Sickle cell disease children at risk for silent strokes

Researchers have shown that high blood pressure and anaemia put children with sickle cell disease at high risk for symptomless or “silent” strokes.

The conditions combined put these children at serious danger of stroke, while either condition on its own signalled high risk, the researchers from the Johns Hopkins Children’s Center, Vanderbilt University and elsewhere have demonstrated.

The results, published online on 17 November in the journal Blood, are part of an ongoing National Institutes of Health-funded international multi-centre trial, believed to be the largest study of its kind to date for children with sickle cell disease.

In Cayman, 12 of the 41 people registered with the Public Health Department as having sickle cell disease are under 18.

In the study, brain MRI scans revealed nearly one-third (31 per cent) of 814 children, age 5 to 15, had suffered silent strokes. None had a history of stroke or seizures, and none showed overt stroke signs at the time of the study.

Extremely rare in children overall, stroke is a common neurologic complication in children with sickle cell disease, a genetic disorder marked by the “sickling” or bending of red blood cells that store and distribute oxygen in the body. The misshapen blood cells cause anaemia and also clog tiny blood vessels, causing pain, tissue damage and stroke. A stroke can occur when a blood vessel in the brain bursts or leaks (haemorrhagic stroke) or be caused by oxygen deprivation (ischemic stroke), the predominant kind of brain injury in children with sickle cell disease.

Overt strokes lead to sudden dramatic symptoms, including excruciating headaches, one-sided paralysis of the face or body and loss of speech or vision. Silent strokes, by contrast, cause none of these overt symptoms but they cause sub-clinical brain damage, can lead to learning disabilities and place children who have them at risk for overt strokes and repeat episodes of silent strokes, the investigators said.

The new findings underscore the need to identify early signs of anaemia and high blood pressure because they are modifiable risk factors, the researchers say. The findings also may pave the way for new therapeutic targets for sickle cell disease.

“Silent strokes are typically seen in older adults and these findings give us additional insight into why they tend to occur so often in children with sickle cell disease,” said senior study investigator Dr. James Casella, director of haematology at Hopkins Children’s.

To analyse the interplay between silent stroke and blood pressure and anaemia, researchers looked at children’s medical histories, neurological exams and levels of haemoglobin, the oxygen carrier of red blood cells. Anaemia — defined by low levels of haemoglobin — and high blood pressure drove up the risk separately and incrementally, but the combination of the two carried the highest risk. Children with the highest systolic blood pressure (above 113) and the lowest haemoglobin (below 7.6 g/decilitre) had a nearly four-fold risk of silent strokes compared with children with the highest haemoglobin and the lowest blood pressure.

As blood pressure went up and haemoglobin down, the researchers found, so did the risk of stroke. Incremental changes in haemoglobin and blood pressure corresponded to changes in risk. Children who had the lowest haemoglobin had more than twice the risk of silent stroke, compared with children with the highest haemoglobin levels.

Children with the highest systolic blood pressure had 1.7 times the risk of silent stroke, compared with children with the lowest blood pressure. The risk was particularly high in a tiny subset of children — those diagnosed with hypertension, or persistently elevated blood pressure. In this group, 83 per cent (five of six) had suffered silent strokes.

The exact cascade of metabolic events leading to a silent stroke remains unknown, but researchers believe anaemia is key.

All children with sickle cell disease are anaemic, resulting in lower oxygen in the blood. To cope with this chronic anaemia, children and adults with sickle cell disease develop a compensatory mechanism in which the brain vessels dilate to improve blood flow and allow more oxygen. In this context, the investigators suspect, even moderate blood pressure elevations can exact further toll on the brain vessels and — when exacerbated by anaemia — lead to stroke.

“Our findings underscore the importance of correcting anaemia, at least partially, and may thus lay the groundwork for primary prevention of silent stroke,” said principal investigator Dr. Michael DeBaun, of Vanderbilt University, the lead author on the current report.

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