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Fig.9.3 Coronal magneticresonance image(T2sequence) oftheparanasalsinuses showingabilateraltumoralmass in theolfactory cleft
(whitearrows):adenomatoidhamartoma.
Fig.9.4a,bTumoralmassesassociatedwitholfactoryloss.
aEndoscopicview(30°)oftherightolfactorycleftshowingatumoralmass(whitearrow)medialtothemiddleturbinate.
bCoronalmagneticresonanceimage(T1sequence)oftheparanasalsinusesshowingarighttumoralmassintheolfactorycleft(whitearrow):
adenocarcinomainwoodworker.
Fig.9.5Coronalmagneticresonanceimage(T2sequence)oftheanteriorcranialbaseshowingatumoralmass(whitearrow)intheolfactory
groove:olfactorymeningioma.
ComplicationsofSurgeryandOlfactoryDysfunction
Evenifnasalandsinussurgeryhavetheprimarygoalofrestoringolfactoryfunction,somesurgical
proceduresmaybeassociatedwithadeteriorationinchemosensoryfunction.
Veryrarecasereportshavebeenpublishedwhereanolfactorydysfunctionoccurredduringthecourseof
surgerynotassociatedwitholfactorypathways.Avarietyofdrugsgivenduringasurgicalproceduremay
impede olfaction after oral administration, systemic injection, or topical application. Halogenated
volatile agents given during anesthesia may also induce an unpleasant smell perception during
inhalational induction.Olfactorydysfunctionis usually transient anda causal relationship between the
anestheticmedicationandthechemosensorydysfunctionisoftendifficulttoascertain.
34–36
After nasal surgery, olfactory function may be worse for several reasons: nasal packing; mucosal
edema;olfactory neuroepithelial lesions;or scar tissueformation. Althoughveryrareandtime-limited,
olfactorydysfunctionaftercommonnasalsurgery(e.g.,septoplasty,rhinoseptoplasty,turbinectomy,etc.)
hasbeenreportedwithvariableprevalence(Table9.4).
37–45
Endoscopicendonasalsurgeryintheethmoidsinusesandintheolfactorycleftmayalsoinducesevere
olfactorydysfunctionasaresultof:metaplasiaoftheolfactoryneuroepithelium;scartissueformationin
the olfactorycleft;superinfection withneurotoxin-producingbacteria;iatrogenicinjury tothe sinonasal
mucosa,whereolfactory receptorneuronsare present;andiatrogenicinjury tothe olfactory cleft (e.g.,
cerebrospinal fluid leak, reconstruction of the anterior cranial base). This is especially true when
extensiveorradicalsurgeryhasbeenperformed,inducingacompleteatrophicrhinitis(Fig.9.6).
46
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Fig. 9.6 Coronal magnetic resonance image (T2 sequence) of the paranasal sinuses showing a postoperative view after radical surgery
(completeremovalofinferiorandmiddleturbinate,andethmoidmucosa:whitearrows)leadingtoatrophicrhinitiswitholfactorydisorder.
Aclassicalapproach totheanteriorcranialfossaforskull basetumorsis almostalwaysassociated
with permanent postoperative olfactory dysfunctionbecause olfactorystructures are an obstacle to the
approach. Alternative routes exist that better spare the olfactory apparatus, although these must not
jeopardizethe approachor thetumorremoval.
45
Olfactory dysfunctioncanalsobe present after trans-
sphenoidalhypophysectomy.
34
TheOlfactoryCleftSyndrome
Congestionoftheolfactorycleftwithoutinflammationoftheparanasalsinusesmayhaveanegative
impactonolfactoryfunctionandmayberelatedtotheso-calledolfactorycleftsyndrome.
Patientswithobstructiveinflammationoftheolfactorycleftsalsohaveimpairedolfactoryfunction.This
syndromeis consideredas a new finding andisdiagnosedwhen clearinflammatory obstruction ofthe
olfactorycleftisdemonstratedonimagingwithoutanyradiologicalsignofopacifiedsinuses(Fig.9.7).
46
Theobstructioncorrespondstolocalinflammationofthemucosaltissuecoveringtheolfactorycleftand
may be secondary to a severe nasopharyngeal infection or to damage to the cleft region, leading to
squamous metaplasia or fibrosis, with negative consequences on olfactory function. Association with
hypertrophyofthemiddleturbinate(conchabullosa)andwithobviousanatomicalmalformationhasbeen
underlinedalso.This diagnosis is radiologicalandendoscopic. Endonasalendoscopy typicallydetects
bilateralandsymmetricalcongestionintheolfactorycleftwithnoextensiontothemoreinferiorpartof
the nasal fossa.Tentative treatment maybebased onoralcorticosteroidtreatment (whichis not really
helpfulforthevastmajorityofpatients)oronconchabullosareduction.
Fig.9.7 Coronal computed tomography oftheparanasal sinusesrevealing a swelling ofthemucosain theolfactorycleftbilaterally(white
arrows):olfactorycleftsyndrome.
Conclusions
•Miscellaneouscausesofolfactorydysfunctionarenumerous,andtreatmentneedstobeadaptedtoeach
specificcase.Eliminatingthecausativetoxicantordrugseemsthelogicalwaytomanagepatientswith
toxicant-ordrug-inducedolfactorydysfunction.
• Endocrine-related disorders should receive appropriate treatment of the underlying disease, but
olfactoryrecoverymaynotensue.
• Idiopathic olfactory disorders should only be diagnosed if others causes have been ruled out. The
possibilityofdevelopingneurodegenerativediseaseshouldbeconsidered.
• Congenital olfactory disorders should be diagnosed by MRI techniquesfocusing on theOBandthe
olfactorysulcus,despitethefactthatnotreatmentexistsforthesepatients.
•Tumor-relatedolfactory dysfunctionis rare asa sole andprimarymanifestationofthe disease.MRI
evaluation and appropriate surgical removal (aiming to spare the olfactory apparatus without
jeopardizingtumorremoval)shouldbeproposed.
•Postsurgicalcomplicationsleadingtoolfactorydysfunctionmayhavemultipleorigins.
•Theprevalenceofthesemiscellaneouscausesofolfactorydysfunctionisverylow.Amalgamatingdata
fromdifferentcasesatdifferentsmellandtastecentersshouldaddvaluableinformationinthisarea.
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10ChemosensoryFunctioninInfantsandChildren
DavidG.Laing,BenoistSchaal
It isnowestablishedthatchemosensoryfunctionsare behaviorallyandcognitivelysignificantinhuman
neonates,infants,andchildren.Thischapteraimstosummarizecurrentknowledgeonthedevelopmentof
nasalandoralchemoreception,andcorrespondingbehavioralfunctions.Further,itwilldiscussdifferent
methods available to assess olfactory and taste capabilities in children both qualitatively and
quantitatively.
DevelopmentofChemosensoryFunctionality
TheFetusandPrematurelyBornInfant
NasalChemoreception
Thestrongestevidenceforhumanprenatalolfactoryfunctioncomesfromstudiesonnewbornsinwhich
theodorofamnioticfluid,
1
orofflavorcompounds(e.g.,anise,alcohol,carrot)transferredintoit,induce
appetitive responses in the newborn.
2,3
Thus, from late gestation, the human fetus is able to detect,
selectively encode, and retain some odor information in the womb. Near-term fetuses may be as
competentasneonates.Sarnat,
4
however,foundthattheproportionofprematurenewbornsdetectingmint
odor at birth (assessed by sucking or arousal responses) was related to gestational age. While most
infantsbornbetween29and36weeks’gestationresponded,lesspredictablereactionsarosebeforeweek
29.Aftergestationalweek32,infantsbornprematurelyrespondedtothemintodorequallytoinfantsborn
atterm.Near-infraredspectroscopyalsoshowedthatpreterminfantsaged33.7gestationalweeks(tested
12.5dayspost birth) evincedifferential cortical hemodynamic variationswhenexposedtotheodor of
colostrumor vanillaor totrigeminal stimuli carried indisinfectantsor detergents:after 10 secondsof
stimulation,anincreaseordecrease,respectively,wasnotedinoxygenatedhemoglobinovertheparietal
region.
5
OralChemoreception
Tastebudsofalltypesareevidentasearlyasgestationalweek10,andbytheendofgestationalmonth4
receptorcellsbecomeaccessibletopotentialstimulithroughopentastepores.Humanfetalresponsesto
sapidagentsinfusedinuteroremainequivocal,but functionaltastehasbeen establishedininfantsborn
preterm withingestationalmonths6to9. Sweet,bitter,oracidtastantselicitresponsesindicatingthat,
fromearlygestationalmonth6,tastebudsareconnectedwiththecentralsystemscontrollingbehavioral
andautonomic (salivation) responses. Sweet solutions lead to mouthing/sucking and positive hedonic
responses(sucking,calming,facialexpressionindicatingacceptance)inpreterminfants,whereasbitter,
acid,andsaltystimulitendtoinhibittheseresponsesordonotaffectthem(e.g.,ref.6).
TheNewborn*
NasalChemoreception
Whentestedwithin12hoursafterbirthandbeforeanypostnatalingestion,odorantschosentobepleasant
or unpleasant to adults (banana, vanilla, and milky odorants versus fishy and rotten odorants,
respectively)elicitedtypicalfacialresponses.
7
Whenphotographsoftheseresponseswereevaluatedby
an adult panel for their hedonic meaning, the odors considered pleasant induced expressions of
acceptance (relaxed face, rising mouth corners, licking, sucking), while unpleasant odors provoked
rejection expressions (lowering mouth corners, lip/tongue protrusion, gaping) (Fig. 10.1). As one
anencephalic newbornreactedwith similar facial expressions toodors as normal infants, an“innate”
brainstem mechanism controlling hedonic facial reactivity was proposed, andtermed the olfactofacial
reflex.
7
However, it was later shown that prenatal experience with odorants can strongly bias such
neonatalresponses,
3
castingdoubtontheinnatenatureofthe“reflex”.
*Thehumanneonatalperiodisgenerallyconsideredasextendingfrombirthtothefirstmonth.
Fig.10.1a,bFacialexpressionsofnewborninfants(aged2–3days)during10-secondexposuretonegativeandpositiveodorantsonQ-tips.
(FromSoussignanetal.
15
)
aButyricacid0.125%.
bCow-basedformulamilk.
OralChemoreception
Taste stimuli are well discriminated by term-born newborns. Facial and oral movements expressing
acceptance(sucking,relaxedand“smiley”face,eyeopening,hand–mouthcontact)areelicitedbywater
solutions of sweet tastants (sucrose, lactose, or saccharin), or by monosodium glutamate (savory)
administeredinasoup.Incontrast,facial–oralresponsesexpressingavoidance(grimaces,crying,gaping,
eye closure) occur with acid and bitter tastants, while salty solutions remain hedonically ambiguous
during thefirstpostnatalmonths.
7
Reactivity measuredbycomparing differential ingestionfrom bottles
containingvarioustastesolutionsagainstareferencebottle(generallywater)providedlessconvincing
data,probablybecausethesuckingdriveover-ridestasteregulationofintakeatthisearlyage.Whilethe
acceptance for sweetsolutions remained, infants consumedsalt and bitter (urea) solutions as much as
water,suggestingindifferencetotheselattertastants,whilesourtastesweregenerallyrejected.
8
Tastecan
regulateinfants’activationstatesbyinhibitingcryingandfacilitatingcalmness.Theoraladministrationof
sucroseactivatesmouthing/licking/suckingmotions.Thissweetness–calminglinkappearstofadeoutafter
2monthsofage,however.
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InfantsandChildren
NasalChemoreception
Owing todifficulties in complianceandindesigning tests forpreverbal children,our understandingof
nasal chemosensation remainsscantybetween theagesof1 monthand3years. However,thereisnoa
priorireasonwhynasalchemosensationshouldnotfunctionwelloverthisperiod:
•Below3yearsofage,reactivitytoodorsisattestedbyinfants’selectiveresponsivenesstofoodsand
persons
9
;between 3 and 4 years, rare studies indicate good odor detection abilities; andbyage 5
children'sresponsesbecomeaccessibletomoresystematicpsychophysicaltesting(seepp.58–75).
• The best evidence for infants’ and children's olfactory responsiveness comes from studies on
preferencesandaversions,whichsuggesta generallygreatertolerancetounpleasantodorsbefore5
yearsofage,andconverginghedonicresponsesinchildrenandadults.
10
Earlystabilityincategorizing
odorsaspleasantorunpleasantoccurs,althoughconsiderableinterindividualdifferencesexistbecause
ofexposureandlearningeffects.
• Sensitivity to trigeminal agents in infants and children under 5 years of age has not been clearly
established.
• Puberty is a period of change in sensitivity and hedonic rating for certain odorant qualities in or
resembling body odors (e.g., steroids, musks); thus, boys become increasingly insensitive to
androstenonewithadvancingpuberty,whilegirlsbecomemoresensitivetoit.
11
However,thispubertal
variationinolfactorysensitivityandpreferencesdoesnotseemtoaffectfoododorants.
12
OralChemoreception
The sense of taste continues to mature until at least 8 years of age, and possibly into adolescence.
Measurement oftastedetectionthresholdsindicatethat 8-year-oldfemales,butnot males,havesimilar
detection thresholds to adults, and 6- to 10-year-olds require larger differences between the
concentrationsofatastanttoperceiveadifference.
13
Inaddition,8-year-olds cannotperceivetastesin
mixtures similarlytoadults,andfailtodetectbothtastesinsome two-componentmixtures.Adultsand
children also differ in their taste preferences (e.g., higher levels of sourness are preferred by many
children of this age, while 9- to 15-year-olds prefer higher salt concentrations than adults). These
behavioraldifferencesare accompaniedbyanatomical changesin8-year-olds,withgreaternumbersof
fungiform papillae per unit area occurring on theanterior tonguethan inadults,whichis reflected in
highertastesensitivityinlocalizedareasofthetongue.Nevertheless,8-year-oldsandadultshavesimilar
responsefunctionsforsuprathresholdsweetstimuli.
ImportanceofChemoreceptioninInfancyandChildhood
TheRangeofOrganismicResponsesInfluencedbyChemosensation
Ingeneral,responseselicitedbyodorants,tastants,orirritantsappeardichotomous,withoppositetrends
inarousalandrelatedattention,directionalactions,informationintake(sniffingandlingualactions),and
lastlypreferentialchoicesandingestion.
Arousal
Odorsandtastescanmarkedlyaffect aninfant'sactivationstate.Thus,between2and10 daysof age,
upsetinfantsbecomelessagitatedwhenexposedtothebreastodorofalactatingmother,whichcanalso
counteractthehyperarousalelicitedbyacutepain.Attenuationofagitationisevenmorepronouncedwhen
theodorsoriginatefromtheinfant'sownmother.
9
DirectionalResponses
Head orientation is a much used index of olfactory discrimination in infants. A two-choice test was
developedthatrecordedsupinenewborns’head-turningresponsestotwoodorstimuli,hanging oneach
sideoftheirfaces.
14
Itdemonstratedthat6-day-oldinfantsspentmoretimeturnedtowardtheirmother's
breastodorratherthantoanothermother'sbreastodor.Infantswerelatershowntoorientmoreinsistently
totheodorofmilkfromanunfamiliarwomanratherthantowardanunfamiliarodorofsimilarintensity.
9
Odorscanalsomotivateinfantstocrawltowardadistantodorsource.
StimulusSamplingResponses
Volitional sniffing remains poor in infants below 2 years of age, but their respiratory pattern is
nevertheless affectedby thehedonic nature ofanodor.For example, newborns show accelerated and
decreased respiratory rates, respectively, to vanilla and butyric acid.
15
Maternal odor of very low
intensity canalsoelicitspecificpatternsofrespiration in newborns.
16
Thus, infantstendtoadjust their
nasal airflow depending on whether it carries a pleasant/familiar or unpleasant/unfamiliar odorant.
Maternalodorsalsostimulateoral(chewing)andlingual(licking,sucking)motionsthatfavorstimulation
bytaste.Four-day-oldsdisplayincreasedoralresponsestotheodoroftheirmother'smilkthantheodor
ofanothermother'smilk,orwhentheyperceivetheiramnioticfluidodor.Oralmovementsdo,therefore,
express an individual's motivation to grasp the offered stimulus orally. In addition to the effects of
odorants administered orthonasally, infants detect retronasal odorants during feeds,andmodulatetheir
ingestivedecisionsaccordingly.
17
PhysiologicalInteractions
Odorantsandtastantsaffectvariousresponsescontrolledbytheautonomicnervoussystem(i.e.,heartand
respirationrates,endocrinerelease).
15
Conversely, themetabolicstateinfluencesinfantile responsesto
odors. When 3-day-old, bottle-fed infants are exposed to the odor of their usual formula milk1 hour
beforeand1hourafterafeed,theyrespondmorenegativelytoitduringthepost-prandialthanduringthe
preprandial stage.
18
Thisfluctuationinhedonicresponsivenessofinfantsresembles thephenomenon of
negativealliesthesia*describedinadults,andisanimportantfactorofvariationtoconsiderinthetesting
ofolfactoryortasteabilities.
EverydayAdaptiveFunctionsofOlfactionandTaste
The processes that have been most investigated are perceptual (i.e., detection, discrimination,
recognition), affective (i.e., preferences, mood, attitudes), and cognitive (i.e., attention, learning,
categorization,memory,semantics,lexicalization)innature.Withsomeobviousconceptualorlinguistic
limitations as a function of age, these processes are competent from earliest development to help
individuals to make sense of the world. Infantile chemosensory abilities are fine-tuned by sensory
experience received in the womb or in contact with the mother, and in confrontation with the ever-
expanding variety in food and environment. Infants can sense flavors associated with milk and the
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