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Misdiagnoses and delay of diagnoses in Moyamoya angiopathy—a large Caucasian case series

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Abstract

Background

The lacking awareness of healthcare providers bears the risk of delayed or false diagnoses in rare diseases. No systematic data about misdiagnoses of Moyamoya angiopathy (MMA) are available.

Objective

To evaluate the rate and pattern of missed diagnoses in MMA.

Methods

Retrospective analysis of a consecutive case series from a single German referral center. Rates of missed or delayed diagnoses in Caucasian MMA patients were calculated based on discharge letters from other hospitals and systematic chart review.

Results

Out of 192 Caucasian patients eventually diagnosed with MMA at our center, an initial misdiagnosis was identified in 119 patients (62%). The time between onset and diagnosis was 1 year in 24 patients, 2 years in 23 patients, 3 years in 10 patients, and > 3 years in 49 patients (mean 5.28, median 3, standard deviation 5.11, and range 4–26 years). The most common misdiagnoses were cerebral vasculitis (31%), etiologically ill-defined stroke diagnoses (30.2%), and MS (3.6%).

Conclusions

This is the first systematic report which shows that patients with MMA are at high risk to be falsely diagnosed and treated. Depiction of typical vascular abnormalities in angiopathy is essential. Normal CSF cell counts, negative oligoclonal bands, and lack of infratentorial lesions as well as gadolinium-positive T1 lesions on MRI may be red flags differentiating this vasculopathy from vasculitis and MS.

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References

  1. Kleinloog R, Regli L, Rinkel GJ, Klijn CJ (2012) Regional differences in incidence and patient characteristics of moyamoya disease: a systematic review. J Neurol Neurosurg Psychiatry 83(5):531–536. https://doi.org/10.1136/jnnp-2011-301387

    Article  Google Scholar 

  2. Baba T, Houkin K, Kuroda S (2008) Novel epidemiological features of moyamoya disease. J Neurol Neurosurg Psychiatry 79(8):900–904. https://doi.org/10.1136/jnnp.2007.130666

    Article  Google Scholar 

  3. Kraemer M, Heienbrok W, Berlit P (2008) Moyamoya disease in Europeans. Stroke 39(12):3193–3200. https://doi.org/10.1161/STROKEAHA.107.513408

    Article  Google Scholar 

  4. Kim JM, Lee SH, Roh JK (2009) Changing ischaemic lesion patterns in adult moyamoya disease. J Neurol Neurosurg Psychiatry 80(1):36–40. https://doi.org/10.1136/jnnp.2008.145078

    Article  Google Scholar 

  5. Calviere L, Ssi Yan Kai G, Catalaa I, Marlats F, Bonneville F, Larrue V (2012) Executive dysfunction in adults with moyamoya disease is associated with increased diffusion in frontal white matter. J Neurol Neurosurg Psychiatry 83(6):591–593. https://doi.org/10.1136/jnnp-2011-301388

    Article  Google Scholar 

  6. Health Labour Sciences Research Grant for Research on Measures for Infractable D (2012) Treatment of Spontaneous Occlusion of the Circle of W. Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis). Neurol Med Chir (Tokyo) 52(5):245–266

    Article  Google Scholar 

  7. Houkin K, Ito M, Sugiyama T, Shichinohe H, Nakayama N, Kazumata K, Kuroda S (2012) Review of past research and current concepts on the etiology of moyamoya disease. Neurol Med Chir (Tokyo) 52(5):267–277

    Article  Google Scholar 

  8. Guey S, Tournier-Lasserve E, Herve D, Kossorotoff M (2015) Moyamoya disease and syndromes: from genetics to clinical management. Appl Clin Genet 8:49–68. https://doi.org/10.2147/TACG.S42772

    Google Scholar 

  9. Preziosa P, Martinelli V, Ferre L, Guaschino C, Simionato F, Moiola L, Comi G, Filippi M (2017) Moyamoya disease mimicking the first attack of multiple sclerosis. J Neurol 264(5):1005–1007. https://doi.org/10.1007/s00415-017-8458-3

    Article  Google Scholar 

  10. Zaheer F, Berger JR (2012) Moyamoya: another multiple sclerosis mimic. Mult Scler Relat Disord 1(2):100–103. https://doi.org/10.1016/j.msard.2011.10.001

    Article  Google Scholar 

  11. Dorfman LJ, Fischbein NJ, Woodard JI, Choudhri O, Bell-Stephens TE, Steinberg GK (2012) Moyamoya disease can masquerade as multiple sclerosis. Neurologist 18(6):398–403. https://doi.org/10.1097/NRL.0b013e31826a99a1

    Article  Google Scholar 

  12. Kraemer M, Berlit P (2010) Primary central nervous system vasculitis and moyamoya disease: similarities and differences. J Neurol 257(5):816–819. https://doi.org/10.1007/s00415-009-5425-7

    Article  Google Scholar 

  13. Heijmen L, van Dijk EJ, Goraj B, van Laarhoven HW (2012) Moyamoya disease misdiagnosed as leptomeningeal metastases. J Clin Oncol 30(36):e382–e385. https://doi.org/10.1200/JCO.2012.43.3227

    Article  Google Scholar 

  14. Gaa J, Weidauer S (2004) Unusual differential diagnosis of leptomeningeal enhancement: moyamoya disease. J Neurol Neurosurg Psychiatry 75(8):1170. https://doi.org/10.1136/jnnp.2003.031393

    Article  Google Scholar 

  15. Scott RM, Smith ER (2009) Moyamoya disease and moyamoya syndrome. N Engl J Med 360(12):1226–1237. https://doi.org/10.1056/NEJMra0804622

    Article  Google Scholar 

  16. Kim T, Oh CW, Kwon OK, Hwang G, Kim JE, Kang HS, Cho WS, Bang JS (2016) Stroke prevention by direct revascularization for patients with adult-onset moyamoya disease presenting with ischemia. J Neurosurg 124(6):1788–1793. https://doi.org/10.3171/2015.6.JNS151105

    Article  Google Scholar 

  17. Liu X, Zhang D, Shuo W, Zhao Y, Wang R, Zhao J (2013) Long term outcome after conservative and surgical treatment of haemorrhagic moyamoya disease. J Neurol Neurosurg Psychiatry 84(3):258–265. https://doi.org/10.1136/jnnp-2012-302236

    Article  Google Scholar 

  18. Kraemer M, Karakaya R, Matsushige T, Graf J, Albrecht P, Hartung HP, Berlit P, Laumer R, Diesner F (2018) Efficacy of STA-MCA bypass surgery in moyamoya angiopathy: long-term follow-up of the Caucasian Krupp Hospital cohort with 81 procedures. J Neurol 265(10):2425–2433. https://doi.org/10.1007/s00415-018-9031-4

    Article  Google Scholar 

  19. Kraemer M, Sassen J, Karakaya R, Schwitalla JC, Graf J, Albrecht P, Hartung HP, Diehl RR, Berlit P, Laumer R, Diesner F (2018) Moyamoya angiopathy: early postoperative course within 3 months after STA-MCA-bypass surgery in Europe-a retrospective analysis of 64 procedures. J Neurol 265(10):2370–2378. https://doi.org/10.1007/s00415-018-8997-2

    Article  Google Scholar 

  20. Yamada S, Oki K, Itoh Y, Kuroda S, Houkin K, Tominaga T, Miyamoto S, Hashimoto N, Suzuki N, Research Committee on Spontaneous Occlusion of Circle of W (2016) Effects of surgery and antiplatelet therapy in ten-year follow-up from the registry study of research committee on Moyamoya disease in Japan. J Stroke Cerebrovasc Dis 25(2):340–349. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.10.003

    Article  Google Scholar 

  21. Becker J, Horn PA, Keyvani K, Metz I, Wegner C, Bruck W, Heinemann FM, Schwitalla JC, Berlit P, Kraemer M (2017) Primary central nervous system vasculitis and its mimicking diseases—clinical features, outcome, comorbidities and diagnostic results—a case control study. Clin Neurol Neurosurg 156:48–54. https://doi.org/10.1016/j.clineuro.2017.03.006

    Article  Google Scholar 

  22. Kraemer M, Horn PA, Roder C, Khan N, Diehl RR, Berlit P, Heinemann FM (2012) Analysis of human leucocyte antigen genes in Caucasian patients with idiopathic moyamoya angiopathy. Acta Neurochir (Wien) 154(3):445–454. https://doi.org/10.1007/s00701-011-1261-5

    Article  Google Scholar 

  23. Kraemer M, Lee SI, Ayzenberg I, Schwitalla JC, Diehl RR, Berlit P, Bosche B, Katsarava Z, Obermann M (2016) Headache in Caucasian patients with Moyamoya angiopathy—a systematic cohort study. Cephalalgia. https://doi.org/10.1177/0333102416643516

    Google Scholar 

  24. Kraemer M, Trakolis L, Platzen J, Schwitalla JC, Bersano A, Albrecht P, Schlamann M, Berlit P (2017) Movement symptoms in European Moyamoya angiopathy—first systematic questionnaire study. Clin Neurol Neurosurg 152:52–56. https://doi.org/10.1016/j.clineuro.2016.11.017

    Article  Google Scholar 

  25. Fukui M (1997) Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis (‘moyamoya’ disease). Research committee on spontaneous occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg 99(Suppl 2):S238–S240

    Article  Google Scholar 

  26. Herve D, Kossorotoff M, Bresson D, Blauwblomme T, Carneiro M, Touze E, Proust F, Desguerre I, Alamowitch S, Bleton JP, Borsali A, Brissaud E, Brunelle F, Calviere L, Chevignard M, Geffroy-Greco G, Faesch S, Habert MO, De Larocque H, Meyer P, Reyes S, Thines L, Tournier-Lasserve E, Chabriat H (2018) French clinical practice guidelines for Moyamoya angiopathy. Rev Neurol (Paris) 174(5):292–303. https://doi.org/10.1016/j.neurol.2017.12.002

    Article  Google Scholar 

  27. Garg N, Reddel SW, Miller DH, Chataway J, Riminton DS, Barnett Y, Masters L, Barnett MH, Hardy TA (2015) The corpus callosum in the diagnosis of multiple sclerosis and other CNS demyelinating and inflammatory diseases. J Neurol Neurosurg Psychiatry 86(12):1374–1382. https://doi.org/10.1136/jnnp-2014-309649

    Google Scholar 

  28. Berlit P, Kraemer M (2014) Cerebral vasculitis in adults: what are the steps in order to establish the diagnosis? Red flags and pitfalls. Clin Exp Immunol 175(3):419–424. https://doi.org/10.1111/cei.12221

    Article  Google Scholar 

  29. Haghikia A, Dendrou CA, Schneider R, Gruter T, Postert T, Matzke M, Stephanik H, Fugger L, Gold R (2017) Severe B-cell-mediated CNS disease secondary to alemtuzumab therapy. Lancet Neurol 16(2):104–106. https://doi.org/10.1016/S1474-4422(16)30382-9

    Article  Google Scholar 

  30. Solomon AJ, Corboy JR (2017) The tension between early diagnosis and misdiagnosis of multiple sclerosis. Nat Rev Neurol 13(9):567–572. https://doi.org/10.1038/nrneurol.2017.106

    Article  Google Scholar 

  31. The L (2018) End of the road for daclizumab in multiple sclerosis. Lancet 391(10125):1000. https://doi.org/10.1016/S0140-6736(18)30565-8

    Google Scholar 

  32. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17(2):162–173. https://doi.org/10.1016/S1474-4422(17)30470-2

    Article  Google Scholar 

  33. Kelly SB, Chaila E, Kinsella K, Duggan M, Walsh C, Tubridy N, Hutchinson M (2012) Using atypical symptoms and red flags to identify non-demyelinating disease. J Neurol Neurosurg Psychiatry 83(1):44–48. https://doi.org/10.1136/jnnp-2011-300679

    Article  Google Scholar 

  34. Solomon AJ, Bourdette DN, Cross AH, Applebee A, Skidd PM, Howard DB, Spain RI, Cameron MH, Kim E, Mass MK, Yadav V, Whitham RH, Longbrake EE, Naismith RT, Wu GF, Parks BJ, Wingerchuk DM, Rabin BL, Toledano M, Tobin WO, Kantarci OH, Carter JL, Keegan BM, Weinshenker BG (2016) The contemporary spectrum of multiple sclerosis misdiagnosis: a multicenter study. Neurology 87(13):1393–1399. https://doi.org/10.1212/WNL.0000000000003152

    Article  Google Scholar 

  35. Miller DH, Weinshenker BG, Filippi M, Banwell BL, Cohen JA, Freedman MS, Galetta SL, Hutchinson M, Johnson RT, Kappos L, Kira J, Lublin FD, McFarland HF, Montalban X, Panitch H, Richert JR, Reingold SC, Polman CH (2008) Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 14(9):1157–1174. https://doi.org/10.1177/1352458508096878

    Article  Google Scholar 

  36. Becker J, Geffken M, Diehl R, Berlit P, Kraemer M (2017) Choosing wisely? Multiple sclerosis and laboratory screening for autoimmune differential diagnoses: do the guideline recommendations of the german society of neurology make sense?. Neurol Int Open. https://doi.org/10.1055/s-0043-115429

    Google Scholar 

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Acknowledgements

This work is dedicated to our deceased neuroradiological colleague Dr. Petra Schooß (1969–2016). The authors are thankful for the cooperation with the Department of Radiology and Neuroradiology, Alfried Krupp Hospital, Essen, Germany.

Funding

They did not receive funding for preparation of the manuscript.

Author information

Author notes

  1. Jonas Graf, Jan Claudius Schwitalla, Orhan Aktas, and Markus Kraemer contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Neurology, University Hospital, Medical Faculty Heinrich-Heine-University, Düsseldorf, Germany

    Jonas Graf, Philipp Albrecht, Hans-Peter Hartung, Orhan Aktas & Markus Kraemer

  2. Department of Neurology, Alfried Krupp Hospital, Alfried Krupp Strasse 21, 45130, Essen, Germany

    Jan Claudius Schwitalla, Roland Veltkamp, Peter Berlit & Markus Kraemer

  3. Department of Medicine, Imperial College London, London, UK

    Roland Veltkamp

  4. Department of Neurology, University Heidelberg, Heidelberg, Germany

    Roland Veltkamp

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  1. Jonas Graf
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Correspondence to Markus Kraemer.

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This study was approved by local ethical committee.

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Graf, J., Schwitalla, J.C., Albrecht, P. et al. Misdiagnoses and delay of diagnoses in Moyamoya angiopathy—a large Caucasian case series. J Neurol 266, 1153–1159 (2019). https://doi.org/10.1007/s00415-019-09245-9

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  • DOI: https://doi.org/10.1007/s00415-019-09245-9

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