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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 1  |  Issue : 2  |  Page : 92-96

Normative time averaged mean maximal velocities value using imaging transcranial Doppler ultrasound in stable sickle cell disease patients in Zaria


Department of Radiology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Submission09-Jun-2020
Date of Decision22-Jun-2020
Date of Acceptance29-Jul-2020
Date of Web Publication30-Nov-2020

Correspondence Address:
Halimat Mono Mohammed
Department of Radiology, ABU, Ahmadu Bello University Teaching Hospital, Zaria
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JRMT.JRMT_11_20

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  Abstract 


Introduction: Middle cerebral artery (MCA) velocimetry in sickle cell patients using noninvasive transcranial ultrasound scan is an important index for predicting stroke. Stroke is one of the most feared clinical complications of sickle cell anemia. Transcranial Doppler (TCD) enables early detection of arterial abnormalities to institute primary preventive measures. Aims and Objectives: The aims and objectives of the study were to determine the normal range of time-averaged mean maximal velocities (TAMMAX) in the MCA on imaging TCD ultrasound in stable sickle cell patients in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. Materials and Methods: This was a cross-sectional study conducted from December 2016 to May 2017 in the Radiology Department of ABUTH, Zaria. Stable sickle cell anemic children numbering 75 within the age of 2–16 years were recruited for the study. Approval was granted by the ethical committee of ABUTH. The TAMMAX of the MCA was measured by Doppler ultrasound which is done with the patient lying supine, the probe is placed on the temporal bone after application of the gel and the MCA assessed on grayscale, color, and spectral Doppler. The results were recorded in the datasheet. Data Analysis: All measurements were analyzed using the Statistical Package for the Social Sciences version 20. P < 0.05 was considered as statistically significant and a confidence interval of 95% was used. TAMMAX was classified based on the STOP criteria. Findings were presented in the form of summarizing indices (tables and charts). Means and standard deviations were computed. Results: A total of 75 patients were included in the final data with a mean age of 8.5 years and male-to-female ratio was 1.04:1. The mean TAMMAX of sickle cell subjects was 84.32 cm/s and 80.31 cm/s in the right and left MCA, respectively. Conclusion: The TAMMAX of stable sickle cell disease patients all fell below 170 cm/s and so the detection of abnormal velocities during the scan is an indicator of the likelihood of stroke and so preventive measures can be instituted early.

Keywords: Transcranial Doppler ultrasound, stroke, sickle cell disease


How to cite this article:
Mohammed HM, Bello N, Aliyu I, Zubair M, Ibrahim M Z, Lawal S, Muhammad R. Normative time averaged mean maximal velocities value using imaging transcranial Doppler ultrasound in stable sickle cell disease patients in Zaria. J Radiat Med Trop 2020;1:92-6

How to cite this URL:
Mohammed HM, Bello N, Aliyu I, Zubair M, Ibrahim M Z, Lawal S, Muhammad R. Normative time averaged mean maximal velocities value using imaging transcranial Doppler ultrasound in stable sickle cell disease patients in Zaria. J Radiat Med Trop [serial online] 2020 [cited 2021 Aug 4];1:92-6. Available from: http://www.jrmt.org/text.asp?2020/1/2/92/301893




  Introduction Top


Sickle cell anemia is a genetic disorder in individuals with sickle cell genes. This gene is estimated to be present in one of every four Nigerian, thus making sickle cell anemia the most common genetic disease in the country.[1],[2]

The relatively high prevalence rate of this catastrophic complication in this young group of patients has been the reason behind the adoption of screening programs conducted early in life to detect and prevent stroke in sickle cell disease (SCD). Nigeria has a population of 160 million and an estimated sickle gene carrier rate of about 40%, with about 150,000 children being born annually with SCD.[3] She should therefore be at the forefront of such preventive programs.

Stroke affects 6% of children with this condition by the age of 10 years with a peak incidence between the ages of 2 and 7 years.[4] Stroke incidence is highest in children with HbSS and the risk of stroke can be identified by transcranial Doppler (TCD) ultrasound scan. The stroke prevention trial in sickle cell anemia (STOP) study showed that the risk of stroke can be reduced by 90% by regular blood transfusions to keep the amount of S hemoglobin in the blood below 30%.[5]

This study aimed at establishing the normal reference values of time-averaged mean maximal velocities (TAMMAX) in the middle cerebral artery (MCA) of stable sickle cell patients using imaging TCD ultrasound. This would serve as a baseline for developing stroke preventive strategies in our own environment

Study design

This was a hospital based cross-sectional study performed in Ahmadu Bello University Teaching Hospital (ABUTH) which is a tertiary hospital in northwestern Nigeria. It is located in the ancient city of Zaria, Kaduna state. The institution serves as a referral center for six states that make up the geopolitical region with an estimated population of about 35 million by census figure of 2006.[6] The department of radiology, ABUTH, provides a wide range of radiological services including ultrasonography with Doppler facilities including imaging TCD.

It was conducted from December 2016 to May 2017 after approval was obtained from the Ethical Committee of ABUTH, Zaria.

Study group

The study population was 75 stable sickle cell patients aged 2–16 years seen at sickle cell clinics in ABUTH Zaria. We define stable as the period when the children are in the optimal state of health, free from all crises or other acute complications of SCD in the preceding month. Inclusion criteria included (1) patients who freely give informed consent through their caregivers or parents and (2) stable sickle cell patients aged 2–16 years with no history of stroke, while the exclusion criteria were (1) patients below 2 and those above 16 years, (2) sickle cell anemic patients with a history of stroke, (3) patients who refused to give informed consent, (4) patients with a history of vascular or hypercoagubility state, (5) patients with a history of blood dyscrasias, (6) history of vascular anomalies, and (7) children with fever, pain crisis, or any ill-health.

Aims

The aim was to determine the normal range of TAMMAX in the middle cerebral circulation on imaging TCD ultrasound in stable sickle cell anemic subjects in ABUTH, Zaria.


  Materials and Methods Top


All consecutive patients who fulfilled the inclusion criteria within this study period were enrolled into the study. An ultrasound machine Mindray DC-8 (China 2011) equipped with Doppler facilities (color and pulsed Doppler) coupled with 2 MHz Phased array TCD probe. The following adjustments and measurement were obtainable on the machine, scale (PRF) range, sample volume range, depth range, and TAMMAX calculation capability.

Technique of imaging transcranial Doppler

The TAMMAX of the MCA was measured by Doppler ultrasound which is done with the patient lying supine, the probe is placed on the temporal bone after application of gel about (1 cm) to the zygomatic arch and immediately anterior and slightly superior to the tragus of the ear. On gray scale, the hypoechoic butterfly-shaped midbrain is visualized. From here, the circle of Willis can be easily depicted [Figure 1].
Figure 1: Grayscale axial transcranial ultrasound section at the level of cerebral peduncles for the demonstration of the circle of Willis

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After locating the circle of Willis, the transducer was angled slightly anteriorly for the insonation of the M1 and M2 segments of the MCAs which has the highest velocities of all the intracranial vessels. The color control was turned on and examination began by visualizing the M1/M2 segment of the MCA [Figure 2]. The pulsed Doppler gate at an angle 0° was placed on the artery to obtain a velocity waveform.
Figure 2: Imaging transcranial Doppler ultrasound on color Doppler showing the ipsilateral middle cerebral artery and posterior cerebral artery of the circle of Willis

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Spectral Doppler tracing of the ipsilateral MCA was obtained. A minimum of five tracings of the artery were generated, and the TAMMAX auto calculated and recorded [Figure 3] for both the hemispheres.
Figure 3: Spectral Doppler waveform of the middle cerebral artery. Provides information about the flow characteristic in an arterial segment

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Examination results were interpreted using the STOP criteria [Table 1], as normal if TAMMAX values were <170 cm/s, conditional if TAMMAX values were between 170 and 184 cm/s [Table 2], high conditional if TAMMAX values were between 185 and 199 cm/s, and abnormal if TAMMAX values were ≥200 cm/s.
Table 1: Stop criteria

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Table 2: The mean age distribution

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Data analysis

The results and data generated for patients with SCD and the control group were first entered into the Excel datasheet before being analyzed using the Statistical Package for the Social Sciences version 20.0 Chicago, Illinois, USA.

Statistical analysis of the Doppler parameters' TAMMAX was performed. Means and standard deviation of the variables were computed and the result presented in appropriate tables and charts. The mean and standard deviation were computed.

Ethical consideration

Prior to the commencement of this study, approval was granted by the Ethical and Research Committee of ABUTH.


  Discussions Top


This study looked at the Doppler parameter values of the MCA in stable sickle cell patients using imaging TCD. While this intervention is a routine standard of care in sickle cell patients in Zaria, Nigeria, a lot of other centers are yet to implement it.

The sex distribution of subjects in this study was male-to-female ratio = 1.04:1. This ratio was similar to that obtained by Lagunju et al. in Ibadan, Southwest Nigeria, where a ratio of 1.5:1 was reported.[7]

The age range of 2–16 years with a mean of 8.5 years ± 4.2 for sickle cell subjects in this study was also similar to that described by Lagunju et al. where the age of their patients ranged from 3 to 16 years with a mean of 9.2 years ± 4.0.[7]

Subject

All the 150 patients recruited in this study had TAMMAX values of <170 cm/s. No abnormal or conditional risk value was obtained. This result is in agreement with the results from other studies conducted in Kenya by Makani where none of the 105 children screened had abnormal results and only two had conditional risk.[8]

In São Paulo, Mary et al. evaluated 77 patients with SCD, aged between 2 and 16 years, and found two patients (1.6%) with abnormal time-averaged maximum mean velocity and 11 (14.3%) with conditional results.[9] Gisele et al. also got no abnormal finding and only one patient had a conditional result.[10]

Higher values of abnormal results were obtained in the STOP study where the proportion of abnormal results was 9.7%.[11] A prevalence of 10% abnormal results was recorded in a study in Philadelphia by Kwiatkowski et al.,[12] Adam et al. reported a similar prevalence of 9.7% of abnormal results in Georgia, USA,[13] while 3%–34% was reported from Germany,[14] France,[15] and African–American cohorts.[16] However, a small sample size of 47 children was used in the above-mentioned German study which may not be truly representative and so may account for the higher values.

In Nigeria, Aminu et al. in Kano had 3% high risk and 84% standard risk.[17] Motunrayo et al. reported a prevalence of 10.8%[18] and Lagunju et al. reported lower prevalence risk of abnormal results of 4.7% and 8.4% in two different studies in Ibadan.[7] In a study done in National Hospital Abuja, Nigeria, by Oluseyi O using imaging TCD, abnormal velocities were recorded in six (4.7%) of the HbSS patients.[18] Kofo S in Lagos, Nigeria, between March 2011 and September 2013 screened 2331 children and classified 70.4% as normal, 19% conditional, and 9.3% abnormal.[17]

The TAMMAX of the subjects from this study was 84.32 cm/s ± 20.42 and 80.31 cm/s ± 24.35, right and left sides, respectively [Table 3]. These values are lower than that obtained in a cross-sectional nonimaging TCD ultrasound study of 388 subjects aged 3–16 years with SCD carried out in the sickle cell foundation Lagos by Motunrayo et al. in 2015 where the TAMMAX was 161 ± 26 cm/s and 149 ± 31 cm/s in HbSS and HbSC groups, respectively.[18] It was also lower than the 116.9 ± 21 cm/s obtained by Gisele et al. in São Paulo, Brazil.[10]
Table 3: The values of TAMMAX in the middle cerebral artery of the right and left cerebral hemispheres

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It is interesting to note that no conditional or abnormal result was recorded in this study. Lower frequencies of abnormal results were also noted in a multicenter study in Nigeria.[19] The reason for this is not quite clear. The most probable explanation could be that Nigerian children, particularly in Northern Nigeria, stroke is developed at relatively lower velocities than has been reported. Alternatively, it could be assumed that our previous stroke preventive measures in SCD are beginning to yield dividends, and the study conducted over longer duration could perhaps provide the answer.

Operator, patient, or machine variables may affect the measurement of TCDs. While operator and patient variables were optimized in this study, machine variables were different from the STOP trial,[20] which had used a conventional TCD machine for nonimaging study. This study used a duplex power Doppler ultrasound machine for TCDI study whose readings have been shown to be about 20% lower than nonimaging.[11] The difference in imaging modality may limit comparisons made between TCD velocities measured by the various methods.

The difference in the values obtained may also be due to the methodology used. As some of the studies were longitudinal (e.g., the study by Lagunju[7] in which subjects had serial TCD done over 2 years, allowing conversion from conditional to abnormal risk), while this case study is cross sectional. This study was carried out on stable SCD patients as opposed to other studies where a stable state was not an inclusion criterion.[10]

The results may also vary depending on the Doppler parameter being used. The STOP study used TAMMAX, while other studies use TAMEAN or PSV, the STOP criteria still being used as a guide.


  Conclusion Top


This study showed that the MCA velocimetry parameters of stable SCD patients were lower than that observed in the STOP study. The reason for this is yet to be ascertained. Could it be that Nigerians and Africans for that matter develop stroke at values lower than that of Caucasians? And so, 170 cm/s being used as cutoff actually allows a lot of patients, especially those with silent stroke to go undetected?

Recommendation

A randomized trial should be carried out on a larger scale.

Acknowledgment

The authors would like to thank Prof. Tabari A M for his support and advice in writing this article.

Financial support and sponsorship

This was a self-sponsored study.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Nnaji A, Ezeagwuna DA, Innaji IJF, Osakwe JO, Nwigwe AC, et al. Prevalence and pattern of sickle cell disease in premarital couples in south eastern Nigerian. Niger J Clin Pract 2013;16:309-14.  Back to cited text no. 2
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Powars D, Wilson B, Imbus C, Pegelow C, Allen J, et al. The natural history of stroke in sickle cell disease. Am J Med 1978;65:461-71.  Back to cited text no. 5
    
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Makani J, Kirkham FJ, Komba A, Ajala-Agbo T, Otieno G, Fegan G, et al. Risk factors for high cerebral blood flow velocity and death in Kenyan children with Sickle Cell Anaemia: Role of haemoglobin oxygen saturation and febrile illness. Br J Haematol 2009;145:529-32.  Back to cited text no. 8
    
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Hokazono M, Gisele SS, Edina MKS, Josefina APB. et al. Results from TCD examination in children and adolescents with SCD and correlation between the TAMMV and hematological characteristics: A cross sectional analytical study. Sao Paulo Med J 2011;129:134-8.  Back to cited text no. 9
    
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Gisele S, Perla V, Maria F, Henrique J, Marcos I, Ayrton M. Brain MRI abnormalities in adult patients with SCD, correlation with TCD findinds. stroke 2009;40:2408-12. [doi: 1161/STROKEAHA.108.537415].  Back to cited text no. 10
    
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Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998;339:5-11.  Back to cited text no. 11
    
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Kwiatkowski JL, Hunter JV, Smith-Whitley K, Katz ML, Shults J, Ohene-Frempong K. Transcranial Doppler ultrasonography in siblings with sickle cell disease. Br J Haematol 2003;121:932-7.  Back to cited text no. 12
    
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Adams RJ, McKie VC, Carl EM, Nichols FT, Perry R, Brock K, et al. Long-term stroke risk in children with sickle cell disease screened with transcranial Doppler. Ann Neurol 1997;42:699-704.  Back to cited text no. 13
    
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19.
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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