Advertisement

Thalassemia and Moyamoya Syndrome: Epidemiology and long-term outcome

Published:October 16, 2022DOI:https://doi.org/10.1016/j.ejpn.2022.10.002

      Highlights

      • Thalassemia related MMS may not be so rare, probably under-recognized compared to SCD.
      • The pathophysiological basis between the MMS & thalassemia remains to be deciphered.
      • Cerebral ischemic insult was the predominant brain lesion.
      • Thalassemia type, severity of anemia & transfusion dependency can affect prognosis.
      • Consensus guideline for diagnosis & management of Thalassemia related MMS is needed.

      Abstract

      Objectives

      Moyamoya Angiopathy (MMA) is a chronic, progressive intracranial vasculopathy. Unlike Sickle-cell-disease, thalassemia-syndrome has rarely been described in association with MMA. This study was aimed to analyze the demographic, clinical, radiological features and long-term outcome (and possible factors influencing prognosis) of Moyamoya Syndrome (MMS) in the largest cohort of thalassemia-related-to-MMS.

      Materials & methods

      A single-centered, observational study with longitudinal follow-up was undertaken for 12 cases of MMS-related-to-thalassemia-syndrome amongst 160 consecutive MMA patients. The baseline demographic, clinical and radiological characteristics were noted; and were longitudinally followed-up to assess disease progression (clinical or radiological). Fifteen previously reported cases of thalassemia and MMA were retrieved by literature search in PubMed and Google-Scholar using keywords “Moyamoya” AND “thalassemia”.

      Results

      The mean age at diagnosis of thalassemia-syndrome and diagnosis of MMS were 6.4 ± 6.55 years (mean ± SD) and 10.4 ± 8.68 years respectively in our 12 cases; 3.2 ± 2.25 years and 10.6 ± 6.1 years respectively in the previously reported 15 cases. Cerebral ischemic insult was the predominant brain lesion at base-line, noted in 91.7% of our cases and 80% of the previous cases. The mean hemoglobin, transfusion-dependency and previous splenectomy were seen in 8.7 ± 3.02 gm%, 33.3% and 8.3% of our cases respectively; 7.0 ± 3.04 gm%, 53.9% and 18.2% of previous cases. All our cases were medically managed for mean follow-up of 28.3 ± 13.9 months, none had evidence of angiographic progression, 1 of our 12 cases (8.3%) had new onset neuro-deficit and subsequent mortality, rest 11 of the 12 cases (91.7%) didn't have any appearance of silent cerebral infarction or evidence of progression of brain atrophy. Among the 15 previous cases, 5 out of 9 medically managed cases and 1 revascularized case described no further clinical recurrence.

      Conclusion

      Thalassemia-related-MMS may not be so rare. Future development of consensus guidelines in diagnosing and managing cases of MMS-associated-with-thalassemia is of essence.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Paediatric Neurology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Das D.S.
        • Dubey D.S.
        • Acharya D.M.
        • Ghosh D.R.
        • Chatterjee D.S.
        • Hazra P.D.A.
        • et al.
        The disease presentation of Moyamoya angiopathy in Eastern India.
        J. Stroke Cerebrovasc. Dis. 2020; 29
        • Das S.
        • Dubey S.
        • Das S.
        • Hazra A.
        • Pandit A.
        • Ghosh R.
        • et al.
        Epidemiology of moyamoya angiopathy in Eastern India.
        Front. Neurol. 2022; ([Internet]) (Mar 4 [cited 2022 Mar 9];0:282. Available from:)
        • Das S.
        • Dubey S.
        • Acharya M.
        • Chatterjee S.
        • Lahiri D.
        • Das G.
        • et al.
        Thalassemia and Moyamoya syndrome: unfurling an intriguing association.
        J. Neurol. 2019 Nov 1; ([Internet]) ([cited 2020 Aug 30];266(11):2838–47. Available from:)
        • Das S.
        • Karmakar K.
        • Mukherjee R.
        • Panda S.
        • Dubey S.
        • Sarkar N.
        • et al.
        Acute Stroke in Young Adult Secondary to Moyamoya Angiopathy Unveiling HbE-β Thalassemia.
        ([Internet]) Annals of Hematology. Springer Science and Business Media Deutschland GmbH, 2021https://doi.org/10.1007/s00277-021-04519-7 ([cited 2021 Jul 5]. p. 1–3. Available from:)
        • Scott R.M.
        • Smith E.R.
        Moyamoya disease and moyamoya syndrome.
        N. Engl. J. Med. 2009 Mar 19; ([Internet]) ([cited 2018 Nov 24];360(12):1226–37. Available from:)
        • Mukherjee A.
        Moyamoya disease and beta-thalassemia.
        J. Assoc. Phys. India. 1995 Oct; ([Internet]) ([cited 2019 Jan 6];43(10):710–1. Available from:)
        • Inati A.
        • Tourjuman O.
        • Bizri D.
        • Dhayni R.
        • Abbas H.A.
        • Tfaili H.
        • et al.
        A rare case of Moyamoya syndrome in a β-thalassemia major patient.
        Blood Cells Mol. Dis. 2013 Oct; ([Internet]) ([cited 2019 Jan 6];51(3):149–50. Available from:)
        • Göksel B.K.
        • Ozdogu H.
        • Yildirim T.
        • Oğuzkurt L.
        • Asma S.
        Beta-thalassemia intermedia associated with moyamoya syndrome.
        J. Clin. Neurosci. 2010 Jul 1; ([Internet]) ([cited 2019 Jan 6];17(7):919–20. Available from:)
        • Sanefuji M.
        • Ohga S.
        • Kira R.
        • Yoshiura T.
        • Torisu H.
        • Hara T.
        Moyamoya syndrome in a splenectomized patient with β-thalassemia intermedia.
        J. Child Neurol. 2006 Jan 26; ([Internet]) ([cited 2019 Jan 6];21(1):75–7. Available from:)
        • Oberoi S.
        • Bansal D.
        • Singh P.
        • Marwaha R.K.
        Stroke in a young boy with β-thalassemia intermedia secondary to moyamoya syndrome.
        J. Pediatr. Hematol. Oncol. 2010 Oct; ([Internet]) ([cited 2019 Jan 3];32(7):568–70. Available from:)
        • Roy S.
        Moyamoya syndrome in a child with β-thalassemia major.
        J. Pediatr. Neurol. 2020 Aug 1; ([Internet]) ([cited 2022 Jan 10];18(4):214–6. Available from:)
        • Agrawal A.
        • Bhinder O.S.
        • Mishra D.
        • Juneja M.
        HbE-Beta thalassemia with moyamoya syndrome: a rare association.
        Indian J Pediatr 2019 876. 2019 Dec 20; ([Internet]) ([cited 2022 Jan 10];87(6):476–7. Available from:)
        • Nadkarni J.
        • Pal P.
        • Dwivedi R.
        • Singh A.
        Case report vasculopathy in beta thalessemia intermedia : a rare case report.
        Scholars J. Appl. Med. Sci. 2014; 2: 345-347
        • Doctor P.N.
        • Choudhari A.
        • Verma M.
        • Merchant R.H.
        Moyamoya syndrome in hemoglobin E-beta thalassemia: a rare presentation and association.
        J. Postgrad. Med. 2018; ([Internet]) ([cited 2019 Jan 6];64(4):240–2. Available from:)
        • Marden F.A.
        • Putman C.M.
        • Grant J.M.
        • Greenberg J.
        Moyamoya disease associated with hemoglobin Fairfax and beta-thalassemia.
        Pediatr. Neurol. 2008 Feb; ([Internet]) ([cited 2019 Jan 6];38(2):130–2. Available from:)
        • El Beltagi A.H.
        • El-Sheikh A.
        • El-Saif R.
        • Norbash A.
        Ivy sign in mildly symptomatic β-thalassemia intermedia, with development of moyamoya disease.
        NeuroRadiol. J. 2014 Feb; ([Internet]) ([cited 2019 Jan 6];27(1):23–8. Available from:)
        • Gupta A.
        • Mathur P.
        • Sharma M.
        • Parmar V.
        Journal of pediatric critical care.
        J. Pediatr Crit CARE. 2017; ([Internet]) ([cited 2019 Jan 6];4(3):110. Available from:)
        • Ray A.
        • Rodriguez N.
        Cerebral infarction in the setting of moyamoya in a pediatric patient with sickle β + -thalassemia.
        Pediatr. Hematol. Oncol. 2011 Aug 22; ([Internet]) ([cited 2019 Jan 6];28(6):535–7. Available from:)
        • Nath Sarkar K.
        • Deoghuria D.
        • Sarkar M.
        • Sarkar S.
        Moya Moya Syndrome in a HbE Beta Thalassemic Child Presenting with Hemiplegia in Rural West Bengal.
        ([Internet]) IOSR J Dent Med Sci e-ISSN, 2016 ([cited 2019 Jan 6];15(4):113–8. Available from:)
        • Parker T.M.
        • Ward L.M.
        • Johnston D.L.
        • Ventureya E.
        • Klaassen R.J.
        A case of moyamoya syndrome and hemoglobin E/beta-thalassemia.
        Pediatr. Blood Cancer. 2009 Mar; ([cited 2019 Jan 6];52(3):42) ([Internet]) (2–4. Available from: http://doi.wiley.com/10.1002/pbc.21850)
        • Haque A.
        • Quint D.J.
        • Castle V.P.
        • Leber S.M.
        Another rare unstable hemoglobinopathy: hemoglobin casper/southampton associated with moyamoya disease.
        Cerebrovasc Dis Extra. 2015 May 21; ([Internet]) ([cited 2022 Jan 10];5(2):52–4. Available from:)
        • Das S.
        • Ray B.K.
        • Pandit A.
        • Kumar S.
        • Dubey S.
        Multiple sclerosis and Moyamoya angiopathy: Mimic and misdiagnosis.
        Mult Scler Relat Disord. 2022 Jul 5; 66104036https://doi.org/10.1016/j.msard.2022.104036
        • Dubey S.
        • Ghosh R.
        • Chatterjee S.
        • Dubey M.J.
        • Ray B.K.
        • Das S.
        • et al.
        Spicy foods triggering clinical symptoms in Moyamoya angiopathy.
        J. Neurosurg. Sci. 2020;
        • Das S.
        • Ghosh R.
        • Dubey S.
        • Pandit A.
        • Ray B.K.
        • Kraemer M.
        Limb-shaking TIA in moyamoya angiopathy.
        Clin. Neurol. Neurosurg. 2021 Aug 1; ([Internet]) ([cited 2021 Jul 5];207:106783. Available from:)
        • Das S.
        • Ray B.K.
        • Dubey S.
        Temporal lobe epilepsy with nocturnal wandering leading to discovery of Moyamoya Angiopathy.
        Acta Neurol. Belg. 2021; ([Internet]. 2021 Oct 26 [cited 2021 Dec 2];1–3. Available from:)
        • Das S.
        • Ray B.K.
        • Ghosh R.
        • Dubey S.
        Asymptomatic” moyamoya angiopathy: is it truly asymptomatic?.
        J. Stroke Cerebrovasc. Dis. 2022 Jun 1; ([Internet]) ([cited 2022 Apr 9];31(6):106432. Available from:)
        • DeBaun M.R.
        • Jordan L.C.
        • King A.A.
        • Schatz J.
        • Vichinsky E.
        • Fox C.K.
        • et al.
        American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.
        Blood Adv. 2020 Apr 28; ([Internet]) ([cited 2022 Jan 10];4(8):1554–88. Available from: http://ashpublications.org/bloodadvances/article-pdf/4/8/1554/1724440/advancesadv2019001142c.pdf)
        • Vassilopoulou S.
        • Anagnostou E.
        • Paraskevas G.
        • Spengos K.
        Etiology and treatment of ischaemic stroke in patients with β-thalassemia major.
        Eur. J. Neurol. 2011 Dec 1; ([Internet]) ([cited 2022 Jan 10];18(12):1426–8. Available from:)
        • Cappellini M.D.
        • Musallam K.M.
        • Poggiali E.
        • Taher A.T.
        Hypercoagulability in non-transfusion-dependent thalassemia.
        Blood Rev. 2012 Apr 1; 26: S20-S23
        • Borgna Pignatti C.
        • Carnelli V.
        • Caruso V.
        • Dore F.
        • De Mattia D.
        • Di Palma A.
        • et al.
        Thromboembolic events in beta thalassemia major: an Italian multicenter study.
        Acta Haematol. 1998; ([Internet]) ([cited 2022 Jan 10];99(2):76–9. Available from:)
        • Taher A.
        • Isma’eel H.
        • Mehio G.
        • Bignamini D.
        • Kattamis A.
        • Rachmilewitz E.A.
        • et al.
        ([Internet])Prevalence of Thromboembolic Events Among 8,860 Patients with Thalassaemia Major and Intermedia in the Mediterranean Area and Iran. vol. 96. Thrombosis and Haemostasis, 2006 ([cited 2022 Jan 10]. p. 488–91. Available from:)
        • Karimi M.
        • Khanlari M.
        • Rachmilewitz E.A.
        Cerebrovascular accident in β-thalassemia major (β-TM) and β-thalassemia intermedia (β-TI).
        Am. J. Hematol. 2008 Jan 1; ([Internet]) ([cited 2022 Jan 10];83(1):77–9. Available from:)
        • Karimi M.
        • Bagheri H.
        • Rastgu F.
        • Rachmilewitz E.A.
        Magnetic resonance imaging to determine the incidence of brain ischaemia in patients with β-thalassaemia intermedia.
        Thromb. Haemostasis. 2010 Nov 22; ([Internet]) ([cited 2022 Jan 10];103(5):989–93. Available from:)
        • Taher A.T.
        • Musallam K.M.
        • Karimi M.
        • El-Beshlawy A.
        • Belhoul K.
        • Daar S.
        • et al.
        Splenectomy and thrombosis: the case of thalassemia intermedia.
        J. Thromb. Haemostasis. 2010 Oct 1; ([Internet]) ([cited 2022 Jan 10];8(10):2152–8. Available from:)
        • Yashar V.B.
        • Barenholz Y.
        • Hy-Am E.
        • Rachmilewitz E.A.
        • Eldor A.
        Phosphatidylserine in the outer leaflet of red blood cells from beta-thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes.
        Am. J. Hematol. 1993; ([Internet]) ([cited 2022 Jan 10];44(1):63–5. Available from:)
        • Lrbbrcgfam MD Cappellini
        Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia.
        Br. J. Haematol. 2000; 111: 467-473
        • Tripatara Ajjtkk A.
        Hemostatic alterations in splenectomized and non-splenectomized patients with beta-thalassemia/hemoglobin E disease.
        Thromb. Res. 2007; 120: 805-810
        • N Goldschmidt GSABOZAGER
        Increased platelet adhesion under flow conditions is induced by both thalassemic platelets and red blood cells.
        Thromb. Haemostasis. 2008; 100: 864-870
        • Mannucci P.
        Red cells playing as activated platelets in thalassemia intermedia.
        J. Thromb. Haemostasis. 2010; 8: 2149-2151
        • A Ruf MPVDHPAGER
        In-vivo platelet activation correlates with red cell anionic phospholipid exposure in patients with beta-thalassaemia major.
        Br. J. Haematol. 1997; 98: 51-56
        • At Taher Kmmkae-Bkbsd
        Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study.
        Blood. 2010; 115: 1886-1892
        • Santoro Tgmkatjsmc C.
        Whole exome sequencing identifies MRVI1 as a susceptibility gene for moyamoya syndrome in neurofibromatosis type 1.
        PLoS One. 2018; 13e0200446
        • Ghosh R.
        • Dubey S.
        • Kanti Ray B.
        • Chatterjee S.
        • Benito-León J.
        COVID-19 presenting with thalamic hemorrhage unmasking moyamoya angiopathy.
        Can. J. Neurol. Sci. 2020; 47 (Cambridge University Press) ([Internet]) ([cited 2021 Mar 18]. p. 849–51. Available from:/pmc/articles/PMC7327161/)
        • Das S.
        • Dubey S.
        • Pandit A.
        • Ray B.K.
        Moyamoya angiopathy unmasking systemic lupus erythematosus.
        BMJ Case Rep. 2021 Jan 27; ([Internet]) ([cited 2021 Jul 5];14(1):e239307. Available from:)
        • Das S.
        • Ray B.K.
        • Ghosh R.
        • Sengupta S.
        • Pandit A.
        • Dubey S.
        Impact of COVID-19 pandemic in natural course of Moyamoya Angiopathy: an experience from tertiary-care-center in India.
        Egypt J Neurol Psychiatry Neurosurg. 2021; 571 ([Internet]. 2021 Dec 11 [cited 2021 Dec 16];57(1):1–6. Available from:)
        • Chamchoi Sskptspskp A.
        Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet activation in hemoglobin E/ß-thalassemia subjects.
        PLoS One. 2018; 13e0203955
        • RE Hirsch NSSFJF
        HbE/β-thalassemia and oxidative stress: the key to pathophysiological mechanisms and novel therapeutics.
        Antioxidants Redox Signal. 2017; 26: 794-813
        • Terrell D.
        • Savardekar A.R.
        • Whipple S.G.
        • Dossani R.H.
        • Spetzler R.F.
        • Sun H.
        Cerebral revascularization for moyamoya syndrome associated with sickle cell disease: a systematic review of the literature on the role of Extracranial-intracranial bypass in treating neurologic manifestations of pediatric patients with sickle cell disease.
        World Neurosurg. 2020 May 1; 137: 62-70
        • Newman S.
        • Boulter J.H.
        • Malcolm J.G.
        • Pradilla I.
        • Pradilla G.
        Outcomes in patients with moyamoya syndrome and sickle cell disease: a systematic review.
        World Neurosurg. 2020 Mar 1; 135: 165-170
        • Karimi M.
        • Haghpanah S.
        • Pishdad P.
        • Zahedi Z.
        • Parand S.
        • Safaei S.
        Frequency of silent brain lesions and aspirin protection evaluation over 3 years follow-up in beta thalassemia patients.
        Ann. Hematol. 2019; (9810 [Internet]. 2019 Aug 6 [cited 2022 Jan 10];98(10):2267–71. Available from:)