Received March 29, 1993; accepted after revision October 5, 1993.This work was supported in part by NIDCD grant P01 DCOO1 61.1 Smell and Taste Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104.2Depantment of Otorhinolanyngology, Head and Neck Surgery, Hospital ofthe University of Pennsylvania, Philadelphia, PA 19104.3Department of Radiology, Hospital ofthe University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104. Address correspondence to D. M. Yousem.

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AJR i994;162:4ii-4i8 0361-803X/94/1622-04i1 ©Amenican Roentgen Ray Society

Review Article

* �L. � � � �

Neuroimaging in Patients with Olfactory Dysfunction

Cheng l2 David M. Yousem,1’2 Richard L. 1 and David W. Kennedy1

This review summarizes neuroimaging findings in patientswith olfactory dysfunction. Neuroimaging techniques offer a

valuable means for evaluating and distinguishing disorders ofolfaction. The new or refined techniques make it possible to pin-point the anatomic and pathologic changes of many disorders ofthe sinonasal cavity and brain that cause olfactory deficits. Froman anatomic point of view, the causes of olfactory deficits gener-ally can be classified as peripheral or central (intracranial). In theassessment of the peripheral causes, CT and MR imaging revealanatomic information and structural changes, enable a differen-tial diagnosis, and provide a road map for surgical intervention.In the evaluation of the central causes, MR imaging, positronemission tomography, or single-photon emission computedtomography can provide the links between olfactory dysfunctionand structural or functional changes in the brain.

Olfactory dysfunction generally is classified as either aperipheral conductive disorder caused by interference withthe access of odonants to the olfactory receptors in the sino-nasal tract or as a central sensonineural disorder resultingfrom injury to the olfactory receptors (within the olfactory

mucosa); the olfactory bulb or tract; or related parts of theCNS such as the prefrontal lobe, septal nuclei, amygdala, andtemporal lobe [1]. Although revolutionary changes in medicalimaging techniques have occurred in the past few decades,

few articles have dealt with imaging studies in patients withchemosensory disorders [2-6]. We reviewed the publicationson this topic in an effort to bridge the chasm between imagingand clinical assessment of patients with olfactory deficits.

Basic Anatomy and Physiology of the Olfactory System

The sensation of smell is induced by the stimulation ofolfactory receptor cells by volatile chemicals. The olfactory

receptor cells-that is, the primary olfactory neurons-areencompassed in the neuroepithelium located at the top ofthe nasal vault, the upper portion of the nasal septum, thesuperior surface of the superior nasal tunbinate, and theregion of the cnibniform plate. Affenent information from thereceptors is transmitted by the olfactory nerves, whichcourse through the cnibniform plate of the ethmoid bone toterminate in the glomeruli of the olfactory bulb [7]. Fromthere, the efferent neurons of the olfactory bulb give rise tofibers that form the olfactory tracts, which lie just under thegyrus rectus region in the olfactory sulcus of the frontallobes. Axons project to central limbic system components,including the piniform cortex and adjacent corticomedialamygdala (which together form the uncus), the ventral stnia-tum, the panahippocampus, and the anterior olfactory nuclei.From these areas there are widespread interconnectionswith many parts of the brain, including the dorsal medial thaI-amus, hypothalamus, orbitofrontal and dorsolatenal regionsof the frontal cortex, temporal cortex, and other areas of thelimbic system [7, 8].

Imaging Techniques

Major advances in pinpointing the anatomic and pathologicchanges of many disorders of the sinonasal cavity and brainhave become possible because of recent developments andrefinements in imaging techniques [9-i6]. Although the imag-ing evaluation is not the diagnostic equivalent of a histologicstudy, an anatomic imaging technique such as high-resolutionCT and MR imaging can not only map regional lesions butalso may enable a differential diagnosis [9, iO, i3, i4]. Func-tional imaging, such as positron emission tomography (PET)and single-photon emission computed tomography (SPECT),

4i2 LI ETAL. AJR:162, February 1994

affords the potential for exploring regional pathophysiologicchanges in the living brain [i2, iS, i6].

Because of their low sensitivity, low specificity, and inabil-ity to show the ostiomeatal complex, plain nadiographs playonly a minor role in the imaging evaluation of olfactory dys-function.

CT is well suited to the study of the sinonasal cavities.Because CT is as sensitive to soft-tissue disease as to bonychanges, each scan can be photographed at an appropriatewindow width and level to optimally show insidious soft-tissuedifferences in attenuation and fine bony detail. The basic CTscanning protocol should include all of the nasal cavity, parana-sal sinuses, hard plate, anterior skull base, orbits, andnasopharynx. The brain should be included if central causes ofolfactory dysfunction are suspected. Thin-section scans arecommonly obtained in both the axial and coronal planes foroptimal assessment of the complex pananasal anatomy, butcoronal scans are the most valuable for the anterior nasoeth-moidal (ostiomeatal complex) region (Fig. i). IV contrastenhancement is usually reserved for identification of vascularlesions, tumors, meningeal or parameningeal processes, andabscess cavities [iO].

The multiplanar capability of MR imaging is especiallyadvantageous in the evaluation of sinonasal tract neoplasmsand brain disorders. MR imaging, however, is less sensitivefor the detection of bony cortical abnormalities and landmarks.Soft-tissue discrimination is more clearly illustrated with MRimaging than with CT. Most soft-tissue diseases can be accu-rately localized with a degree of tissue differentiation, that is,infection vs tumor vs hemorrhage. T2-weighted and enhancedMR images can better delineate the contrast between normaland inflammatory (rim-enhancing) or neoplastic (solidlyenhancing) tissue [ii , 14]. MR imaging is the study of choiceto evaluate the olfactory bulbs, olfactory tracts, and intracra-nial causes of olfactory dysfunction [4, 6].

In general, scintigraphy plays no significant role in thediagnostic workup of patients with suspected sinonasal tractdisease, except in the case of CSF leaks. Functional imag-ing studies, such as PET and SPECT, are valuable in detect-

ing alterations of regional brain function and biochemistry invivo [i5-i8].

Peripheral Causes of Olfactory Disturbance

Sinonasal tract disease is one of the common causes ofolfactory disturbance [5]. The cause of olfactory deficitsamong patients with nasal and pananasal sinus disease ismost likely nasal airway obstruction. Any cause of bilateralobstruction can decrease smell sensations by limiting air flowto the olfactory receptors [i 9]. Besides the obstructive effect,lesions in the upper nasal vault and!or cnibniform plate regioncan also directly damage the olfactory epithelium and olfac-tory neurons. The common peripheral sinonasal tract causesof olfactory deficits include infections, tumors, allergic rhinosi-nusitis, and congenital on developmental abnormalities.

Sinonasal Infectious Disease

Although the exact cause of chemosensory dysfunction dueto sinusitis is elusive, alterations in nasal air flow and mucocili-ary clearance or obstruction from secretory products, polyps, orretention cysts may contribute to olfactory dysfunction [20].

At present, high-resolution CT is the preferred imagingtechnique, preceded by endoscopic nasal examination. Air-fluid levels are usually indicative of acute sinusitis, whereasmucopeniosteal thickening can be seen in acute and chronicdisease. CT is an excellent imaging technique for the evalu-ation of bony abnormalities, such as osteitis or remodelingseen in some inflammatory lesions. CT will help the func-tional endoscopic sinus surgeon in planning effective sun-gery to restore normal mucociliary clearance. MR imagingalso is highly sensitive for detecting mucosal thickening andother soft-tissue abnormalities [9]. By and large, inflamedmucosa is usually high in signal intensity on T2-weightedMR images and low in intensity on Ti-weighted images.Secondary formation of polyposis, retention cysts, or muco-celes of sinonasal cavities can be clearly detected witheither CT or MR [9,21 , 22] (Fig. 2).

Fig. 1 .-Normal ostiomeatal complex. Coro-nal bone-targeted CT scan shows maxillary 51-nus ostium (0) and infundibulum (open arrow)between uncinate processes (solid arrow) andethmoidal bulla (b). Air channel (arrowhead)medial to uncinate process is middle meatus.= middle turbinate.

Fig. 2.-Sinonasal polyposis in a 43-year-oldman with a history of decreasing smell sensa-tion and nasal obstruction. Coronal CT scanshows nearly complete opacification of sinona-sal cavity bilaterally. Expansion of maxillary si-nus ostium (solid arrow) and erosion ofethmoldal labyrinth (e) and uncinate processes(open arrows) are caused by polyps.

AJR:162, February 1994 NEUROIMAGING IN OLFACTORY DYSFUNCTION 4i 3

Tumors of the Nasal Cavity and Paranasal Sinuses Others

Almost all sinonasal tract tumors and tumonlike entitiesthat grow to a large size can cause a decline in olfactoryacuity by interfering with patency of the nasal airway or bydirectly destroying the olfactory receptors. A classic exampleof an intrinsic sinonasal tract tumor, an olfactory neunoblas-toma, often causes hyposmia or anosmia and may serve asthe prototype for masses in this region.

Olfactory neunoblastoma, on esthesioneunoblastoma, is anasal tumor originating from the olfactory neuroepitheliumlining the roof of the nasal vault and in close proximity to thecnibniform plate. In the detection and staging of olfactory neu-noblastoma, CT and MR imaging are essential. Generallyspeaking, MR imaging is more accurate than CT in showingthe tumor’s intracranial extent (Fig. 3A). MR imaging also isuseful for differentiating neoplasm from postobstructionsecretions because of differences in signal intensity (mostsecretions are bright on T2-weighted images, whereastumor has intermediate signal intensity) and contrastenhancement (tumor enhances solidly, secretions show rimmucosal enhancement). Unfortunately, the signal intensitycharacteristics of various sinonasal tract tumors overlap, soMR imaging often cannot be used to predict specific tumorhistology [i3, 23]. Other sinonasal tract tumors, such asinverted papilloma, squamous cell carcinoma (Fig. 3B), ade-nocarcinoma, and melanoma, also can cause hyposmia onanosmia during their late stage.

Allergic Rhinitis

Allergic rhinitis is a common condition in the upper airwaythat affects about 30 million Americans, with peak preva-lence in persons 35-54 years old. Hyposmia on anosmia iscommon with allergic rhinitis, which is caused mainly bynasal obstruction by polyps on inflamed mucosa that limitsaccess of inspired air to the roof of the nasal vault [24]. CTand MR imaging are important for detecting any complica-tions such as sinusitis, mucoceles, and aggressive polyps inpatients with allergic rhinitis. Rounded excrescences andenlargement of ostia are seen in the airway of patients withpolyposis.

Congenital or DevelopmentalAbnormalities

Congenital and developmental abnormalities include choa-nal atnesia, hereditary nasal septal deviation, facial hypopla-sia, cleft palate, nasal denmoids, epidenmoids, cephaloceles,and gliomas. Medical imaging techniques, especially high-resolution CT, play a key role in detecting and evaluating thefacial and bony changes [25, 26], because surgical correctionrequires identification and closure of the osseous abnonmali-ties. MR imaging is most effective in defining soft-tissue orCSF-containing masses such as cephaloceles and nasalgliomas.

Thirty million Americans have used cocaine, and 5 millionuse it regularly [27]. Although hyposmia or anosmia hasbeen suggested to occur often in cocaine abusers, few stud-ies using quantitative measures of olfactory function haveconfirmed such reports. The mechanism of olfactory distun-bance with heavy cocaine use is still unclean. Conceivably,the disturbance could be due to conductive disorders, nasalairway obstruction, alteration in sinonasal aerodynamics,damage to olfactory epithelium, osteolysis of the cnibniformplate, or damage to the central olfactory system. Several CTreports of osteolytic sinusitis and extensive osteocartilagi-nous necrosis of the nasal septum due to cocaine abusehave been published recently [28-30].

Vasculitic infancts, hypertensive hemorrhages, and whitematter ischemic foci can be seen in cocaine users. Tumethet al. [3i] showed muitifocal cortical deficits with a specialpredilection for the frontal and temporal lobes on SPECTperfusion brain scans in chronic cocaine abusers.

Olfactory deficits can also accompany Wegenen’s granulo-matosis, Paget’s disease, fibrous dysplasia, and leprosy [32].The mechanism of the olfactory deficits from these diseasesis most likely related to conductive disorders of the sinonasaltract due to bony on soft-tissue destruction of the airway.

Central Causes of Olfactory Disturbance

Numerous CNS disorders may be associated with olfactorydysfunction. The most common types fall into the categoriesof degenerative neuropsychiatnic disorders, hereditary condi-tions, trauma, and neoplasms.

Alzheimer’s Disease

It is well documented that olfaction is significantly alteredin persons with Alzheimer’s disease. Nearly all studies ofolfactory function in patients with Alzheimer’s disease havereported decreased smell relative to that of age-matchedcontrol subjects. These studies show marked impairment ofsmell identification and an increased threshold for odordetection in early Alzheimer’s disease [33-35].

The anterior olfactory nuclei, olfactory bulbs, and centralolfactory structures (amygdala, temporal lobes) in patientswith Alzheimen’s disease show senile plaques, neunofibnillarytangles, granulovasculan degeneration, and cell loss [36, 37].

Early CT studies in patients with Alzheimer’s diseaseshowed generalized enlargement of the ventricular system andsulci [38]. Several reports have noted that ventricular and sulcalenlargement correlate well with the severity of the disease [39].De Leon et al.[40] have emphasized the rate of change inyen-

tnculan size with CT scans obtained over time as an importantindex in the diagnosis of this disease. Recently, several investi-gators have recognized that CT or MR imaging delineation ofatrophic changes in the temporal lobe and the hippocampuswith enlargement of hippocampal-choroidal fissures stronglysupports the diagnosis ofAlzheimen’s disease [4i-43] (Fig. 4).

Fig. 3.-Sinonasal neoplasms.A, 76-year-old woman with anosmia and a pathologically proved olfactory neuroblas-

toma. Sagittal Ti-weighted MR image shows a soft-tissue mass (m) in upper nasal vaultthat reaches cribriform plate and grows into anterior cranial fossa (arrows).

B, 54-year-old woman with a squamous cell carcinoma (M) of maxillary antrum thatgrew through medial wall into left nasal cavity and caused unilateral decrease in smellsensation. T2-weighted MR image shows mass of intermediate intensity.

Fig. 4.-Alzheimer’s disease in a 60-year-old patientwith severe bilateral loss of olfactory function, evaluatedwith University of Pennsylvania Smell Identification Test.Coronal Ti-weighted MR image through temporal lobesshows temporal horn enlargement (arrows) and atrophicchanges of temporal lobe (T) greater on right side than onleft.

4i4 LI ETAL. AJR:162, February 1994

The major findings of functional imaging studies inpatients with Alzheimer’s disease are abnormal regionalblood flow pattern and flow reduction in the cerebrum. Thecommon sites of blood flow reduction are in the temporopani-etal region and the frontal areas. In a recent report [44], onlyfrontal flow abnormalities were seen on SPECT scans ofseven patients with a possible diagnosis of Alzheimen’s dis-ease. Is this an early imaging finding that may suggest apathophysiologic basis to explain the decreased smell sen-sation in patients with Alzheimer’s disease?

Parkinson’s Disease

Odor detection and identification are significantly impairedin patients with Parkinson’s disease [45]. Research into thecause of smell dysfunction in patients with Parkinson’s dis-ease has focused on dopammnergic changes. Patients withParkinson’s disease show significantly reduced meanuptake of 18F-dopa in the caudate nuclei and putamen, areduction of stniatal dopamine storage, and reduced activityin basal ganglia [i 7]. However, the olfactory deficit is unre-lated to severity of motor or cognitive symptoms, and is notimproved by L-dopa therapy [46].

The major feature of Parkinson’s disease on MR imagingappears to be a trend toward a decreased width of the panscompacta of the substantia nigra [47]. T2-weighted MRimages occasionally show abnormal decreased signal inten-sity in the putamen and to a lesser degree in the caudatenuclei and substantia nigra, suggestive of iron deposition[48]. PET and SPECT studies in patients with Parkinson’sdisease show a moderate global decrease in the cerebralmetabolism, especially in the temporopanietal region (Fig. 5).

Huntington’s Disease

Patients with Huntington’s disease may have olfactorydysfunction [35]. Theoretically, the input of fibers from thecaudate and putamen to the limbic system and stniatum maybe altered, leading to olfactory dysfunction, but the exactmechanism for hyposmia in patients with Huntington’s dis-ease has not been established. On CT scans and MRimages, a decrease in the volume of the caudate head andan increase in the intercaudate distance are seen [49, 50].PET scans of patients with Huntington’s disease have con-sistently shown decreased metabolism in the caudate nuclei,often before the development of atrophy is shown by CT[i7]. SPECT studies involving patients with Huntington’s dis-ease have also revealed decreased uptake of 1231-isopropyliodoamphetamine in the caudate nuclei.

Korsakoff’s Psychosis

Patients with Korsakoff’s psychosis exhibit impaired odordetection, identification, and intensity estimation [Si]. Olfac-tony perception may be selectively impaired in patients withKorsakoff’s psychosis by the diencephalon lesions that arecharacteristic of this disease. Degeneration of the dorsalmedial thalamic nucleus (the common neuropathologiclesion seen in Korsakoff’s psychosis) and atrophy in the pre-frontal areas also can cause the olfactory dysfunction.

Patients with Korsakoff’s psychosis show widespread vol-ume reductions in gray matter, diencephalic structures,mesial temporal lobe structures, and orbitofrontal cortices(areas involved in olfaction perception). Reversible dien-cephalic (medial thalamic) and mesencephalic (peniaque-ductal) lesions can be seen on T2-weighted MR images [52].

I I_ I

AJR:162, February 1994 NEUROIMAGING IN OLFACTORY DYSFUNCTION 4i 5

Fig. 5.-Parkinson’s disease. �mTc�hexame�thylpropyleneamine oxime SPECT scans showuniformity and mildly decreased perfusion totemporal and parietal cortices (arrowheads), ascompared with subcortical nuclei. Frontal cortexperfusion is preserved. Widening of Interhemi-spheric and sylvian fissures (arrows) is appar-ent. (Courtesy of A. Alavi, Philadelphia.)

Schizophrenia

Impaired olfactory function has been reported in schizo-phrenic patients, especially males [53, 54]. These olfactorydeficits, which are not of the same magnitude as those seenin Alzheimer’s disease and Parkinson’s disease, are perhapsnot unexpected, given the occurrence of olfactory hallucina-tions as symptoms in a number of patients with schizophreniaand the evidence linking both to temporal lobe dysfunction[55, 56]. Functional imaging has provided some evidence thatcertain schizophrenic patients have decreased blood flow andmetabolism in the frontal lobes (hypofrontality) [i7] (Fig. 6).

The most consistent finding, on both CT scans and MRimages, is enlargement of the cerebral ventricular system,especially in the frontal and temporal horns, and come-sponding decreases in cerebral tissue [57, 58]. One study

�=H � -_����-�

[57] found that the volume of gray matter in the temporallobe was 20% less in patients than in control subjects, andlateral ventricular volume was 67% larger in the schizophne-nia group than in the control group.

CongenitalAnosmia

Congenital anosmia, which traditionally has been definedas anosmia present from a patient’s earliest recollection, hasbeen recognized for centuries. The most common form of

congenital anosmia is Kallmann’s syndrome or olfactory dys-plasia, which is characterized by hypogonadotropic hypogo-nadism and anosmia [59]. Pathologic and surgical studies ofpatients with Kallmann’s syndrome have shown agenesis ofthe olfactory bulbs [60, 6i].

Fig. 6.-Schizophrenia. 18F-deoxyglucosePET scans show blood flow and metabolismare decreased in frontal and temporal lobes (ar-rows). (Courtesy of A. Alavi, Philadelphia.)

4i6 LI ET AL. AJR:162, February 1994

10

Surface-coil MR imaging is the optimal technique forrevealing the intricate details of the olfactory bulbs, olfactorytracts, and rhinencephalon in vivo (Fig. 7). Three recently pub-lished studies of the imaging findings in Kallmann’s syndromehave reported these findings: (1) absence of olfactory bulbsand tracts, (2) hypoplasia of olfactory bulbs and tracts, and/or(3) absence or hypoplasia of olfactory sulci [6, 62, 63] (Fig. 8).

The volumes of the pituitary gland, hypothalamus, and frontaland temporal lobes were characteristically normal.

Head Trauma

Craniofacial trauma can alter olfactory ability through oneof several mechanisms: damage to the nose, sinuses, onboth with resultant mechanical obstruction to odonants;shearing of olfactory filaments as they course through thecnibriform plate; contusion of the olfactory bulb; and contu-sion on shearing injury of the cerebral cortex, particularly thefrontal and temporal lobes [32, 64]. The prevalence ofanosmia or hyposmia after head trauma has been reportedquite variably from 2% to 38% [65-69], and the prevalenceincreases with the severity of injury [66]. Evidence hasshown that frontal or temporal lobe hematomas on contu-sions are one of the most common causes of olfactory dys-function after head injury (Fig. 9).

CT currently is the study of choice when diagnostic imagingis necessary after acute head trauma [70, 7iJ. CT can showsubanachnoid hemorrhage, fractures, and intraventniculanblood, lesions for which MR imaging is less sensitive acutely.However, MR imaging is superior to CT for detecting andcharacterizing subacute injuries, hemorrhage outside the sub-arachnoid space as in subdural hematomas, cortical contu-sion, and shearing injuries. MR imaging is exquisitelysensitive to diffuse axonal injuries leading to demyelination. Inthe lower frontal regions and near the olfactory bulbs, boneartifacts will inhibit the ability of CT to determine the cause ofposttnaumatic hyposmia. MR imaging may be required.

Brain Tumor

The prevalence of chemosensory changes caused by intra-cranial tumors has rarely been investigated. In a recent study of750 consecutive patients with chemosensory disorders seen atthe University of Pennsylvania Smell and Taste Center, only twocases (0.3%) were induced by brain tumors [65].

In general, tumors or other destructive lesions invoMng the

olfactory bulb, olfactorytract, on prefrontal lobe can cause olfactorydeficits [72, 73]. Temporal lobe tumors usually cause olfactory hal-lucinations (Fig. iO). The presence of olfactory deficits correlatesmore with the location oftumors than with the histologic findings.

Fig. 7.-Normal olfactory bulbs in a 64-year-old healthy female volunteer with normal smellfunction. Coronal surface-coil MR image (500/20 [TRITE]) shows normal olfactory bulbs (ar-rows).

Fig. 8.-29-year-old man with Kallmann’ssyndrome. Coronal MR image (500/20 (TRITE])shows bilateral absence of olfactory bulbs andtracts, a flattened gyrus rectus (arrow) on rightside, and a normal-appearing gyrus rectus onleft side.

Fig. 9.-20-year-old woman with posttrau-matic anosmia. Coronal T2-weighted MR imageshows encephalomalacia. Hyperintense signal(S) has replaced inferior part of frontal lobes(where smell processing occurs).

Fig. 10.-Glioblastoma multiforme in tempo-ral lobe of a 62-year-old woman with olfactoryhallucinations. Contrast-enhanced Ti -weightedMR image shows moderate enhancement ofmass in temporal lobe and a satellite nodule (n)laterally. Sulci are effaced and temporal horn isobliterated.

Discussion

Loss of smell sensation is a common finding associated withmany diseases. It has been estimated by the National Institutesof Health that more than 2 million people in the United Stateshave a smell dysfunction [32]. The investigation of smell loss haslong been neglected because the lack of olfaction has seldombeen considered a major disability, and easy-to-use quantitativetests of olfactory function applicable to clinical assessment havenot been generally available. However, olfactory deficits can pro-

duce significant impairment in the quality of life. Once an olfac-tory disorder has been recognized, the most important step in thediagnostic process is to determine the site of the lesion. Unfortu-nately, current clinical olfactory testing is unable to localize themorphologic changes [79]. Modem imaging techniques can be ofgreat value in the anatomic classification and localization of thecommon causes of olfactory dysfunction. The most commonsource of olfactory dysfunction is the penpherai pathway [32]. Atpresent, high-resolution CT, especially coronal scanning, is thetechnique of choice for studying the bony sinonasal structuresand the ostiomeatal complex. CT can also provide importantinformation as a road map for surgical treatment.

MR imaging is especially useful in soft-tissue discriminationand offers multiplanan capabilities. In the evaluation of thecentral causes of olfactory disturbances, MR imaging has aparamount role. Neunoimaging studies of patients in the neu-ropsychiatnic group with olfactory deficits have revealed inter-esting findings: the links between olfactory deficits andpathophysiologic changes in the brain. The neuroimagingfindings in patients with Alzheimer’s disease, Konsakoff’s psy-chosis, or schizophrenia have some similarities. Almost all ofthe abnormalities of the brain panenchyma revealed by radio-logic studies in patients with these diseases have involved theareas that are the central olfactory projections, such as theprefrontal lobe, temporal lobe, hippocampus, and thalamus.

In the group with congenital disease, such as Kallmann’ssyndrome, the cause of anosmia can be seen on MR studies

AIDS

Impaired olfaction might serve as a marker of earlyinvolvement of the CNS in HIV-infected patients [74]. Everallet al. [75] found that the numeric density of neurons in thefrontal cortex was significantly lower in a group with HIV thanin a control group; patients with AIDS had about 38% fewerneurons in the superior frontal gyrus. This may account forthe olfactory deficits in these patients.

Patients with HIV infection have widened cortical sulci,enlarged ventricles, and cerebral and brainstem atrophywhen compared with control subjects [76-78]. Opportunisticinfections and CNS lymphoma may be superimposed onthese changes. In addition to CNS changes, sinusitis in HIV-infected patients is common and severe. The possibility of aperipheral cause of olfactory deficits in patients with AIDSalso has to be considered in certain cases.

Others

There are also reports of olfactory dysfunction with majordepression, hypochondniasis, and multiple sclerosis [32].Although the pathogenesis of olfactory dysfunction in thesedisorders is still unclear, it appears that a central mechanismrather than a peripheral one is operational.

as absence on hypoplasia ofthe olfactory bulbs [6]. Other con-genital abnormalities such as choanal atresia and meningoen-cephaloceles also can be detected with the imaging studies.

In the categories of head trauma and brain tumors, imagingstudies have shown strong links between olfactory dysfunctionand the location ofthe damaged brain. The histology ofthe tumoron traumatic injury is less critical than its location [2, 64, 72].

Hyposmia on anosmia induced by occupational, necre-

ational (cocaine), or accidental exposure to toxins also hasbeen thought to be due to damage to the peripheral path-ways. However, one study has suggested that olfactory def i-

cits caused by occupational exposure to toxins may have

both peripheral toxic and CNS effects [80].

Conclusions

Medical imaging is an essential part ofthe evaluation of olfac-tory disorders. In the assessment of penphenal causes of olfac-tory deficits, CT and/on MR imaging will reveal anatomicinformation and structural changes, enable a differential diagno-sis, and provide a road map that may be needed for surgicalintervention. In the evaluation of central causes, MR imaging,PET, or SPECT can provide the links between olfactory dysfunc-tion and the structural on functional changes in the living brain.

ACKNOWLEDGMENT

We thank Loretta Plunkett for typing the manuscript.

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