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Silent Cerebral Infarct in Sickle Cell Anemia Patients of Southern Turkey

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Silent Cerebral Infarct in Sickle Cell Anemia Patients of Southern Turkey Turkish Journal of Medical Sciences Turk J Med Sci (2020) 50: 1887-1893 http://journals.tubitak.gov.tr/medical/ © TÜBİTAK Research Article doi:10.3906/sag-2003-192 Silent cerebral infarct in sickle cell anemia patients of southern Turkey 1, 2 3 Ezgi NAFİLE SAYMAN *, Göksel LEBLEBİSATAN , Şerife LEBLEBİSATAN , 4 2 1 Kenan BIÇAKÇI , Yurdanur KILINÇ , Adnan BARUTÇU 1 Department of Pediatrics, Faculty of Medicine, Çukurova University, Adana, Turkey 2 Department of PediatricHematology, Faculty of Medicine, Çukurova University, Adana, Turkey 3 Department of Radiology, Adana City Hospital, Adana, Turkey 4 Department of Radiology, Faculty of Medicine, Çukurova University, Adana, Turkey Received: 23.03.2020 Accepted/Published Online: 27.06.2020 Final Version: 17.12.2020 Background/aim: Silent cerebral infarct (SCI) is an ischemic lesion seen before clinical signs of brain infarct and ischemic changes in brain tissue. This study aimed to detect SCI with noninvasive methods and to determine related risk factors in patients with sickle cell anemia (SCA). Materials and methods: Fifty-four SCA patients who had no history of cerebral infarct and whose neurological examinations were normal were included in this study. Brain magnetic resonance imaging (MRI) and diffusion MRI were taken and the acquired data was compared statistically. Results: SCI was detected in 11.1% (6/54) of the patients. No statistical differences in age, sex, physical examination findings, or treatments were detected between the 2 groups (with and without SCI). When examined in terms of HbS, the median (min–max) value in SCI-positive patients was 85.4 (80.5–92.1); the median value was 77.2 (49.0–96.7) in SCI-negative patients. The HbS values of the SCI group were statistically significantly higher than those of the group without SCI (P = 0.014). Patients with the HbSS or HbSβ0 genotypes had a significantly higher prevalence of SCI when compared with other sickle cell syndromes (P = 0.038). Conclusion: SCI is not uncommon among SCA patients in Turkey. The presence of homozygote HbSS/Sβ0 genotype, high MCV, and HbS are risk factors for SCI. Key words: Sickle cell anemia, silent cerebral infarct, stroke, magnetic resonance imaging, children 1. Introduction noninvasive imaging methods in patients with SCA before Sickle cell anemia (SCA) is widely distributed in Africa any possible serious complications, such as CNS events, as and the Mediterranean region [1,2]. Sickle hemoglobin well as to identify the predisposing factors and shed light (Hb) is the most common abnormal Hb in Turkey, with a on treatment protocols. frequency of 0.37%–0.60%, and an HbS heterozygosity of 3%–44% in the Çukurova region [3]. 2. Materials and methods Central nervous system (CNS) complications, such Fifty-four SCA patients,including children, adolescents, as stroke, are among the most devastating manifestations and young adults(26 female, 28 male), who had no of SCA. Silent cerebral infarcts (SCI) are detected by previous stroke history or abnormal neurological findings magnetic resonance imaging procedures but do not and were followed-up with by the PediatricHematology cause abnormalities on neurological examination. These Clinic of Çukurova University, were included in the study. ischemic lesions seem to be related to the recurrence of The patients were aged between 5 and 31 years. These an infarct; either clinical stroke or SCI are associated with patients underwent brain magnetic resonance imaging transient ischemic attack (TIA), and also related with mild (MRI) and diffusion MRI for SCI. mental retardation and future hemorrhagic stroke [4,5]. A detailed evaluation of the patients’ history A plethora of literature is available on SCI in children, (treatments, crises, erythrocyte transfusions, or apheresis) but much less research is available where SCA is concerned, was noted. Exclusion criteria included abnormal findings and rarely includes studies from Turkey. Our study, on neurological examination, a painful or hemolytic crisis conducted in southern Turkey, aimed to detect SCI by during outpatient clinic control, a history of painful or * Correspondence: [email protected] 1887 This work is licensed under a Creative Commons Attribution 4.0 International License. NAFİLE SAYMAN et al. / Turk J Med Sci hemolytic crisis within the past 3 months, a history of SCI positivity and the area under the ROC curve was infection within the last month, or a blood transfusion examined. Statistical significance level was established as within the last 3 months. Patients without any neurological 0.05 in all tests. findings on physical examination were included in the study. 3. Results Verbal and written informed consent about the purpose Of the 54 SCA patients undergoing follow-up and of the examinations was obtained from patients aged >18 treatment at the Pediatric Hematology Department, 6 years, or from patients’ families (for patients <18 years). patients had SCI based on the brain MRI and diffusion Conventional MRI and diffusion MRI of each patient’s MRI examinations. When the patients are distributed by brain was performed at our hospital, using a 1.5 Tesla MRI age group, 3 of the patients were under the age of 8, 34 device located in the Department of Radiodiagnostics. were between the ages of 8 and 16, and 17 were older than During MRI imaging, the patient was not given any 16 years. Five (14.7%) of the patients in the 8–16 group anesthetic agent. The MRI data were reported by members and 1 (5.9%) of the patients over the age of 16 were SCI of the Radiodiagnostics Academic Staff. (+).When examining the presence of SCI within these Cerebral silent infarcts were identified as hyperintense age groups, there was no statistically significant difference focal lesions in T2 and hypointense focal lesions in T1 among the age groups (P = 0.756). Distribution of patients that were less than 15mm and greater than 3mm on MRI, by age group is shown in Table 1. which enables the detection of lesions in regions such as Patient 1 (S.D.): A 15-year-old female patient was the basal ganglia that are indistinguishable in computed regularly using folic acid and 18 mg/kg of hydroxyurea. tomography (CT) [6–8]. Her liver was normal in size, but she had developed Ethics committee approval (Session No.40, Decision otosplenectomy, regularly received blood transfusions, No. 16, date: 06.03.2015) was obtained from the Non- and had a history of more than 5 painful crises per year. Interventional Clinical Research Ethics Committee of Without a blood transfusion, her HbS level was 84.7%. Çukurova University Faculty of Medicine. Patient 2 (S.G.): A 19-year-old male patient was Statistical analysis regularly using folic acid, zinc sulfate, deferasirox, and The statistical package for the social sciences, which 15 mg/kg hydroxyurea. He had a normal-sized liver prior is known as SPSS (IBM Corp., Armonk, NY, USA) v. surgical splenectomy, a history of painful crises, and acute 23.0 program was used for statistical analysis of the data. chest syndrome. His HbS level was 90.5% (Figures 1 and Categorical measurements were summarized as numbers 2). and percentages, while continuous measurements were Patient 3 (F.D): A 16-year-old male patient was summarized as median and minimum–maximum. regularly using folic acid, zinc sulfate, and 8 mg/kg of Fischer’s exact test was used to compare categorical hydroxyurea. Hepatomegaly was present. The spleen was variables. The Shapiro–Wilk test was used to determine normal in size, and the patient had a history of more than whether the parameters in the study showed normal 5 painful crises per year. His HbS level was 83.3%. distribution. In comparing continuous measurements Patient 4 (S.B): A 16-year-old female patient was between groups, distributions were checked, and the regularly using folic acid. She had a normal-sized liver, Mann–Whitney U test was used for parameters that did prior surgical splenectomy, and had only had 1 painful not show normal distribution. In the study, based on the crisis event. Her HbS level was 80.5%. HbS value according to the MRI results, the sensitivity Patient 5 (Ç.S.T.): An 8-year-old male patient was and specificity values ​​were calculated according to the regularly using folic acid, zinc sulfate, and 22 mg/kg of Table 1. Distribution of patients by age groups. SCI (+) SCI (–) Total P* Age groups (n = 6) (n = 48) (n = 54) n (%) n (%) n (%) < 8 years 0 (0) 3 (100) 3 (100) 0.756 8–16 years 5 (14.7) 29 (85.3) 34 (100) >16 years 1 (5.9) 16 (94.1) 17 (100) *Fisher’s exact test 1888 NAFİLE SAYMAN et al. / Turk J Med Sci Figure 2. Silent cerebral infarctions in the left frontal and parietal Figure 1. Axial FLAIR MR image. Biparietal white matter white matter. hyperintensities with cystic changes at right. When the drugs used by the patients with sickle cell hydroxyurea. Hepatomegaly was present, the spleen was anemia were investigated, approximately 80% of the normal in size, and there was a history of acute chest pain patients were using hydroxyurea (43 people). However, and painful crises. His HbS level was 92.1%. in terms of the presence of SCI, no statistical difference Patient 6 (D.T.): A 16-year-old male patient regularly was found between them (P =0.590). Comparison of the used folic acid and zinc sulfate. The liver was normal in groups in terms of drugs used by patients is summarized size, and autosplenectomy had developed. He had a history in Table 4. of painful crisis and priapism. His HbS level was 86.1%. ROC analysis was performed in terms of the presence The hemoglobin electrophoresis results of the patients of a cut-off value in determining the statistically significant were examined.
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