Discussion
Several studies are bearing out the relative rarity of neurological
events among patients with SCD in the Arabian Gulf. This is particularly
true of patients with the AI haplotype and increased HbF level, where
the prevalence of stroke is <1.0%11,13,14.
Moreover, it has been shown consistently that cerebral blood flow is
hardly impeded, with very low prevalence of abnormal or conditional
TAMMV in studies from Kuwait and other Gulf15,16countries. This suggests low progression of cerebral vasculopathy among
these patients. Interestingly, however, this sparing of the cerebral
vessels is not only limited to patients with the AI haplotype, as
reports from Oman17,18, Iran15 and
Iraq16,19, where this haplotype is not particularly
common, also report relatively normal TCDI indices. Therefore, there may
be other obscure factors in this population that protect them from
neurological events.
There are not many prospective studies of TCD among SCD patients in the
literature. We therefore thought it was intriguing to investigate what
would happen over time to cerebral blood flow velocities among our
Kuwaiti patients. Hence we recalled patients who were studied about 10
years ago as relatively young children. We wanted to see if the effects
of vasculopathy would now be evident as increased TAMMV values or if,
indeed they would remain static or, in fact, decrease. It was
interesting that uniformly, the TAMMV and other indices showed
significant decreases compared to the values in the initial study.
Even, in the normal population, TAMMV decreases with
age19 and in our previous study12,
we found a negative correlation between the 2 variables. It was
therefore not surprising that TAMMV decreased over the 10-year interval
in the patients in whom we succeeded in repeating the study. It also
indicates that there has been no significant vasculopathy that would
produce stenosis and associated increased TAMMV. The other possible
factor is the effect of hydroxyurea, which has been associated with
decreasing TAMMV and useful in preventing primary stroke as an
alternative to chronic transfusion therapy20-22.
Moreover, the significant increase in the HbF level between the 2
studies, could be attributed to hydroxyurea effect.
Our previous studies12,23 also showed that silent
brain infarcts (SBI) are uncommon in our patients under the age of 12
years, although among adult Kuwait patients, the prevalence is
~20%24. This is the reverse of what
has been reported among American patients in whom SBI is common in early
childhood and rare after 16 years. We have interpreted this as effective
protection from cerebral vasculopathy, that is provided by elevated HbF
levels at the critical period of 2 - 3 years of age, when vasculopathy
is established, hence the peak incidence of ischemic stroke in
susceptible patients is between the ages of 7 and 10
years6. However, before the age of 3 years, most of
our patients have HbF levels of 20 -
>30%25, thus inhibiting the development
of significant vasculopathy. There is still ongoing low-level chronic
inflammation, hence the relative severity of SCD among our adult
patients and the increased prevalence of SBI13,24,26.
The major limitation of this study is the small sample size. Larger
prospective studies are required to investigate long-term effects of SCD
on cerebral vasculopathy in patients with elevated HbF. It is also
important to correlate TCDI indices with MRI/MRA findings, as well as
neurological and psychological examination results especially in
patients with very low TAMMV since we do not have many patients with
abnormally elevated values.