Olfactory and gustatory dysfunction in Myasthenia gravis: A study in Turkish patients

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Highlights

  • Olfactory function is significantly decreased in patients with MG.

  • Olfactory loss is correlated with the severity of the disease.

  • Likewise, a decreased taste function was found in the same groups of patients.

  • MG patients must be alerted as to potential risks associated with olfactory and gustatory loss.

Abstract

Objective

Myasthenia gravis (MG) is commonly viewed as a muscle disorder. Less is known about neurosensory function and dysfunction in MG. We aim to evaluate olfactory and gustatory behavior in Turkish patients with MG, and compare these results with age and sex-matched healthy controls.

Material/methods

30 individuals with MG, and 30 healthy volunteers were studied. Olfactory function was studied with the Sniffin' sticks test. Taste strip test was used for studying taste function. The t-test was used for analyzing continuous variables, and the chi-square test for categorical data. Clinical staging and medication status were included in a model analyzed using analysis of variances.

Results

MG patients showed significantly lower olfactory (p < 0.001) and gustatory scores (p < 0.001) than the healthy controls. In addition, olfactory loss correlated with the severity of the disease. Medications for MG did not influence these results.

Conclusion

This study replicates the olfactory dysfunction found elsewhere in MG. Further, gustatory dysfunction, an activity unrelated to muscle strength, was also unveiled. Medications used for treating MG must not be blamed for the chemosensory dysfunction found in this neurological disorder.

Introduction

Stimulation of a peripheral nerve results in the release of acetylcholine (ACh) molecules at the neuromuscular junction (NMJ). These molecules bind to a number of receptors located on the striated muscle, resulting in the depolarization of the postsynaptic muscle membrane, generating a muscle contraction [1]. When this complex machinery fails, neural disorders appear. Myasthenia gravis (MG) is one of the prototypes of such disorders. MG is an autoimmune disease that classically damages the transduction of signals on the postsynaptic cell membrane, affecting the function of the NMJ [2]. Antibodies against nicotinic acetylcholine receptors have been found in about 85% of patients with MG [3], [4]. Fluctuating muscle weakness and fatigue are the classical signs and symptoms in MG [5]. Sensory complaints, including smell or taste, are not commonly and quantitatively studied in MG [6].

Chemosensory function plays a significant role in environmental and nutritional safety, as well as in the quality and enjoyment of life. Complex neural pathways, not well understood, are involved in chemosensation modulation. In brief, olfactory neurons are situated in the nasal mucosa, at the upper third of the nasal cavity [7]; their axons connect with the dendrites of glomeruli in the olfactory bulb. Odors binding to the olfactory receptor neurons trigger olfactory activity [8]. The processing of odors within the central nervous system includes the orbitofrontal cortex, the limbic system, insula and cerebellum, among other structures [9], [10]. Gustatory fibers, on the other hand, reach the brain via the facial, glossopharyngeal, and vagal nerves. These nerves send the afferent impulses to the nucleus tractus solitarii, central tegmentum, posteromedial ventral thalamic nucleus and anterior insula and the orbitofrontal cortex [11].

Gender and age influence smell and taste function [12]. Men show lower scores of smell function than women [13]. Smell loss correlates stronger than taste loss with aging [14]. Smell can also be affected by environmental factors such as airborne pollution and toxic odors [15], head trauma [16], as well as rhinitis and allergies [17]. Taste can be reduced by middle ear infections [18], medications [19], chemotherapy and radiation, among other cofactors [20], [21], [22]. Olfactory and gustatory disturbances have also been found to be key early markers of neurodegenerative disorders. Alzheimer's disease (AD) and Parkinson's disease (PD) are the prototype of these [22] neural disorders [23], [24], [25], suggesting that chemosensory disorders in AD and PD may originate in altered acetylcholine mechanisms [23], [24], [25].

Importantly, Leon-Sarmiento et al. discovered that individuals with MG, a unique disorder with pure dysfunctional Ach neural transmission, had smell disorders as measured by the University of Pennsylvania Smell Identification Test (UPSIT) [26]. These authors reported that the UPSIT scores in patients with MG were similar to scores reported from the above-mentioned neurodegenerative diseases [26]. However, no gustatory function was investigated in Leon-Sarmiento et al.'s study [26].

We aim to replicate the olfactory anomalies reported by Leon-Sarmiento et al. in MG [28] using the Sniff and Stick test. We also aim to expand chemosensory research in MG, and study gustatory function in the same group of patients. The results of this study confirm that MG patients have, in fact, olfactory dysfunction; moreover, it is demonstrated here that taste dysfunction is also present in MG. Altogether, these studies point out a global chemosensory dysfunction in a neurological syndrome disorder classically viewed as a muscle-related disorder.

Section snippets

Subjects

30 MG patients (22 men, 8 women) were studied. The mean age of patients was 38.7 ± 13.2 years.

The age- and sex-matched control group consisted of 30 healthy individuals (22 men, 8 women), who had a mean age of 38.9 ± 13.1 years. Each participant underwent clinical evaluation, which included general, otorhinolaryngology and cardiovascular evaluations. Past and current olfactory and gustatory functions were questioned. The mini mental state examination (MMSE) was applied. Since smell and taste are

Olfactory function

Patients and healthy controls differed significantly in terms of the olfactory tests (F[1,58] = 132, p < 0.001) (Table 1; Fig. 1-A). Likewise, the three olfactory test scores differed from each other (F[2,116] = 803, p < 0.001). Interestingly, the significant interaction between “group” and “olfactory test” factors (F[2,116] = 37, p < 0.001) indicated that the differences between groups were larger for the two suprathreshold olfactory tests compared to the odor threshold test. Four out of 30 MG patients

Discussion

We have quantitatively demonstrated that the chemosensory damage in MG, a disorder with an altered cholinergic system, is more widespread than previously thought. Case reports have anecdotally reported on chemosensory dysfunction in individuals with MG [35]. Leon-Sarmiento et al. [26] proved, using the UPSIT, that MG patients had a clear smell loss. However, no quantitative testing of taste dysfunction, using up-to-date techniques, had been performed to date in MG. Thus, the present study is

Conflicts of interest

None.

Acknowledgments

None.

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