Correspondence

Olfactory Dysfunction in Multiple Sclerosis

N Engl J Med 1997; 336:1918-1919June 26, 1997

Article

To the Editor:

Multiple sclerosis, the most common neurologic disease in young adults, is accompanied by focal demyelinating plaques within the central nervous system, which can be quantified in vivo by using high-resolution magnetic resonance imaging (MRI). Thus, multiple sclerosis may be an excellent model for the study of the influences of focal lesions on some forms of sensory function. Since multiple-sclerosis–related plaques vary in number over time, differ considerably from patient to patient, and often occur in regions of the brain associated with the ability to smell,1 we determined whether the number of multiple-sclerosis–related plaques in olfactory regions correlates with scores on the University of Pennsylvania Smell Identification Test (UPSIT), a standardized 40-odorant quantitative test of olfactory function.2

Nine men and 17 women (mean [±SD] age, 42.2±7.2 years) with confirmed multiple sclerosis were tested. Thin-section MRIs of the brain with gadolinium enhancement were performed on the same day as olfactory testing by using a 1.5-T Signa scanner (General Electric, Milwaukee) employing a standard head coil. Plaques were counted without knowledge of the patients' UPSIT scores.

We found a strong negative relation (Spearman r = -0.94, P<0.001) between the UPSIT scores and the number of demyelinating plaques within the inferior frontal- and temporal-lobe regions, which are involved in olfaction (Figure 1AFigure 1Relation between UPSIT Scores and the Numbers of Multiple-Sclerosis–Related Plaques in Olfactory (Panel A) and Nonolfactory (Panel B) Brain Regions.). No such relation was found between the scores and the numbers of plaques in brain regions not related to olfaction (r = -0.08, P not significant) (Figure 1B), implying that the relation was restricted to brain structures directly involved in olfactory processing.

Relative to normative data based on nearly 4000 subjects,3 38.5 percent of the patients had demonstrable olfactory loss; 7.7 percent had severe bilateral microsmia, 19.2 percent moderate bilateral microsmia, and 11.5 percent mild bilateral microsmia. None had anosmia. No sex differences or meaningful left–right asymmetries in UPSIT scores or numbers of plaques were found.

These findings clarify the ongoing controversy over the presence of olfactory dysfunction in multiple sclerosis and invalidate claims of normal olfactory function in patients with the disease.4 Notably, they support the concept that multiple sclerosis, with its relatively discrete focal regions of inflammation, demyelination, and gliosis, can serve as a useful model for the study of the influences of lesions of the central nervous system on sensory perception. Although numerous studies have reported olfactory dysfunction in several neurodegenerative disorders, including Alzheimer's disease and idiopathic Parkinson's disease,5 our findings provide a clear physiologic explanation for decreased olfactory function in patients with any major neurologic disease. Given that olfaction influences the quality of life and provides a basic means for detecting smoke, leaking natural gas, and other environmental hazards, persons involved in the care of patients with multiple sclerosis should be aware of the potential for olfactory losses and counsel their patients accordingly.

Richard L. Doty, Ph.D.
Cheng Li, M.D.
Lois J. Mannon, B.S.
David M. Yousem, M.D.
University of Pennsylvania Medical Center, Philadelphia, PA 19104

5 References

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   Doty RL. The Smell Identification Test administration manual. Haddon Heights, N.J.: Sensonics, 1995.
   

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   Lumsden CE. The neuropathology of multiple sclerosis. In: VinkenPJ, Bruyn GW, eds. Multiple sclerosis and other demyelinating diseases. Handbook of clinical neurology. Vol. 9. New York: Elsevier, 1970:217-309.
   

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   Doty RL. Olfactory dysfunction in neurodegenerative disorders. In: Getchell TV, Doty RL, Bartoshuk LM, Snow JB Jr, eds. Smell and taste in health and disease. New York: Raven Press, 1991:735-51.
   

Citing Articles (8)

Citing Articles

1. 1

   Eleni Siopi, Silvia Calabria, Michel Plotkine, Catherine Marchand-Leroux, Mehrnaz Jafarian-Tehrani. (2011) Minocycline Restores Olfactory Bulb Volume and Olfactory Behavior after Traumatic Brain Injury in Mice. Journal of Neurotrauma111107125937003
   CrossRef

2. 2

   SM Bromley, RL Doty. (2010) Olfaction in dentistry. Oral Diseases 16:3, 221-232
   CrossRef

3. 3

   Alan Hirsch. 2009. Chemosensory Disorders. .
   CrossRef

4. 4

   Richard L. Doty, Anupam Mishra. (2001) Olfaction and Its Alteration by Nasal Obstruction, Rhinitis, and Rhinosinusitis. The Laryngoscope 111:3, 409-423
   CrossRef

5. 5

   Richard L. Doty. (2001) O LFACTION. Annual Review of Psychology 52:1, 423-452
   CrossRef

6. 6

   R Zivadinov, M Zorzon, L Monti Bragadin, G Pagliaro, G Cazzato. (1999) Olfactory loss in multiple sclerosis. Journal of the Neurological Sciences 168:2, 127-130
   CrossRef

7. 7

   David M Yousem, Joseph A Maldjian, Faez Siddiqi, Thomas Hummel, David C Alsop, Rena J Geckle, Warren B Bilker, Richard L Doty. (1999) Gender effects on odor-stimulated functional magnetic resonance imaging. Brain Research 818:2, 480-487
   CrossRef

8. 8

   RICHARD L. DOTY, CHENG LI, LOIS J. MANNON, DAVID M. YOUSEM. (1998) Olfactory Dysfunction in Multiple Sclerosis: Relation to Plaque Load in Inferior Frontal and Temporal Lobesa. Annals of the New York Academy of Sciences 855:1 OLFACTION AND, 781-786
   CrossRef