for Children. We found that, unlike other studies of cognitive function in SCD, our study did not find a correlation between cognitive function and hemoglobin level. It is, therefore, possible that other local environmental or disease-specific factors may be associated with CI in our SCD cohort, or that anemia may affect other cognitive domains not explored by our research. Larger, longitudinal studies should be performed to further elucidate the cognitive function of pediatric SCD patients in Nigeria so that appropriate, locally targeted, preventive interventions can be developed. Disclosures: No relevant conflicts of interest to declare.

White Matter Integrity and Core Cognitive Function in Children Diagnosed With Sickle Cell Disease

2011 ◽  
Vol 33 (3) ◽  
pp. 163-171 ◽  
Author(s):  
Nadia Scantlebury ◽  
Donald Mabbott ◽  
Laura Janzen ◽  
Conrad Rockel ◽  
Elysa Widjaja ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
White Matter Integrity ◽  
Cell Disease
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