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.