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Neuroimaging. The sensitivity of computed tomography (CT) to soft tissue disease and bony changes makes it ideal for the investigation of the sinonasal cavities. All of the nasal cavity, paranasal sinuses, hard palate, anterior skull base, orbits, and nasopharynx should be scanned and, if central causes of olfactory dysfunction are suspected, the brain as well. Coronal scans are particularly valuable for the assessment of the paranasal anatomy, namely, the anterior nasoethmoid (ostiomeatal) region (i.e., the maxillary sinus ostium, infundibulum, uncinate process, and middle meatus). To better identify vascular lesions, tumors, abscess cavities, and meningeal or parameningeal processes, intravenous contrast enhancement is frequently employed. Presently, high-resolution CT appears to be the most useful and cost-effective screening tool for the assessment of sinonasal tract inflammatory disorders.

Magnetic resonance imaging (MRI) is superior to CT in the discrimination of soft tissue but is less sensitive than CT to bony cortical abnormalities or landmarks. Thus, MRI is the technique of choice for the evaluation of the olfactory bulbs, olfactory tracts, and intracranial causes of olfactory dysfunction because they can be visualized rather clearly on coronal scans. MRI is also the method of choice for the evaluation of skull base invasion by sinonasal tumors. Gadolinium-enhanced scans are particularly valuable in detecting dural or leptomeningeal involvement at the skull base. The paramagnetic contrast agent gadolinium-DTPA has been widely used to enhance the margins of sinonasal tumors and to distinguish solidly enhancing tumors from rim-enhancing inflammatory processes. y

Electrophysiology. Outpatient testing for EEG activity in individuals with dysosmia may be enhanced by using electrodes placed in the nasopharyngeal region or over the lower temporal areas. Inpatient EEG monitoring is indicated if epileptic-like olfactory events occur frequently but cannot be discerned by outpatient testing procedures.

Although odor-evoked potentials can now be measured accurately in most patients, the stimulus presentation equipment is complex and is at present very expensive (more than $100,000); thus, such testing is available in very few clinics. The major technical problem is that trains of well-defined odorant pulses, with steep-onset gradients, must be imbedded in a humidified airstream that is flowed through the nose in a manner that does not evoke somatosensory afferents. To date, only late near-field potentials have been recorded using this technique. When available, evoked potential olfactometry is useful in detecting malingering as well as for providing information about olfactory function that does not depend on verbal or other overt responses of the patient.

Fluid and Tissue Analysis. In patients in whom a clear cause is not found, a complete blood count (CBC) may be indicated to better define whether infective, nutritional, or hematopoietic processes are involved. A nonspecific indication of an autoimmune or inflammatory process can be obtained from the erythrocyte sedimention rate. Although frank zinc deficiency has the potential to alter olfactory function, there is no evidence that zinc treatment of persons without stark zinc deficiency influences any olfactory disorder. Indeed, a double-blind clinical trial using a cross-over design in which zinc was compared to placebo showed no advantage of zinc over placebo in the treatment of hyposmia or hypogeusia. y Since vitamin B-, deficiency is clearly implicated in the Wernicke-Korsakoff syndrome, determination of the erythrocyte thiamine level is indicated in patients with a significant history of suspected or documented

chronic alcohol abuse. Early reports that vitamin A therapy may be of value in some cases did not include controls, making the efficacy of this therapy enigmatic.

Neuropsychological Tests. Given the close association between olfactory loss and several forms of dementia, including Alzheimer's disease and multi-infarct dementia, neuropsychological testing may be indicated to better identify the presence of dementia (for details of the tests listed below, see reference 36). The mini-mental state examination is a widely used brief screening instrument for dementia and can be used alone or as a component of examination protocols such as the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery. More extensive assessment of dementia can be obtained using either the Mattis Dementia Rating Scale, the Blessed Dementia Scale, the Boston Naming Test, or the logical memory and visual reproduction subtests of the Wechsler Memory Scale-Revised (WMS-R). The WMS-R and the California Verbal Learning Test have proved useful in patients in whom schizophrenia is suspected.

Malingering can be detected or is strongly suspected when a person scores below chance level on the UPSIT. Further verification of malingering can be obtained by administering neuropsychological tests specifically designed for this purpose. Among those that are widely used are Rey's memory test (RMT), also known as Rey's 3 x 5 test and the Rey 15-item memory test. The rationale behind this test is that malingerers typically fail at a memory task that all but the most retarded or severely brain-damaged persons perform easily. Another widely used test, the Portland digit recognition test, incorporates, like the UPSIT, a forced-choice procedure to ascertain whether test performance falls below that expected on the basis of chance. Unfortunately, this test takes nearly an hour to administer and provides no other neuropsychological information. Abbreviated versions of this test, however, are available.

Other Tests. To document changes in cellular aspects of the olfactory neuroepithelium, olfactory biopsies can be performed. In this procedure, a small amount of olfactory neuroepithelial tissue is stripped from the nasal septum by the rhinologist using small forceps or a specialized instrument and subsequently analyzed histologically. y , y This procedure must be performed by a surgeon who is experienced in the technique, and multiple biopsies are usually needed, given the considerable metaplasia of respiratory-like epithelium in the region of the olfactory neuroepithelium.


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