The Pediatric Clinician's Approach to Acute or Chronic Neurologic Symptoms in Children with Sickle Cell Disease.

Obstructive sleep apnea (OSA) is associated with cardiovascular and cerebrovascular morbidity. Patients with sickle cell disease (SCD) are at increased risk for both neurologic complications (NC) and OSA. However, the relationship between OSA and SCD complications is unclear. We hypothesized that there would be an association between OSA diagnosis and SCD complications. Hospital discharge records of patients with SCD aged < 19 years were obtained for the years 1997, 2000, 2003, 2006, 2009, and 2012 from the Kid's Inpatient Database. The primary outcome, NC, a composite of stroke, transient ischemic attack, and seizures. Secondary outcomes included acute chest syndrome (ACS), vaso-occlusive crisis, length of hospital stay, and inflation-adjusted cost of hospitalization. Multivariable regression was conducted to ascertain the association of OSA with primary and secondary outcomes. Analyses were adjusted for the use of noninvasive mechanical ventilation (NIMV) to determine its role as NC risk modifier. There were 203,705 SCD discharges included in the analysis, of which 2,820 (1.4%) and 4,447 (2.2%) also included OSA and NC diagnoses. Multivariable logistic regression indicated that OSA was associated with NC (adjusted odds ratio [OR], 1.50 [95% CI 1.02-2.21], p = 0.039) and ACS (OR, 1.34 [95% CI 1.08-1.67], p = 0.009) in children with SCD. In the multivariable analysis adjusted for NIMV, the significant association between OSA and NC was no longer observed (OR, 1.39 [95% CI 0.94-2.05], p = 0.100). OSA is associated with a 50% increase of odds of NC in children with SCD in this nationwide dataset. The use of NIMV to treat OSA may modify the risk of OSA-associated NC.

Therapeutic challenges in childhood sickle cell disease. Part 1: current and future treatment options.

Are current interventions for preventing silent cerebral infarcts in people with sickle cell disease effective and safe? A Cochrane Review summary with commentary.

Incidence of Maternal and Perinatal Morbidity in Sickle Cell Disease and Sickle Cell Trait Patients during Pregnancy

To determine if glial fibrillary acidic protein (GFAP) is associated with brain injury in children with sickle cell disease (SCD), we measured plasma GFAP among cross-sectional groups of unselected children with SCD, subsets of children with SCD and normal brain MRI or MRI evidence of cerebral infarct, healthy pediatric controls, and adults with brain injury. Children with SCD had higher plasma GFAP than healthy pediatric controls (mean concentrations 0.14 ± 0.37 vs. 0.07 ± 0.08 ng/mL; P 5 0.003); also, 16.0% (16/100) of children with SCD and cerebral infarct had GFAP elevations above the 95th percentile of healthy pediatric controls (P 5 0.04). Although not statistically significant, children with SCD and cerebral infarct had more elevated GFAP levels than with SCD and no infarct (16/100, 16.0% vs. 14/168, 8.3%; P 5 0.07). Children with SCD and acute brain ischemia had a higher proportion of elevated GFAP than SCD children with normal MRI (3/6, 50% vs.8.3%; P 5 0.01). GFAP was associated with elevated systolic blood pressure in the preceding year and correlated positively with white blood cell count and negatively with age and performance IQ. Plasma GFAP is elevated among children with SCD and may be associated with subclinical brain injury.

Background: Sickle Cell Disease (SCD) is an autosomal recessive hemoglobinopathy containing mutant sickle cell Hemoglobin (HbS). Acute and chronic organ dysfunction, chronic hemolytic anemia, and recurrent painful episodes are the main features of sickle cell disease. There is a wide variety of neurological complications, including: headache, cognitive difficulties, seizures, visual loss, ischemic and hemorrhagic stroke, transient ischemic attacks, soft neurological signs coma, altered mental status and covert or silent infarction. Moyamoya is an uncommon cerebral vasculopathy that’s also found in children with SCD. Case Presentation: Here, we reported two children diagnosed with SCD who presented with headache, recurrent ischemic strokes, seizures and cognitive decline. They showed abnormalities on different neuroimaging including: CT and /or MRI, MRA and/or CT angiography, also transcranial color coded duplex, EEG and Stanford-Binet Intelligence scales-Fifth Edition. They also showed abnormal level of protein C and protein S. They also had irregular blood transfusion and were diagnosed as Moyamoya syndrome. Conclusion: According to our findings, Moyamoya syndrome was a rare complication of SCD in children, but should be considered with proper approach, diagnosis and management.

Neuropathy, neuropathic pain, and sickle cell disease

Guidelines for the management of the acute painful crisis in sickle cell disease.

Acute and Chronic Neurological Symptoms among Paint Workers Exposed to Mixtures of Organic Solvents

Acute and Chronic Neurological Symptoms Among Paint Workers Exposed to Mixtures of Organic Solvents

Although individuals with sickle cell disease (SCD) are at increased risk for stroke, the underlying pathophysiology is incompletely understood. Intracardiac shunting via a patent foramen ovale (PFO) is associated with cryptogenic stroke in individuals without SCD. Recent evidence suggests that PFOs are associated with stroke in children with SCD, although the role of PFOs in adults with stroke and SCD is unknown. Here, we report 2 young adults with SCD, stroke, and PFOs. The first patient had hemoglobin SC and presented with a transient ischemic attack and a subsequent ischemic stroke. There was no evidence of cerebral vascular disease on imaging studies and the PFO was closed. The second patient had hemoglobin SS and two acute ischemic strokes. She had cerebral vascular disease with moyamoya in addition to a peripheral deep venous thrombosis (DVT). Chronic transfusion therapy was recommended, and the DVT was managed with warfarin. The PFO was not closed, and the patients' neurologic symptoms were stabilized. We review the literature on PFOs and stroke in SCD. Our cases and the literature review illustrate the dire need for further research to evaluate PFO as a potential risk factor for stroke in adults with SCD.

Growing Up With Sickle Cell Disease: Hospital Medicine and Health Care Transitions.

Progression of Central Nervous System Vasculopathy in Young Adults with Sickle Cell Anemia

Interventions for preventing silent cerebral infarcts in people with sickle cell disease.

Background and purposeSilent cerebral infarcts (SCIs) are the most common neurological complication in children and adults with sickle cell disease (SCD). In this systematic review, we provide an overview of studies that have detected SCIs in patients with SCD by cerebral magnetic resonance imaging (MRI). We focus on the frequency of SCIs, the risk factors involved in their development and their clinical consequences.MethodsThe databases of Embase, MEDLINE ALL via Ovid, Web of Science Core Collection, Cochrane Central Register of Trials via Wiley and Google Scholar were searched from inception to June 1, 2019.ResultsThe search yielded 651 results of which 69 studies met the eligibility criteria. The prevalence of SCIs in patients with SCD ranges from 5.6 to 80.6% with most studies reported in the 20 to 50% range. The pooled prevalence of SCIs in HbSS and HbSβ0 SCD patients is 29.5%. SCIs occur more often in patients with the HbSS and HbSβ0 genotype in comparison with other SCD genotypes, as SCIs are found in 9.2% of HbSC and HbSβ+ patients. Control subjects showed a mean pooled prevalence of SCIs of 9.8%. Data from included studies showed a statistically significant association between increasing mean age of the study population and mean SCI prevalence. Thirty-three studies examined the risk factors for SCIs. The majority of the risk factors show no clear association with prevalence, since more or less equal numbers of studies give evidence for and against the causal association.ConclusionsThis systematic review and meta-analysis shows SCIs are common in patients with SCD. No clear risk factors for their development were identified. Larger, prospective and controlled clinical, neuropsychological and neuroimaging studies are needed to understand how SCD and SCIs affect cognition.