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A Quantitative Meta-analysis of Olfactory Dysfunction in Epilepsy

  • Kiran Khurshid
  • Andrew J. D. Crow
  • Petra E. Rupert
  • Nancy L. Minniti
  • Melissa A. Carswell
  • Dawn J. Mechanic-Hamilton
  • Vidyulata Kamath
  • Richard L. Doty
  • Paul J. Moberg
  • David R. RoalfEmail author
Review

Abstract

Olfactory dysfunction in epilepsy is well-documented in several olfactory domains. However, the clinical specificity of these deficits remains unknown. The aim of this systematic meta-analysis was to determine which domains of olfactory ability were most impaired in individuals with epilepsy, and to assess moderating factors affecting olfactory ability. Extant peer-reviewed literature on olfaction in epilepsy were identified via a computerized literature search using PubMed, MEDLINE, PsycInfo, and Google Scholar databases. Twenty-one articles met inclusion criteria. These studies included a total of 912 patients with epilepsy and 794 healthy comparison subjects. Included studies measured olfaction using tests of odor identification, discrimination, memory, and detection threshold in patients with different types of epilepsy, including temporal lobe epilepsy (TLE), mixed frontal epilepsy (M-F), and mixed epilepsy (MIX). Olfactory deficits were robust in patients with epilepsy when compared to healthy individuals, with effect sizes in the moderate to large range for several olfactory domains, including odor identification (d = −1.59), memory (d = −1.10), discrimination (d = −1.04), and detection threshold (d = −0.58). Olfactory deficits were most prominent in patients with TLE and M-F epilepsy. Amongst patients with epilepsy, sex, age, smoking status, education, handedness, and age of illness onset were significantly related to olfactory performance. Overall, these meta-analytic findings indicate that the olfactory system is compromised in epilepsy and suggest that detailed neurobiological investigations of the olfactory system may provide further insight into this disorder.

Keywords

Olfaction Smell Epilepsy Seizures Seizure disorder 

Notes

Funding Sources

This work was supported by K01 MH102609 (Roalf), the Brain and Behavior Foundation NARSAD Young Investigator grant program (Roalf), and the John Hopkins Clinical Research Scholars Program KL2TR001077 (Kamath).

Role of the Funding Sources

The funding sources had no role in the design, collection, analysis or manuscript preparation for this study.

Compliance with Ethical Standards

Ethical Publication Statement

We affirm that we have read the Neuropsychology Review’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Conflicts of Interest Disclosures

The authors declare that they have no conflict of interest.

Supplementary material

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ESM 1 (XLSX 31 kb)
11065_2019_9406_MOESM2_ESM.doc (64 kb)
ESM 2 (DOC 64 kb)

References

Uncategorized References

  1. Abraham, A., & Mathai, K. (1983). The effect of right temporal lobe lesions on matching of smells. Neuropsychologia, 21(3), 277–281.CrossRefGoogle Scholar
  2. Acharya, V., Acharya, J., & Lüders, H. (1998). Olfactory epileptic auras. Neurology, 51(1), 56–61.CrossRefGoogle Scholar
  3. Bath, K. G., & Scharfman, H. E. (2013). Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research. Epilepsy & Behavior, 26(3), 427-439.Google Scholar
  4. Bertram, E. H. (1997). Functional anatomy of spontaneous seizures in a rat model of limbic epilepsy. Epilepsia, 38(1), 95–105.CrossRefGoogle Scholar
  5. Brand, G., & Millot, J.-L. (2001). Sex differences in human olfaction: between evidence and enigma. The Quarterly Journal of Experimental Psychology: Section B, 54(3), 259–270.CrossRefGoogle Scholar
  6. Cain, W. S., de Wijk, R., Lulejian, C., Schiet, F., & See, L.-C. (1998). Odor identification: perceptual and semantic dimensions. Chemical Senses, 23(3), 309–326.CrossRefGoogle Scholar
  7. Cain, W. S., & Rabin, M. D. (1989). Comparability of two tests of olfactory functioning. Chemical Senses, 14(4), 479–485.CrossRefGoogle Scholar
  8. Caminiti, F., De Salvo, S., Nunnari, D., Bramanti, P., Ciurleo, R., Granata, F., & Marino, S. (2016). Effect of the antiepileptic therapy on olfactory disorders associated with mesial temporal sclerosis. Neurocase, 22(4), 357–361.CrossRefGoogle Scholar
  9. Campanella, G., Filla, A., & De Michele, G. (1978). Smell and taste acuity in epileptic syndromes. European Neurology, 17(3), 136–141.CrossRefGoogle Scholar
  10. Chen, C., Shih, Y. H., Yen, D. J., Lirng, J. F., Guo, Y. C., Yu, H. Y., & Yiu, C. H. (2003). Olfactory auras in patients with temporal lobe epilepsy. Epilepsia, 44(2), 257–260.CrossRefGoogle Scholar
  11. Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences (2nd ed.). Hillsdale. New Jersey: Erlbaum.Google Scholar
  12. Doty, R. L. (2015). Olfactory dysfunction and its measurement in the clinic. World Journal of Otorhinolaryngology-Head and Neck Surgery, 1(1), 28–33.  https://doi.org/10.1016/j.wjorl.2015.09.007 CrossRefGoogle Scholar
  13. Doty, R. L., Applebaum, S., Zusho, H., & Settle, R. G. (1985). Sex differences in odor identification ability: a cross-cultural analysis. Neuropsychologia, 23(5), 667–672.CrossRefGoogle Scholar
  14. Doty, R. L., & Bromley, S. M. (2004). Effects of drugs on olfaction and taste. Otolaryngologic Clinics of North America, 37(6), 1229–1254.CrossRefGoogle Scholar
  15. Doty, R. L., & Kamath, V. (2014). The influences of age on olfaction: a review. Frontiers in Psychology, 5, 20.CrossRefGoogle Scholar
  16. Doty, R. L., & Kerr, K.-L. (2005). Episodic odor memory: influences of handedness, sex, and side of nose. Neuropsychologia, 43(12), 1749–1753.CrossRefGoogle Scholar
  17. Doty, R. L., McKeown, D. A., Lee, W. W., & Shaman, P. (1995). A study of the test-retest reliability of ten olfactory tests. Chemical Senses, 20(6), 645–656.CrossRefGoogle Scholar
  18. Duval, S., & Tweedie, R. (2000). Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis. Biometrics, 56(2), 455–463.CrossRefGoogle Scholar
  19. Eichenbaum, H., Morton, T. H., Potter, H., & Corkin, S. (1983). Selective olfactory deficits in case HM. Brain, 106(2), 459–472.CrossRefGoogle Scholar
  20. Eskenazi, B., Cain, W. S., Novelly, R. A., & Mattson, R. (1986). Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy. Neuropsychologia, 24(4), 553–562.CrossRefGoogle Scholar
  21. Eslinger, P. J., Damasio, A. R., & Van Hoesen, G. W. (1982). Olfactory dysfunction in man: anatomical and behavioral aspects. Brain and Cognition, 1(3), 259–285.CrossRefGoogle Scholar
  22. Gabrieli, J. D., Cohen, N. J., & Corkin, S. (1988). The impaired learning of semantic knowledge following bilateral medial temporal-lobe resection. Brain and Cognition, 7(2), 157–177.CrossRefGoogle Scholar
  23. Ghanizadeh, A. (2009). Loss of taste and smell during treatment with topiramate. Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity, 14(2–3), e137–e138.CrossRefGoogle Scholar
  24. Hudry, J., Perrin, F., Ryvlin, P., Mauguière, F., & Royet, J. P. (2003). Olfactory short-term memory and related amygdala recordings in patients with temporal lobe epilepsy. Brain, 126(8), 1851–1863.CrossRefGoogle Scholar
  25. Jones-Gotman, M., Zatorre, R., Cendes, F., Olivier, A., Andermann, F., McMackin, D., … Wieser, H. (1997). Contribution of medial versus lateral temporal-lobe structures to human odour identification. Brain: A Journal of Neurology, 120(10), 1845–1856.CrossRefGoogle Scholar
  26. Kjelvik, G., Evensmoen, H. R., Brezova, V., & Håberg, A. K. (2012). The human brain representation of odor identification. Journal of Neurophysiology, 108(2), 645–657.CrossRefGoogle Scholar
  27. Kohler, C. G., Moberg, P. J., Gur, R. E., O'connor, M. J., Sperling, M. R., & Doty, R. L. (2001). Olfactory dysfunction in schizophrenia and temporal lobe epilepsy. Cognitive and Behavioral Neurology, 14(2), 83–88.Google Scholar
  28. Kuzniecky, R., de la Sayette, V., Ethier, R., Melanson, D., Andermann, F., Berkovic, S., … Feindel, W. (1987). Magnetic resonance imaging in temporal lobe epilepsy: pathological correlations. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 22(3), 341–347.CrossRefGoogle Scholar
  29. Lehrner, J. P. (1993). Gender differences in long-term odor recognition memory: verbal versus sensory influences and the consistency of label use. Chemical Senses, 18(1), 17–26.CrossRefGoogle Scholar
  30. Leopold, D. (2002). Distortion of olfactory perception: diagnosis and treatment. Chemical Senses, 27(7), 611–615.CrossRefGoogle Scholar
  31. Mesholam, R. I., Moberg, P. J., Mahr, R. N., & Doty, R. L. (1998). Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases. Archives of Neurology, 55(1), 84–90. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9443714
  32. Moher, D., Liberati, A., Tetzlaff, J., Altman, DG., PRISMA Group. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med, 6(7):e1000097.Google Scholar
  33. Mummery, C. J., Patterson, K., Price, C. J., Ashburner, J., Frackowiak, R. S., & Hodges, J. R. (2000). A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory. Annals of Neurology, 47(1), 36–45.CrossRefGoogle Scholar
  34. Rausch, R., & Serafetinides, E. (1975). Specific alterations of olfactory function in humans with temporal lobe lesions. Nature, 255(5509), 557.CrossRefGoogle Scholar
  35. Savic, I., Bookheimer, S. Y., Fried, I., & Engel, J. (1997). Olfactory bedside test: a simple approach to identify temporo-orbitofrontal dysfunction. Archives of Neurology, 54(2), 162–168.CrossRefGoogle Scholar
  36. Savic, I., & Engel, J. (1998). Sex differences in patients with mesial temporal lobe epilepsy. Journal of Neurology, Neurosurgery and Psychiatry, 65(6), 910–912.CrossRefGoogle Scholar
  37. Ship, J. A., & Weiffenbach, J. M. (1993). Age, gender, medical treatment, and medication effects on smell identification. Journal of Gerontology, 48(1), M26–M32.CrossRefGoogle Scholar
  38. West, S. E., & Doty, R. L. (1995). Influence of epilepsy and temporal lobe resection on olfactory function. Epilepsia, 36(6), 531–542.CrossRefGoogle Scholar
  39. Willander, J., & Larsson, M. (2007). Olfaction and emotion: The case of autobiographical memory. Memory and Cognition, 35(7), 1659–1663.CrossRefGoogle Scholar
  40. Zald, D. H., & Pardo, J. V. (1997). Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. Proceedings of the National Academy of Sciences, 94(8), 4119–4124.CrossRefGoogle Scholar
  41. Zatorre, R. J., & Jones-Gotman, M. (1990). Right-nostril advantage for discrimination of odors. Perception & Psychophysics, 47(6), 526–531.CrossRefGoogle Scholar
  42. Zatorre, R. J., & Jones-Gotman, M. (1991). Human olfactory discrimination after unilateral frontal or temporal lobectomy. Brain, 114(1), 71–84.Google Scholar
  43. Zilstorff, K. (1966). Parosmia. The Journal of Laryngology & Otology, 80(11), 1102–1104.CrossRefGoogle Scholar

Studies Included in Meta-analysis *See associated Supplemental File*

  1. Carroll, B., Richardson, J., & Thompson, P. (1993). Olfactory information processing and temporal lobe epilepsy. Brain and Cognition, 22(2), 230–243.CrossRefGoogle Scholar
  2. Dade, L. A., Zatorre, R. J., & Jones-Gotman, M. (2002). Olfactory learning: convergent findings from lesion and brain imaging studies in humans. Brain, 125(1), 86–101.CrossRefGoogle Scholar
  3. Desai, M., Agadi, J., Karthik, N., Praveenkumar, S., & Netto, A. (2015). Olfactory abnormalities in temporal lobe epilepsy. Journal of Clinical Neuroscience, 22(10), 1614–1618.CrossRefGoogle Scholar
  4. Doty, R. L., Tourbier, I., Neff, J. K., Silas, J., Turetsky, B., Moberg, P., … Detre, J. A. (2018). Influences of temporal lobe epilepsy and temporal lobe resection on olfaction. Journal of Neurology, 265(7), 1654–1665.CrossRefGoogle Scholar
  5. Eskenazi, B., Cain, W. S., Novelly, R. A., & Friend, K. B. (1983). Olfactory functioning in temporal lobectomy patients. Neuropsychologia, 21(4), 365–374.CrossRefGoogle Scholar
  6. 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 & Behavior, 25(4), 477–480.CrossRefGoogle Scholar
  7. Hudry, J., Ryvlin, P., Saive, A.-L., Ravel, N., Plailly, J., & Royet, J.-P. (2014). Lateralization of olfactory processing: Differential impact of right and left temporal lobe epilepsies. Epilepsy & Behavior, 37, 184–190.CrossRefGoogle Scholar
  8. Hummel, T., Henkel, S., Negoias, S., Galván, J. R., Bogdanov, V., Hopp, P., … Haehner, A. (2013). Olfactory bulb volume in patients with temporal lobe epilepsy. Journal of Neurology, 260(4), 1004–1008.CrossRefGoogle Scholar
  9. Juran, S. A., Lundström, J. N., Geigant, M., Kumlien, E., Fredrikson, M., Åhs, F., & Olsson, M. J. (2016). Unilateral resection of the anterior medial temporal lobe impairs odor identification and valence perception. Frontiers in Psychology, 6, 2015.CrossRefGoogle Scholar
  10. Lehrner, J., Baumgartner, C., Serles, W., Olbrich, A., Pataraia, E., Bacher, J., … Deecke, L. (1997). Olfactory prodromal symptoms and unilateral olfactory dysfunction are associated in patients with right mesial temporal lobe epilepsy. Epilepsia, 38(9), 1042–1044.CrossRefGoogle Scholar
  11. Martinez, B. A., Cain, W. S., de Wijk, R. A., Spencer, D. D., Novelly, R. A., & Sass, K. J. (1993). Olfactory functioning before and after temporal lobe resection for intractable seizures. Neuropsychology, 7(3), 351–363.CrossRefGoogle Scholar
  12. Pouliot, S., & Jones-Gotman, M. (2008). Medial temporal-lobe damage and memory for emotionally arousing odors. Neuropsychologia, 46(4), 1124–1134.CrossRefGoogle Scholar
  13. Rausch, R., Serafetinides, E., & Crandall, P. H. (1977). Olfactory memory in patients with anterior temporal lobectomy. Cortex, 13(4), 445–452.CrossRefGoogle Scholar
  14. Savage, S. A., Butler, C. R., Milton, F., Han, Y., & Zeman, A. Z. (2017). On the nose: Olfactory disturbances in patients with transient epileptic amnesia. Epilepsy & Behavior, 66, 113–119.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kiran Khurshid
    • 1
  • Andrew J. D. Crow
    • 2
  • Petra E. Rupert
    • 3
  • Nancy L. Minniti
    • 4
  • Melissa A. Carswell
    • 5
  • Dawn J. Mechanic-Hamilton
    • 6
  • Vidyulata Kamath
    • 7
  • Richard L. Doty
    • 8
  • Paul J. Moberg
    • 2
    • 6
    • 8
  • David R. Roalf
    • 2
    Email author
  1. 1.Department of NeurologyIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of PsychiatryUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  3. 3.Department of PsychologyUniversity of PittsburghPittsburghUSA
  4. 4.Department of Physical Medicine and RehabilitationTemple University HospitalPhiladelphiaUSA
  5. 5.The Neurology CenterRockvilleUSA
  6. 6.Department of NeurologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  7. 7.Department of Psychiatry and Behavioral SciencesJohns Hopkins School of MedicineBaltimoreUSA
  8. 8.Smell & Taste Center, Department of Otorhinolaryngology: Head & Neck SurgeryUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA

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