Distortions of taste and smell are among the most unbearable sensory symptoms patients can endure. Distorted smells are labeled dysosmia and are defined as phantosmia (distortions in the absence of an environmental odor) or aliosmia (distortions in the presence of environmental odors such as foods or perfumes). Distorted obnoxious tastes are labeled dysgeusia and are defined as phantageusia and aliageusia, respectively. Distorted smells are usually obnoxious and can appear to be burned, chemical, or rotten. They can appear without any stimuli (phantosmia) or in the presence of the smell of cooking foods, coffee brewing, gasoline, or any fragranced product (aliosmia). Spontaneous onset of obnoxious tastes without any stimulus appear to be metallic, chemical, salty, or bitter (phantageusia). Obnoxious distortions of the taste of any food or drink are usually also chemical, rotten, or burned (aliageusia).
These symptoms usually follow loss of taste and/or smell acuity. These symptoms reflect an attempt of the brain to correct the smell or taste loss by “functionally rewiring” the olfactory and/or taste systems. This rewiring commonly goes awry and is associated with a dysplastic process that initiates this smell/taste distortion.
We have studied these distortions by use of a specialized technique called magnetic resonance spectroscopy of the brain. These studies revealed that this functional brain rewiring resulted in significant changes in brain neurotransmission manifested by a decrease in the normal inhibitory neurotransmitter called gamma-aminobutyric acid (GABA). This decrease was measured in specific brain regions and was associated with the release of inhibition by which the brain normally operates, giving rise to the misperception of tastes and odors — dysgeusia and dysosmia.
Since we understand the mechanism responsible for the onset of these sensory misperceptions we devised specific therapies to increase brain GABA by using either (1) neurophysiological or (2) pharmacological treatment.
The neurophysical treatment is called transcranial magnetic stimulation (TCMS). We have used this successfully in many patients to increase brain GABA and inhibit their sensory distortions. There are no side effects of this procedure. It is safe and painless. However, its efficacy can “wear off,” requiring repeated stimulus applications. Patients must come to the clinic at specific times to have this done, which is both time consuming and expensive.
The pharmacological treatment we have used is to give patients GABAergic drugs. These drugs can increase brain GABA and thereby inhibit these distortions. However, GABAergic drugs have side effects in addition to their beneficial effects of inhibiting sensory distortions.
Are there better treatments techniques to increase brain GABA that may not be accompanied by significant side effects? Yes, there are new concepts by which an array of CNS disorders that include cognitive dysfunction are being addressed. These involve therapies with small molecules that influence GABA function in novel ways.
GABA is processed by its action on receptors labeled GABA (A), (B), and (C) receptors. GABA binds to these receptors in order to initiate and perpetuate its inhibitory effect. There are two methods to increase GABA activity. One way is to increase brain GABA concentrations; we have done this by use of TCMS or giving patients GABAergic drugs. The second way is to make the GABA receptors themselves more sensitive so that a smaller amount of GABA will activate and perpetuate GABA inhibitory effects. This second way uses these newly defined small molecules, which can enhance and increase GABA receptor function despite the loss of GABA itself. This effect occurs because these small molecules make these receptors more sensitive and more amenable to GABA action, whatever its concentration in the brain. These small molecules are called GABA receptor agonists. Such drugs are not yet fully developed but we are attempting to influence drug companies to help define these agents so that patients with distortions of taste and smell can be better cared for and their sensory distortions inhibited.
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