Orbito-Rhinocerebral Syndrome

  • Gauri S. Mankekar
  • Rahul Mehta
  • Daniel W. Nuss


Rhino-orbito-cerebral syndrome (ROCS) is the extension of invasive fungal disease from the nose and paranasal sinuses to the orbit and brain resulting in neuro-ophthalmic manifestations. Once considered a rare entity, it is being reported with increasing frequency from all parts of the world. Although it occurs primarily in immunocompromised and debilitated patients, it has also been reported in immunocompetent patients. Management of ROCS depends on early clinical diagnosis, rapid identification of the causative fungal agent, aggressive surgical debridement, concomitant appropriate systemic antifungal and supportive therapy along with treatment of underlying comorbid condition.


Rhino Orbital Cerebral Invasive Fungal sinusitis Mucormycosis Aspergillosis 



Acquired immunodeficiency syndrome


Allergic fungal rhinosinusitis


Acute invasive fungal rhinosinusitis


Chronic granulomatous fungal rhinosinusitis


Chronic invasive fungal rhinosinusitis


Computed tomography


Hematoxylin and eosin


Invasive fungal rhinosinusitis


Potassium hydroxide


Magnetic resonance imaging


Rhino-orbito-cerebral syndrome


  1. Anders UM, Taylor EJ, Martel JR, Martel JB. Acute orbital apex syndrome and rhino-orbito-cerebral mucormycosis. Int Med Case Rep J. 2015;8:93–6.PubMedPubMedCentralGoogle Scholar
  2. Bhattacharyya AK, Deshpande AR, Nayak SR, Kirtane MV, Ingle MV, Vora IM. Rhinocerebral mucormycosis: an unusual case presentation. J Laryngol Otol. 1992;106(1):48–9.CrossRefGoogle Scholar
  3. Chakrabarti A, Das A, Mandal J, Shivaprakash MR, George VK, Tarai B, et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol. 2006;44:335–42.CrossRefGoogle Scholar
  4. Cheng SC, Joosten LAB, Kullberg BJ, Netea MG. Interplay between Candida albicans and the mammalian innate host defense. Infect Immun. 2012;80:1304–13.CrossRefGoogle Scholar
  5. Chopra H, Dua K, Malhotra V, Gupta RP, Puri H. Invasive fungal sinusitis of isolated sphenoid sinus in immunocompetent subjects. Mycoses. 2006;49(1):30–6.CrossRefGoogle Scholar
  6. Das A, Bal A, Chakrabarti A, Panda N, Joshi K. Spectrum of fungal rhinosinusitis; histopathologist’s perspective. Histopathology. 2009;54(7):854–9.CrossRefGoogle Scholar
  7. Deshazo RD. Syndromes of invasive fungal sinusitis. Med Mycol. 2009;47(Suppl 1):S309–14.CrossRefGoogle Scholar
  8. deShazo RD, Swain RE. Diagnostic criteria for allergic fungal sinusitis. J Allergy Clin Immunol. 1995;96(1):24–35. Available from: CrossRefGoogle Scholar
  9. deShazo RD, O’Brien M, Chapin K, Soto-Aguilar M, Gardner L, Swain R. A new classification and diagnostic criteria for invasive fungal sinusitis. Arch Otolaryngol Head Neck Surg. 1997;123(11):1181–8. Available from: CrossRefGoogle Scholar
  10. Dhiwakar M, Thakar A, Bahadur S. Invasive sino-orbital aspergillosis: surgical decisions and dilemmas. J Laryngol Otol. 2003a;117(4):280–5.CrossRefGoogle Scholar
  11. Dhiwakar M, Thakar A, Bahadur S. Improving outcomes in rhinocerebral mucormycosis—early diagnostic pointers and prognostic factors. J Laryngol Otol. 2003b;117(11):861–5.CrossRefGoogle Scholar
  12. Diwakar A, Dewan RK, Chowdhary A, Randhawa HS, Khanna G, Gaur SN. Zygomycosis—a case report and overview of the disease in India. Mycoses. 2007;50(4):247–54. Available from: CrossRefGoogle Scholar
  13. Epstein VA, Kern RC. Invasive fungal sinusitis and complications of rhinosinusitis. Otolaryngol Clin N Am. 2008;41(3):497–524.CrossRefGoogle Scholar
  14. Gamaletsou MN, Sipsas NV, Roilides E, Walsh TJ. Rhino-orbital-cerebral mucormycosis. Curr Infect Dis Rep. 2012;14(4):423–34.CrossRefGoogle Scholar
  15. Garcia-Covarrubias L, Bartlett R, Barratt DM, Wassermann RJ. Rhino-orbitocerebral mucormycosis attributable to apophysomyces elegans in an immunocompetent individual: case report and review of the literature. J Trauma. 2001;50(2):353–7.CrossRefGoogle Scholar
  16. Garcia-Covarrubias L, Barratt DM, Bartlett R, Metzinger S, Van Meter K. Invasive aspergillosis treated with adjunctive hyperbaric oxygenation: a retrospective clinical series at a single institution. South Med J. 2002;95(4):450–6. Available from: CrossRefGoogle Scholar
  17. Gillespie MB, O’malley BW. An algorithmic approach to the diagnosis and management of invasive fungal rhinosinusitis in the immunocompromised patient. Otolaryngol Clin N Am. 2000;33:323–34.CrossRefGoogle Scholar
  18. Gillespie MB, O’Malley BW, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg. 1998;124(5):520–6.CrossRefGoogle Scholar
  19. Green BJ, Sercombe JK, Tovey ER. Fungal fragments and undocumented conidia function as new aeroallergen sources. J Allergy Clin Immunol. 2005;115(5):1043–8.CrossRefGoogle Scholar
  20. Hargrove RN, Wesley RE, Klippenstein KA, Fleming JC, Haik BG. Indications for orbital exenteration in mucormycosis. Ophthal Plast Reconstr Surg. 2006;22(4):286–91.CrossRefGoogle Scholar
  21. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann J-W, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15. Available from: CrossRefGoogle Scholar
  22. Hontelez S, Sanecka A, Netea MG, van Spriel AB, Adema GJ. Molecular view on PRR cross-talk in antifungal immunity. Cell Microbiol. 2012;14:467–74.CrossRefGoogle Scholar
  23. Idris N, Lim LHY. Nasal eschar: a warning sign of potentially fatal invasive fungal sinusitis in immunocompromised children. J Pediatr Hematol Oncol. 2012;34(4):e134–6.CrossRefGoogle Scholar
  24. Ingram CW, Sennesh J, Cooper JN, Perfect JR. Disseminated zygomycosis: report of four cases and review. Rev Infect Dis. 1989;11(5):741–54.CrossRefGoogle Scholar
  25. Jiménez C, Lumbreras C, Paseiro G, Loinaz C, Romano DR, Andrés A, et al. Treatment of mucor infection after liver or pancreas-kidney transplantation. Transplant Proc. 2002;34(1):82–3.CrossRefGoogle Scholar
  26. Kim JH, Kang BC, Lee J-H, Jang YJ, Lee B-J, Chung Y-S. The prognostic value of gadolinium-enhanced magnetic resonance imaging in acute invasive fungal rhinosinusitis. J Infect. 2015;70(1):88–95.CrossRefGoogle Scholar
  27. Koc Z, Koc F, Yerdelen D, Ozdogu H. Rhino-orbital-cerebral mucormycosis with different cerebral involvements: infarct, hemorrhage, and ophthalmoplegia. Int J Neurosci. 2007;117(12):1677–90.CrossRefGoogle Scholar
  28. Kohn R, Hepler R. Management of limited rhino-orbital mucormycosis without exenteration. Ophthalmology. 1985;92(10):1440–4.CrossRefGoogle Scholar
  29. Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis. 2000;30(6):851–6.CrossRefGoogle Scholar
  30. Kontoyiannis DP, Lewis RE, Spellberg B, Edwards J, Ibrahim A, Roden M, et al. How I treat mucormycosis. Blood. 2011;118(5):1216–24. Available from: CrossRefGoogle Scholar
  31. Bae MS, Kim EJ, Lee KM, Choi WS. Rapidly progressive rhino-orbito-cerebral mucormycosis complicated with unilateral internal carotid artery occlusion: a case report. Neurointervention. 2012;7:45–9.CrossRefGoogle Scholar
  32. Maheshwari M, Richa D, Kaur R. Invasive Aspergillus sinusitis in a young immunocompetent host: call for early diagnosis and treatment. Ann Trop Med Public Heal. 2013;6(1):120. Available from: CrossRefGoogle Scholar
  33. Mankekar G. Invasive fungal rhinosinusitis; 2014. p. 1–93.
  34. Montone KT, Livolsi VA, Feldman MD, Palmer J, Chiu AG, Lanza DC, et al. Fungal rhinosinusitis: a retrospective microbiologic and pathologic review of 400 patients at a Single University Medical Center. Int J Otolaryngol. 2012;2012:1–9.CrossRefGoogle Scholar
  35. Morduchowicz G, Shmueli D, Shapira Z, Cohen SL, Yussim A, Block CS, et al. Rhinocerebral mucormycosis in renal transplant recipients: report of three cases and review of the literature. Rev Infect Dis. 1986;8(3):441–6.CrossRefGoogle Scholar
  36. Nishimura K, Takahashi Y, Yamagishi Y, Banno S, Uchida Y, Tanigawa T, et al. Advanced surgical technique for invasive fungal sinusitis: endoscopic orbit-sinus combined approach. Minim Invasive Ther Allied Technol. 2017;26(5):307–13.CrossRefGoogle Scholar
  37. Otto K, DelGaudio J. Invasive fungal rhinosinusitis: what is the appropriate follow-up? Am J Rhinol. 2006;20(6):582–5. Available from: CrossRefGoogle Scholar
  38. Palejwala S, Zangeneh T, Goldstein S, Lemole GM. An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis. Surg Neurol Int. 2016;7(1):61. Available from: CrossRefGoogle Scholar
  39. Panda NK, Sharma SC, Chakrabarti A, Mann SB. Paranasal sinus mycoses in north India. Mycoses. 1998;41:281–6. Available from: CrossRefGoogle Scholar
  40. Parikh SL, Venkatraman G, DelGaudio JM. Invasive fungal sinusitis: a 15-year review from a single institution. Am J Rhinol. 2004;18(2):75–81.CrossRefGoogle Scholar
  41. Peterson KL, Wang M, Canalis RF, Abemayor E. Rhinocerebral mucormycosis: evolution of the disease and treatment options. Laryngoscope. 1997;107(7):855–62. Available from: CrossRefGoogle Scholar
  42. Plowes Hernandez O, Prado Calleros HM, Soberon Marmissolle Daguerre GS, Sadek Gonzalez A. Rhino-orbito-cerebral mucormycosis. Management strategies to avoid or limit intracraneal affection and improve survival. Acta Otorrinolaringol Esp. 2015;66(6):348–52.CrossRefGoogle Scholar
  43. Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect. 2004;10(Suppl 1):31–47.CrossRefGoogle Scholar
  44. Price JC, Stevens DL. Hyperbaric oxygen in the treatment of rhinocerebral mucormycosis. Laryngoscope. 1980;90:737–47. Available from: CrossRefGoogle Scholar
  45. Schell WA. Histopathology of fungal rhinosinusitis. Otolaryngol Clin N Am. 2000;33:251–76.CrossRefGoogle Scholar
  46. Schwartz LE. Acute invasive fungal rhinosinusitis. Pathol Case Rev. 2011;16(6):230–3.CrossRefGoogle Scholar
  47. Skiada A, Lanternier F, Groll AH, Pagano L, Zimmerli S, Herbrecht R, et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica. 2013;98(4):492–504.CrossRefGoogle Scholar
  48. Soler ZM, Schlosser RJ. The role of fungi in diseases of the nose and sinuses. Am J Rhinol Allergy. 2012;26(5):351–8.CrossRefGoogle Scholar
  49. Songu M, Unlu HH, Gunhan K, Ilker SS, Nese N. Orbital exenteration: a dilemma in mucormycosis presented with orbital apex syndrome. Am J Rhinol. 2008;22(1):98–103. Available from: CrossRefGoogle Scholar
  50. Spellberg B, Edwards J, Ibrahim A. Novel perspectives on Mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005;18(3):556–69.CrossRefGoogle Scholar
  51. Sridhara SR, Paragache G, Panda NK, Chakrabarti A. Mucormycosis in immunocompetent individuals: an increasing trend. J Otolaryngol. 2005;34(6):402–6. Available from: CrossRefGoogle Scholar
  52. Talbot GH, Huang A, Provencher M. Invasive aspergillus rhinosinusitis in patients with acute-leukemia. Rev Infect Dis. 1991;13(2):219–32.CrossRefGoogle Scholar
  53. Thompson GR, Patterson TF. Fungal disease of the nose and paranasal sinuses. J Allergy Clin Immunol. 2012;129:321–6.CrossRefGoogle Scholar
  54. Vironneau P, Kania R, Morizot G, Elie C, Garcia-Hermoso D, Herman P, et al. Local control of rhino-orbito-cerebral mucormycosis dramatically impacts survival. Clin Microbiol Infect. 2014;20(5):O336–9.CrossRefGoogle Scholar
  55. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, KA M, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.CrossRefGoogle Scholar
  56. Walsh TJ, Skiada A, Cornely OA, Roillides E, Ibrahim A, Zaoutis T, et al. Development of new strategies for early diagnosis of mucormycosis from bench to bedside. Mycoses. 2014;57(03):2–7.CrossRefGoogle Scholar
  57. Yohai RA, Bullock JD, Aziz AA, Markert RJ. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. 1994;39:3–22.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gauri S. Mankekar
    • 1
    • 2
  • Rahul Mehta
    • 3
  • Daniel W. Nuss
    • 3
  1. 1.Neurotology and Skull Base SurgeryOur Lady of the LakeBaton RougeUSA
  2. 2.Louisiana State University Health Sciences CenterNew OrleansUSA
  3. 3.Department of OtolaryngologyLouisiana State University Health Sciences CenterNew OrleansUSA

Personalised recommendations