Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4693_Библиотеки_им_академика_М_И_Перельмана
.pdf
Improvementismorelikelytooccurinindividualswithhyposmiaratherthananosmia,andinthose
youngerthan74years.
Conclusion
Both postinfectious and post-traumatic olfactory disorders have the potential to cause significant
functionaldisturbancesofbothquantitativeandqualitativeolfaction.Thischapterhighlightssomeofthe
potential therapeutic options, but theauthors acknowledgethat there is still much work to be done in
findingmoreeffectivesolutionsfortheseconditions.
References
1. Brämerson A, Johansson L, Ek L, Nordin S, Bende M. Prevalence of olfactory dysfunction: the Skövde population-based study.
Laryngoscope2004;114(4):733–737
2.LandisBN,KonnerthCG,HummelT.Astudyonthefrequencyofolfactorydysfunction.Laryngoscope2004;114(10):1764–1769
3.MurphyC,SchubertCR,Cruickshanks KJ,KleinBE,KleinR,NondahlDM.Prevalenceofolfactoryimpairmentinolderadults.JAMA
2002;288(18):2307–2312
4.WysockiCJ,GilbertAN.NationalGeographicSmellSurvey.Effectsofageareheterogenous.AnnNYAcadSci1989;561:12–28
5.DammM,Temmel A,Welge-LüssenA,etal.Olfactorydysfunctions.Epidemiologyandtherapy in Germany,AustriaandSwitzerland.
[ArticleinGerman]HNO2004;52(2):112–120
6.Welge-LüssenA,WolfensbergerM.Olfactorydisordersfollowing upperrespiratory tractinfections.AdvOtorhinolaryngol2006;63:125–
132
7.EcclesR.Understandingthesymptomsofthecommoncoldandinfluenza.LancetInfectDis2005;5(11):718–725
8.WangJH,KwonHJ,JangYJ.Detectionofparainfluenza virus 3in turbinateepithelialcells ofpostviralolfactory dysfunction patients.
Laryngoscope2007;117(8):1445–1449
9.SugiuraM,AibaT,MoriJ,NakaiY.Anepidemiologicalstudyofpostviralolfactorydisorder.ActaOtolaryngolSuppl1998;538:191–196
10.KonstantinidisI,HaehnerA,FrasnelliJ,etal.Post-infectiousolfactorydysfunctionexhibitsaseasonalpattern.Rhinology2006;44(2):135–
139
11.SuzukiM,SaitoK,MinWP,etal.Identificationofvirusesinpatientswithpostviralolfactorydysfunction.Laryngoscope2007;117(2):272–
277
12. van Kempen M, Bachert C, VanCauwenberge P. An update onthe pathophysiology of rhinovirus upper respiratory tract infections.
Rhinology1999;37(3):97–103
13. YamagishiM,Fujiwara M,Nakamura H. Olfactory mucosal findings and clinicalcourse in patients witholfactorydisorders following
upperrespiratoryviralinfection.Rhinology1994;32(3):113–118
14. Moran DT, Jafek BW, Eller PM, Rowley JC III. Ultra-structural histopathology of human olfactory dysfunction. Microsc Res Tech
1992;23(2):103–110
15.JafekBW,GordonAS,MoranDT,EllerPM.Congenitalanosmia.EarNoseThroatJ1990;69(5):331–337
16.LooAT,YoungentobSL,KentPF, Schwob JE.Theagingolfactory epithelium:neurogenesis, responsetodamage,andodorant-induced
activity.IntJDevNeurosci1996;14(7-8):881–900
17.Portier F,FaulconP,Lamblin B,BonfilsP.Signs andsymptoms, etiologies andclinical courseofparosmia +in a seriesof 84patients.
[ArticleinFrench]AnnOtolaryngolChirCervicofac2000;117(1):12–18
18. MuellerA,Rodewald A, RedenJ, GerberJ, von Kummer R,HummelT.Reduced olfactory bulb volume in post-traumatic and post-
infectiousolfactorydysfunction.Neuroreport2005;16(5):475–478
19. Rombaux P, MourauxA, BertrandB,Nicolas G,Duprez T, HummelT.Olfactory functionand olfactory bulb volume inpatientswith
postinfectiousolfactoryloss.Laryngoscope2006;116(3):436–439
20. LevyLM, HenkinRI,Lin CS,FinleyA. Rapidimagingofolfactionbyfunctional MRI (fMRI): identification of presence and type of
hyposmia.JComputAssistTomogr1999;23(5):767–775
21. Charles PC,Walters E, Margolis F, JohnstonRE. Mechanismof neuroinvasion of Venezuelan equine encephalitisvirusinthe mouse.
Virology1995;208(2):662–671
22.ReissCS,Plakhov IV,KomatsuT.Viralreplicationin olfactory receptor neuronsandentryintotheolfactorybulbandbrain.AnnNY
AcadSci1998;855:751–761
23.SumnerD.Post-traumaticanosmia.Brain1964;87:107–120
24.DotyRL,YousemDM,PhamLT, KreshakAA,Geckle R,LeeWW.Olfactorydysfunctioninpatientswithheadtrauma.ArchNeurol
1997;54(9):1131–1140
25.TemmelAF,Quint C,Schickinger-Fischer B,KlimekL,Stoller E,HummelT. Characteristicsofolfactorydisorders in relationtomajor
causesofolfactoryloss.ArchOtolaryngolHeadNeckSurg2002;128(6):635–641
26.MurphyC,SchubertCR,CruickshanksKJ,KleinBE,KleinR,NondahlDM.Prevalenceofolfactoryimpairmentinolderadults.JAMA
2002;288(18):2307–2312
27.ZushoH.Posttraumaticanosmia.ArchOtolaryngol1982;108(2):90–92
28.SymondsC.Discussionondifferentialdiagnosisandtreatmentofpost-contusionalstates.ProcRSocMed1942;35(9):601–614
29.SumnerD.Disturbanceofthesense ofsmellandtasteafterheadinjuries.In:VinkenP,Bruyn G,eds.HandbookofClinicalNeurology.
Amsterdam:NorthHollandPublishingCo;1975:1–25.
30.JafekBW,EllerPM,EssesBA,MoranDT.Post-traumaticanosmia.Ultrastructuralcorrelates.ArchNeurol1989;46(3):300–304
31.Costanzo RM, TakakiM. Posttraumatic olfactoryloss. In: HummelT, Welge-LussenA,eds. TasteandSmell:AnUpdate.NewYork:
Karger;2006:99–107.
32.CostanzoRM,ZaslerN.Headtrauma.In:GetchellT,DotyRL,BartoshukL,SnowJ,eds.SmellandTasteinHealthandDisease.New
York:RavenPress;1991:711–730.
33.LevinHS,HighWM,EisenbergHM.Impairmentofolfactoryrecognitionafterclosedheadinjury.Brain1985;108(Pt3):579–591
34. Bonfils P, Avan P, Faulcon P, Malinvaud D. Distorted odorant perception: analysis of a series of 56 patients with parosmia. Arch
OtolaryngolHeadNeckSurg2005;131(2):107–112
35.HummelT,LötschJ.Prognosticfactorsofolfactorydysfunction.ArchOtolaryngolHeadNeckSurg2010;136(4):347–351
36.YousemDM,GeckleRJ,BilkerWB,McKeownDA,Doty RL.Posttraumatic olfactory dysfunction:MRandclinicalevaluation.AJNR
AmJNeuroradiol1996;17(6):1171–1179
37.SchechterPJ,HenkinRI.Abnormalitiesoftasteandsmellafterheadtrauma.JNeurolNeurosurgPsychiatry1974;37(7):802–810
38.MottAE,LeopoldDA.Disordersintasteandsmell.MedClinNorthAm1991;75(6):1321–1353
39.DeemsDA,DotyRL,SettleRG,etal.Smellandtastedisorders,astudyof750patientsfromtheUniversityofPennsylvaniaSmelland
TasteCenter.ArchOtolaryngolHeadNeckSurg1991;117(5):519–528
40. Costanzo RM, Heywood P, Ward D, Young H. Neurosurgical application of clinical olfactory assessment. Ann N Y Acad Sci
1987;510:242–244
41. DuncanHJ, SeidenAM. Long-term follow-up of olfactorylosssecondary to head trauma andupper respiratory tract infection. Arch
OtolaryngolHeadNeckSurg1995;121(10):1183–1187
42.RombauxP,MourauxA,BertrandB,NicolasG,DuprezT,HummelT.Retronasalandorthonasalolfactoryfunctioninrelationtoolfactory
bulbvolumeinpatientswithposttraumaticlossofsmell.Laryngoscope2006;116(6):901–905
43.DinardoL,CostanzoR.Posttraumaticolfactoryloss.In:SeidenAM,ed.TasteandSmellDisorders.NewYork:Thieme;1997:79–87.
44.SmeetsMA,VeldhuizenMG,GalleS,etal.Senseofsmelldisorderandhealth-relatedqualityoflife.RehabilPsychol2009;54(4):404–412
45.MiwaT,FurukawaM,TsukataniT,CostanzoRM,DiNardoLJ,ReiterER.Impactofolfactoryimpairmentonqualityoflifeanddisability.
ArchOtolaryngolHeadNeckSurg2001;127(5):497–503
46. Landis BN,Scheibe M, Weber C, et al. Chemosensory interaction: acquired olfactoryimpairmentis associated with decreased taste
function.JNeurol2010;257(8):1303–1308
47. Hummel T, SekingerB, Wolf SR,PauliE,KobalG. ‘Sniffin’sticks’: olfactoryperformance assessedbythecombined testing ofodor
identification,odordiscriminationandolfactorythreshold.ChemSenses1997;22(1):39–52
48. Lötsch J, Reichmann H, Hummel T. Different odor tests contribute differently to the evaluation of olfactory loss. Chem Senses
2008;33(1):17–21
49.PhilpottCM,RimalD,TassoneP,PrinsleyPR,PremachandraDJ.Astudyofolfactorytestinginpatientswithrhinologicalpathologyinthe
ENTclinic.Rhinology2008;46(1):34–39
50. Mrowinski D, Eichholz S, Scholz G. Objective test of smell with cognitive potentials. [Article in German] Laryngorhinootologie
2002;81(9):624–628
51. Rombaux P, Bertrand B, Keller T, Mouraux A. Clinical significance of olfactory event-related potentials related to orthonasal and
retronasalolfactorytesting.Laryngoscope2007;117(6):1096–1101
52.RombauxP,MourauxA,BertrandB,GueritJM,HummelT.Assessmentofolfactoryandtrigeminalfunctionusingchemosensoryevent-
relatedpotentials.NeurophysiolClin2006;36(2):53–62
53. Rombaux P, Mouraux A,Collet S, EloyP, Bertrand B. Usefulness and feasibilityof psychophysical andelectrophysiologicalolfactory
testingintherhinologyclinic.Rhinology2009;47(1):28–35
54. Rombaux P, Mouraux A, Keller T, Hummel T. Trigeminal event-related potentials in patients with olfactory dysfunction. Rhinology
2008;46(3):170–174
55.IannilliE,GerberJ,FrasnelliJ,HummelT.Intranasaltrigeminalfunctioninsubjectswithandwithoutanintactsenseofsmell.BrainRes
2007;1139:235–244
56.RombauxP,HuartC,ColletS,EloyP,NegoiasS,HummelT.Presenceofolfactoryevent-relatedpotentialspredictsrecoveryinpatients
witholfactorylossfollowingupperrespiratorytractinfection.Laryngoscope2010;120(10):2115–2118
57. Blomqvist EH, Lundblad L, Bergstedt H, Stjärne P. Placebo-controlled, randomized, double-blind study evaluating the efficacy of
fluticasonepropionatenasalsprayforthetreatmentofpatientswithhyposmia/anosmia.ActaOtolaryngol2003;123(7):862–868
58. Seo BS, Lee HJ,Mo JH,Lee CH, Rhee CS,Kim JW. Treatmentof postviral olfactory loss with glucocorticoids, Ginkgo biloba,and
mometasonenasalspray.ArchOtolaryngolHeadNeckSurg2009;135(10):1000–1004
59.SeidenAM,DuncanHJ.Thediagnosisofaconductiveolfactoryloss.Laryngoscope2001;111(1):9–14
60.HeilmannS,HuettenbrinkKB,HummelT.Local andsystemicadministrationofcorticosteroidsin the treatmentofolfactory loss.AmJ
Rhinol2004;18(1):29–33
61.FukazawaK.Alocalsteroidinjection method forolfactorylossduetoupperrespiratoryinfection.ChemSenses2005;30(Suppl 1):i212–
i213
62. HenkinRI, Schecter PJ,FriedewaldWT, Demets DL,Raff M. Adoubleblind study ofthe effects ofzinc sulfate on taste andsmell
dysfunction.AmJMedSci1976;272(3):285–299
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
63.AlexanderTH,DavidsonTM.Intranasalzincandanosmia:thezinc-inducedanosmiasyndrome.Laryngoscope2006;116(2):217–220
64. Viswaprakash N, Dennis JC, Globa L, et al. Enhancement of odorant-induced responses in olfactory receptor neurons by zinc
nanoparticles.ChemSenses2009;34(7):547–557
65.StennerM,VentJ,HüttenbrinkKB,HummelT,DammM.Topicaltherapyinanosmia:relevanceofsteroid-responsiveness.Laryngoscope
2008;118(9):1681–1686
66.HummelT,HeilmannS,HüttenbriukKB.Lipoicacidinthetreatmentofsmelldysfunctionfollowingviralinfectionoftheupperrespiratory
tract.Laryngoscope2002;112(11):2076–2080
67.GudziolV,HummelT.Effectsofpentoxifyllineonolfactorysensitivity:apostmarketingsurveillancestudy.ArchOtolaryngolHeadNeck
Surg2009;135(3):291–295
68.HenkinRI,VelicuI,SchmidtL.Anopen-labelcontrolledtrialoftheophyllinefortreatmentofpatientswithhyposmia.AmJMedSci2009;
337(6):396–406
69. Gudziol V, Pietsch J, Witt M, Hummel T. Theophylline induces changes in the electro-olfactogram of the mouse. Eur Arch
Otorhinolaryngol2010;267(2):239–243
70. Panagiotopoulos G, Naxakis S, Papavasiliou A, Filipakis K, Papatheodorou G, Goumas P. Decreasing nasal mucus Ca++ improves
hyposmia.Rhinology2005;43(2):130–134
71.ZufallF,Leinders-ZufallT.Thecellularandmolecularbasisofodoradaptation.ChemSenses2000;25(4):473–481
72.QuintC,TemmelAF,HummelT,EhrenbergerK.Thequinoxalinederivativecaroverineinthetreatmentofsensorineuralsmelldisorders:a
proof-of-conceptstudy.ActaOtolaryngol2002;122(8):877–881
73.VentJ,WangDW,DammM.EffectsoftraditionalChineseacupunctureinpost-viralolfactorydysfunction.OtolaryngolHeadNeckSurg
2010;142(4):505–509
74.HummelT,StuckBA.Treatmentofolfactorydisorders.[ArticleinGerman]HNO2010;58(7):656–660
75.HummelT,RissomK,RedenJ,HähnerA,WeidenbecherM,HüttenbrinkKB.Effectsofolfactorytraininginpatientswitholfactoryloss.
Laryngo-scope2009;119(3):496–499
76. Jiang RS, Wu SH, Liang KL, Shiao JY, Hsin CH, Su MC. Steroid treatment of posttraumatic anosmia. Eur Arch Otorhinolaryngol
2010;267(10):1563–1567
77.IkedaK,SakuradaT,TakasakaT,OkitsuT,YoshidaS.Anosmiafollowingheadtrauma:preliminarystudyofsteroidtreatment.TohokuJ
ExpMed1995;177(4):343–351
78. Müller A, Landis BN, Platzbecker U, Holthoff V, Frasnelli J, Hummel T. Severe chemotherapy-induced parosmia. Am J Rhinol
2006;20(4):485–486
79.FikentscherR,RasinskiC.Parosmias—definitionandclinicalpicture.[ArticleinGerman]LaryngolRhinolOtol(Stuttg.)1986;65(12):663–
665
80.ZilstorffK,HerbildO.Parosmia.ActaOtolaryngolSuppl1979;360:40–41
81.SarangiP,AzizTZ.Post-traumaticparosmiatreatedbyolfactorynervesection.BrJNeurosurg1990;4(4):358
82. Devere R, Calvert M. Food preparation. In: DeVere R, Calvert M, eds. Navigating Smell and Taste Disorders. New York: Demos
Health/TheAmericanAcademyofNeurologyPublishers;2011:81–149.
83.SeidenAM.Postviralolfactoryloss.OtolaryngolClinNorthAm2004;37(6):1159–1166
84.RedenJ,MuellerA,MuellerC,etal.Recoveryofolfactoryfunctionfollowing closedheadinjuryorinfectionsoftheupperrespiratory
tract.ArchOtolaryngolHeadNeckSurg2006;132(3):265–269
85. Hummel T. Perspectives in olfactoryloss followingviral infections ofthe upperrespiratorytract. ArchOtolaryngol Head Neck Surg
2000;126(6):802–803
86. Costanzo RM,Becker D. Smellandtaste disorders in headinjuryandneurosurgery patients.In:MeiselmanH,RivlinR,eds. Clinical
MeasurementofSmellandTaste.NewYork:MacmillanPublishingCo;1986:565–578
87. LondonB,NabetB,Fisher AR,White B,Sammel MD,DotyRL. Predictors ofprognosisinpatients witholfactory disturbance.Ann
Neurol2008;63(2):159–166
88.BraakH,BraakE,YilmazerD,deVosRA,JansenEN,BohlJ.PatternofbraindestructioninParkinson'sandAlzheimer'sdiseases.J
NeuralTransm1996;103(4):455–490
9MiscellaneousCausesofOlfactoryDysfunction
PhilippeRombaux
Introduction
Olfactoryandgustatorydisorderscanbeduetoawidevarietyofcausesandcanprofoundlyinfluencea
patient'squalityoflife.Thischaptercoverstoxicants,industrialagents,andtherapeuticagentsthatcause
olfactorydysfunction, idiopathicolfactoryloss,congenitalanosmia,endocrinediseasesassociatedwith
olfactory dysfunction, postsurgical olfactory dysfunction, and tumor-related olfactory disorders.
Miscellaneouscausesofolfactorydysfunction,asdefinedinthischapter,accountforless than10% of
cases.
1,2
Adetailedhistoryandexaminationisnecessarytodetermineanylifestylefactorsortoxicantor
drugconsumptionthatmayberelatedtoolfactorydysfunction.Counselingofthepatientismandatoryto
reduce toxicant exposure; change any implicated medications; give anaccurate prognosis; or treat, as
soonaspossible,atumorforwhicholfactorydysfunctionisthesoleandprimarymanifestation.
Diagnosis of olfactory dysfunction is often difficult, especially for toxicant and therapeutic agent
exposure. The patient'shistory,including the delaybetween exposure and clinical manifestation, is the
keystoneofdiagnosis.Moreover,theclinicianmustconsiderthatcombinationsofcausalfactorsmaybe
present.Thisisespeciallytrueforapatientinwhomatherapeuticagentissuspectedtobethecausative
agent.It should also be stressed that inthis categoryofmiscellaneous causes ofolfactorydysfunction,
olfactoryfunctionneedstobeobjectivelyevaluated(seeChapter6)becauseclinicalfindingsmayleadto
legalaction,changesinprescribed medications,changesinprofessionalhabit,ordecisionsconcerning
thesurgicalmanagementofthepatient.
ToxicantsandIndustrialAgents
Acute or chronic exposure to toxicants and industrial agents may have deleterious effects on
olfactoryfunction.
Althoughmanyreports inthe literaturesuggestthat awidevariety oftoxicantsmayhavea deleterious
effectonthe chemosensory function in general and on theolfactioninparticular, specific information
regardingthepathophysiology,thetime–doseeffect,andthepotentialofrecoveryispoor.Theolfactory
neuroepitheliumishighlysensitivetothechemicalormicrobiologicalenvironmentbecauseitactsasan
interface between the outside world inthe upper airwaysandthe inside world inthe central nervous
system.Manydefensemechanismsexistattheolfactoryneuroepithelialleveltoinducedetoxificationand
rapidregenerationafterchronicandrepetitiveoracuteandbriefexposuretoirritantsandtoxins.
Exposuretotoxicvolatilesatlevelssufficienttoimpairolfactionusuallyoccursbyaccident.Thelist
of chemicals that is theoretically toxic to the olfactory system is extensive and reported cases are
numerouseventhoughtoxicantexposureisthoughttoberesponsibleforlessthan2%ofcasesofolfactory
dysfunction(Table 9.1).
1,2
The degreeofexposure,concentration,andintrinsictoxicity oftheagent,as
wellaslocalconditionsattheneuroepitheliallevel,maygreatlyinfluencethesignificanceofthedamage
anditsclinicalmanifestation.
3,4
Chronicexposuretobenzene(anindustrialsolventusedintheproductionofdrugs,plastic,synthetic
rubbers,anddyes),butylacetate(asolventusedintheproductionoflacquersandsyntheticfruitflavoring
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
infoods),formaldehyde(aprecursorofmanychemicalproductsusedforresinandpolymerformation),
andpaintsolventcancausevaryingdegreesofolfactorydysfunction.Otherscompoundssuchasindustrial
dusts(cotton, silicone,cement,lead, coal, chromium,andnickel) andchemicals such as sulfuric acid,
trichloroethyleneandhydrogenhavebeenalsoassociatedwitholfactorydysfunction.
Chronic exposure to cadmium has been well reported in a large cohort of workers who handle
electrical batteries containingcadmium and can lead to olfactory disorder. Chronic exposureto gases
(carbon disulfide, carbonmonoxide, sulfur dioxide) or tosolvents (acetone,acetophenone, turpentine)
canalsoinducesmelldisorders.
5–12
Table 9.1Majortoxicantsandindustrialagentswiththepotentialtoinduceolfactorydisorder
Me talliccompounds
•Cadmium
•Dichromates
•Nickel
•Zinc
•Alum
•Arsenic
•Silvernitrate
•Copperarsenite
Organiccompounds
•Acetaldehyde
•Acetophenone
•Benzene
•Butylacetate
•Chlorometanes
•Ethylacetate
•Trichloroethylene
•Aceticacid
•Formaldehyde
•Trichloroethane
•Chloroform
Me tallurgicalprocess e s
•Chromium
•Nickelplatingorrefining
•Leadsmelting
•Magnetproduction
•Steelproduction
•Zinc,copper,manganese,andtinfumes
•Arsenic
Dusts
•Cement
•Chemicals
•Hardwoods
•Cotton
•Cyanides
•Wax
•Potash
•Silicondioxide
Nonmetallicinorganiccompounds
•Ammonia
•Carbondisulfide
•Carbonmonoxide
•Chlorine
•Fluorides
•Hydrogen
•Nitricacid
•Seleniumdioxide
Manufacturingproce s s e s
•Acids
•Asphalt
•Cuttingoils
•Fragrances
•Leadpaints
•Rubbervulcanization
•Spices
•Tobacco
•Tanning
Pathophysiology focuses mainly on histological damage (replacement of the neuroepithelium by
respiratory epithelium), decreased function in the Bowman gland, and direct toxicity to the olfactory
receptorcell(bythemoleculeitself,orafterenzymaticactivationtotheproximatetoxicant).Thehealthof
thehostisimportantandmayinfluencetheoutcomeofexposureoftheolfactoryepitheliumtotoxins.An
upperrespiratoryinfection,forexample,mayinducesevereolfactorydysfunctionifpresentatthesame
timeasatoxicexposurethatwouldnotinflictseveredamageifpresentalone.
Exposure of the olfactory neuroepithelium to a toxic agent stimulates defense mechanisms such as
secretion ofenzymes or proteins that protect the integrity of the neuroepithelium, or activation of the
trigeminal reflex, whichhasa directrole in eliminating and reducing the risk of olfactorydamage by
inducing glandular secretions, sneezing, and watery discharge from the nasal mucosa and the eye.
Protectionoftheolfactoryneuroepitheliumisachievedthroughstructuralrecoveryofolfactorytissue,an
increase in metabolizing enzymes that facilitate olfactory receptor neuron (ORN) recovery, and an
increase in metal chelating agents. Localization of membranetransporters and efflux mechanisms also
protecttheintegrityoftheneuroepithelium.
Epidemiological studies in workplaces known to be causative for olfactory dysfunction should be
performed,alongwithanimalstudiestotestcompoundsforpotentialolfactorytoxicity.Intheabsenceof
such evidence, the precautionary principle should be applied to workers in whom toxicant-related
olfactorydysfunctionissuspected.
13
TherapeuticAgents
Therapeuticagentsaffectolfactionqualitativelymorethanquantitatively,andaffecttastemoreoften
thanolfaction.Drug-inducedchemosensorydysfunctionisoftenreversible.
Drug-induced olfactory dysfunction is often reversible and related to the duration of intake. In drug-
relatedchemosensorydysfunction, tasteismuch more affected thansmell
14,15
andqualitativedisorders
are more common than quantitative disorders.
16
Manydifferent therapeutic agents may be responsible
(Table9.2), anddocumentationofthe time course between medicationintake andthe development of
clinicalsymptomsisessential.Inclinicalpractice,itissometimesdifficulttodifferentiatebetweendrug-
induced chemosensory dysfunction and other conditions such as postinfectious olfactory loss. A
comprehensivehistoryisessentialtoaidthediagnosis.Theconditionforwhichthemedicationhasbeen
prescribedmustbeconsideredasapossiblecause,aswellasendocrinedisorders,chronicrenalfailure,
chronic hepatic dysfunction, severe infection, or diabetes. Therapeutic agents can cause olfactory
dysfunctionattheperipheryandatreceptorlevel.Typically,theolfactorydysfunctionisreversibleonce
themedicaltreatmentisdiscontinued(ifpossible).Recoverydependsonmanyfactors,suchasage,sex,
environmentalstatus(e.g.,tobaccointake,exposuretoothertoxicants),andsinonasalstatus(e.g.,chronic
rhinosinusitis,allergy).Therapeuticagentsleading to a negative effectonolfactory perceptionmay be
distinguishedasa class effect(e.g.,quinolone antibiotics) or onanindividual basis with single cases
reported.Informingthepharmaceuticalcompanyofthepotentialassociationbetweenamedicationanda
sideeffectonolfactoryfunctionisalsomandatory.
IdiopathicOlfactoryDisorder
Ifnocauseisfoundforthediagnosis,apatientisconsideredtohaveidiopathicolfactoryloss.
Apreclinicalstateofneurodegenerativediseaseshouldnotbeforgotten.
Despiteextensivework-upwithpsychophysicaltesting(uni-orbilateral),electrophysiologicalrecording,
structuralmagnetic resonanceimaging (MRI),patient history,andendonasalendoscopic examinationof
theolfactorycleft,noexplanationforolfactorysymptomsisfoundinasignificantnumberofpatients.This
isclassifiedasidiopathicolfactoryloss.
Table 9.2Therapeuticagentswithwell-demonstratednegativeeffectsonolfactoryfunction
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Antibiotics
•Aminoglycoside:rare
•Penicillin:rare
•Quinolone<1%
•Macrolides:rare(taste>smell)
•Tetracycline:rare
Cytostatics
•Cytarabine
•Doxorubicin
•Methotrexate
•Vincristine
Topicalintranasaldrugs
•Steroids:<1%
•Decongestants:1–3%
•Cocaine:5–10%
Antidepressants
•Amitriptyline
•Clomipramine
•Desipramine
•Doxepin
•Imipramine
•Nortriptyline
Cardiovasculardrugs
•Calciumchannelblockers
•Antiarrhythmics
•Lipidloweringagents
Antipsychotics
•Clozapine
•Trifluoperazine
Antithyroidagents
•Carbimazole
•Thiamazole
Muscle relaxants
•Baclofen
•Dantrolene
Antiparkinsoniandrugs
•Levodopa
Inalargecohortofpatients,olfactoryloss wasclassedas idiopathicinupto18%ofcases.
17
This
mustbeadiagnosisofexclusionmadeaftercompleteandextensiveevaluationoftheconfirmedolfactory
dysfunction.Inpatientswithidiopathicolfactoryloss,theolfactorybulb(OB)issmallerthanincontrols,
which seems to suggest an involvement of the OB in its pathophysiology.
18
An unsuccessful oral
corticosteroidtrialshouldalsoserveasadiagnosticcriterion.
19
Caremustalsobetakentorememberthat
olfactory dysfunction may be a preclinical sign of neurodegenerative disorder (e.g., Alzheimer or
Parkinson diseases). It is generallyassumed that patients with idiopathicolfactory lossneedtobere-
examinedafterseveralmonths,withendonasalendoscopicexamination,psychophysicaltesting,andeven
structuralimaging,toruleoutanydevelopingdiseasesuchasneurodegenerativediseases.
EndocrineDisorders
Variousendocrinedisordersmayaffectchemosensoryfunction.
Manypatients with endocrine disorders complain of olfactory dysfunction,but the pathophysiological
mechanism is poorly understood.
20–22
This chemosensory dysfunction is often accompanied by other
sensory(hearing,vision)orproprioceptivedisorders.Ingeneral,endocrinedisorderisassociatedwitha
decrease in olfactory function, although adrenocortical insufficiency (Addison disease) may lead to
increasedsensitivitytochemosensorystimuli.Turnersyndrome(chromatin-negativegonadaldysgenesis),
Cushing syndrome (excessive secretion of adrenal corticosteroids), hypothyroidism, and
pseudohypoparathyroidism are also medical conditions where olfactory function is impaired. The
mechanismseemstoaffecttheneuroepitheliallevel,whereendocrinedysfunctionmayaltertransduction
andsensorineuralfunction.Itisnotcleariftreatmentoftheendocrinedisorderhasapositiveimpacton
olfactoryrecovery,oriftheprognosisofbothconditionsislinked.
CongenitalOlfactoryDisorder
Absence or hypoplasia of the OBor abnormal depthofthe olfactorysulcus may be relatedto a
congenitalolfactorydisorder.
Olfactorydysfunction sincebirth orchildhoodmaybeclassedas syndromic(genetic andcomplete)or
nonsyndromic(isolatedandincomplete).Incompleteandgeneticdysfunction,theolfactorydysfunctionis
partofthegeneraldeficiencyinthemorphotype.Inthisfield,Kalmannsyndrome,Klinefeltersyndrome,
or CHARGEsyndrome are welldescribed.
23–30
Kalmann syndromeencompasses ahypogonadotrophic
hypogonadismassociatedwithsevereolfactorydysfunction.Kalmannsyndromeisanautosomaldominant
condition with incomplete expressivity and with a morpho type including cryptorchidism, midline
craniofacial abnormalities, toothagenesis, deafness,andrenal abnormalities. Its incidenceis higher in
men (1 in 10,000) than in women (1 in 50,000). This syndrome occurs far less often than isolated
olfactorydysfunction,andthetermisolatedanosmia(IA)hasbeenintroducedtodescribepatientswithan
absenceofanyolfactorystructureonMRIwithnootherendocrine,sensory,orrenaldisorders.
Congenitalolfactorydysfunctionischaracterizedbytheabsenceofanyolfactoryperceptionsincebirth
orchildhood,andistypicallyrelatedtoaplasiaorabsenceoftheOBasrevealedbyMRI.Aplasiaofthe
OBmaybebilateralandsymmetrical,morepronouncedononeside,orunilateral.AbsenceofanOBis
associatedwithdecreaseddepth—orevencompleteabsence—oftheolfactorysulcus,andwithabsence
ofanyolfactorytract.
28–30
Inbothsyndromicandisolatedcongenitalanosmia,threedifferentvariations
havebeenreported:(1) hypoplasia oftheOBwith olfactorytractspresent; (2)aplasiaoftheOBwith
olfactorytractspresent;and(3)aplasiaofboththeOBandolfactorytracts(Fig.9.1).
Time of diagnosis in childrenwith nonsyndromic dysfunction is oftenaround 8 to 14 years, when
olfactorydysfunctionisfirstreportedbythepatient.AbsenceoftheOBonMRIexaminationissometimes
difficulttoascertainbecauseoftechnicaldifficulties.Decreasedolfactorydepth,calculatedintheplane
posteriortotheeyeball,isthereforeanimportantfeaturethatconfirmsthediagnosisofcongenitalabsence
oftheOB.Inalargecohortofpatients,theminimaldepthofolfactorysulcusassociatedwithpresenceof
theOBandolfactorytract,withaspecificityof1,was8mm.Thismeansthat,belowthisvalue,thereisa
highprobabilitythattheOBandolfactorytractsareabsent.
31
There is notreatment,medical or surgical, thatimproves olfactory functionin congenitallyaffected
patients.Counselinganddiscussionofcopingstrategiesseemtobethebestwaytohelpthesepatients.
TumoralCausesofOlfactoryDisorder
(SeeTable9.3)
Some head and neck tumors may present as an olfactory disorder or when exploring olfactory
function,especiallywithunilateraldysfunctionorwhen a significant discrepancy between thetwo
nostrilsisobserved.
Thediagnosisofatumoral(benignormalignant)lesionwitholfactorydysfunctionasitsprimaryandsole
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
manifestationisveryrare.
Extracranial (intranasal) tumoral lesions usually cause other clinical symptoms, such as nasal
obstruction, and expresses unilateral symptoms: inverted papilloma, Schwannoma, angiofibroma,
adenocarcinoma,esthesioneuroblastoma,andepidermoidcarcinoma.Pathologyoftheolfactorycleftsuch
as hamartoma adenomatoid or adenocarcinoma leads to homolateral olfactorydysfunction if explored
withunilateralolfactorytesting(Figs.9.2,9.3and9.4).Dependingonthehistologicaldiagnosis,theage
ofthepatient,theextentofthesurgicalprocedure,ortheproposedtreatment,theevolutionoftheolfactory
dysfunctionmaybevariable.
Intracranial tumoral lesionsmay also impede olfactoryfunction by compromising OB andolfactory
tract function. Olfactory groove meningiomas, suprasellar ridge meningiomas, and pituitary growths
extendingabovethediaphragmofthesellaturcicamaydevelopfromtheduraofthecribriformplateand
surroundingtissue,andcauseolfactorydysfunction(Fig.9.5). Frontalortemporallobe tumorsor non-
neoplasticspace-fillinglesions(e.g.,aneurysm,hydrocephaluslocatedintheareaofthethirdventricle)
havealsobeenreportedwitholfactorydysfunction.
Althougholfactoryevaluation isnot theprimary diagnostic toolintheclinicalwork-up ofheadand
necktumors, a unilateral disorder or an extensive side difference inolfactoryfunction should arouse
suspicionandleadtofurtherevaluationusingimagingtechniques.
32,33
Fig. 9.1a,b Coronalmagnetic resonance image(T2sequence) ofthe anterior cranial base revealingnoolfactory bulbstructure (a,white
arrows)andnoolfactorysulcus(b,whitearrows).
Table 9.3Tumorallesionsassociatedwitholfactorydysfunction
Tumor Feature s
Extracranial
Benign
•Angiofibroma •Pterygopalatinefossa,male,adolescent
•Invertedpapilloma •Ethmoidormaxillary,unilateral,male
•Schwannoma •Veryrare
•Adenomatoidhamartoma •Olfactorycleft,oldpeople
•Others(osteoma,etc.) •Veryrare
Malignant
•Adenocarcinoma •Olfactorycleft,woodworker
•Esthesioneuroblastoma •Fromtheolfactoryneuroepithelium
•Epidermoidcarcinoma •Tobaccoandalcoholconsumption
•Others(carcinomaadenoidcystic,etc.)
Intracranial
Benign
•Meningioma •Fromtheolfactorygroove
•Pituitarytumors •Extendingoutsidethesellaturcica
Malignant
•Frontalortemporaltumors •Olfactorydysfunctionrareasasolemanifestation
Space-fillinglesions
•Non-neoplastic(aneurysm,hydrocephalus)
Fig.9.2Coronalmagneticresonanceimage(T1sequence)oftheparanasalsinusesshowingatumoralmassintheleftolfactorycleft(white
arrow):Schwannoma.
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Соседние файлы в папке Библиотека им академика М.И. Перельмана