RESUMO
Cerebral arteriopathy (CA) in children with sickle cell disease (SCD) is classically described as chronic stenosis of arteries in the anterior brain circulation, leading to ischemic stroke. Some studies have however reported strokes in children with SCD but without CA. In order to better understand the etiology and risk factors of these strokes, we retrospectively analyzed ischemic strokes occurring in a large cohort of children over a 13 year-period. Between 2007 and 2020, 25/1500 children with SCD had an ischemic stroke in our center. Among them, 13 (52%) had CA, described as anatomical arterial stenosis, while 12 (48%) did not. Patients with stroke without CA were older than patients with stroke attributed to SCD-CA (9.0 years old vs 3.6 years old, p=0.008), and had more frequently a SC genotype (25% vs 0% respectively). Their stroke involved posterior circulation more frequently, with cerebellar involvement in 42%. Retained stroke etiologies in patients without typical SCD-related CA were reversible cerebral vasoconstriction syndrome, cerebral fat embolism, arterial thrombosis or thromboembolism, hyperviscosity, vasculitis in a context of infectious meningoencephalitis, and severe hemodynamic failure. No recurrence was observed in the 24 months following stroke, even though 67% of the patients were no longer receiving exchange transfusions in this group. In conclusion, in a cohort of pediatric SCD patients with efficient stroke screening strategy, half of occurring ischemic strokes were related to causes other than CA. They affected a different population of SCD children and systematic long-term transfusion programs may not be necessary in these cases.
RESUMO
BACKGROUND: An important prevalence (32%-45%) of masked hypertension has been reported in children with sickle cell disease (SCD). Stroke screening is well established using transcranial Doppler (TCD) ultrasound. The objectives of our proof-of-concept study in childhood SCD were to evaluate the prevalence of hypertension and its relationships with cerebral vasculopathy (TCD velocity) and to further evaluate in a subgroup of children the correlations of cardiovascular autonomic nervous system indices with TCD velocity. METHODS: Ambulatory blood pressure measurement (ABPM) and TCD velocity were obtained in children with SCD and in a restricted sample, cardiac sympathovagal balance using heart rate variability analyses, baroreflex sensitivity, and pulse wave velocity were measured. RESULTS: In 41 children with SCD (median age 14.0 years, 19 girls, SS/Sß + thalassemia/SC: 33/2/6), ABPM results showed masked hypertension in 2/41 (5%, 95% confidence interval, 0-11) children, consistent with the prevalence in the general pediatric population, elevated blood pressure (BP) in 4/41 (10%) children, and a lack of a normal nocturnal dip in 19/41 children (46%). Children with increased TCD velocity had lower nocturnal dipping of systolic BP. In the 10 participants with extensive cardiovascular assessment, increased TCD velocity was associated with parasympathetic withdrawal and baroreflex failure. Exaggerated orthostatic pressor response or orthostatic hypertension was observed in 7/10 children that was linked to parasympathetic withdrawal. CONCLUSIONS: Autonomic nervous system dysfunction, namely loss of parasympathetic modulation, of SCD contributes to increase TCD velocity but is not associated with an increased prevalence of masked hypertension. CLINICAL TRIALS REGISTRATION: NCT04911049.