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      Neurologic complications of sickle cell disease in Africa : A systematic review and meta-analysis

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      , MD, , MD, , MD, , MD, FEBN
      Neurology
      Lippincott Williams & Wilkins

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          Abstract

          Objective:

          To summarize prevalence data on the neurologic complications of sickle cell disease (SCD) in Africa.

          Methods:

          We searched EMBASE, PubMed, and African Index Medicus to identify all relevant articles published from inception to May 31, 2016. Each study was reviewed for methodologic quality. A random-effects model was used to estimate the prevalence of neurologic complications of SCD across studies.

          Results:

          Thirty-one studies were included. Methodologic quality was high or moderate in 90% of studies. Stroke, conditional and abnormal cerebral blood flow, seizures, and headache were the complications most frequently reported, with overall prevalence rates of 4.2%, 10.6%, 6.1%, 4.4%, and 18.9%, respectively. Some complications, like silent brain infarcts, peripheral neuropathies, neurocognitive deficits, or moyamoya disease, have been rarely or not studied at all in the African setting. Incidence data were scarce and of poor quality.

          Conclusions:

          The burden of neurologic complications of SCD is important in Africa and most likely underestimated. A better evaluation of this burden requires larger prospective studies using standard up-to-date screening methods. Accessibility to diagnostic tools such as neuroimaging, transcranial Doppler, EEG, and neuropsychological evaluation, as well as to preventive and therapeutic interventions and trained health care providers, should be improved in routine clinical practice.

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          Most cited references43

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          Stroke With Transfusions Changing to Hydroxyurea (SWiTCH).

          Stroke is a devastating complication of sickle cell anemia (SCA) with high recurrence if untreated. Chronic transfusions reduce recurrent strokes but have associated morbidities including iron overload. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) was a multicenter phase 3 randomized trial comparing standard treatment (transfusions/chelation) to alternative treatment (hydroxyurea/phlebotomy) for children with SCA, stroke, and iron overload. SWiTCH was a noninferiority trial with a composite primary end point, allowing an increased stroke risk but requiring superiority for removing iron. Subjects on standard treatment received monthly transfusions plus daily deferasirox iron chelation. Subjects on alternative treatment received hydroxyurea plus overlap transfusions during dose escalation to maximum tolerated dose (MTD), followed by monthly phlebotomy. Subjects on standard treatment (N = 66) maintained 30% sickle hemoglobin (HbS) and tolerated deferasirox at 28.2 ± 6.0 mg/kg/d. Subjects on alternative treatment (N = 67) initiated hydroxyurea and 60 (90%) reached MTD at 26.2 ± 4.9 mg/kg/d with 29.1% ± 6.7% fetal hemoglobin (HbF). Adjudication documented no strokes on transfusions/chelation but 7 (10%) on hydroxyurea/phlebotomy, still within the noninferiority stroke margin. The National Heart, Lung, and Blood Institute closed SWiTCH after interim analysis revealed equivalent liver iron content, indicating futility for the composite primary end point. Transfusions and chelation remain a better way to manage children with SCA, stroke, and iron overload.
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            Central nervous system complications and management in sickle cell disease.

            With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ∼11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA (3% and 10%, respectively). In high-income countries, RCTs (Stroke Prevention in Sickle Cell Anemia [STOP], STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TCD With Transfusions Changing to Hydroxyurea [TWiTCH]). Also in high-income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (Stroke With Transfusions Changing to Hydroxyurea [SWiTCH]) or silent cerebral infarcts (Silent Infarct Transfusion [SIT] Trial). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention.
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              A global perspective on sickle cell disease.

              The global burden of sickle cell disease (SCD) is now being increasingly realized. SCD poses a significant public health problem in sub-Saharan Africa, the Middle East, some regions of India, the Caribbean, and Brazil. In many of these regions, progress in the management of SCD has been slow. Long-term North-South and South-South partnerships between SCD professionals, funding agencies, governments, and industry are needed to help reduce the high disease burden in developing countries, through widespread SCD education, relevant research and implementation of evidence-based cost-effective interventions. A group of SCD professionals have responded with action by forming a global network. Copyright © 2012 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                Journal
                Neurology
                Neurology
                neurology
                neur
                neurology
                NEUROLOGY
                Neurology
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0028-3878
                1526-632X
                03 October 2017
                03 October 2017
                : 89
                : 14
                : 1516-1524
                Affiliations
                From the Department of Medicine (J.J.N.), Groote Schuur Hospital and University of Cape Town, South Africa; Department of Medicine and Medical Specialties, Faculty of Medicine and Biomedical Sciences (M.K.M.), University of Yaoundé, Cameroon; Division of Neurorehabilitation, Department of Clinical Neurosciences (N.N.), Geneva University Hospitals, Switzerland; Brain Infections Group, Institute of Infection and Global Health (J.K.-T.), University of Liverpool; and Department of Neurology (J.K.-T.), The Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
                Author notes
                Correspondence to Dr. Kamtchum-Tatuene: tatuene@ 123456liverpool.ac.uk
                [*]

                These authors contributed equally to this work.

                Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by the University of Liverpool through the Wellcome Trust/COAF block grant for Open Access.

                Article
                NEUROLOGY2017793844
                10.1212/WNL.0000000000004537
                5631172
                28864674
                35aa83da-c2a6-4825-95c9-9b03db355985
                Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

                This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 January 2017
                : 22 June 2017
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