Olfactory bulb volume changes associated with trans-sphenoidal pituitary surgery

Autoři: Dino Podlesek aff001;  Amir Zolal aff002;  Matthias Kirsch aff003;  Gabriele Schackert aff001;  Thomas Pinzer aff001;  Thomas Hummel aff004
Působiště autorů: Department of Neurosurgery, Dresden University of Technology, Carl Gustav Carus Faculty of Medicine, Dresden, Germany aff001;  Department of Spine Surgery and Neurotraumatology, SRH-Wald Clinic Gera, Gera, Germany aff002;  Department of Neurosurgery, Asklepios Clinic Schildautal Seesen, Germany aff003;  Interdisciplinary Smell & Taste Clinic, Department of Otorhinolaryngology, Dresden University of Technology, Carl Gustav Carus Faculty of Medicine, Dresden, Germany aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224594



The trans-sphenoidal approach is most frequently used for pituitary adenoma (PA) enucleation. However, effects of this surgery on neighboring structures have received little attention so far. In particular, no investigations on olfactory bulb (OB) anatomy after trans-sphenoidal surgery have been reported. Because impairment of olfaction has been shown in small groups following trans-sphenoidal surgery we hypothesized that the transnasal approach is likely to alter OB volume which is associated with changes of olfactory function.


The study comprised 33 patients with pituitary adenoma (14 women and 19 men, mean age 50 years). Comprehensive assessment of olfactory function was conducted with the "Sniffin' Sticks" test kit. Based on magnetic resonance imaging scans OBs were measured before and approximately one year after trans-sphenoidal PA enucleation.


Owing to postoperative non-compliance and MRI artifacts partly due to drill friction complete evaluation of “Sniffin' Sticks” in term of obtaining the TDI score was possible pre- and postoperatively in 21 patients whereas OB volumes were available in 32 patients. Approximately one year after surgery olfactory function was not significantly different from baseline. However, left- and right-sided OB volume in patients treated via trans-sphenoidal surgery decreased (p = 0.001). The side of the surgical approach did not affect OB volume in a side-specific manner. Changes in odor threshold were significantly correlated to changes in right-sided OB volume (r = 0.45, p = 0.024).


Overall olfactory performance one year after surgery was not significantly different from baseline. However, changes in OB volume are associated with changes in olfactory performance and OB volumes decreased in patients.

Klíčová slova:

Lesions – Magnetic resonance imaging – Olfactory bulb – Pituitary gland – Surgical and invasive medical procedures – Pituitary adenomas – Endocrine system procedures


1. Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol. 2013;15 Suppl 2:ii1–56. doi: 10.1093/neuonc/not151 24137015; PubMed Central PMCID: PMC3798196.

2. Hong SD, Nam DH, Seol HJ, Choi NY, Kim HY, Chung SK, et al. Endoscopic binostril versus transnasal transseptal microscopic pituitary surgery: Sinonasal quality of life and olfactory function. Am J Rhinol Allergy. 2015;29(3):221–5. doi: 10.2500/ajra.2015.29.4165 25975255.

3. Kim BY, Son HL, Kang SG, Kim SW, Hong YK, Jeun SS, et al. Postoperative nasal symptoms associated with an endoscopic endonasal transsphenoidal approach. Eur Arch Otorhinolaryngol. 2013;270(4):1355–9. doi: 10.1007/s00405-012-2226-x 23081674.

4. Hart CK, Theodosopoulos PV, Zimmer LA. Olfactory changes after endoscopic pituitary tumor resection. Otolaryngol Head Neck Surg. 2010;142(1):95–7. doi: 10.1016/j.otohns.2009.09.032 20096230.

5. Gondim JA, Almeida JP, Albuquerque LA, Schops M, Gomes E, Ferraz T, et al. Endoscopic endonasal approach for pituitary adenoma: surgical complications in 301 patients. Pituitary. 2011;14(2):174–83. doi: 10.1007/s11102-010-0280-1 21181278.

6. Wang F, Zhou T, Wei S, Meng X, Zhang J, Hou Y, et al. Endoscopic endonasal transsphenoidal surgery of 1,166 pituitary adenomas. Surg Endosc. 2015;29(6):1270–80. doi: 10.1007/s00464-014-3815-0 25270611; PubMed Central PMCID: PMC4422857.

7. Cappabianca P, Briganti F, Cavallo LM, de Divitiis E. Pseudoaneurysm of the intracavernous carotid artery following endoscopic endonasal transsphenoidal surgery, treated by endovascular approach. Acta Neurochir (Wien). 2001;143(1):95–6. doi: 10.1007/s007010170144 11345725.

8. Cappabianca P, Cavallo LM, Colao A, de Divitiis E. Surgical complications associated with the endoscopic endonasal transsphenoidal approach for pituitary adenomas. J Neurosurg. 2002;97(2):293–8. doi: 10.3171/jns.2002.97.2.0293 12186456.

9. Chabot JD, Chakraborty S, Imbarrato G, Dehdashti AR. Evaluation of Outcomes After Endoscopic Endonasal Surgery for Large and Giant Pituitary Macroadenoma: A Retrospective Review of 39 Consecutive Patients. World Neurosurg. 2015;84(4):978–88. doi: 10.1016/j.wneu.2015.06.007 26074433.

10. Kessler L, Legaludec V, Dietemann JL, Maitrot D, Pinget M. Sphenoidal sinus mucocele after transsphenoidal surgery for acromegaly. Neurosurg Rev. 1999;22(4):222–5. doi: 10.1007/s101430050021 10682932.

11. Nasseri SS, Kasperbauer JL, Strome SE, McCaffrey TV, Atkinson JL, Meyer FB. Endoscopic transnasal pituitary surgery: report on 180 cases. Am J Rhinol. 2001;15(4):281–7. 11554662.

12. Morrison M, Momjian S, Friedrich H, Landis BN. [Olfactory function after transsphenoidal pituitary surgery]. Rev Med Suisse. 2014;10(444):1806, 8–10. 25417336.

13. Wang S, Chen Y, Li J, Wei L, Wang R. Olfactory function and quality of life following microscopic endonasal transsphenoidal pituitary surgery. Medicine (Baltimore). 2015;94(4):e465. doi: 10.1097/MD.0000000000000465 25634190; PubMed Central PMCID: PMC4602950.

14. Dehdashti AR, Ganna A, Karabatsou K, Gentili F. Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery. 2008;62(5):1006–15; discussion 15–7. doi: 10.1227/01.neu.0000325862.83961.12 18580798.

15. Huart C, Rombaux P, Hummel T. Plasticity of the human olfactory system: the olfactory bulb. Molecules. 2013;18(9):11586–600. doi: 10.3390/molecules180911586 24048289.

16. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. 'Sniffin' sticks': olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses. 1997;22(1):39–52. doi: 10.1093/chemse/22.1.39 9056084.

17. Kobal G, Klimek L, Wolfensberger M, Gudziol H, Temmel A, Owen CM, et al. Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol. 2000;257(4):205–11. doi: 10.1007/s004050050223 10867835.

18. Hummel T, Kobal G, Gudziol H, Mackay-Sim A. Normative data for the "Sniffin' Sticks" including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. Eur Arch Otorhinolaryngol. 2007;264(3):237–43. doi: 10.1007/s00405-006-0173-0 17021776.

19. Katotomichelakis M, Balatsouras D, Tripsianis G, Tsaroucha A, Homsioglou E, Danielides V. Normative values of olfactory function testing using the 'sniffin' sticks'. Laryngoscope. 2007;117(1):114–20. doi: 10.1097/01.mlg.0000246518.79894.7e 17202939.

20. Gudziol V, Lotsch J, Hahner A, Zahnert T, Hummel T. Clinical significance of results from olfactory testing. Laryngoscope. 2006;116(10):1858–63. doi: 10.1097/01.mlg.0000234915.51189.cb 17003712.

21. Buschhuter D, Smitka M, Puschmann S, Gerber JC, Witt M, Abolmaali ND, et al. Correlation between olfactory bulb volume and olfactory function. Neuroimage. 2008;42(2):498–502. doi: 10.1016/j.neuroimage.2008.05.004 18555701.

22. Gudziol V, Buschhuter D, Abolmaali N, Gerber J, Rombaux P, Hummel T. Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis—a longitudinal study. Brain. 2009;132(Pt 11):3096–101. doi: 10.1093/brain/awp243 19773353.

23. Yousem DM, Oguz KK, Li C. Imaging of the olfactory system. Semin Ultrasound CT MR. 2001;22(6):456–72. doi: 10.1016/s0887-2171(01)90001-0 11770926.

24. Altman J. Are new neurons formed in the brains of adult mammals? Science. 1962;135(3509):1127–8. doi: 10.1126/science.135.3509.1127 13860748.

25. Graziadei PP, Karlan MS, Graziadei GA, Bernstein JJ. Neurogenesis of sensory neurons in the primate olfactory system after section of the fila olfactoria. Brain Res. 1980;186(2):289–300. doi: 10.1016/0006-8993(80)90976-2 6766784.

26. Winner B, Cooper-Kuhn CM, Aigner R, Winkler J, Kuhn HG. Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb. Eur J Neurosci. 2002;16(9):1681–9. doi: 10.1046/j.1460-9568.2002.02238.x 12431220.

27. Byrd CA, Burd GD. Morphological and quantitative evaluation of olfactory bulb development in Xenopus after olfactory placode transplantation. J Comp Neurol. 1993;331(4):551–63. doi: 10.1002/cne.903310410 8509511.

28. Byrd CA, Burd GD. The quantitative relationship between olfactory axons and mitral/tufted cells in developing Xenopus with partially deafferented olfactory bulbs. J Neurobiol. 1993;24(9):1229–42. doi: 10.1002/neu.480240909 8409980.

29. Cowan CM, Roskams AJ. Apoptosis in the mature and developing olfactory neuroepithelium. Microsc Res Tech. 2002;58(3):204–15. doi: 10.1002/jemt.10150 12203699.

30. Whitesides JG 3rd, LaMantia AS. Differential adhesion and the initial assembly of the mammalian olfactory nerve. J Comp Neurol. 1996;373(2):240–54. doi: 10.1002/(SICI)1096-9861(19960916)373:2<240::AID-CNE7>3.0.CO;2-3 8889925.

31. Schaefer AT, Margrie TW. Spatiotemporal representations in the olfactory system. Trends Neurosci. 2007;30(3):92–100. doi: 10.1016/j.tins.2007.01.001 17224191.

32. Oppenheim RW, Houenou LJ, Parsadanian AS, Prevette D, Snider WD, Shen L. Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: regulation of programmed cell death among motoneuron subtypes. J Neurosci. 2000;20(13):5001–11. doi: 10.1523/JNEUROSCI.20-13-05001.2000 10864958.

33. Rochefort C, Gheusi G, Vincent JD, Lledo PM. Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory. J Neurosci. 2002;22(7):2679–89. doi: 20026260. doi: 10.1523/JNEUROSCI.22-07-02679.2002 11923433.

34. Nie S, Li K, Huang Y, Zhao J, Gao X, Sun J. Endoscopic endonasal transsphenoidal surgery for treating pituitary adenoma via a sub-septum mucosa approach. Int J Clin Exp Med. 2015;8(4):5137–43. 26131087; PubMed Central PMCID: PMC4483803.

35. Rioja E, Bernal-Sprekelsen M, Enriquez K, Ensenat J, Valero R, de Notaris M, et al. Long-term outcomes of endoscopic endonasal approach for skull base surgery: a prospective study. Eur Arch Otorhinolaryngol. 2016;273(7):1809–17. doi: 10.1007/s00405-015-3853-9 26688432.

36. Kim SW, Park KB, Khalmuratova R, Lee HK, Jeon SY, Kim DW. Clinical and histologic studies of olfactory outcomes after nasoseptal flap harvesting. Laryngoscope. 2013;123(7):1602–6. doi: 10.1002/lary.24107 23798331.

37. Alobid I, Ensenat J, Marino-Sanchez F, de Notaris M, Centellas S, Mullol J, et al. Impairment of olfaction and mucociliary clearance after expanded endonasal approach using vascularized septal flap reconstruction for skull base tumors. Neurosurgery. 2013;72(4):540–6. doi: 10.1227/NEU.0b013e318282a535 23246823.

38. Actor B, Sarnthein J, Prommel P, Holzmann D, Bernays RL. Olfactory improvement in acromegaly after transnasal transsphenoidal surgery. Neurosurg Focus. 2010;29(4):E10. doi: 10.3171/2010.7.FOCUS10162 20887120.

39. Leopold DA, Hummel T, Schwob JE, Hong SC, Knecht M, Kobal G. Anterior distribution of human olfactory epithelium. Laryngoscope. 2000;110(3 Pt 1):417–21. doi: 10.1097/00005537-200003000-00016 10718430.

40. Damm M, Vent J, Schmidt M, Theissen P, Eckel HE, Lotsch J, et al. Intranasal volume and olfactory function. Chem Senses. 2002;27(9):831–9. doi: 10.1093/chemse/27.9.831 12438209.

41. Zhao K, Scherer PW, Hajiloo SA, Dalton P. Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction. Chem Senses. 2004;29(5):365–79. doi: 10.1093/chemse/bjh033 15201204.

42. Upadhyay S, Buohliqah L, Dolci RLL, Otto BA, Prevedello DM, Carrau RL. Periodic olfactory assessment in patients undergoing skull base surgery with preservation of the olfactory strip. Laryngoscope. 2017;127(9):1970–5. doi: 10.1002/lary.26546 28349579.

43. Bedrosian JC, McCoul ED, Raithatha R, Akselrod OA, Anand VK, Schwartz TH. A prospective study of postoperative symptoms in sinonasal quality-of-life following endoscopic skull-base surgery: dissociations based on specific symptoms. Int Forum Allergy Rhinol. 2013;3(8):664–9. doi: 10.1002/alr.21161 23520019.

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