Comment on: Burden of central nervous system complications in
sickle cell disease: A systematic review and meta-analysis
R. Grant Steen, PhD
103 Van Doren Place
Chapel Hill, NC 27517
G_Steen_MediCC@yahoo.com
Dear Editor;
I read with interest a recent paper in Pediatric Blood & Cancer(1), about cognitive impairment in children with sickle cell disease
(SCD). I’m always grateful to have my work cited, especially since our
paper is almost 20 years old (2).
However, it seems that Lee et al . have gone to great lengths to
mischaracterize our work. They write (pg. 5) that, “SCI [silent
cerebral infarct] and absence of SCI/CVA [cerebrovascular
accident] were verified by review of brain MRIs in all studies except
Ghafuri et al . and Steen et al . In these studies, absence
of SCI/CVA was defined as no mention of cerebral infarcts in the
subject’s medical records.” Also on pg. 5, they write that, “An
alternative analysis was conducted excluding studies with insufficient
definition of overt stroke and/or SCI based on clinical opinion (Ghafuriet al . and Steen et al .)”. I cannot speak for Ghafuriet al , but we did a careful review of MRI findings for every
single patient in our study, as is necessary for a paper in theAmerican Journal of Neuroradiology . This should be pellucidly
clear because the title of our paper is, “Cognitive Impairment in
Children with Hemoglobin SS Sickle Cell Disease: Relationship to MR
Imaging Findings and Hematocrit ”. All our SCD patients were evaluated
by at least two neuroradiologists, and patients thought to be abnormal
were evaluated by a third neuroradiologist blinded as to previous
findings (2). One wonders what other errors may be present in Leeet al (1).
Fortunately, this mischaracterization of our work did not lead to
incorrect conclusions (1). A comparison of Table 1 to Supplementary
Table 6, in which our paper and Ghafuri et al were deleted from
analysis, shows that none of the major findings were changed much by
deleting these papers (1). I agree with most conclusions in Lee et
al .; in fact, I would go further. In uncited work from St. Jude
Children’s Research Hospital, we found that children with SCD can suffer
cognitive impairment even in the absence of MRI evidence of brain injury
(3). We tested a hypothesis that children with SCD who are completely
normal by MRI can still be cognitively impaired, as predicted by a model
of diffuse brain injury. A total of 54 patients with hemoglobin SS
(average age 10.9 years ± 2.9 years SD) were examined with the Wechsler
Intelligence Scale for Children-III (WISC-III) and were randomly matched
by age, race, and gender to healthy children from the Wechsler normative
database. Patients were also imaged at 1.5 Tesla with standard imaging
sequences. Among 30 patients judged normal by MRI, there were
substantial deficits in Wechsler Full-Scale IQ, Verbal IQ, and
Performance IQ (all P < 0.01), when compared to
African-American controls. The patient Wechsler Full-Scale IQ was 12.9
points lower than that of matched controls and decreased as a function
of age (P = 0.014). These findings strongly suggest that there is
diffuse brain injury in SCD patients, perhaps associated with chronic
hypoxia (3).