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Characteristics of aneurysmal subarachnoid hemorrhage associated with rheumatic disease

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Spontaneous subarachnoid hemorrhage (SAH) occurs due to intracranial aneurysm rupture in most cases. Rheumatic disease may cause vessel wall inflammation, which can increase the risk of rupture. However, the characteristics of SAH with rheumatic disease are unknown. This study aimed to evaluate SAH features in patients with rheumatic disease. We retrospectively analyzed clinical data of 5066 patients from the Nagasaki SAH Registry Study who had been diagnosed with aneurysmal SAH between 2001 and 2018. We evaluated the SAH characteristics in patients with rheumatic disease using multivariable logistic regression analysis. In total, 102 patients (2.0%, 11 men and 91 women, median age 69.0 [57.0–75.5]) had rheumatic disease. In these patients, univariate logistic regression analysis showed that sex, hypertension, family history of SAH, smoking history, World Federation of Neurosurgical Societies grade on admission, aneurysm size, multiple aneurysms, treatment, and symptomatic spasms were associated with SAH. Multivariable logistic regression analysis showed that characteristics independently associated with SAH in rheumatic disease were female sex (odds ratio [OR] 3.38; 95% confidence interval [CI] 1.81–6.93, P < 0.001), hypertension (OR 0.60; 95% CI 0.40–0.90, P = 0.012), family history of SAH (OR 0.18; 95% CI 0.01–0.80, P = 0.020), small ruptured aneurysms (OR 1.50; 95% CI 1.02–2.24, P = 0.048), and multiple aneurysms (OR 1.69; 95% CI 1.09–2.58, P = 0.021) in comparison with SAH without rheumatic disease. In conclusion, SAH in patients with rheumatic disease was characterized by small multiple aneurysms, regardless of the low incidence of hypertension and family history of SAH.

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  1. Bernatsky S, Joseph L, Pineau CA, Belisle P, Lix L, Banerjee D, Clarke AE (2009) Polymyalgia rheumatica prevalence in a population-based sample. Arthritis Rheum 61:1264–1267.

    Article  CAS  PubMed  Google Scholar 

  2. Brinjikji W, Zhu YQ, Lanzino G, Cloft HJ, Murad MH, Wang Z, Kallmes DF (2016) Risk factors for growth of intracranial aneurysms: a systematic review and meta-analysis. AJNR Am J Neuroradiol 37:615–620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chalouhi N, Hoh BL, Hasan D (2013) Review of cerebral aneurysm formation, growth, and rupture. Stroke 44:3613–3622.

    Article  PubMed  Google Scholar 

  4. Criado PR, Marques GF, Morita TC, de Carvalho JF (2016) Epidemiological, clinical and laboratory profiles of cutaneous polyarteritisnodosa patients: report of 22 cases and literature review. Autoimmun Rev 15:558–563.

    Article  PubMed  Google Scholar 

  5. Feigin VL, Rinkel GJ, Lawes CM, Algra A, Bennett DA, van Gijn J, Anderson CS (2005) Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke 36:2773–2780.

    Article  PubMed  Google Scholar 

  6. Futami K, Yamashita J, Tachibana O, Higashi S, Ikeda K, Yamashima T (1995) Immunohistochemical alterations of fibronectin during the formation and proliferative repair of experimental cerebral aneurysms in rats. Stroke 26:1659–1664.

    Article  CAS  PubMed  Google Scholar 

  7. Genta MS, Genta RM, Gabay C (2006) Systemic rheumatoid vasculitis: a review. Semin Arthritis Rheum 36:88–98.

    Article  PubMed  Google Scholar 

  8. Graffeo CS, Tanweer O, Nieves CF, Belmont HM, Izmirly PM, Becske T, Huang PP (2015) Rapid aneurysm growth and rupture in systemic lupus erythematosus. Surg Neurol Int 6:9.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Horie N, Sato S, Kaminogo M, Morofuji Y, Izumo T, Anda T, Matsuo T (2019) Impact of perioperative aneurysm rebleeding after subarachnoid hemorrhage. J Neurosurg:1–10.

  10. Kaku Y, Kouda K, Yoshimura S, Sakai N (2004) Cerebral aneurysms in scleroderma. Cerebrovasc Dis 17:339–341.

    Article  PubMed  Google Scholar 

  11. Kaminogo M, Yonekura M, Shibata S (2003) Incidence and outcome of multiple intracranial aneurysms in a defined population. Stroke 34:16–21.

    Article  PubMed  Google Scholar 

  12. Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R (1999) Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke 30:1396–1401.

    Article  CAS  PubMed  Google Scholar 

  13. Kravvariti E, Konstantonis G, Sfikakis PP, Tektonidou MG (2018) Progression of subclinical atherosclerosis in systemic lupus erythematosus versus rheumatoid arthritis: the impact of low disease activity. Rheumatology 57:2158–2166.

    Article  CAS  PubMed  Google Scholar 

  14. Kurata A, Kawakami T, Sato J, Sakamoto A, Muramatsu T, Nakabayashi K (2011) Aortic aneurysms in systemic lupus erythematosus: a meta-analysis of 35 cases in the literature and two different pathogeneses. Cardiovasc Pathol 20:e1-7.

    Article  PubMed  Google Scholar 

  15. Lall RR, Eddleman CS, Bendok BR, Batjer HH (2009) Unruptured intracranial aneurysms and the assessment of rupture risk based on anatomical and morphological factors: sifting through the sands of data. Neurosurg Focus 26:E2.

    Article  PubMed  Google Scholar 

  16. Longstreth WT Jr, Koepsell TD, Yerby MS, van Belle G (1985) Risk factors for subarachnoid hemorrhage. Stroke 16:377–385.

    Article  PubMed  Google Scholar 

  17. Macdonald RL, Schweizer TA (2017) Spontaneous subarachnoid haemorrhage. Lancet 389:655–666.

    Article  PubMed  Google Scholar 

  18. McGill HC Jr, McMahan CA, Zieske AW, Tracy RE, Malcom GT, Herderick EE, Strong JP (2000) Association of coronary heart disease risk factors with microscopic qualities of coronary atherosclerosis in youth. Circulation 102:374–379.

    Article  PubMed  Google Scholar 

  19. Mimata C, Kitaoka M, Nagahiro S, Iyama K, Hori H, Yoshioka H, Ushio Y (1997) Differential distribution and expressions of collagens in the cerebral aneurysmal wall. Acta Neuropathol 94:197–206.

    Article  CAS  PubMed  Google Scholar 

  20. Mimori A (2015) II. Systemic lupus erythematosus. J JpnSocInt Med 104:2118–2124.

    Article  Google Scholar 

  21. Okamoto K, Horisawa R, Kawamura T, Asai A, Ogino M, Takagi T, Ohno Y (2003) Family history and risk of subarachnoid hemorrhage: a case-control study in Nagoya, Japan. Stroke 34:422–426.

    Article  PubMed  Google Scholar 

  22. Ramagopalan SV, Pakpoor J, Seminog O, Goldacre R, Graham L, Goldacre MJ (2013) Risk of subarachnoid haemorrhage in people admitted to hospital with selected immune-mediated diseases: record-linkage studies. BMC Neurol 13:176.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rees F, Doherty M, Grainge MJ, Lanyon P, Zhang W (2017) The worldwide incidence and prevalence of systemic lupus erythematosus: a systematic review of epidemiological studies. Rheumatology 56:1945–1961.

    Article  PubMed  Google Scholar 

  24. Sakaki T, Morimoto T, Utsumi S (1990) Cerebral transmural angiitis and ruptured cerebral aneurysms in patients with systemic lupus erythematosus. Neurochirurgia 33:132–135.

    Article  CAS  PubMed  Google Scholar 

  25. Scofield RH (2011) Vasculitis in Sjogren’s syndrome. CurrRheumatol Rep 13:482–488.

    Article  CAS  Google Scholar 

  26. Seneviratne AN, Monaco C (2015) Role of inflammatory cells and toll-like receptors in atherosclerosis. Curr Vasc Pharmacol 13:146–160.

    Article  CAS  PubMed  Google Scholar 

  27. Shovman O, Tiosano S, Comaneshter D, Cohen AD, Amital H, Sherf M (2016) Aortic aneurysm associated with rheumatoid arthritis: a population-based cross-sectional study. Clin Rheumatol 35:2657–2661.

    Article  PubMed  Google Scholar 

  28. Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388:2023–2038.

    Article  CAS  PubMed  Google Scholar 

  29. Sonobe M, Yamazaki T, Yonekura M, Kikuchi H (2010) Small unruptured intracranial aneurysm verification study: SUAVe study, Japan. Stroke 41:1969–1977.

    Article  PubMed  Google Scholar 

  30. Sparks JA (2019) Rheumatoid arthritis. Ann Intern Med 170:Itc1-itc16.

    Article  PubMed  Google Scholar 

  31. Toyoda K, Tsutsumi K, Hirao T, Ono T, Takahata H, Toda K, Baba H, Ito M, Yonekura M (2012) Ruptured intracranial aneurysms in pediatric polyarteritis nodosa: case report. Neurol Med Chir (Tokyo) 52:928–932.

    Article  Google Scholar 

  32. Tsuboi H, Asashima H, Takai C, Hagiwara S, Hagiya C, Yokosawa M, Hirota T, Umehara H, Kawakami A, Nakamura H, Sano H, Tsubota K, Ogawa Y, Takamura E, Saito I, Inoue H, Nakamura S, Moriyama M, Takeuchi T, Tanaka Y, Hirata S, Mimori T, Yoshifuji H, Ohta A, Matsumoto I, Sumida T (2014) Primary and secondary surveys on epidemiology of Sjögren’s syndrome in Japan. Modern Rheumatol 24:464–470.

    Article  Google Scholar 

  33. Tulamo R, Frosen J, Hernesniemi J, Niemela M (2018) Inflammatory changes in the aneurysm wall: a review. J Neurointerv Surg 10:i58–i67.

    Article  PubMed  Google Scholar 

  34. Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, Krestin GP, Niessen WJ, Breteler MM, van der Lugt A (2007) Incidental findings on brain MRI in the general population. N Engl J Med 357:1821–1828.

    Article  CAS  PubMed  Google Scholar 

  35. Wiseman SJ, Ralston SH, Wardlaw JM (2016) Cerebrovascular disease in rheumatic diseases: a systematic review and meta-analysis. Stroke 47:943–950.

    Article  PubMed  Google Scholar 

  36. Yamanaka H, Sugiyama N, Inoue E, Taniguchi A, Momohara S (2014) Estimates of the prevalence of and current treatment practices for rheumatoid arthritis in Japan using reimbursement data from health insurance societies and the IORRA cohort (I). Modern Rheumatol 24:33–40.

    Article  CAS  Google Scholar 

  37. Yong WC, Sanguankeo A, Upala S (2019) Association between primary Sjogren’s syndrome, arterial stiffness, and subclinical atherosclerosis: a systematic review and meta-analysis. Clin Rheumatol 38:447–455.

    Article  PubMed  Google Scholar 

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We would like to thank all members who supported the Nagasaki SAH Registry Study and Editage ( for English language editing.

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Authors and Affiliations




All authors read and approved the final manuscript. SY drafted and revised the manuscript, participated in the study concept and design, conducted statistical analyses, and analyzed the data. NH participated in the study concept, and made a substantial contribution to revising the manuscript and design, and interpreted the data. SS is a biostatistician who conducted statistical analyses and analyzed the data. MK, YM, TA, and TI collected and managed patients’ data. KS participated in the study concept. TM was a supervisor and participated in the study concept and design.

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Correspondence to Susumu Yamaguchi.

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The authors declare that they have no conflict of interest.

Ethical approval and informed consent

This cohort study was approved by the ethics committee of the Nagasaki University Hospital (No. 17112012-4). In this retrospectively designed study, we used anonymized patient data; therefore, the requirement for obtaining patients’ informed consent for publication of the data was waived. However, concerning Fig. 1, we obtained the patient’s written informed consent for publication of their images.

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Yamaguchi, S., Horie, N., Sato, S. et al. Characteristics of aneurysmal subarachnoid hemorrhage associated with rheumatic disease. Neurosurg Rev 44, 2611–2618 (2021).

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