Executive Function and Processing Speed in Children Living with Sickle Cell Anemia.

Executive function and processing speed difficulties are observed in children living with sickle cell anemia (SCA). The influence of processing speed on executive function is not well understood. We recruited 59 children living with SCA and 24 matched controls aged 8-18 years between 2010 and 2016 from clinics in the UK. Children completed tests in processing speed and cognitive flexibility, subdomains of executive function. MRI scans were conducted within one year of testing; oxygen saturation was obtained on the day of testing. Hemoglobin levels were obtained from medical records. Caregivers completed the executive function questionnaire. Hierarchical linear regressions found that hemoglobin, oxygen saturation, age, infarct status, and processing speed were not independent predictors for any model. However, for all cognitive flexibility tests, there was a significant interaction between infarct status and processing speed; children without silent cerebral infarction (SCI) with faster processing speed had better cognitive flexibility. Our findings indicate that, when interpreting executive function difficulties, it is important to account for the relationship between SCI status and processing speed. More research is needed to elucidate the mechanisms, but clinically, including executive function testing as part of clinic visits by embedding psychologists within the healthcare team would appear to be a critical step.

Disfunción crónica de órganos en pacientes con drepanocitosis. Parte II: manifestaciones renales, neurológicas y sensoriales / Chronic organ dysfunction in patients with sickle cell disease. Part II: renal, neurological and sensory manifestations

Introducción: El aumento de la expectativa de vida de pacientes con drepanocitosis, provoca que se sumen comorbilidades y disfunción crónica de órganos a las manifestaciones clínicas de la enfermedad. Objetivos: Analizar las alteraciones renales, neurológicas y sensoriales que aparecen en pacientes con drepanocitosis como manifestaciones de la disfunción orgánica crónica. Métodos: Se realizó una revisión de artículos publicados en los últimos 10 años con el uso de los buscadores PubMed, SciELO y Google Académico. Los términos de búsqueda fueron: drepanocitosis, disfunción orgánica, mortalidad, proteinuria, enfermedad renal crónica, infarto cerebral silente, trastornos neurocognitivos, retinopatía, sordera neurosensorial. Análisis y síntesis de la información: El efecto combinado de afectación glomerular, tubular e intersticial acarrea una disminución paulatina de la función renal. La progresión a la enfermedad renal crónica terminal es común y se asocia a incremento de la mortalidad. Las complicaciones del sistema nervioso central también pueden tener un impacto negativo en la supervivencia o provocar secuelas que influyen en la calidad de vida de los enfermos. Las afectaciones sensoriales tienen repercusiones biopsicosociales. Se describen aspectos relacionados con la prevalencia, diagnóstico y tratamiento de estas complicaciones. Conclusiones: Un seguimiento de los pacientes basado en estrategias para prevenir y diagnosticar de forma precoz las manifestaciones de disfunción crónica de órganos, puede disminuir las consecuencias desfavorables de estas complicaciones(AU)

Introduction: The increase in life expectancy of patients with sickle cell disease causes co-morbidities and chronic organ dysfunction to be added to the clinical manifestations of the disease. Objectives: To analyze the renal, neurological and sensory alterations that appear in patients with sickle cell disease as manifestations of chronic organic dysfunction. Methods: A review of the articles published in the last ten years was carried out using the search engines PubMed, SciELO and Google Scholar. The search terms were: sickle cell disease, organ dysfunction, mortality, proteinuria, chronic kidney disease, silent cerebral infarction, neurocognitive disorders, retinopathy, sensorineural deafness Analysis and synthesis of information: The combined effect of glomerular, tubular and interstitial involvement leads to a gradual decline in kidney function. Progression to end-stage chronic kidney disease is common and is associated with increased mortality. Central nervous system complications can also have a negative impact on survival or cause sequelae that influence the quality of life of patients. Sensory impairments have biopsychosocial repercussions. Aspects related to the prevalence, diagnosis and treatment of these complications are described. Conclusions: A follow-up of patients based on strategies to prevent and diagnose early the manifestations of chronic organ dysfunction can reduce the unfavorable consequences of these complications(AU)

Academic Challenges and School Service Utilization in Children with Sickle Cell Disease.

OBJECTIVES: To describe the academic concerns and risk strata of children with sickle cell disease (SCD) as identified through a parent-directed screening tool and to compare the rates of these concerns with actual school service utilization in the clinic population. STUDY DESIGN: We completed a retrospective review of patients with SCD referred to the school intervention program during the 2017-2018 and 2018-2019 school years because of a school-related concern raised by parents or noted by the clinical team. All parents completed the Brief School Needs Inventory (BSNI), a validated parent-response tool used to stratify academic risk. Rates of special education services, grade retention, and results from neuropsychologic testing were captured. Clinical history, the use of disease-modifying therapy, and results from laboratory and neuroimaging studies were also obtained. Descriptive statistics were performed to examine demographic information, clinical history, and BSNI results. RESULTS: In total, 137 unique patients (age range, 14 months to 19 years) completed the BSNI during the study period, for 181 events. According to BSNI risk-stratification, 45% of patients were deemed low, 36% moderate, and 19% high academic risk. Over one-half of parents were concerned about their ability to advocate for their child's needs. Despite legal qualification for a Section 504 accommodation plan, only 20% had established plans. Academic concerns were common with 31% of children reporting an individualized education program and 20% with grade retention/remediation. CONCLUSIONS: Concerns for academic challenges remain high among parents of children with SCD; however, school service utilization remains disproportionately low attributable to numerous reasons.

Cerebrovascular Disease and Cognition in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) affects both brain structure and function. Patients with CKD have a higher risk of both ischemic and hemorrhagic strokes. Age, prior disease history, hypertension, diabetes, atrial fibrillation, smoking, diet, obesity, and sedimentary lifestyle are most common risk factors. Renal-specific pathophysiologic derangements, such as oxidative stress, chronic inflammation, endothelial dysfunction, vascular calcification, anemia, gut dysbiosis, and uremic toxins are important mediators. Dialysis initiation constitutes the highest stroke risk period. CKD significantly worsens stroke outcomes. It is essential to understand the risks and benefits of established stroke therapeutics in patients with CKD, especially in those on dialysis. Subclinical cerebrovascular disease, such as of silent brain infarction, white matter lesions, cerebral microbleeds, and cerebral atrophy are more prevalent with declining renal function. This may lead to functional brain damage manifesting as cognitive impairment. Cognitive dysfunction has been linked to poor compliance with medications, and is associated with greater morbidity and mortality. Thus, understanding the interaction between renal impairment and brain is important in to minimize the risk of neurologic injury in patients with CKD. This article reviews the link between chronic kidney disease and brain abnormalities associated with CKD in detail.

Sickle Cell Disease and Stroke.

Cerebral infarction is a common complication of sickle cell disease and may manifest as overt stroke or cognitive impairment associated with "silent" cerebral infarction on magnetic resonance imaging. Vasculopathy may be diagnosed on transcranial Doppler or magnetic resonance angiography. The risk factors in sickle cell disease for cognitive impairment, overt ischemic stroke, silent cerebral infarction, overt hemorrhagic stroke, and vasculopathy defined by transcranial Doppler or magnetic resonance angiography overlap, with severe acute and chronic anemia, acute chest crisis, reticulocytosis, and low oxygen saturation reported with the majority. However, there are differences reported in different cohorts, which may reflect age, geographic location, or neuroimaging techniques, for example, magnetic resonance imaging field strength. Regular blood transfusion reduces, but does not abolish, the risk of neurological complications in children with sickle cell disease and either previous overt stroke or silent cerebral infarction or abnormal transcranial Doppler. There are relatively few data on the use of hydroxyurea or other management strategies. Early assessment of the risk of neurocognitive complications is likely to become increasingly important in the management of sickle cell disease.

Increased VEGF and decreased SDF-1α in patients with silent brain infarction are associated with better prognosis after first-ever acute lacunar stroke.

BACKGROUND: Pre-existing silent brain infarctions (SBIs) have been reported to be associated with better outcomes after first-ever symptomatic ischemic stroke, although the mechanism of this remains unclear. We investigated the association between SBIs, outcomes of acute lacunar infarction, and biomarkers including vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α), macrophage migration inhibitory factor (MIF), and high-mobility group box-1 (HMGB1). METHODS: A total of 68 consecutive patients diagnosed with first-ever lacunar infarction (<20 mm) within 24 hours of symptom onset were included in this study. Clinical, laboratory, and imaging data were obtained. Plasma levels of VEGF, SDF-1α, MIF, and HMGB1 were assessed using Enzyme-Linked Immunosorbent Assay kits. RESULTS: SBIs were noted in 31 of the 68 patients. Although the initial National Institutes of Health Stroke Scale scores were not related with the presence of SBIs (P = .313), patients with SBIs had better outcomes at 3 months (P = .029). Additionally, plasma VEGF levels were higher (P = .035) and SDF-1α levels were lower (P < .001) in patients with SBIs. Logistic regression analysis indicated that VEGF and SDF-1α were independently associated with the presence of SBIs. CONCLUSIONS: SBIs are associated with favorable outcomes in patients with first-ever acute lacunar infarction and higher levels of VEGF, and lower levels of SDF-1α in these patients may contribute to their more favorable prognosis.

Pediatric Moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) is a progressive cerebrovascular occlusive disease of the bilateral internal carotid arteries that leads to a compensatory abnormal vascular network at the base of the brain. Its average annual incidence 0.54 per 100,000 population but it is the most common pediatric cerebrovascular disease in East Asia. The reported incidence in USA is approximately 0.086 per 100,000 patients. CASE REPORT: We present a case of Moyamoya disease that was to detected in a 7-year-old female who presented with transient altered mental status. CONCLUSIONS: Moyamoya disease can be diagnosed if history, physical exam and brain imaging is highly suspicious. Conventional angiography remains the gold standard for diagnosis and aids in surgical planning for patients with suspected Moyamoya disease.