Double Trouble: Stroke in a Child with Down's Syndrome

Abstract

Down's syndrome (trisomy 21) is well recognized to be associated with several autoimmune conditions such as hypothyroidism, celiac disease, and diabetes mellitus. Antiphospholipid syndrome (APS), an immune disorder, can cause a stroke due to the prothrombotic state. APS is associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and systemic vasculitis, as well as Down's syndrome. Down's syndrome is linked to several other risk factors for stroke including congenital heart disease, moyamoya disease, and arterial dissection. We present the case of a 3-year-old girl child patient with Down's syndrome, who presented with an acute arterial ischemic stroke secondary to carotid artery dissection and subsequently was also confirmed to have APS. We review the literature on Down's syndrome and APS, the proposed pathophysiology, and management strategies. We present a case of a 3-year-old girl with Down's syndrome and who presented with stroke, review previously published cases, and discuss the conditions and their management. Autoimmune conditions, such as antiphospholipid syndrome, are more common in individuals with Down's syndrome, and as such should be investigated when these children present with symptoms suggestive of stroke.

Keywords

Down's syndrome - trisomy 21 - antiphospholipid syndrome - stroke - carotid dissection - pediatrics

Author's Contributions

R.B., J.R., and L.K. researched and prepared the manuscript. R.B., G.H., A.K., and S,R, reviewed the article. R.J. supplied images.

Publication History

Received: 22 November 2021

Accepted: 02 January 2022

Article published online:
14 February 2022

• References

• 1 Akins PT, Axelrod YV, Arshad ST, Guppy KH. Initial conservative management of severe hemispheric stroke reduces decompressive craniectomy rates. Neurocrit Care 2016; 25 (01) 3-9
• 2 RCPCH. 2020 Stroke in childhood - clinical guideline for diagnosis, management and rehabilitation. Accessed December 7, 2020: https://www.rcpch.ac.uk/resources/stroke-childhood-clinical-guideline-diagnosis-management-rehabilitation
• 3 Grau AJ, Brandt T, Buggle F. et al. Association of cervical artery dissection with recent infection. Arch Neurol 1999; 56 (07) 851-856
• 4 Beslow LA, Smith SE, Vossough A. et al. Hemorrhagic transformation of childhood arterial ischemic stroke. Stroke 2011; 42 (04) 941-946
• 5 Sammaritano LR. Antiphospholipid syndrome. Best Pract Res Clin Rheumatol 2020; 34 (01) 101463
• 6 Sherer Y, Levy Y, Shoenfeld Y. Intravenous immunoglobulin therapy of antiphospholipid syndrome. Rheumatology (Oxford) 2000; 39 (04) 421-426
• 7 Avcin T, Cimaz R, Silverman ED. et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics 2008; 122 (05) e1100-e1107
• 8 Sarecka-Hujar B, Kopyta I. Antiphospholipid syndrome and its role in pediatric cerebrovascular diseases: a literature review. World J Clin Cases 2020; 8 (10) 1806-1817
• 9 Groot N, de Graeff N, Avcin T. et al. European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis 2017; 76 (11) 1788-1796
• 10 Sato T, Nakamura H, Fujieda Y. et al. Factor Xa inhibitors for preventing recurrent thrombosis in patients with antiphospholipid syndrome: a longitudinal cohort study. Lupus 2019; 28 (13) 1577-1582
• 11 Benhamou Y, Miranda S, Armengol G. et al. Infliximab improves endothelial dysfunction in a mouse model of antiphospholipid syndrome: Role of reduced oxidative stress. Vascul Pharmacol 2015; 71: 93-101
• 12 Wincup C, Ioannou Y. The differences between childhood and adult onset antiphospholipid syndrome. Front Pediatr 2018; 6: 362
• 13 Requena-Silla Y, Rosenfield CG, Miller LC. Antiphospholipid antibodies and Down syndrome: a case series. J Pediatr Hematol Oncol 2002; 24 (07) 575-578
• 14 Keeling D, Mackie I, Moore GW, Greer IA, Greaves M. British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol 2012; 157 (01) 47-58
• 15 Gatenby P, Tucko R, Andrews C, O'Neil R. Antiphospholipid antibodies and stroke in Down syndrome. Lupus 2003; 12 (01) 58-62
• 16 Medina G, Calleja C, Morán M, Vera-Lastra O, Jara LJ. Catastrophic antiphospholipid syndrome in a patient with Down syndrome. Lupus 2009; 18 (12) 1104-1107
• 17 Gru A, Dehner LP. Catastrophic antiphospholipid syndrome in a child with trisomy 21. An acquired thrombopathy with a discussion of thrombopathies in childhood. Pediatr Dev Pathol 2010; 13 (03) 178-183
• 18 Imagi T, Matsushita T, Matsushita M. et al. Brain stem infarction in a 6-year-old boy with Down syndrome. Brain Dev 2019; 41 (06) 555-558
• 19 Hoxha A, Calligaro A, Bortolati M, Tonello M, Guariso G, Ruffatti A. The antiphospholipid syndrome and infections in a child with trisomy 21. Autoimmun Rev 2008; 8 (02) 121-123