Cognitive deficits in children with sickle cell disease (SCD) were associated with the neuroimaging findings of higher cerebral blood flow velocity, stroke or silent cerebral infarction, decreased functional magnetic resonance imaging (fMRI) activation, and abnormal functional connectivity, according to a systematic review published in Children.
The findings, which stemmed from an analysis of literature published since the late 1990s, highlight the importance of blood flow velocity on transcranial Doppler for identification of deficits. However, in the current state of knowledge, abnormalities on MRI were not so definitive as to warrant MRI to be done routinely in all children with SCD, said one of the study authors, Fenella Kirkham, MD, of University College London in the U.K.
Researchers searched Pubmed and Embase for studies related to SCD and cognition published between 1960 and 2022 and found 33 reports published between 1993 and 2022 that met their criteria.
Eleven of the studies looked at blood flow velocities on transcranial Doppler, which generally found that elevated flow velocity was associated with worse cognition, although there were exceptions in which researchers found no association. In one such study with no association, patients had routinely received blood transfusions, researchers noted.
In some of the studies, experts suggested that children living with SCD who have deficits have a pattern of strengthening other cognitive areas to compensate. As such, although there might be varying profiles of cognitive strengths and weaknesses in individual children, the overall cognitive picture is within normal bounds in some studies.
The association of higher flow, rather than lower flow, with cognitive difficulties seems counterintuitive, Dr. Kirkham said. In these cases, though, the blood flow might be maxed out.
“It may be so high that you can’t increase any more if you needed to increase it,” she said. “You may reach a ceiling.” One way in which this might be problematic is during sleep. “Blood flow can go up during sleep, and if it can’t go up enough then maybe you get a little bit of hypoxia” that has negative effects over time.
In 21 studies, MRI was used to assess stroke, silent cerebral infarction (SCI), and brain structure. Overt stroke was associated with cognitive deficits, and SCI often was as well, but several studies did not find an association between cognitive deficits and SCI.
“We found some evidence of association with SCI, but it wasn’t as strong as previous studies,” some of which were based on data from the 1970s and 1980s, Dr. Kirkham said. “The world has changed since then.”
“A lot of kids are already on hydroxyurea,” Dr. Kirkham noted, which makes red blood cells less likely to become sickle-shaped, “and maybe that makes a difference. We didn’t have the data to show that for sure, but we certainly showed a less strong relationship between cognition and the silent infarction in more recent studies.”
Far fewer studies looked at volume on MRI and fMRI activation, but associations were seen between cognitive deficits and fMRI activation and reduced volumes.
Overall, Dr. Kirkham noted, the systematic review’s findings could be taken to underscore the value of transcranial Doppler.
“If you are doing transcranial Doppler screening, which is very much at the top of the list of tests, if the child has a high velocity, they are at risk of cognitive difficulties,” she said. “If you have a child with a high velocity, they should have cognitive testing.”
The value of MRI in this setting is not as conclusive, Dr. Kirkham noted. “The jury is still out on whether MRI gives you enough information on cognitive function to be something that should be mandated,” she said. “It’s relatively easy to do a transcranial Doppler on a child. It’s much more difficult to get a child into a scanner and lie still for an hour or half an hour.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Abdi SS, De Haan M, Kirkham FJ. Neuroimaging and cognitive function in sickle cell disease: a systematic review. Children (Basel). 2023;10(3):532.