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IndianJDermatol.2010JanMar55(1):814.

PMCID:PMC2856357

doi:10.4103/00195154.60343

BOTULINUMTOXIN
PKNigamandAnjanaNigam1
FromtheDepartmentofDermatologyandSTD,Pt.J.N.M.MedicalCollegeandAssoc.Dr.B.R.A.M.Hospital,Raipur492001,India.
1
FromtheDepartmentofSurgery,Pt.J.N.M.MedicalCollegeandAssoc.Dr.B.R.A.M.Hospital,Raipur492001,India.
Addressforcorrespondence:Dr.PKNigam,Prof.andHead,DepartmentofDermatologyandSTD,Pt.J.N.M.MedicalCollegeandAssoc.Dr.
B.R.A.M.Hospital,Raipur492001,(C.G.),India.Email:drpknigam@yahoo.co.in
Received2007DecAccepted2008May.
CopyrightIndianJournalofDermatology
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.

ThisarticlehasbeencitedbyotherarticlesinPMC.

Abstract

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Botulinumtoxin,oneofthemostpoisonousbiologicalsubstancesknown,isaneurotoxinproducedbythe
bacteriumClostridiumbotulinum.C.botulinumelaborateseightantigenicallydistinguishableexotoxins(A,B,C1,
C2,D,E,FandG).Allserotypesinterferewithneuraltransmissionbyblockingthereleaseofacetylcholine,the
principalneurotransmitterattheneuromuscularjunction,causingmuscleparalysis.Theweaknessinducedby
injectionwithbotulinumtoxinAusuallylastsaboutthreemonths.Botulinumtoxinsnowplayaverysignificant
roleinthemanagementofawidevarietyofmedicalconditions,especiallystrabismusandfocaldystonias,
hemifacialspasm,andvariousspasticmovementdisorders,headaches,hypersalivation,hyperhidrosis,andsome
chronicconditionsthatrespondonlypartiallytomedicaltreatment.Thelistofpossiblenewindicationsisrapidly
expanding.Thecosmetologicalapplicationsincludecorrectionoflines,creasesandwrinklingallovertheface,
chin,neck,andchesttodermatologicalapplicationssuchashyperhidrosis.Injectionswithbotulinumtoxinare
generallywelltoleratedandsideeffectsarefew.Apreciseknowledgeandunderstandingofthefunctionalanatomy
ofthemimeticmusclesisabsolutelynecessarytocorrectlyusebotulinumtoxinsinclinicalpractice.
Keywords:Botulinumtoxin,Clostridiumbotulinum,clinicalapplications,adverseeffects

Introduction

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Botulinumtoxin,alsocalledmiraclepoison,isoneofthemostpoisonousbiologicalsubstancesknown.[1]Itisa
neurotoxinproducedbythebacteriumClostridiumbotulinum,ananaerobic,grampositive,sporeformingrod
commonlyfoundonplants,insoil,waterandtheintestinaltractsofanimals.Scott[2]firstdemonstratedthe
effectivenessofbotulinumtoxintypeAforthemanagementofstrabismusinhumans.Subsequently,botulinum
toxinwasapprovedforthetreatmentofnumerousdisordersofspasticiy[1]andahostofotherconditions.Currently
itisusedinalmosteverysubspecialtyofmedicine.In2002,theFDAapprovedtheuseofBotox(Botulinum
toxinA)forthecosmeticpurposeoftemporarilyreducingglabellerforeheadfrownlines.
Biochemicalaspects

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C.botulinumelaborateseightantigenicallydistinguishableexotoxins(A,B,C1,C2,D,E,FandG).TypeAisthe
mostpotenttoxin,followedbytypesBandFtoxin.TypesA,BandEarecommonlyassociatedwithsystemic
botulisminhumans.[3]Allbotulinumneurotoxinsareproducedasrelativelyinactive,singlepolypeptidechains
withamolecularmassofabout150kDawithahighdegreeofaminoacidsequencehomologyamongthetoxin
types.Thepolypeptidechainconsistsofaheavy(H)chainandalight(L)chainofroughly100and50kDa
respectively,linkedbyadisulfidebond.[4]Thebotulinumtoxinneurotoxincomplexisalsoassociatedwithvarious
othernontoxicproteins,whichmayalsohavehemagglutinatingproperties.[5]
Howbotulinumtoxinworks
Alltheserotypesinterferewithneuraltransmissionbyblockingthereleaseofacetylcholine,whichistheprincipal
neurotransmitterattheneuromuscularjunction.Intramuscularadministrationofbotulinumtoxinactsatthe
neuromuscularjunctiontocausemuscleparalysisbyinhibitingthereleaseofacetylcholinefrompresynapticmotor
neurons.[6]Botulinumtoxinsactatfourdifferentsitesinthebody:Theneuromuscularjunction,autonomicganglia,
postganglionicparasympatheticnerveendingsandpostganglionicsympatheticnerveendingsthatrelease
acetylcholine.[5]Theheavy(H)chainofthetoxinbindsselectivelyandirreversiblytohighaffinityreceptorsatthe
presynapticsurfaceofcholinergicneurones,andthetoxinreceptorcomplexistakenupintothecellbyendocytosis.
Thedisulphidebondbetweenthetwochainsiscleavedandthetoxinescapesintothecytoplasm.Thelight(L)
chaininteractwithdifferentproteins(synaptosomalassociatedprotein(SNAP)25,vesicleassociatedmembrane
proteinandsyntaxin)inthenerveterminalstopreventfusionofacetylcholinevesicleswiththecellmembrane.[5,7]
Thepeakoftheparalyticeffectoccursfourtosevendaysafterinjection.Dosesofallcommerciallyavailable
botulinumtoxinsareexpressedintermsofunitsofbiologicactivity.Oneunitofbotulinumtoxincorrespondstothe
calculatedmedianintraperitoneallethaldose(LD50)infemaleSwissWebstermice.[8]Theaffectednerveterminals
donotdegenerate,buttheblockageofneurotransmitterreleaseisirreversible.Functioncanberecoveredbythe
sproutingofnerveterminalsandformationofnewsynapticcontactsthisusuallytakestwotothreemonths.
Botulinumtoxininducesweaknessofstriatedmusclesbyinhibitingtransmissionofalphamotorneuronesatthe
neuromuscularjunction.Thishasledtoitsuseinconditionswithmuscularoveractivity,suchasdystonia.
Transmissionisalsoinhibitedatgammaneuronesinmusclespindles,whichmayalterreflexoveractivity.[9]The
toxinalsoinhibitsreleaseofacetylcholineinallparasympatheticandcholinergicpostganglionicsympathetic
neurons.Thishasgeneratedinterestinitsuseasatreatmentforoveractivesmoothmuscles(forexample,in
achalasia)orabnormalactivityofglands(forexample,hyperhidrosis).[1]
Thetoxinrequires2472hourstotakeeffect,reflectingthetimenecessarytodisruptthesynaptosomalprocess.In
veryrarecircumstances,someindividualsmayrequireasmanyasfivedaysforthefulleffecttobeobserved.
Peakingatabout10days,theeffectofbotulinumtoxinlastsnearly812weeks.
Immunologicconsiderations
Anestimated515%ofpatientsinjectedseriallywithearlierpreparationsofBotox(7911)developedsecondary
nonresponsivenessfromtheproductionofneutralizingantibodies.[10]
Riskfactorsassociatedwiththedevelopmentofneutralizingantibodiesinclude,injectionofmorethan200units
persessionandrepeatorboosterinjectionsgivenwithinonemonthoftreatment.Hopefully,thenew(BCB2024)
Botoxhasreducedimmunogenicityandalowerpotentialforneutralizingantibodyproductionbecauseofits
decreasedproteinload,thoughthefactisnotproveninclinicaltrialyet.[11]Inrabbitstudies,noantibodyformation
occurredwithnew(BCB2024)Botoxaftersixmonthsoftreatment,whileold(7911)Botoxcausedantibody
formationinallrabbitsbyfivemonths.
Limitedinformationisavailableonwhetherneutralizingantibodiesresolveovertimeand,consequently,whether
attemptsatreinjectionshouldbemadeafteraprolongedperiod.Aninvestigationisunderwaytodeterminewhether
injectionsofbotulinumtoxintypeBareusefulinpatientswithneutralizingantibodiestotypeA.Usingthelowest
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doseoftoxinnecessarytoachievethedesiredclinicaleffectandavoidingreinjectionwithinonemonthappear
prudentinanefforttokeepantibodyformationaslowandunlikelyaspossible.
Formulation
SerotypeAistheonlycommerciallyavailableformofbotulinumtoxinforclinicaluse,althoughexperienceis
emergingwithdevelopmentofotherserotypes:B,C,andFpreparations.[12]Twopreparationsofbotulinumtoxin
Aexist:DysportandBotox.Unfortunately,therehasbeenmuchconfusionoverthedosesandunitsofpotency
ofthetwopreparations.[13,14]Althoughdosesarequotedinmouseunits(whichistheamountoftoxinthatkills
50%ofagroupof1820gfemaleSwissWebstermice),implyingsomestandardization,Botoxseemstobemore
potent.Recently,ithasbeenshownthataunitofBotoxisthreetimesaspotentasaunitofDysport.[14]Botox
isasterilelyophilizedformofbotulinumtoxintypeA.ItisproducedfromacultureoftheHallstrainofC.
botulinumandpurifiedbyaseriesofacidprecipitationstoacrystallinecomplexcontainingthetoxinandother
proteins.TheFDAapprovedBotoxinDecember1989asanorphandrugforthetreatmentofstrabismus,
hemifacialspasms,andblepharospasm.ThespecificactivityofBotoxisapproximately20Units/nanogramof
neurotoxinproteincomplex.EachvialofBotoxcontains100Units(U)ofClostridiumbotulinumtypeA
neurotoxincomplex,0.5milligramsofAlbumin(Human),and0.9milligramsofsodiumchlorideinasterile,
vacuumdriedformwithoutapreservative.TheoriginalbatchofneurotoxinpreparedbyShantz[15]inNovember
1979(designatedbatch7911)constitutedtheoriginalBotoxformulationandwasuseduntilDecember1997.It
wasreplacedbyanewneurotoxincomplexbatchdesignatedBCB2024.Thenewbulkbatchisfivetosixtimes
morepotentonaweightbasis.Ina100unitvial,only4.8ngofneurotoxinisneededcomparedto25ngof7911.
ThenewBotoxiscomparableinclinicalefficacyandsafetytotheold,andaunitdoseofnewBotoxprovides
anequivalentresponsetothesameunitdoseofoldBotox.
Dysport,anotherformulationofbotulinumtoxintypeAavailableinEuropeandafewothercountries,isprepared
usingcolumnbasedpurificationtechniquesanddistributedin500unitvialsthatcanbestoredatroomtemperature.
BotoxandDysportarebothbotulinumtoxintypeApreparationsbutarequitedistinctfromoneanother.
Differencesinthesetoxinsmayrelatetodifferencesinthestrainofbacterium,preparation,diffusion,andpotency
testing.
MyoblocisabotulinumtoxintypeBpreparation.[16]

Preparations

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Botoxcosmetic
BotulinumtoxintypeA(BOTOXAllergan,Irvine,Calif)wasthefirstcommerciallyavailabletypeintheUnited
States.Itssafetyiswellestablished.Thedrawbackisthatoncethecontentsofavialaredissolved,thereconstituted
productlosesitspotency.Therefore,dermatologiststendtoschedulethetreatmentsforseveralpatientsonthesame
daysothattheycanusetheentirecontentsofthevial.Thisschedulingmaybeinconvenientforsomepatients,who
maydecidenottoproceed.
Dysport(Ipsenpharmaceuticals)(BotulinumtoxintypeA)
InEurope,botulinumtoxinofthesameserotypeismarketedbyanothercompany(DysportSpeywood,United
Kingdom).OneunitofBOTOXhasapotencythatisapproximatelyequalto4unitofDysport.
Xeomin
XeoministhethirdbotulinumtoxintypeAlicensedintheUK.XeominisaninnovativeBotulinumtypeA
formulation,inwhichthecomplexingproteinshavebeenremovedbyanextensivepurificationprocessfromthe
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botulinumtoxincomplex.Incontrasttotheothercommerciallyavailablepreparations,Xeomincontainsthepure
150kDneurotoxin.Xeomin,withoutthecomplexingproteins,hasthelowestcontentofbacterialproteinofallof
theavailablebotulinumtoxinsandfurthermoreshowthatrepeatedapplicationofXeomin,eveninhighdoses,
doesnotinducetheformationofneutralisingantibodies.ClinicalstudieshavesuggestedthatXeominhasbeen
foundsimilarinitseffecttoBotoxinclinicalstudies.oneunitofXeominisequalto1unitofBotox
Neurobloc
Neurobloc(Myobloc)isaregisteredtrademarkofSolsticeNeurosciencesInc,SanFrancisco,Calif.Itisa
ClostridiumbotulinumtypeBneurotoxincomplexwhichbecameavailableintheU.K.in2001.Thereislimited
experienceintheuseofthistypeoftoxin,andtheproductdoesnotcurrentlyhaveapprovalforcosmeticuse
anywhereintheworld.ItismarketedasMyoblocInjectableSolution(botulinumtoxintypeB)intheUnited
StatesandCanadaandNeuroblocinEurope.
Myobloc(Elan)
Myobloc(Elan),Dysportwhenreconstituted,hasashelflifeofmorethan12months.Thisfeatureis
advantageousintermsofpatientscheduling.However,largervolumesofMyoblocmaybeneededtoobtain
effectssimilartothoseofBotox.Antibodyformationagainstthisproductmayoccurmoreoftenbecauseofits
higherproteincontent.
Reconstitutionandstorage
Botoxisstoredinafreezeratorbelow5C.Thepackageinsertrecommendsreconstitutionusingsterilesaline
withoutpreservative0.9%sodiumchlorideisthepreferreddiluent.Someinvestigatorssuggestthatreconstitution
withsterilesalinesolutionwithpreservative(0.9%benzylalcohol)reducesmicrobialcontaminationandprovidesa
weaklocalanestheticeffect.
Botoxisdenaturedeasilybybubblingoragitationgentlyinjectthediluentontotheinsidewallofthevialand
discardthevialifavacuumdoesnotpullthediluentin.ThefinaldilutionofBotoxismostlyamatterofpersonal
preference100unitscommonlyarereconstitutedin110mlofdiluent.Theoretically,moreconcentratedsolutions
reducereliabilityindeliveringaspecificunitdose,andmoredilutesolutionsleadtogreaterdiffusionofthetoxin.
Oncereconstituted,Botoxiskeptrefrigeratedat28C.ThereconstitutedBotoxshouldbeusedwithin4hours.
Onestudyfoundnolossofactivityat6hoursbuta44%lossafter12hoursanda70%losswithrefreezingat12
weeks.[17]Otherauthorsreportnosubstantiallossofpotencyina10U/1mlreconstitutedsolutionkept
refrigeratedfor1month.
Howbotulinumtoxinisgiven
Botulinumtoxinisinjectedintoaffectedmusclesorglandsusinga30gauge1inchneedle.Dosesaretailored
accordingtothemodeofuseandindividualpatients,andthedosedependsonthemassofmusclebeinginjected:
Thelargerthemusclemassthehigherthedoserequired.However,lowerdosesmayberequiredinpatientswith
preexistingweaknessandinfemales.
Toxininjectionsaregiventhroughhollowtefloncoatedneedlesdirectlyintoaffected/overactivemuscles.In
localizedmuscleoveractivity,especially,indelicateplacessuchasstrabismus,theinjectionsareusuallyguidedby
electromyography.
Electromyographmonitoring
Manyauthors[18]havechosentoadministerinjectionsundertheguidanceofelectromyograph(EMG)monitoring.
Thistechniqueinvolvesusinga27gauge(1.5in)polytefcoatedEMGneedleconnectedtoanEMGrecorderby
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analligatorcliponitsshaft.Thepatientisaskedtocontractthemuscleinquestion.Theinjectionisplacedwhere
themaximalEMGrecordingcanbefoundwithinthemuscle.Thistechniqueensuresthattheinjectionisatthe
pointofthemusclethatiscontributingmosttothehyperfunctionalfacialline.Astheseinjectionshavebecome
routine,manycentershaveobtainedsatisfactoryresultswithoutEMGguidance.Manyphysiciansuseareadily
available30gaugeinsulinsyringeinstead.However,EMGguidedinjectionsremainausefuladjunctinpatients
whohaveresidualfunctionaftertheirinitialinjection.
Precautionsafterbotulinumtoxininjection
Asageneralprecaution,oneshouldgohomeimmediatelyandrestafterBotox.Donothingstrenuousforoneor
twodaysandrefrainfromlaser/IPLtreatments,facialsandfacialmassageforonetotwoweeksafterinjections.
Thisistominimizetoxinsdislodgingandtraveling(duetoincreasedbloodcirculationordirectpressure)tothe
surroundingmuscles.
Followupmonitoring
TheweaknessinducedbyinjectionwithbotulinumtoxinAusuallylastsaboutthreemonths.Hence,further
injectionsatregularintervalsarerequiredandtheintervalvarieswidelydependingonthedoseandindividual
susceptibility.Responseaftertheinjectionsshouldbeassessedbothbysubjectiveandbyobjectivemeasures.Most
patientstreatedwithbotulinumtoxinrequirerepeatedinjectionsovermanyyears.Somepatientswhorespondwell
initiallydeveloptolerancetotheinjectionsduetodevelopmentofneutralizingantibodiestothetoxin.Patientswho
receivehigherindividualdosesorfrequentboosterinjectionsseemtohaveahigherriskofdevelopingantibodies.
Injectionsshouldthereforebegivenatthelowesteffectivedoseandasinfrequentlyaspossible.Severaltypesof
antibodyassayareavailable.[4]InclinicaltrialspatientsresistanttobotulinumAhavebenefitedfrominjections
withotherserotypes,includingB,C,andF.[19]
Clinicalapplications
Botulinumtoxinsnowplayaverysignificantroleinthemanagementofawidevarietyofmedicalconditions,
especiallystrabismusandfocaldystonias,hemifacialspasm,andvariousspasticmovementdisorders.[9,20]Besides
these,encouragingclinicalreportshaveappearedforotherusessuchasheadaches,[21]hypersalivation,[22]
hyperhidrosis,[23]andsomechronicconditionsthatrespondonlypartiallytomedicaltreatment.Sometimesitcan
beusedasanalternativetosurgicalintervention.[24]Itseemstobeapromisingalternativetosphincterotomyin
patientswithchronicanalfissures[25]andiseffectiveinachalasia.[26]Someautonomicdisordersresultingin
hypersecretionofglandslikeptyalismorgustatorysweating,whichoftenoccuraftersurgerytotheparotidgland,
respondwelltobotulinumtoxin.[23,27,28]Surprisingly,theresponseseemstolastmuchlongerthaninconditions
causedbyoveractivityofstriatedorsmoothmuscles.[28]Thelistofpossiblenewindicationsisrapidlyexpanding[
Table1].
Table1
Indicationsforbotulinumtoxin

Dermatocosmetologicalapplications
CosmeticuseofBTXhasskyrocketedinrecentyears,especiallysincetheapprovalofBTXAfortreatmentof
glabellarlines.Untilrecently,Botoxusewasmainlyconfinedtocorrectmusclesoffacialexpressionoverthe
upperonethirdoftheface.Presentlyit'sapplicationrangesfromcorrectionoflines,creasesandwrinklingallover
theface,chin,neck,andchest,depressorangulioris,nasolabialfolds,mentalis,medialandlateralbrowlifts,to
lessenshadowsonone'sfaceandmaintainasmoothoutlineofthejawandcheeksfromalldirections,to
dermatologicalapplicationssuchaslocalizedaxillaryorpalmarhyperhidrosisthatisnonresponsivetotopicalor
systemictreatment[Table1].
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Adverseeffects
Injectionswithbotulinumtoxinaregenerallywelltoleratedandsideeffectsarefew.Generalizedidiosyncratic
reactionsareuncommon,generallymild,andtransient.Therecanbemildinjectionpainandlocaledema,erythema,
transientnumbness,headache,malaiseormildnausea.Itseffectdiminisheswithincreasingdistancefromthe
injectionsite,butspreadtonearbymusclesandothertissuesispossible.Themostfearedadverseeffectis
temporaryunwantedweakness/paralysisofnearbymusculaturecausedbytheactionofthetoxin.Itusuallyresolves
inseveralmonthsandinsomepatientsinafewweeks,dependingonthesite,strengthoftheinjections,andthe
musclesmadeexcessivelyweak.Approximately13%ofpatientsmayexperienceatemporaryupperlidorbrow
ptosis.Thisresultsfrommigrationofthebotulinumtoxintothelevatorpalpebraesuperiorismuscle.Patientsoften
areinstructedtoremaininanuprightpositionforthreetofourhoursfollowinginjectionandavoidmanual
manipulationofthearea.Activecontractionofthemusclesundertreatmentmayincreasetheuptakeoftoxinand
decreaseitsdiffusion.
Theptosisusuallylaststwotosixweeks.Itcanbetreatedwithapraclonidine0.5%eyedrops.Thisisanalpha
adrenergicagentthatstimulatestheMllermuscleandimmediatelyelevatestheuppereyelid.Thistreatmentusually
canraisetheeyelid13mm.Thetreatmentofonetotwodropsthreetimesperdaycontinuesuntiltheptosis
resolves.Toavoidptosis,placeinjections1cmabovetheeyebrowanddonotcrossthemidpupillaryline.
Apraclonidineiscontraindicatedinpatientswithdocumentedhypersensitivity.Phenylephrine2.5%canbeused
alternatively.NeoSynephrineiscontraindicatedinpatientswithnarrowangleglaucomaandinpatientswith
aneurysms.
Weaknessofthelowereyelidorlateralrectuscanoccurfollowinginjectionofthelateralorbicularisoculi.Ifsevere
lowerlidweaknessoccurs,anexposurekeratitismayresultandifthelateralrectusisweakened,diplopiaresults.
Treatmentissymptomatic.
Patientsreceivinginjectionsintotheneckmusclesfortorticollismaythereforedevelopdysphagiabecauseof
diffusionofthetoxinintotheoropharynx.Whenthisoccurs,itusuallylastsonlyafewdaysorweeks.Some
patientsmayrequiresoftfoods.Althoughaswallowingweaknessdoesnotheraldsystemictoxicity,ifitissevere,
patientsmaybeatriskofaspiration.Somepatientsexperienceneckweakness,whichisespeciallynoticeablewhen
attemptingtoraisetheheadfromasupineposition.Thisoccursafterweakeningofthesternocleidomastoid
muscles,eitherfromdirectinjectionordiffusion.Thisismorecommoninwomenwithlongthinnecks.Avoidthese
adverseeffectsbyusingthelowesteffectivedosesandpreciselyplacingtoxinintotheplatysma.
Distanteffectsshownbyspecializedelectromyographictestscanalsooccur,butweaknessofdistantmusclesor
generalizedweakness,possiblyduetothetoxinspreadingintheblood,isveryrare.[29,30]however,avoid
intravascularinjectionsbecausediffusespreadoflargeamountsoftoxincanmimicthesymptomsofbotulism.
Bruisingcanoccur,particularlyifasmallveinislaceratedorapatientistakingaspirin,vitaminE,orNSAIDs.
Ideally,patientsshouldstoptakingtheseproductstwoweeksbeforetheprocedure.Headachescanoccurafter
Botoxinjectionshowever,inonestudybyCarruthersetal,[31]thisdidnotexceedtheplacebogroup.Thisis
thoughttobeduetothetraumaoftheinjectionandnotsomethinginherentinthetoxin.Infact,botulinumtoxin
injectionsareextremelysafe.Todate,nosignificantlongtermhazardsofbotulinumtoxininjectionshavebeen
identifiedinexcessofplacebogroups.
Othersystemicsideeffectsincludeaninfluenzalikeillnessand,rarely,brachialplexopathy,whichmaybeimmune
mediated.[32]Nosevereallergicreactionshavebeenreported,however,patientmaybeallergictoanyofits
components.Gallbladderdysfunctionattributedtoautonomicsideeffectsofthetoxinandacaseofnecrotizing
fasciitisinaimmunosuppressedwomanwithblepharospasmhavebeennoted.[33,34]
Contraindicationstobotulinumtoxininjection
Botulinumtoxiniscontraindicatedinpatientsafflictedwithapreexistingmotorneurondisease,myastheniagravis,
EatonLambertsyndrome,neuropathies,psychologicalunstability,historyofreactiontotoxinoralbumin,
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pregnancyandlactatingfemales,andinfectionattheinjectionsite.Carefulmonitoringshouldbedoneinchildren
asitmightaltercellfunctionssuchasaxonalgrowth.[35]
Relativecontraindications
Somemedicationsdecreaseneuromusculartransmissionandgenerallyshouldbeavoidedinpatientstreatedwith
botulinumtoxin.Theseincludeaminoglycosides(mayincreaseeffectofbotulinumtoxin),penicillamine,quinine,
chloroquineandhydroxychloroquine(mayreduceeffect),calciumchannelblockers,andbloodthiningagentseg.
warfarinoraspirin(mayresultinbruising).
Therapeuticfailure
Somepatientsdonotrespondtoinjectionsand,havingneverpreviouslyresponded,aredesignatedasprimary
nonresponders.Manyreasonsmayleadtoalackofresponse.Patientswithrhytidsthatarenotdynamicinorigin
(eg,photodamage,agerelatedchanges)donotrespond.Improperinjectiontechniqueorthedenaturedtoxinmay
alsoresultintotherapeuticfailure.Somepatientsmayhaveneutralizingantibodiesfrompriorsubclinicalexposure,
orindividualvariationsindockingproteinsmayexist.[36]Secondarynonrespondersrespondinitiallybutlosethe
responseonsubsequentinjections.Mostofthesepatientsmayhavedevelopedneutralizingantibodies.

Futureresearch

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TypeAbotulinumtoxinhaswideneditsclinicalrangeofapplications,buttheriskofdevelopingantibodieslimits
therepeateduseofhighdoseinjection.Otherserotypesofbotulinumtoxinarebeinginvestigatedasuseful
alternatives.BotulinumtoxintypeFdiffersfromtypeA,mainlybyitslowerpotency,efficacyandshorterduration
ofaction[37]andblocksadifferentSNAREproteinascomparedtotypeAtoxin.Therefore,acombinationof
toxinsAandFhasbeensuggestedtoreducethetotalunitsandoverallantigenicdose.[38]

Conclusion

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Theuseofbotulinumtoxinshasrevolutionisedthetreatmentofvariousophthalmicspasticdisorders,facial
dystoniasandperiocularwrinkles.Apreciseknowledgeandunderstandingofthefunctionalanatomyofthe
mimeticmusclesisabsolutelynecessarytocorrectlyusebotulinumtoxinsinclinicalpractice.Adverseeffectsare
usuallymildandtransient.Themostcommonsubstantivecomplicationisexcessiveorunwantedweakness,and
thisresolvesastheactionofthetoxinislost.Browptosis,eyelidptosis,neckweakness,dysphagia,anddiplopia
mayoccur.Knowledgeofthefunctionalanatomyandexperiencewiththeprocedurehelpinjectorsavoid
complications.Infuture,thedevelopmentofnewpotenttoxinswithincreasingeffectivenessanddurationofeffect
willfurtheraidthisexpandingandinterestingfieldofchemodenervation.

Footnotes

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SourceofSupport:Nil
ConflictofInterest:Nil.

References

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