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used in legal contexts where medical evidence is required. Furthermore, biopsies from the olfactory
mucosa,andimagingmethods,bothstructuralandfunctional,yieldadditionalwaysofevaluatingolfaction
orprognosisofsmelldisorders.However,thepracticalvalueofthesetoolsonanintra-individuallevel
hasyettobeclarified.
Ofcourse,priortoapplyingatestorstartinganexamination,thepatient'shistoryhastobeascertained.
A detailed introduction to establishing the history of smell and taste disorders may be found in the
GuidelinesoftheGermanENTSociety(comparewithref.11).
TestsofOlfaction
PsychophysicalAssessmentofOrthonasalOlfaction
ShortTests
Severaltestsarebaseduponodornaming,becauseoftheeaseandcomprehensibilityofthisapproach.
12
However,asmostofthesetoolsincludeverbalcomponents,onehastoconsidertheinfluenceofcognition
and language on these tests. Short screening tests are able to differentiate between normosmia and
hyposmia/anosmia.Theiradvantageistheirshortduration;theirdisadvantageistheircomparativelypoor
validitywithrespecttodetailedresults,whichrenderstheshorttestsunsuitableformedicolegalcontexts
and—atleastonanindividualbasis—evaluationofthecourseoftherapy.
Cross-CulturalSmellIdentificationTest
The “Cross-Cultural Smell IdentificationTest”(CCSIT) is a shorttestrequiringthe patient toidentify
odors from lists of four identifiers.
13
In a multiple forced-choice procedure, 12 odors are tested.
Microencapsulatedodorsareattachedtopaper,andmaybereleasedbyrubbingthepaperwithapencil.
Thetesthasalongshelf-lifeandiswellvalidated.Itmaybeperformedbypatientsunassisted.
Sniffin’SticksScreening
The “Sniffin’ Sticks,” too, allow screening of olfactory function, analogous to the CCSIT. Odors are
released from small cylinders withcapped points, similar tofeltpens.The screening procedure is an
identificationtestandmaybeperformedwitheither12pens
14
or16pensinanextendedversion.
15
The
testis well validated and,unlike theCCSIT,may be used repeatedly. Depending on the frequency of
application,thepens’shelf-lifemaybeayearorlonger.Patientsmayperformthetestbythemselves.
16
Note
Severalwell-validated,inexpensive,easy,andquicktestsareavailableforolfactoryscreening.
EuropeanTestofOlfactoryCapabilities
The “European Test of Olfactory Capabilities”
17
is based upon 12 odors (Fig. 6.1a) in small glass
bottles.Twoproceduresareperformed:Thefirsttaskistoidentifyoneoutoffourbottlescontainingan
odorant,whichthenhastobeidentifiedfromafour-itemlistinmultiplechoicemode.
ZürcherRiechtest
The“ZürcherRiechtest”
18
includeseightodorsonso-calledsmelldisks;odorshavetobeidentifiedfrom
threeitems.Thedisksarereusableandmaybeappliedbypatientsunassisted.Thetesthasbeenvalidated
inarelativelysmallsample.
IdentificationTestswithVeryFewOdors
Among the identification tests using very few odors are those from the UPSIT family (“University of
PennsylvaniaSmellIdentificationTests”),namely,the“Pocket-Smell-Test”andanothertool,bothbased
upon three odors.
19
The “Sniffin’ Sticks” family, too, includes short versions with three
20
and five
21
odors, which distinguish normosmic patients from anosmic patients with high specificity at very low
scores,occasionallyfailing,however,toidentifyananosmicpatient.Thesetestsareprimarilyusefulin
contextsrequiringaglobalestimateratherthanadetailedolfactoryassessment.
Another very simple tool is the “Alcohol-Sniff-Test.”
22
The sachet of a disposable, prepackaged
alcoholswabisopenedandthepadisslowlymovedtowardthenose;thedistancefromwhichthesmell
isperceivedyieldsadiagnosticcluewithrespecttoolfactoryfunction.
Note
Humansaretypically pooratcorrectly identifyingodors.Basically,thiscan onlybeachievedifa
listofitemstochoosefromisavailable.Thus,themerepresentationofatinofgroundcoffeeora
flaskofperfumeis,atbest,afragranceassistedinterview,andcannotbeconsideredasmelltest.
PsychophysicalTestsAssessingOlfactioninaMoreExtensiveManner
Inrecentyears,bothstandardizedandvalidatedpsychophysicaltestshavebeendevelopedtoinvestigate
olfactory functioninadetailed fashion. Several aspectsare assessed, suchas perceptionthresholdsof
oneormoreodorants;theabilitytodiscriminatebetweenodorsandtoidentifythem;olfactorymemory;
andtheratingofsuprathresholdodorconcentrations.
UniversityofPennsylvaniaSmellIdentificationTests
Exclusivelyanodoridentificationtest,theUPSITconsistsoffortymicroencapsulatedodorantsembedded
inpaper,whichare releasedbyrubbing(“scratch and sniff,”see Fig.6.1b),andidentified in multiple
forced-choicemodefromitemlists.
23
Althoughthisdisposabletoolisthemostfrequentlyappliedsmell
identification test worldwide, the original version is somewhat regionally restricted because of
interculturaldifferencesinfamiliarityofodors(e.g.,rootbeer,wintergreen).However,UPSITversions
areavailabletodaythathavebeenadaptedtoanumberoflanguages(www.sensonics.com).
Sniffin’Sticks
“Sniffin’ Sticks” permit a more detailed evaluation of the sense of smell
24–26
(Fig. 6.1c). They are
reusable.Thewholetestisdividedintoathreshold,adiscrimination,andanidentificationpart,withthe
last two beingsuprathreshold tests.Thetestbatteryisbased upon the notion that differenttestsassess
different dimensions of olfaction.
27,28
In this concept, it is assumed that threshold tests rather reflect
peripheral aspects of the olfactory system, as opposed to more advanced, complex processing levels
represented in identification and discrimination tasks. However, anabsolutely clear-cut separation of
thesefunctionscannotbeachievedbyspecificolfactorytests(seeref.29),asdiscriminatingandmemory
processesdoplayanimportantroleinthresholdtesting,and,conversely,odorintensityiscorrelatedwith
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theactivityofolfactoryreceptorneurons(ORNs).
30
Threshold testing with Sniffin’ Sticks yields the concentration above which an odor is perceived.
Olfactorysensitivitymaybetestedwithn-butanolorphenylethylalcohol.Duringthistest,patientsweara
blindfoldtoconcealthepens’labels.Concentrationsoftheodorsolutionsrepresentageometricseries,
startingataconcentrationof4%,andprogressinginatotalof16stepswithadilutionratioof1:2ateach
step.
PatientsarepresentedwithtripletsofSniffin’Sticks.Eachtripletconsistsofoneodorouspenandtwo
penscontaininganodorlesssolvent.Thesequenceofpresentationwithintripletsisrandom.Patientsare
requiredtoidentifythesmellingpenineachtriplet.Startingatalowconcentration,andcontinuingwith
increasingconcentrationsaslongasnocorrectresponseisobtained,thefirst“turningpoint”isreached
when the odorous pen is identified in two succeeding triplets (indicating that the threshold has been
passed). At any turning point, the direction of concentration changes is reversed from decreasing to
increasing orviceversa, andpresentationthuscontinuesuntil thenextfailureor success, respectively.
The procedureiscompletedatthe seventhturningpoint,andthemeanofthe lastfourturningpointsis
establishedasthethreshold.Asimilartest,baseduponodorflasks,isavailableinconjunctionwiththe
UPSIT.Othermethodsofodorthresholddetectionareused(forexample,refs.31–37),butatleastsome
ofthemappeartobelesssuitablethanSniffin’Sticksinclinicalcontexts.
36
ThenonverbaldiscriminationtestoftheSniffin’Sticksbatteryteststheabilitytodiscriminatebetween
odors. Again, patients are blindfolded, and triplets are presented, in this case with suprathreshold
concentrationsinallpens.Ineach triplet,twoitemscontainthesameodorant, whereasthethirdoneis
different,andisrequiredtobedetected.Patientsarepresentedwitheachpenonlyonce.Altogether,16
tripletsareused;thenumberofcorrectlyidentifieditems represents thediscriminationscore.Thistest
appearstobestronglyaffectedbycognitiveabilities.
28
Identification is tested as in the UPSIT procedure, with Sniffin’ Sticks used rather than
microencapsulated odors, and the number of items typically being 16 or 32.
26
Odor identification is
influenced bynumerousfactors(e.g.,cognitive abilities, verbal skills, number ofitems in the multiple
choicelist,orsimilarityoftheseitems,etc.).
38,39
Aftercompletionoftheentiretestbattery,thesumofthescoresfromallthreesubtestsiscalculated
(Threshold + Discrimination + Identification= TDI score). A TDIscore differenceof sixandabove
indicatesaclinicallysignificantchange.
40
Forcomputerassistedtestprocedureanddocumentation,free
software may be downloaded from: http://www.tu-
dresden.de/medkhno/riechen_schmecken/download.htm
Fig.6.1a–e Fivesmelltestsaredisplayed.(ImagescourtesyofRichardL.Doty,Philadelphia;WilliamS.Cain,SanDiego;MoustafaBensafi,
Lyon;Tadashi Ishimaru, Kanazawa.) (FromHummel T, Welge-Lüssen A. Riechund Schmeckstorungen: Physiologie,Pathophysiologie und
TherapeutischeAnsatze.Stuttgart:Thieme;2005.)
a“EuropeanTestforOlfactoryCapabilities,”witheightodorantsineightconcentrations,forthresholdandidentificationtesting.
b“UniversityofPennsylvaniaSmellIdentificationTest,”aso-calledscratch-and-snifftest.
c“Sniffin’Sticks”identificationsubtestwith12items.
d “Connecticut Chemosensory Clinical Research Centers” test, comes in bottles for assessing butanol thresholdand a salt dispenser-like
containerfortheidentificationtask.Thetablepresentsverbaldescriptorsofodors, someofwhicharepresentedduring odoridentification
andsomeofwhicharenot(distractors).
e“T&Tolfactometer,”withfiveodorantsineightconcentrations,totestthresholdsofodorperceptionandodoridentification.
Note
Olfactorythreshold, discrimination, andidentification teststap into different portionsofolfactory
function.
ConnecticutChemosensoryClinicalResearchCenterTest
The test developed by the Connecticut Chemosensory Clinical Research Center (CCCRC-Test
32
) is
available in two parts (Fig. 6.1d). The threshold is assessed for butanol. Starting at a very low
concentration,increasingodorantconcentrationsarepresented,alongwithanonodoroussample;patients
areaskedtoidentifythesamplecontainingtheodorant.Thethresholdisrepresentedbytheconcentration
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that is correctly identified in three to five consecutive trials. In the identification task, patients are
presentedwitheightodorantsthathavetobeidentifiedfrom a16-itemlist.Scoresofbothsubtestsare
combinedtoasinglescore.
Note
Clinically,testingisalmost exclusivelyperformedforbothnostrilstogether;monorhinaltestingis
frequently omitted.Thisprocedure misses lateralizeddifferencesinolfactory function (whichare
frequent;seeref.41).Suchdifferencesmaybeindicativeoflateralizedbrainlesions(e.g.,olfactory
meningioma).Theymayalsocontaininformationontheprognosisoftheolfactoryloss.
42
T&TTest
TheJapaneseT&TTest(thenamereferstothedevelopersofthetest,ProfessorSFTakagiandProfessor
BToyoda
43
)isbaseduponfiveodors(β-phenylethylalcohol,methylcyclopentenolone,isovalericacid,
γ-undecalactone, scatole) in eight concentrations (Fig. 6.1e). Presenting samples in increasing
concentrations,firsttheperceptionthreshold(theconcentrationatwhichtheodorisfirstperceived),and
then the identification threshold (the concentration at which the odor is correctly recognized), is
established.
Allextensive testspermitdifferentiation amongnormosmia,hyposmia,andanosmia(Table 6.1). By
wayofcommercialavailabilityandstandardizedapplicationinseveralcenters,comparabilityofvarious
investigationscouldbeaccomplished.
Table 6.1Definitionofolfactorydisorders:quantitativedisordersarehighlightedinlightred,andqualitativedisordersindarkerred
Diagnosis De scription
Anosmia Totallossofolfactoryfunction
Functionalanosmia Significantlyimpairedolfaction,includingbothtotallossandminimalresidualperception
Partialanosmia
Significantlyreducedsensibilitytowardoneodorantorgroupofodorants,comparedwiththegeneralpopulation
—withoutclinicalrelevance
Hyposmia Partialloss(frequent,e.g.,inoldage)
Olfactoryintolerance Subjectivehypersensitivitytowardodorants,butnormalolfactoryfunction
Hyperosmia Hypernormalolfactorysensitivity(veryrare,e.g.,inmigraine)
Parosmia(synonym,
troposmia)
Abnormalperception,withsensoryinputpresent
Phantosmia Abnormalperception,withsensoryinputabsent
Note
Forced-choiceproceduresareindispensabletoavoidpatientsdecidingonthe“nosmell”option,as
thisis easyandtemptingandwillbe chosen by severalpatients, irrespective ofwhetheranything
was perceivedor not.Only ifthese patientsarerequestedtoconcentrate onthepresented stimuli
using forced-choice tasks, may they realize their perceptive abilities—which often come as a
surprisetothepatientsthemselves!
PsychophysicalAssessmentofRetronasalOlfaction
Retronasal olfaction represents the perception of smell during eating and drinking (Fig. 6.2a). As
retronasal olfaction occurs virtually exclusively in the context of food and drink intake, it is mostly
mistakenfor tasteperception.This explainswhy ~60%ofpatientssuffering from onlysmelldisorders
complainaboutlossofsmellandtaste.
44
Therefore,atleastsomecursorytastetest(sweet,bitter,sour,
andsalty),oughttobeperformedalongwithasmelltestinanypatientpresentingwithatasteproblem.
Frequently, exclusive olfactory disorders are found in these cases, without any impairment of taste
function.
44
To our knowledge, the first clinical test ofretronasal olfactionwas introduced by Güttich,
45
who
believedhehadfoundtheidealtooltoexposemalingerersinmedicolegalinvestigations.Thebasicidea
wasthatanosmicpeoplewouldbeunabletoperceivethe“taste”ofliquidodorantsappliedtothemouth
(e.g.,“cherryinrum”).Ifanallegedanosmiccouldstillidentifythe“taste”ofthesolutions,thiswould
indicateodorperception.Thetestis,however,unstructuredandthusunreliable.
46
In spite of impaired orthonasal olfaction, some patients are able to identify retronasally presented
odors.
47
Aside from that, in disorders such as nasal polyposis or hyperplastic tonsils, discrepancies
between ortho- and retronasal olfaction occur. In addition, in a small group of patients, ortho nasal
smellingwasfoundtobeselectivelyaffected,whereasretronasalolfactionwasstillintact.
48
The Aachen“rhinotest”
49
is a screening test of retronasal smell identification, using six odorous
spraysappliedtothemouth.Individualsarerequiredtoselectodorqualityfromalistofsixidentifiers
(flowery,disgusting,fruity,raisiny, stinging, spicy).This reusable testhasalong shelf-lifeand canbe
appliedbythepatientsthemselves.
In a test developed in Japan, odorants such as prosultiamine (smell of garlic) are administered
intravenously
50
andthelatencyatwhichtheodorisperceived(ifatall)isassessed.Thistestisbasedon
thepulmonaryexhalationoftheodorant.
Anothertestofretronasalolfactionis thestandardized“taste powder”tool
47
(Fig. 6.2b).So-called
taste powders (20 pulverized food and spice samples, e.g., cinnamon) are applied to the mouth and
identified by patients from lists of four items. This relatively simple test may be easily performed
anywhere with powders purchased from a grocery. It is suitable to validate complaints of complete
olfactory loss with (nearly)unimpaired gustationandvice versa.
48
Recently,another test of retronasal
sensitivityhasbeenintroduced,
51
whichisbasedonaromatizedsorbitolcandies.
Fig. 6.2a, b Retronasal olfaction. (From Hummel T, Welge-Lüssen A. Riech- und Schmeckstorungen: Physiologie, Pathophysiologie und
TherapeutischeAnsatze.Stuttgart:Thieme;2005.)
aSchematicsketchofairflowinortho-andretronasalolfaction.(ImagecourtesyofThomasBeleites,Dresden.)
bRetronasalsmelltest“tastepowders:”Smellingfoodpowdersarewhiffedontothetonguebymeansofpowderapplicators.Similartothe
orthonasaltest,patientsidentifythe“taste”inforced-choicemodefromafour-itemlist.
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Note
Ortho- and retronasal olfaction may be selectively affected. Therefore, separate testing of both
pathwaysisworthwhile.
ElectrophysiologicalProcedurestoAssessOlfaction
OlfactoryEvent-relatedPotentials
Electroencephalography (EEG)-based olfactory event-related potentials (ERP)
52,53
is a method to
validatesmelldisordersquantitatively.Ithasbecomearoutinetechniqueinmanycountries.Prerequisites
ofthestimulatingdevice(olfactometer),apartfrompreciseduration,concentration,andsteepriseofthe
chemicalstimuli,areconstantflow,temperature,andhumidityoftheairstream(Fig.6.3).
Stimulus durationsof200 millisecondsatintervals of30 to40seconds are recommended, with an
airflow of 7 to 8 L/min(but see also ref.54). Typically, 16 to 80 stimuli (optimally80) are used to
calculateanaverageERP.
55
AnessentialrequirementofolfactoryERPisasufficientlysteeprisingedge
ofthestimuli.Attheolfactometer'soutlet,airtemperatureshouldapproximatebodytemperature,andair
humidity should be 70 to 80%. Chemical stimulation must not be accompanied by any mechanical,
thermal, or acoustic phenomena, as these are likelyto elicit evoked responses that interfere with the
olfactoryresponse.
53
OlfactoryERPshavebeenshowntobegeneratedinareasofthebrainincludingthe
amygdala,theinsula,andtheorbitofrontalcortex.
56
Only “pure” olfactory stimulants such as hydrogen sulfide (“rotten eggs”), vanillin, or phenylethyl
alcohol (“rose fragrance”) should be used to elicitolfactory ERPs. Inaddition,a trigeminal stimulant
shouldbeappliedseparatelyforcontrolpurposes(e.g.,odorlesscarbondioxide).Forclinicalevaluation
ofsmell disorders,olfactory ERPsshould be obtainedfrom atleastthreerecordingpositions,with the
patient'seyesopen.ThemainERPrecordingsareanegativedeflectionatlatenciesbetween200and700
milliseconds, and a positive peak atlatencies between 300 and 800 milliseconds. In cases in which
olfactory ERPs are obtained, it can be assumed that olfactory function is present.
55,57,58
This is of
particularsignificanceincontextswhereexpertmedicalopinionsarerequired.
53
Fig.6.3a–cOlfactoryevokedpotentials.(From HummelT,Welge-LüssenA.Riech-undSchmeckstorungen: Physiologie,Pathophysiologie
undTherapeutischeAnsatze.Stuttgart:Thieme;2005.)
aStimulatingdevicetoobtainolfactory-evokedpotentials(OEP):OlfactometerOM6b(Burghartinstruments,Wedel).
bSubjectwitholfactometeroutletandelectroencephalography(EEG)electrodesduringOEPrecording.
cTypicalOEPafterstimulationwithphenylethylalcohol(rosefragrance);mainpeaksmarkedN1andP2.InanosmicpatientsnosuchOEPis
obtained.
Electro-olfactogram
Peripheral mucosal potentials (so-called electro-olfactograms) can be obtained in humans from the
olfactory epithelium.
52,59,60
However attractive this method is in an experimental context, its clinical
valueisdecreasedbythefactthatitisnotrecordableinallpatients,eveninthosewithanormalsenseof
smell,
30
and that there are situations where it can be recorded even though the stimulus is not
perceived.
61,62
ContingentNegativeVariation
Theso-calledcontingentnegativevariation(CNV)isanegativedeflectionintheEEGoccurringwhen
aneventisexpected.Thisphenomenonisalsoexploitedintheassessmentofolfactoryfunction.
63
Inaso-
calledS1–S2paradigm,patientsareacquainted withasequencewherebyanolfactorystimulus(S2)is
precededbyanother(e.g.,acoustic)stimulus(S1).AfterpresentationofS1,CNVdevelopsinanticipation
ofS2 andcollapses atoccurrence of S2. CNV continuationafter S2 indicates that the smell was not
perceived.Alternatively,theolfactorystimuluscouldalsobeS1;ifsubjectsdonotperceivetheodor,no
CNVwill develop. Thistechniquerequiresthe patient's cooperation.Furthermore,theoccurrenceofa
CNVdependsonseveralpsychologicalvariables,meaningthatitdoesnotoccurineveryperson.
64
Others
GeneralEEGshiftsfollowingthepresentationofolfactorystimulihavealsobeenusedtovalidatesmell
disorders.However,caseshavebeenreportedwhere,althoughodorswereperceived,noEEGreaction
couldbeobtained.
65
WithadvancedEEGamplifiersandsoftwarethismethodmayexperiencearevival
(Huart,personalcommunication).Anothermethodtestedforitsprognosticvalueinolfactorydisordersis
measurement of trigeminal ERPs after intranasal stimulation with carbon dioxide,
66
but large,
prospectivestudieshavenotyetbeenconducted.Thepsychogalvanicskinreaction(“liedetectortest”)
hasalsobeenusedtotestolfactoryfunctioninamedicolegalcontext.
67
InvestigationofReactionsFollowingOlfactoryStimulation
GudziolandWächterwereabletoshowthatrespiratorychangesafterolfactorystimulationareclinically
significantintermsofthedistinctionbetweenhyposmiaandanosmia.
68
Thismethodisalsoapplicablein
medicolegalcontexts.Basedonthesamereaction—smell-inducedchangesinrespiration—butrequiring
less technical expenditure, is the so-called Compu-Sniff test
69
(Fig. 6.4), which assesses sniffing
parametersinrelationtothepresenceorabsenceofodors.Astheseproceduresarenonverbal,theyalso
appeartobesuitablefortestingchildren.
Bothpupillary
70,71
andwinkreflexes
72
havealsobeentested;theseprocedures,however,remainof
pureexperimentalinterestandarenotclinicallyapplied.
FunctionalMagneticResonanceImaging
In functional magnetic resonance imaging (fMRI), the so-called BOLD (Blood Oxygenation Level–
Dependent)effect is assessed in responseto olfactoryor gustatorystimuli
73
(Fig. 6.5). As theeffects
reflectregionalblood flowchangesinthebrain,andthus,indirectly,changesofneuronalactivation,it
permitsassessmentofbothcerebral activationandthelocationwhereitoccurs.Inthelastdecade,this
techniquehasgainedwidespread currency andyieldedamultitude ofnewfindings.
74,75
However,itis
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questionable whether it is useful in clinical practice, because of high interindividual variability. In
addition,itseemsthatevenanosmicpatientsexhibitsomerandombrainactivation.
Note
OlfactoryERPsareparticularlysignificantinmedicolegalcontexts,andhavebeenstudiedinmuch
moredetailthanothernonpsychophysicalinstrumentsvalidatingolfactoryfunction.
VolumetricAssessmentoftheOlfactoryBulb
Plasticityoftheolfactorybulb(OB)isoutstandingamongthecentralnervoussystem.
76
Itisensuredby
continuous neurogenesis, which itself seems to be dependent on peripheral neuronal activity.
77
Anatomical changes in the OB may be gauged from structural magnetic resonance images (circularly
polarized coil, T2-weighted, frontal constructive interference in steady-state precession sequences
acquiredinthree-dimensionalmode;resolutionlessthan0.2 ×0.5×0.7mm
3
).Asexpected,theOBis
hypo-oraplasticinpatientswithcongenitalanosmia
78
;thisisalsoexpedientasadiagnosticcriterion.In
addition,aflatteningoftheolfactorysulcusischaracteristicinthesepatients.
79,80
Patientssufferingfrom
postinfectiousor post-traumaticolfactorydeficitshavesmallerOBvolumesthannormosmicsubjects.
81
Moreover, OB volumes correlate with the degree of olfactory impairment,
82
and with intraindividual
changes in sense of smell
83,84
(Fig. 6.6). Therefore, OB volumetry is considered a possible tool to
estimateindividualprognosisinolfactorydisorders.
Fig. 6.4a, b Compu-Sniff test. (Images courtesy of Robert Frank, Cincinnatti.) (From Hummel T, Welge-Lüssen A. Riech- und
Schmeckstorungen:Physiologie,PathophysiologieundTherapeutischeAnsatze.Stuttgart:Thieme;2005.)
aSubjectwithnasalprobe(connectedtoapiezopressuretransducer)containingodoranttobereleaseduponsniffing.
bResults(pressure–timediagrams;samplingrate100Hz)ofnoodorandunpleasantodor:perceptionofunpleasantsmellsignificantlychanges
sniffingbehavior.
Fig. 6.5a, b Functional magnetic resonance imaging: Typical cerebralactivation of insula (a) andorbito-frontalcortex (b) after gustatory
stimulationwithsucroseandcitricacidinahealthysubject(seeref.73).
Fig. 6.6a, b Assessment of olfactory bulb volume. (From Hummel T, Welge-Lüssen A. Riech- und Schmeckstorungen: Physiologie,
PathophysiologieundTherapeutischeAnsatze.Stuttgart:Thieme;2005.)
aCranialmagneticresonanceimagingcrosssection(frontal plane)fromahealthysubject,withbotholfactorybulbs(OBs)markedbywhite
circles.
bDependencyofOBvolumeonthresholdchangesforphenylethylalcohol(rosefragrance);modifiedfromref.83.
BiopsiesfromtheOlfactoryMucosa
Morphological examinations can assess the presence ofperipheral ORNs, and gaininformation about
peripheralconditionscausingsmelldisorders.
85,86
Biopsiescancorrelatethemostfrequentolfactorydisorderswiththeirhistopathologicalfindings.(1)
Post-traumaticalterationsareassociatedwithdisorganizationandthickeningoftheolfactoryepithelium,
andasmallnumberofdegeneratedcells.
87
(2)Postviralanosmiabiopsiesoftenshowreducednumbers
ofORNsand,occasionally,squamousepithelialmetaplasia.
88
(3)Insmelldisorderscausedbysinonasal
conditions,olfactoryepitheliumisnormalintheearlystages
89,90
butmaydemonstratesquamousepithelial
metaplasiaorfibrosisinchroniccases.Potentially,biopsyoftheolfactorymucosaappearsreasonableto
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