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Influences of temporal lobe epilepsy and temporal lobe resection on olfaction

Abstract

Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring  the tests’ associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study.

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References

  1. Abraham A, Mathai KV (1983) The effect of right temporal lobe lesions on matching of smells. Neuropsychologia 21:277–281

    Article  PubMed  CAS  Google Scholar 

  2. Araujo D, Santos AC, Velasco TR, Wichert-Ana L, Terra-Bustamante VC, Alexandre V Jr, Carlotti CG Jr, Assirati JA Jr, Machado HR, Walz R, Leite JP, Sakamoto AC (2006) Volumetric evidence of bilateral damage in unilateral mesial temporal lobe epilepsy. Epilepsia 47:1354–1359

    Article  PubMed  Google Scholar 

  3. Bernasconi N, Bernasconi A, Caramanos Z, Antel SB, Andermann F, Arnold DL (2003) Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region. Brain 126:462–469

    Article  PubMed  CAS  Google Scholar 

  4. Campanella G, Filla A, De MG (1978) Smell and taste acuity in epileptic syndromes. Eur Neurol 17:136–141

    Article  PubMed  CAS  Google Scholar 

  5. Carroll B, Richardson JT, Thompson P (1993) Olfactory information processing and temporal lobe epilepsy. Brain Cogn 22:230–243

    Article  PubMed  CAS  Google Scholar 

  6. Choudhury ES, Moberg P, Doty RL (2003) Influences of age and sex on a microencapsulated odor memory test. Chem Senses 28:799–805

    Article  PubMed  Google Scholar 

  7. Ciumas C, Lindstrom P, Aoun B, Savic I (2008) Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy. Neuroimage 39:578–592

    Article  PubMed  Google Scholar 

  8. De Michele G, Filla A, Campanella G (1976) Ulteriori dati sull’acuitá olfattiva negli epilettici. Acta Neurol (Napoli) 31:250–256

    CAS  Google Scholar 

  9. Desai M, Agadi JB, Karthik N, Praveenkumar S, Netto AB (2015) Olfactory abnormalities in temporal lobe epilepsy. J Clin Neurosci 22:1614–1618

    Article  PubMed  CAS  Google Scholar 

  10. Doty RL (2017) Olfactory dysfunction in neurodegenerative diseases: is there a common pathological substrate? Lancet Neurol 16:478–488

    Article  PubMed  Google Scholar 

  11. Doty RL, Brugger WE, Jurs PC, Orndorff MA, Snyder PJ, Lowry LD (1978) Intranasal trigeminal stimulation from odorous volatiles: psychometric responses from anosmic and normal humans. Physiol Behav 20:175–185

    Article  PubMed  CAS  Google Scholar 

  12. Doty RL, Frye RE, Agrawal U (1989) Internal consistency reliability of the fractionated and whole University of Pennsylvania Smell Identification Test. Percept Psychophys 45:381–384

    Article  PubMed  CAS  Google Scholar 

  13. Doty RL, McKeown DA, Lee WW, Shaman P (1995) A study of the test–retest reliability of ten olfactory tests. Chem Senses 20:645–656

    Article  PubMed  CAS  Google Scholar 

  14. Doty RL, Shaman P, Dann M (1984) Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 32:489–502

    Article  PubMed  CAS  Google Scholar 

  15. Duvernoy HM (1999) The human brain: surface, three-dimensional sectional anatomy with MRI and blood supply. Springer, New York

    Book  Google Scholar 

  16. Duzel E, Schiltz K, Solbach T, Peschel T, Baldeweg T, Kaufmann J, Szentkuti A, Heinze HJ (2006) Hippocampal atrophy in temporal lobe epilepsy is correlated with limbic systems atrophy. J Neurol 253:294–300

    Article  PubMed  Google Scholar 

  17. Eichenbaum H, Morton TH, Potter H, Corkin S (1983) Selective olfactory deficits in case H.M. Brain 106:459–472

    Article  PubMed  Google Scholar 

  18. Eskenazi B, Cain WS, Novelly RA, Friend KB (1983) Olfactory functioning in temporal lobectomy patients. Neuropsychologia 1983 21:365–374

    Article  PubMed  CAS  Google Scholar 

  19. Eskenazi B, Cain WS, Novelly RA, Mattson R (1986) Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy. Neuropsychologia 24:553–562

    Article  PubMed  CAS  Google Scholar 

  20. Falconer MA, Taylor DC (1968) Surgical treatment of drug-resistant epilepsy due to mesial temporal sclerosis. Arch Neurol 19:353–361

    Article  PubMed  CAS  Google Scholar 

  21. Haehner A, Henkel S, Hopp P, Hallmeyer-Elgner S, Reuner U, Reichmann H, Hummel T (2012) Olfactory function in patients with and without temporal lobe resection. Epilepsy Behav 25:477–480

    Article  PubMed  Google Scholar 

  22. Henkin RI, Comiter H, Fedio P, O’Doherty D (1977) Defects in taste and smell recognition following temporal lobectomy. Trans Am Neurol Assoc 102:146–150

    PubMed  CAS  Google Scholar 

  23. Hogan RE, Wang L, Bertrand ME, Willmore LJ, Bucholz RD, Nassif AS, Csernansky JG (2004) MRI-based high-dimensional hippocampal mapping in mesial temporal lobe epilepsy. Brain 127:1731–1740

    Article  PubMed  Google Scholar 

  24. Huber Z, Pruszewicz A, Szmeija Z, Bialek E (1965) Study of smell, taste, hearing, balance, sight, and tactile sensation following excision of the anterior temporal lobe. Pol Neurol Neurosurg Psychiatry 15:475–480

    CAS  Google Scholar 

  25. Hudry J, Perrin F, Ryvlin P, Mauguiere F, Royet JP (2003) Olfactory short-term memory and related amygdala recordings in patients with temporal lobe epilepsy. Brain 2003 126:1851–1863

    Google Scholar 

  26. Hummel T, Henkel S, Negoias S, Galvan JR, Bogdanov V, Hopp P, Hallmeyer-Elgner S, Gerber J, Reuner U, Haehner A (2013) Olfactory bulb volume in patients with temporal lobe epilepsy. J Neurol 260:1004–1008

    Article  PubMed  Google Scholar 

  27. Hummel T, Pauli E, Schuler P, Kettenmann B, Stefan H, Kobal G (1995) Chemosensory event-related potentials in patients with temporal lobe epilepsy. Epilepsia 36:79–85

    Article  PubMed  CAS  Google Scholar 

  28. Jones TA (1999) Multiple synapse formation in the motor cortex opposite unilateral sensorimotor cortex lesions in adult rats. J Comp Neurol 414:57–66

    Article  PubMed  CAS  Google Scholar 

  29. Jones-Gotman M, Zatorre RJ (1988) Olfactory identification deficits in patients with focal cerebral excision. Neuropsychologia 26:387–400

    Article  PubMed  CAS  Google Scholar 

  30. Jones-Gotman M, Zatorre RJ, Cendes F, Olivier A, Andermann F, McMackin Staunton H, Siegel AM, Wieser HG (1997) Contribution of medial versus lateral temporal-lobe structures to human odour identification. Brain 120:1845–1856

    Article  PubMed  Google Scholar 

  31. Mai J, Assheuer J, Paxinos G (2004) Atlas of the human brain. Elsevier, Amsterdam

    Google Scholar 

  32. Martinez BA, Cain WS, de Wijk RA, Spencer DD, Novelly RA, Sass KJ (1993) Olfactory functioning before and after temporal lobe resection for intractable seizures. Neuropsychology 7:351

    Article  Google Scholar 

  33. Moran NF, Lemieux L, Kitchen ND, Fish DR, Shorvon SD (2001) Extrahippocampal temporal lobe atrophy in temporal lobe epilepsy and mesial temporal sclerosis. Brain 124:167–175

    Article  PubMed  CAS  Google Scholar 

  34. Noulhiane M, Samson S, Clemenceau S, Dormont D, Baulac M, Hasboun D (2006) A volumetric MRI study of the hippocampus and the parahippocampal region after unilateral medial temporal lobe resection. J Neurosci Methods 156:293–304

    Article  PubMed  CAS  Google Scholar 

  35. Olivier A (1997) Surgical techniques in temporal lobe epilepsy. Clin Neurosurg 44:211–241

    PubMed  CAS  Google Scholar 

  36. Penfield W, Flanigin W (1950) Surgery of temporal lobe seizure. AMA Arch Neurol Psychiatry 64:491–500

    Article  PubMed  CAS  Google Scholar 

  37. Quigg M, Bertram EH, Jackson T, Laws E (1997) Volumetric magnetic resonance imaging evidence of bilateral hippocampal atrophy in mesial temporal lobe epilepsy. Epilepsia 38:588–594

    Article  PubMed  CAS  Google Scholar 

  38. Rausch R, Serafetinides EA (1975) Human temporal lobe and olfaction. In: Denton DA, Coghlan JP (eds) Olfaction and taste V. Academic Press, New York, pp 321–324

    Chapter  Google Scholar 

  39. Rausch R, Serafetinides EA (1975) Specific alterations of olfactory function in humans with temporal lobe lesions. Nature 255:557–558

    Article  PubMed  CAS  Google Scholar 

  40. Rausch R, Serafetinides EA, Crandall PH (1977) Olfactory memory in patients with anterior temporal lobectomy. Cortex 13:445–452

    Article  PubMed  CAS  Google Scholar 

  41. Santorelli G, Marotta A (1964) La sogli olfattometrica dell’epilettico in condizioni di base e dopo crisi. Osp Psichiatr Prov 32:185–190

    CAS  Google Scholar 

  42. Savage SA, Butler CR, Milton F, Han Y, Zeman AZ (2017) On the nose: Olfactory disturbances in patients with transient epileptic amnesia. Epilepsy Behav 66:113–119

    Article  PubMed  Google Scholar 

  43. Savic I, Bookheimer SY, Fried I, Engel J Jr (1997) Olfactory bedside test. A simple approach to identify temporo-orbitofrontal dysfunction. Arch Neurol 54:162–168

    Article  PubMed  CAS  Google Scholar 

  44. Seidenberg M, Kelly KG, Parrish J, Geary E, Dow C, Rutecki P, Hermann B (2005) Ipsilateral and contralateral MRI volumetric abnormalities in chronic unilateral temporal lobe epilepsy and their clinical correlates. Epilepsia 46:420–430

    Article  PubMed  Google Scholar 

  45. Soares JI, Valente MC, Andrade PA, Maia GH, Lukoyanov NV (2017) Reorganization of the septohippocampal cholinergic fiber system in experimental epilepsy. J Comp Neurol 525:2690–2705

    Article  PubMed  CAS  Google Scholar 

  46. Toulouse E, Vashide N (1899) Influence des crises épileptiques sur l’olfaction. C R Soc Biol 51:742–744

    Google Scholar 

  47. Turetsky B, Cowell PE, Gur RC, Grossman RI, Shtasel DL, Gur RE (1995) Frontal and temporal lobe brain volumes in schizophrenia. Relationship to symptoms and clinical subtype. Arch Gen Psychiatry 52:1061–1070

    Article  PubMed  CAS  Google Scholar 

  48. Yushkevich PA, Piven J, Hazlett HC, Smith RG, Ho S, Gee JC, Gerig G (2006) User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 31:1116–1128

    Article  PubMed  Google Scholar 

  49. Zatorre RJ, Jones-Gotman M (1991) Human olfactory discrimination after unilateral frontal or temporal lobectomy. Brain 114:71–84

    Article  PubMed  Google Scholar 

  50. Zatorre RJ, Jones-Gotman M, Evans AC, Meyer E (1992) Functional localization and lateralization of human olfactory cortex. Nature 360:339–340

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank the following individuals for their contributions to this project: David Adelman, Ritvijj Bowry, Charles Glass, Ruben Gur, Mark Korczykowski, Laurie Loevner, Dawn Mechanic-Hamilton, Helen Li, David L. Minkoff, Jessica Morton, Veena Narayan, Michael O’Connor, Kiana Owzar, David Roalf, Muhammad Shah, Joseph Tracy, John Treem, Steven E. West, and Paul A. Yushkevich. Marilyn Jones-Gotman provided comments on the final draft.

Funding

Supported by NIH Grant RO1 DC04278 awarded to RLD.

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Correspondence to Richard L. Doty.

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Conflicts of interest

RLD is President and major shareholder of Sensonics International, the company that manufactures and distributes olfactory and gustatory tests, including the commercial version of the University of Pennsylvania Smell Identification Test (UPSIT) used in this study. The remaining authors report no potential conflicts with commercial relationships of direct relevance to the current research.

Ethical standards

The study was approved by the University of Pennsylvania’s Office of Regulatory Affairs. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants were paid $20/hour for their time.

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Informed written consent was obtained from all participants.

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Doty, R.L., Tourbier, I., Neff, J.K. et al. Influences of temporal lobe epilepsy and temporal lobe resection on olfaction. J Neurol 265, 1654–1665 (2018). https://doi.org/10.1007/s00415-018-8891-y

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  • DOI: https://doi.org/10.1007/s00415-018-8891-y

Keywords

  • Olfaction
  • Epilepsy
  • Temporal lobe
  • Lobectomy
  • Anosmia