Smell and taste in cervical dystonia

Abstract

The pathophysiology of cervical dystonia is not completely understood. Current concepts of the pathophysiology propose that it is a network disorder involving the basal ganglia, cerebellum and sensorimotor cortex. These structures are primarily concerned with sensorimotor control but are also involved in non-motor functioning such as the processing of information related to the chemical senses. This overlap lets us hypothesize a link between cervical dystonia and altered sense of smell and taste. To prove this hypothesis and to contribute to the better understanding of cervical dystonia, we assessed olfactory and gustatory functioning in 40 adults with idiopathic cervical dystonia and 40 healthy controls. The Sniffin Sticks were used to assess odor threshold, discrimination and identification. Furthermore, the Taste Strips were applied to assess the combined taste score. Motor and non-motor deficits of cervical dystonia including neuropsychological and psychiatric alterations were assessed as cofactors for regression analyses. We found that cervical dystonia subjects had lower scores than healthy controls for odor threshold (5.8 ± 2.4 versus 8.0 ± 3.2; p = 0.001), odor identification (11.7 ± 2.3 versus 13.1 ± 1.3; p = 0.001) and the combined taste score (9.5 ± 2.2 versus 11.7 ± 2.7; p < 0.001), while no difference was found in odor discrimination (12.0 ± 2.5 versus 12.9 ± 1.8; p = 0.097). Regression analysis suggests that age is the main predictor for olfactory decline in subjects with cervical dystonia. Moreover, performance in the Montreal Cognitive Assessment is a predictor for gustatory decline in cervical dystonia subjects. Findings propose that cervical dystonia is associated with diminished olfactory and gustatory functioning.

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References

  1. Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK (2013) Phenomenology and classification of dystonia: a consensus update. Mov Disord 28:863–873

    PubMed  PubMed Central  Google Scholar 

  2. Alexander GE, Delong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381

    CAS  PubMed  Google Scholar 

  3. Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, Raethjen J, Stamelou M, Testa CM, Deuschl G, Tremor Task Force of the International Parkinson, and Movement Disorder Society (2018) Consensus statement on the classification of tremors. from the task force on tremor of the international parkinson and movement disorder society. Mov Disord 33:75–87

    PubMed  PubMed Central  Google Scholar 

  4. Bodranghien F, Bastian A, Casali C, Hallett M, Louis ED, Manto M, Mariën P, Nowak DA, Schmahmann JD, Serrao M, Steiner KM, Strupp M, Tilikete C, Timmann D, van Dun K (2016) Consensus paper: revisiting the symptoms and signs of cerebellar syndrome. Cerebellum 15:369–391

    PubMed  PubMed Central  Google Scholar 

  5. Bostan AC, Dum RP, Strick PL (2013) Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cognit Sci 17:241–254

    Google Scholar 

  6. Bower JM (1997) Control of sensory data acquisition. Int Rev Neurobiol 41:489–513

    CAS  PubMed  Google Scholar 

  7. Brown EC, Casey A, Fisch RI, Neuringer C (1958) Trial making test as a screening device for the detection of brain damage. J Consult Psychol 22:469–474

    CAS  PubMed  Google Scholar 

  8. Cecchini MP, Fasano A, Boschi F, Osculati F, Tinazzi M (2015) Taste in Parkinson’s disease. J Neurol 262:806–813

    PubMed  Google Scholar 

  9. Connelly T, Farmer JM, Lynch DR, Doty RL (2003) Olfactory dysfunction in degenerative ataxias. J Neurol Neurosurg Psychiatry 74:1435–1437

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Consky ES, Lang AE (1994) Clinical assessments of patients with cervical dystonia. In: Jankovic J, Hallett M (eds) Therapy with botulinum toxin. Marcel Dekker, New York, pp 211–237

    Google Scholar 

  11. Conte A, Defazio G, Hallett M, Fabbrini G, Berardelli A (2019) The role of sensory information in the pathophysiology of focal dystonias. Nat Rev Neurol 15:224–233

    PubMed  Google Scholar 

  12. Croy I, Hummel T (2017) Olfaction as a marker for depression. J Neurol 264:631–638

    CAS  PubMed  Google Scholar 

  13. Croy I, Nordin S, Hummel T (2014) Olfactory disorders and quality of life-an updated review. Chem Senses 39:185–194

    PubMed  Google Scholar 

  14. Dalton P (2004) Olfaction and anosmia in rhinosinusitis. Curr Allergy Asthma Rep 4:230–236

    PubMed  PubMed Central  Google Scholar 

  15. De Paula JJ, Malloy-Diniz LF, Romano-Silva MA (2016) Reliability of working memory assessment in neurocognitive disorders: a study of the Digit Span and Corsi Block-Tapping tasks. Braz J Psychiatry 38:262–263

    PubMed  Google Scholar 

  16. Doty RL (2018) Age-related deficits in taste and smell. Otolaryngol Clin N Am 51:815–825

    Google Scholar 

  17. Doty RL (ed) (2019) Epidemiology of smell and taste dysfunction. Handbook of clinical neurology. Elsevier, Amsterdam, pp 3–13

    Google Scholar 

  18. Dressler D, Benecke R (2003) Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis. Eur Neurol 49:34–38

    CAS  PubMed  Google Scholar 

  19. Eisinger RS, Urdaneta ME, Foote KD, Okun MS, Gunduz A (2018) Non-motor characterization of the basal ganglia: evidence from human and non-human primate electrophysiology. Front Neurosci 12:385

    PubMed  PubMed Central  Google Scholar 

  20. Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group (2000) A prevalence study of primary dystonia in eight European countries. J Neurol 247:787–792

    Google Scholar 

  21. Eslinger PJ, Damasio AR, Van Hoesen GW (1982) Olfactory dysfunction in man: anatomical and behavioral aspects. Brain Cogn 1:259–285

    CAS  PubMed  Google Scholar 

  22. Fahn S, Tolosa E, Marin C (1988) Clinical rating scale for tremor. In: Jankovic J, Tolosa E (eds) Parkinson’s disease and movement disorders. Urban and Schwarzenberg, Munich, pp 271–280

    Google Scholar 

  23. Franke GH (2000) BSI: brief symptom inventory—Deutsche version, manual. Beltz, Göttingen

    Google Scholar 

  24. Freitas S, Simões MR, Marôco J, Alves L, Santana I (2012) Construct validity of the Montreal Cognitive Assessment (MoCA). J Int Neuropsychol Soc 18:242–250

    PubMed  Google Scholar 

  25. Fudge JL, Breitbart MA, Danish M, Pannoni V (2005) Insular and gustatory inputs to the caudal ventral striatum in primates. J Comp Neurol 490:101–118

    PubMed  PubMed Central  Google Scholar 

  26. Gerwig M, Guberina H, Eßer AC, Siebler M, Schoch B, Frings M, Kolb FP, Aurich V, Beck A, Forsting M, Timmann D (2010) Evaluation of multiple-session delay eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar degeneration. Behav Brain Res 212:143–151

    PubMed  Google Scholar 

  27. Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA, Johnston AN, Mellick GD, Herting B, Reichmann H, Hummel T (2009) Prevalence of smell loss in Parkinson’s disease—a multicenter study. Parkinsonism Relat Disord 15:490–494

    CAS  PubMed  Google Scholar 

  28. Heckmann JG, Heckmann SM, Lang CJG, Hummel T (2003) Neurological aspects of taste disorders. Arch Neurol 60:667–671

    PubMed  Google Scholar 

  29. Hedner M, Larsson M, Arnold N, Zucco GM, Hummel T (2010) Cognitive factors in odor detection, odor discrimination, and odor identification tasks. J Clin Exp Neuropsychol 32:1062–1067

    PubMed  Google Scholar 

  30. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G (1997) ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22:39–52

    CAS  PubMed  Google Scholar 

  31. Hummel T, Kobal G, Gudziol H, Mackay-Sim A (2007) 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 264:237–243

    CAS  PubMed  Google Scholar 

  32. Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, Damm M, Frasnelli J, Gudziol H, Gupta N, Haehner A, Holbrook E, Hong SC, Hornung D, Hüttenbrink KB, Kamel R, Kobayashi M, Konstantinidis I, Landis BN, Leopold DA, Macchi A, Miwa T, Moesges R, Mullol J, Mueller CA, Ottaviano G, Passali GC, Philpott C, Pinto JM, Ramakrishnan VJ, Rombaux P, Roth Y, Schlosser RA, Shu B, Soler G, Stjärne P, Stuck BA, Vodicka J, Welge-Luessen A (2016) Position paper on olfactory dysfunction. Rhinology 58(1):1–30

    Google Scholar 

  33. Ikai Y, Takada M, Shinonaga Y, Mizuno N (1992) Dopaminergic and non-dopaminergic neurons in the ventral tegmental area of the rat project, respectively, to the cerebellar cortex and deep cerebellar nuclei. Neuroscience 51:719–728

    CAS  PubMed  Google Scholar 

  34. Ikai Y, Takada M, Mizuno N (1994) Single neurons in the ventral tegmental area that project to both the cerebral and cerebellar cortical areas by way of axon collaterals. Neuroscience 61:925–934

    CAS  PubMed  Google Scholar 

  35. Junker J, Paulus T, Brandt V, Weissbach A, Tunc S, Loens S, Reilly RB, Hutchinson M, Baumer T (2019) Temporal discrimination threshold and blink reflex recovery cycle in cervical dystonia—two sides of the same coin? Parkinsonism Relat Disord 68:4–7

    PubMed  Google Scholar 

  36. Kamath V, Paksarian D, Cui L, Moberg PJ, Turetsky BI, Merikangas KR (2018) Olfactory processing in bipolar disorder, major depression, and anxiety. Bipol Disord 20:547–555

    Google Scholar 

  37. Kareken DA, Mosnik DM, Doty RL, Dzemidzic M, Hutchins GD (2003) Functional anatomy of human odor sensation, discrimination, and identification in health and aging. Neuropsychology 17:482–495

    PubMed  Google Scholar 

  38. Kjelvik G, Evensmoen HR, Brezova V, Håberg AK (2012) The human brain representation of odor identification. J Neurophysiol 108:645–657

    PubMed  Google Scholar 

  39. Kuyper DJ, Parra V, Aerts S, Okun MS, Kluger BM (2011) Nonmotor manifestations of dystonia: a systematic review. Mov Disord 26:1206–1217

    PubMed  PubMed Central  Google Scholar 

  40. Landis BN, Scheibe M, Weber C, Berger R, Brämerson A, Bende M, Nordin S, Hummel T (2010) Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function. J Neurol 257:1303–1308

    PubMed  Google Scholar 

  41. Landis BN, Marangon N, Saudan P, Hugentobler M, Giger R, Martin PY, Lacroix JS (2011) Olfactory function improves following hemodialysis. Kidney Int 80:886–893

    CAS  PubMed  Google Scholar 

  42. Lang CJG, Leuschner T, Ulrich K, Stössel C, Heckmann JG, Hummel T (2006) Taste in dementing diseases and Parkinsonism. J Neurol Sci 248:177–184

    CAS  PubMed  Google Scholar 

  43. Machado TH, Fichman HC, Santos EL, Carvalho VA, Fialho PP, Koenig AM, Fernandes CS, Lourenço RA, Paradela EMP, Caramelli P (2009) Normative data for healthy elderly on the phonemic verbal fluency task—FAS. Dement Neuropsychol 3:55–60

    PubMed  PubMed Central  Google Scholar 

  44. Mainland JD, Johnson BN, Khan R, Ivry RB, Sobel N (2005) Olfactory impairments in patients with unilateral cerebellar lesions are selective to inputs from the contralesional nostril. J Neurosci 25:6362–6371

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Marek M, Linnepe S, Klein C, Hummel T, Paus S (2018) High prevalence of olfactory dysfunction in cervical dystonia. Parkinsonism Relat Disord 53:33–36

    PubMed  Google Scholar 

  46. Mascioli G, Berlucchi G, Pierpaoli C, Salvolini U, Barbaresi P, Fabri M, Polonara G (2015) Functional MRI cortical activations from unilateral tactile-taste stimulations of the tongue. Physiol Behav 151:221–229

    CAS  PubMed  Google Scholar 

  47. Mueller C, Kallert S, Renner B, Stiassny K, Temmel AF, Hummel T, Kobal G (2003) Quantitative assessment of gustatory function in a clinical context using impregnated “taste strips”. Rhinology 41(1):2–6

    CAS  PubMed  Google Scholar 

  48. Murphy C, Schubert CR, Cruickshanks KJ et al (2002) Prevalence of olfactory impairment in older adults. J Am Med Assoc 288:2307–2312

    Google Scholar 

  49. Paracka L, Wegner F, Blahak C, Abdallat M, Saryyeva A, Dressler D, Karst M, Krauss JK (2017) Sensory alterations in patients with isolated idiopathic dystonia: an exploratory quantitative sensory testing analysis. Front Neurol 8:553

    PubMed  PubMed Central  Google Scholar 

  50. Patel RM, Pinto JM (2014) Olfaction: anatomy, physiology, and disease. Clin Anat 27:54–60

    PubMed  Google Scholar 

  51. Prudente CN, Hess EJ, Jinnah HA (2014) Dystonia as a network disorder: what is the role of the cerebellum? Neuroscience 260:23–35

    CAS  PubMed  Google Scholar 

  52. Quartarone A, Hallett M (2013) Emerging concepts in the physiological basis of dystonia. Mov Disord 28:958–967

    PubMed  PubMed Central  Google Scholar 

  53. Rolls ET (2005) Taste, olfactory, and food texture processing in the brain, and the control of food intake. Physiol Behav 85:45–56

    CAS  PubMed  Google Scholar 

  54. Russchen FT, Bakst I, Amaral DG, Price JL (1985) The amygdalostriatal projections in the monkey. An anterograde tracing study. Brain Res 329:241–257

    CAS  PubMed  Google Scholar 

  55. Saint-Cyr JA (2003) Frontal-striatal circuit functions: Context, sequence, and consequence. J Int Neuropsychol Soc 9:103–127

    PubMed  Google Scholar 

  56. Sarasso E, Agosta F, Piramide N, Bianchi F, Butera C, Gatti R, Amadio S, Carro U, Filippi M (2020) Sensory trick phenomenon in cervical dystonia: a functional MRI study. J Neurol. https://doi.org/10.1007/s00415-019-09683-5(Epub ahead of print)

    Article  PubMed  Google Scholar 

  57. Savic I (2002) Brain imaging studies of the functional organization of human olfaction. Neuroscientist 8:204–211

    PubMed  Google Scholar 

  58. Savic I, Gulyas B, Larsson M, Roland P (2000) Olfactory functions are mediated by parallel and hierarchical processing. Neuron 26:735–745

    CAS  PubMed  Google Scholar 

  59. Shah M, Deeb J, Fernando M, Noyce A, Visentin E, Findley LJ, Hawkes CH (2009) Abnormality of taste and smell in Parkinson’s disease. Parkinsonism Relat Disord 15:232–237

    PubMed  Google Scholar 

  60. Shakkottai VG, Batla A, Bhatia K, Dauer WT, Dresel C, Niethammer M, Eidelberg D, Raike RS, Smith Y, Jinnah HA, Hess EJ, Meunier S, Hallett M, Fremont R, Khodakhah K, LeDoux MS, Popa T, Gallea C, Lehericy S, Bostan AC, Strick PL (2017) Current opinions and areas of consensus on the role of the cerebellum in dystonia. Cerebellum 16:577–594

    PubMed  PubMed Central  Google Scholar 

  61. Silveira-Moriyama L, Schwingenschuh P, O'Donnell A, Schneider SA, Mir P, Carrillo F, Terranova C, Petrie A, Grosset DG, Quinn NP, Bhatia KP, Lees AJ (2009) Olfaction in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDDs). J Neurol Neurosurg Psychiatry 80:744–748

    CAS  PubMed  Google Scholar 

  62. Sobel N, Prabhakaran V, Hartley CA, Desmond JE, Zhao Z, Glover GH, Gabrieli JD, Sullivan EV (1998) Odorant-induced and sniff-induced activation in the cerebellum of the human. J Neurosci 18:8990–9001

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Spitzer RL, Williams JBW, Gibbon M, First MB (1992) The structured clinical interview for DSM-III-R (SCID): I: history, rationale, and description. Arch Gen Psychiatry 49:624–629

    CAS  PubMed  Google Scholar 

  64. Strick PL, Dum RP, Fiez JA (2009) Cerebellum and nonmotor function. Annu Rev Neurosci 32:413–434

    CAS  PubMed  Google Scholar 

  65. Suzuki Y, Critchley HD, Suckling J, Fukuda R, Williams SC, Andrew C, Howard R, Ouldred E, Bryant C, Swift CG, Jackson SH (2001) Functional magnetic resonance imaging of odor identification: the effect of aging. J Gerontol A Biol Sci Med Sci 56:756–760

    Google Scholar 

  66. Tarescavage AM, Ben-Porath YS (2014) Psychotherapeutic outcomes measures: a critical review for practitioners. J Clin Psychol 70:808–830

    PubMed  Google Scholar 

  67. Tinazzi M, Squintani GM, Bhatia KP, Segatti A, Donato F, Valeriani M, Erro R (2019) Pain in cervical dystonia: evidence of abnormal inhibitory control. Parkinsonism Relat Disord 65:252–255

    PubMed  Google Scholar 

  68. Vemula SR, Puschmann A, Xiao J, Zhao Y, Rudzińska M, Frei KP, Truong DD, Wszolek ZK, LeDoux MS (2013) Role of Gα(olf) in familial and sporadic adult-onset primary dystonia. Hum Mol Genet 22:2510–2519

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Vennemann MM, Hummel T, Berger K (2008) The association between smoking and smell and taste impairment in the general population. J Neurol 255:1121–1126

    PubMed  Google Scholar 

  70. Weintraub DB, Zaghloul KA (2013) The role of the subthalamic nucleus in cognition. Rev Neurosci 24(2):125–138

    PubMed  PubMed Central  Google Scholar 

  71. Westervelt HJ, Ruffolo JS, Tremont G (2005) Assessing olfaction in the neuropsychological exam: the relationship between odor identification and cognition in older adults. Arch Clin Neuropsychol 20:761–769

    PubMed  Google Scholar 

  72. Whitcroft KL, Cuevas M, Haehner A, Hummel T (2017) Patterns of olfactory impairment reflect underlying disease etiology. Laryngoscope 127:291–295

    PubMed  Google Scholar 

  73. Wistehube T, Rullmann M, Wiacek C, Braun P, Pleger B (2018) Fat perception in the human frontal operculum, insular and somatosensory cortex. Sci Rep 8:11825–11833

    PubMed  PubMed Central  Google Scholar 

  74. Zobel S, Hummel T, Ilgner J, Finkelmeyer A, Habel U, Timmann D, Schulz JB, Kronenbuerger M (2010) Involvement of the human ventrolateral thalamus in olfaction. J Neurol 257:2037–2043

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Professor Ulf Schminke, Department of Neurology, University of Greifswald, Greifswald, Germany for critical comments on the manuscript. Additionally, we would like to thank Rosalie L. Donaldson-Kronenbuerger for English language editing. The study was funded by internal grants of the Department of Neurology, University of Greifswald, Greifswald, Germany.

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Conceptualization: TH, MK, TH, BL; methodology: TH, MK, TH, BL; formal analysis and investigation: TH, MK, TH, MV; writing—original draft preparation: TH; writing—review and editing: TH, TH, MV, CW, BV, JG, RF, BL, MJ-U, AS, MK; funding acquisition: MK; resources: TH, MK; supervision: MK.

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Correspondence to Martin Kronenbuerger.

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All procedures performed in this study were in accordance with the ethical standards of the University of Greifswald, Faculty of Medicine (study reference number: BB 188/17) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All study participants gave their informed consent prior to their inclusion in the study.

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Herr, T., Hummel, T., Vollmer, M. et al. Smell and taste in cervical dystonia. J Neural Transm 127, 347–354 (2020). https://doi.org/10.1007/s00702-020-02156-4

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Keywords

  • Olfaction
  • Gustatory functioning
  • Network disorder
  • Cerebellum
  • Basal ganglia
  • Sensorimotor cortex