Pattern of Cerebral Blood Flow Velocity Using Transcranial Doppler Ultrasonography in Children with Sickle Cell Disorder in Lagos State, Nigeria
Received: March 23, 2017
Accepted: July 3, 2017
Mediterr J Hematol Infect Dis 2017, 9(1): e2017050 DOI 10.4084/MJHID.2017.050
This article is available on PDF format at:
| This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
accident (CVA) is a common, devastating neurological complication of
sickle cell disorder (SCD) with a high recurrent and mortality rate.
The Stroke Prevention Trial in Sickle Cell Anaemia study (STOP)
recommends routine screening with transcranial Doppler ultrasonography
in children aged two to sixteen years with SCD. The present study
assessed cerebral blood flow velocities of children with SCD in
accordance with the recommendation of routine screening by the STOP
Cerebrovascular accident (CVA) is one of the most devastating complications of SCD that causes high morbidity and mortality in children; approximately 11% of children with SCD have a CVA before the age of twenty years with a recurrence rate as high as 85% with the first three years of the first episode. The reported prevalence of CVA in children with SCD in Nigeria varied between 4.3% and 6.8%,[5–7] the recurrence rate was as high as 61.5% in one of the studies.
Children at risk of CVA can be identified using transcranial Doppler ultrasonography which enables evaluation of cerebral artery blood flow velocity with a sensitivity of ninety percent and specificity of one hundred percent when compared with cerebral angiography. The Stroke Prevention Trial in Sickle Cell Anaemia study (STOP) recommends that yearly TCD screening should be done for children with SCD between the ages of two years and sixteen years with a repeat within three months for those children with abnormal results. Following identified risk for a cerebrovascular accident in the anterior cerebral vessels in the extended STOP trial study, the vessels were insonated.
Early identification of children at risk of CVA with cerebral blood flow velocity of at least 200 cm/second and prompt interventions help to curtail the devastating neurological complication.
Few studies have reported the prevalence of abnormal cerebral blood flow velocities in children in Nigeria. Lagunju et al.[11,12] in Ibadan, Nigeria in two studies reported 4.7% and 8.4% results of high risk for a CVA, 22.1% of the subjects had a conditional risk for a CVA. Oniyangi et al. at Abuja, Nigeria reported that 6.9% of subjects had abnormal cerebral blood flow velocity and 81.4% had a normal study.
The present study aimed to determine the pattern of cerebral blood flow velocities of children with SCD that presents at Sickle Cell Foundation Centre, Nigeria within the studied period.
Materials and Methods
In all, 388 subjects were recruited with sample size calculation based on the previously reported prevalence of 8.4% by Lagunju et al. Total sample size was divided into three age strata. 130 subjects for the age group of less than five years, and 129 subjects each for the age group of five to ten years and eleven to sixteen years.
Approval for the present study was obtained from the Health Research Ethics Committee of Lagos State University Teaching Hospital.
The study was done using a Compumedics DWL Doppler machine (FDA K051 085) which is non-imaging. Recruited subjects TCD evaluations were done by one of the authors (M.O.) who had learned transcranial Doppler ultrasonography previously at the study center by a qualified trainer that does the transcranial Doppler ultrasonography at the center.
All recruited subjects had the Cerebral Blood Flow Velocities measured using a 2-MHz hand held probe attached to a Doppler box according to the Stroke Prevention in Sickle Cell Disease protocol. The velocities of blood flow in the middle cerebral artery, internal carotid artery and anterior cerebral arteries were measured. The highest velocity in each artery was recorded as the Time-Averaged Maximum Mean Velocity (TAMMV). TAMMV less than 170 cm/second was considered normal, values greater or equal 170 centimetre per second but less than 200 cm/second were conditional risks and velocity at least 200 cm/second was considered abnormal. Further classification as low and high Conditional Risk according to TAMMV of 170 to 184 cm/second and 185 to 199 cm/second respectively was done.
The minimum and maximum cerebral velocities were recorded in the left anterior cerebral velocity and right middle cerebral velocity respectively as shown in table 1.
The mean total TAMMV was highest in subjects below five years and lowest in subjects above ten years with a value of 161±26 and 149±31cm/sec respectively. Amongst the HbSS subjects, the mean TAMMV of 163±25 cm/second was highest in under-5s. The mean TAMMV values were consistently higher in all the age strata in HbSS than in HbSC subjects.
|Table 2. Mean Time-Average Maximum Mean Velocity according to age groups.|
In Table 3, the occurrence of abnormal TAAMV was seen only in HbSS subjects. The prevalence of abnormal cerebral blood flow velocity was 10.8%. Concerning HbSC subjects, all but one eight-year-old child had Conditional Cerebral Blood Flow Velocity.
For HbSS subjects, the frequency of normal Cerebral Blood Flow Velocity was highest in the 11 to 16-year-old age group (71.9%). The corresponding figures for younger age groups were 59.6% for under-5s and 59.1% for those between five and ten years. Thus, HbSS subjects in the 11 to 16-year-old age bracket had a higher frequency of normal Cerebral Blood Flow Velocity. Subjects within the age bracket of five and ten years had the highest prevalence of Abnormal Cerebral Blood Flow Velocity.
Conditional velocities were highest in subjects less than five years, intermediate in five to ten years and lowest in subjects eleven years above. Further classification of conditional velocities into high and low risk, eleven of the forty subjects in children below five years had a high conditional risk. The corresponding figure for five to ten years and eleven to sixteen years is five and three respectively.
|Table 3. Risk levels of Cerebral Blood Flow Velocities result (TAMMV) of subjects based on hemoglobin variants.|
|Table 4. Association between risk level of Cerebral Blood Flow Velocity and age group.|
The Stroke Prevention Trial in Sickle Cell Anaemia study (STOP) was carried out in African-American children with SCD. Values generated has been widely used in determining the risk for a CVA as applied in the present study. However, need for reassessment of cut-off values based on ethnicities and haplotypes has been suggested. So studies for re-evaluating race specific cut-off values for TAMMV are worthwhile.
Younger subjects had a higher prevalence of abnormal Cerebral Blood Flow Velocity in the current study, similarly to the findings by Adam et al. and Lagunju et al. However, there were specific differences in the age ranges. Subjects aged five to ten years in the current study had the highest value of abnormal velocity compared to under 5s in the study by Lagunju et al. and two peaks of two to nine years and nine to twelve years in the study by Adam et al. However, the under-5 age group in the present study had the highest prevalence of high conditional risk. A possible explanation for the disparity in the age with the highest prevalence could be that while this study is cross-sectional, the study by Lagunju et al. was a longitudinal study in which the subjects had serial TCD done over a two-year period. As noted by the authors, this allowed a number of the subjects with conditional risk to convert to abnormal risk. Also, the authors reported that the rate of conversion to abnormal risk was higher among subjects with high conditional risk than those with low conditional risk. In the current study, under-5were subjects have the highest prevalence of high conditional risk. Thus it can be suggested that if followed up with serial TCD this group is at significant risk of conversion to abnormal risk. Prevalence of CVA in SCD is commonest among children aged two to nine years, and this can account for the finding of high abnormal velocity in this age group compared to eleven years and above.
The mean value of Time-Averaged Maximum Mean Velocity was lower in HbSC subjects compared to HbSS subjects. In addition, none of the HbSC subjects had abnormal Cerebral Blood Flow Velocity. This datum is in keeping with reported lower TCD values and lower risk of CVA in HbSC people. The explanation for the fact that none of the HbSC subjects had abnormal velocity could be that hemoglobin SC disorder is associated with less severe hemolysis and the red cell life span is two times longer than HbSS. Thus they are less prone to hemolysis related vasculopathy and consequent abnormal TAMMV. Use of lower cut-off values of TAMMV have however been suggested in heterozygote children with SCD.[21,22] The occurrence of abnormal risk that was solely seen in HbSS subjects in the current study and others implies the need of prioritizing transcranial Doppler ultrasonography for HbSS subjects especially in regions like Nigeria where the machine and expertise are not readily available.
- Diallo D, Tchernia G. Sickle Cell Disease in Africa. Curr Opin Haematol 2002;9:111 https://doi.org/10.1097/00062752-200203000-00005
ME, Okolo AA, Rahimy CM. Newborn screening for sickle cell disease in a
Nigerian hospital. Public Health, 2008 Oct;122(10):1111-6 https://doi.org/10.1016/j.puhe.2008.01.008 PMid:18486954.
K, Weiner S, Sleeper L, Miller S, Embury S, Moohr J. Cerebrovascular
accidents in Sickle Cell Disease: Rates and Risk Factors. Blood.
- Hsu L. Specific Problems: Neurologic symptoms and strokes. Available at: scinfo.org/problem-oriented-clinical-guidelines/specific-problems-neurologic-symptoms-and-stroke. Accessed December 9, 2013
I, Frank-Briggs A. Stroke in Nigerian Children with Sickle Cell
Anaemia. J Public Health Epidemiol. 2011;3(9):407-9..
OJ, Adamson FG, Ogunseyinde O, Sodeinde O, Familusi JB. Stroke in
Nigerian children with sickle cell disease. Afr J Med Med Sci
2005;34(2):157-60. PMid:16749340 .
- Lagunju IA, Brown BJ, Famosaya AA. Childhood stroke in sickle cell disease in Nigeria. J Pediatr Neurol. 2011;9(1):49-53.
RJ, Nichols FT, Figueroa R, McKie V, Lott T. Transcranial Doppler
correlation with cerebral angiography in sickle cell disease. Stroke.
1992;23(8):1073-7 https://doi.org/10.1161/01.STR.23.8.1073 PMid:1636180.
F, Jones A, Adams R. Stroke Prevention in Sickle Cell Disease(STOP)
Study Guidelines for Transcranial Doppler Testing. J neeuroimaging.
2001;11(4):354-62 https://doi.org/10.1111/j.1552-6569.2001.tb00063.x .
JL, Granger S, Brambilla DJ, Brown RC, Miller st, Adams RJ, STOP Trial
Investigators. Elevated blood flow velocity in the anterior cerebral
artery and stroke risk in sickle cell disease: extended analysis from
the STOP trial. Br J Haematol. 2006; 134(3):333-9 https://doi.org/10.1111/j.1365-2141.2006.06193.x PMid:16848777 .
I, Sodeinde O, Brown B, Akinbami F, Adedokun B. Transcranial doppler
ultrasonography in children with sickle cell anemia: Clinical and
laboratory correlates for elevated blood flow velocities. J Clin
Ultrasound. 2014;42(2):89-95 https://doi.org/10.1002/jcu.22099 PMid:24166013 .
I, Sodeinde O, Telfer P. Prevalence of transcranial Doppler
abnormalities in Nigerian children with sickle cell disease. Am J
Hematol 2012;87(5):544-7. https://doi.org/10.1002/ajh.23152 PMid:22460323 .
O, Akano AO, Wakama TT, Oyesakin AB. Transcranial Doppler ultrasound
studies for the primary prevention of strokes among children with
sickle cell disease in Nigeria- a single tertiary center experience.
Research 2014;1:825. https://doi.org/10.13070/rs.en.1.825 .
JL, Hunter JV, Smith-Whitley K, Katz ML, Shults J. Transcranial doppler
ultrasonography in siblings with sickle cell disease. Br J Haematol.
RJ, McKie VC, Brambilla D, Carl E, Gallagher D, Nichols FT, et al.
Stroke prevention trial in sickle cell anemia. Control Clin Trials
RJ, Ohene-Frempong K, Wang W. Sickle cell and the brain. American
Society of Haematology. 2001;31-46 PMCid:PMC60990.
LL, Miller ST, Wright E, Kutlar A, McKie V, Wang W, et al. Stroke
Prevention Trial (STOP) and the Cooperative Study of Sickle Cell
Disease (CSSCD). J Paediatr Haematol Oncol.2003 Aug;25(8):622-8 https://doi.org/10.1097/00043426-200308000-00007 PMid:12902915.
IA, Brown BJ, Sodeinde OO. Chronic blood transfusion for primary and
secondary stroke prevention in Nigerian children with sickle cell
disease: a 5-year appraisal. Paediatr Blood Cancer.2013;60(12):1940-5 https://doi.org/10.1002/pbc.24698 PMid:23956197.
RB, Mortazavi MM, Kristian B, Keikhaei B, Mousakhani H, Azarpazhooh MR,
et al. Can STOP Trial Velocity Criteria Be Applied to Iranian Children
with Sickle Cell Disease. JOS 2014;16(2):97-101.
CR, Goss D, ODriscoll S, Mellor S, Pohl KR, Dick MC, et al.
Transcranial Doppler scanning and the assessment of stroke risk in
children with haemoglobin sickle cell disease. Arch Dis Child.
2008;93(2):138. https://doi.org/10.1136/adc.2007.125799 PMid:17925326 .
M, Silva GS, Silva EM, Braga JA. Results from transcranial Doppler
examination on children and adolescents with sickle cell disease and
correlation between the time-averaged maximum mean velocity and
haematologic characteristics: a cross sectional analytical study. Paulo
Med J. 2011 May;129(3):134-8 https://doi.org/10.1590/S1516-31802011000300003.
- Vieira C, de Oliveira CNC, de Figueiredo LAB, Santiago RP, Adanho CSA, Santana SS, et al. Transcranial Doppler in haemoglobin SC disease. Paediatr Blood & Cancer. 2017 May;64(5):e26342 https://doi.org/10.1002/pbc.26342 PMid:27957790.
Metrics powered by PLOS ALM
Copyright (c) 2017 Mediterranean Journal of Hematology and Infectious Diseases
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The Mediterranean Journal of Hematology and Infectious Diseases [eISSN 2035-3006] is owned by the U.C.S.C. and it is published by PAGEPress®, Pavia, Italy. All credits and honors to PKP for their OJS.