Effect of transfusion therapy on intracranial stenosis in a child with sickle cell anaemia

Abstract

Dear Editor, A boy of Congolese origin, born in the UK in 2009 from sickle cell disease (SCD) carrier parents and diagnosed with homozygous SCD through new-born screening, was under annual transcranial Doppler (TCD) surveillance since the age of 2 at a UK district general hospital. Despite regular reviews for health monitoring in the Sickle Cell Disease clinic, optimal penicillin prophylaxis and immunisation programme, he had required multiple admissions to hospital due to frequent acute pain crises, gall stones, hepatic sequestration, and ischial bone infarction, and had been started on hydroxycarbamide 29 mg/kg/day at the age of 5 because of recurrent chest syndrome requiring blood transfusion. His annual TCD time-averagedmaximummean velocity (TAMMV) had beenwithin the limits for “standard stroke risk” (<170 cm/ s) [1] (Fig. 1a), and he had always been asymptomatic from a neurological point of view. However, in 2018, a decrease in TCD TAMMV below 70 cm/s (67 cm/s) was noted focally in the right middle cerebral artery (MCA), which progressed to 38 cm/s on close follow-up in February 2019 (Fig. 1b); there were no associated neurological symptoms. Magnetic resonance angiography (MRA) confirmed right MCA stenosis, with tight stricture at the level of M1-M2, distal narrowing and beading (Fig. 1c). There was no evidence of MoyaMoya disease, and contralateral vessels were normal both on TCD and MRA. There were no silent infarcts on brain imaging. He was started on monthly blood transfusions aiming to maintain HbS level below 30% of total haemoglobin [2, 3], in addition to hydroxycarbamide; he subsequently had to be started on iron chelation treatment due to progressive increase in ferritin levels. A TCD scan repeated in June 2019, 4 months after starting transfusion treatment, was still abnormal, with low TAMMV of 39 cm/s, indicative of persistent right MCA stenosis. However, in September 2019, a follow-up MRA showed resolution of the previously demonstrated right MCA stenosis (Fig. 1d); a TCD scan repeated in November 2019 showed significant increase in right MCA TAMMV with normalised values (94 cm/s), consistent with MRA results (Fig. 1e). Transfusion treatment was continued for 18 months, before being stopped in August 2020, and hydroxycarbamide continued at a daily dose of 30 mg/kg. Last TCD follow-up in February 2021 confirmed normalised velocities, with right MCA TAMMV of 130 cm/s. No neurological or non-neurological symptoms have been recorded, and the patient is keeping well. Albeit considered a rare disease in high-income countries, SCD is the most common severe genetic disease in the UK and France, with up to 15,000 patients in each country [1], and is a leading cause of paediatric stroke worldwide. Children with SCD have a 410-fold increase in ischemic stroke risk as compared to their peers; stroke and silent cerebral infarcts are associated with significant cognitive impairment, lower educational attainment in childhood, worse employment status in adult life, overall reduced quality of life, and major public health expenditure, making implementation of existing primary prevention strategies crucial [1]. In the absence of prevention programmes, stroke accounts for up to 10% of deaths in SCD, with reduction of 25–30 years of life expectancy. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) showed that by identifying neurologically asymptomatic children at high risk of stroke through TCD screening, and * Sara Mazzucco [email protected]