105JournalofNeurology,Neurosurgery,andPsychiatry1992;55:105-111Internu - PDF document

105JournalofNeurology,Neurosurgery,andPsychiatry1992;55:105-111Internuclearophthalmoplegiaofabduction:clinicalandelectrophysiologicaldataontheexistenceofanabductionparesisofprenuclearoriginFrankThomke,HannsChristianHopf,GunterKramerAbstractThreepatientsshowedunilateralandfivebilateralabductionparesis.Fivehadassociatedadductionnystagmusofthecontralateraleye.Electrophysiologicaltestingofmasseterandblinkreflexesindicatedanipsilateralrostralpontineormesencephaliclesion,andexcludedalesionoftheinfranuclearportionoftheabducensnerve.Abductionparesiswasattributedtoimpairedinhibitionofthetonicrestingactivityoftheantagonisticmedialrectusmuscle.Theprenuclearoriginofthedisorderisbasedonmorphologicalandneurophysiologicalevidenceofanipsilateralinhibitorycon-nectionbetweentheparamedianpontinereticularformationandtheoculomotornucleusrunningclosetobutseparatedfromthemediallongitudinalfasciculus.DepartmentofNeurology,UniversityofMainz,GermanyFThomkeHCHopfGKramnerCorrespondenceto:DrThomke,NeurologischeUniversitatsklinik,Langenbeckstr1,D-6500Mainz1,GermanyReceived4July1990andinfinalrevisedform14March1991.Accepted26March1991In1923Lutz'proposedtheexistenceofanabductionparesisofprenuclearorigin("oph-thalmoplegiainternuclearisposterior",pINO).Ashisbasicneuroanatomicalassump-tionswereerroneous,theexistenceofapINOremainedcontroversial.However,patientshavebeenreportedwithabductionparesis,whichdifferedfromabducensnervepalsyinseveralaspects,suchas,absenceofstrabismusanddiplopiaintheprimaryposition,2-5adduc-tionnystagmusofthecontralateraleyeonlateralgaze,346isolatedimpairmentofsaccadicabductionmovements,7andunimpairedabductionduringcaloricstimulation.8Therehasbeenlittleagreementonthelocationoftheresponsiblelesionandthepathophysiologicalexplanation.Someauthors,rejectingtheexistenceofaprenuclearabduc-tionparesis,attributedsuchcasestoapontinelesioninvolvingtheabducensnervealongitsinfranuclearintrapontinecourse.9'0Otherspostulateddecreasedexcitationoflateralrectusmotorneuronsduetoalesionofprenuclearstructures,thatis,aberrant"pyramidaltract"fibrestotheabducensnucleus"ortheconnec-tionbetweentheparamedianpontinereticularformation(PPRF)andtheipsilateralabducensnucleus.57Animpairedinhibitionoftheantagonisticmedialrectusmusclewasdiscus-sedbyCollardetal'suggestingamediallongitudinalfasciculus(MLF)lesioncon-tralateraltothepareticeye.Were-examinethisissuebasedonthefindingsineightpatientswithelectrophysiologicalevidenceofarostralpontineand/ormesencephaliclesionipsilateraltotheeyeshowingabductionparesis.CasereportsPatient1A63yearoldwomanwithafiveyearhistoryofatrialfibrillationandarterialhypertensionsud-denlydevelopeddiplopiaandunsteadinessofgait.Onadmissionshewassomnolentanddisorientedintimeandplace.Examinationshowedparalysisofupwardanddownwardgazeandconvergence.Abductionoftherightorthophoriceyewaslimitedto300.Thegaitwasataxicwithatendencytofallbackwards.Afterthreedayssheregainedfullorientation.Neuro-ophthalmologicalfindingswereunchangedandshecomplainedofdiplopiaongazetotheright.CTscanwasnormal.Afterthreeweeksabductionoftherighteyewasrestored.Patient2A58yearoldmanwhohadexperienceddiabetesmellitusfor20years,insulindepen-dentforsixmonths,hadsuddendiplopiaandmilddullheadache.Onexaminationabductionoftheslightlyesotropic(2°)righteyewaslimitedto20°andtherewasadditionaladduc-tionnystagmusonthelefteye.Anklejerkswerediminishedbilaterally.CSFshowedslightpleocytosis(9cells/Ml)andincreasedproteincontent(126mg/dl;IgG:16-2mg/dl).CTscanwasnormal.Completeclinicalrecoveryoccurredafterthreemonths.Patient3A48yearoldheavysmoking(40-50cigarettesperday)manhadsuddendiplopia.Onexamin-ationabductionoftheleftorthophoriceyewasrestrictedto40°andtheleftsuperiorobliquemusclewasparetic.CSFwasnormal.CTandMRIscansrevealedpre-existingsmallischaemiclesionsoftherighttemporo-occipitalregionandtherightparietallobe.Thebrain-stemwasnotinvolved.Duplexsonographyshowedseveralarterioscleroticplaquesoftheproximalintemalcarotidarteries.TranscranialDopplersonographyofthecerebralandver-tebrobasilararterieswasnormal.Afterthreeweekstheclinicalabnormalitieshadrestored.Patient4A65yearoldmanwhohadexperiencedtypeIIdiabetesforoneyearhaddiplopiawhenlookingtotheleftandmilddiffusedullheadache.Onexaminationabductionoftheslightlyesotropic(30)lefteyewaslimitedto300.Bilaterallossofanklejerksandimpairedvibrationsensewere Th6mke,Hopf,Krdmerattributedtodiabeticneuropathy.Twodayslaterhealsonoticeddiplopiawhenlookingtotheright.Abductionoftheorthophoricrighteyewasnowlimitedto20°andafterfourdaysto10°onlateralgazeandduringocularcephalicreflex.Therewasadditionaladductionnystag-musonthelefteye.CSFproteinwasslightlyincreased(49mg/dl).CTandMRIscanswerenormal.Therewascompleteclinicalrecoveryaftersixmonths.Patient5A69yearoldmanwhohadhaddiabetesmellitusfor15years,andwasinsulindepen-dentforoneyear,suddenlyexperienceddiplopiaandviolentleftfronto-temporalheadache.Examinationfourdayslatershowedrestrictedabduction(to300)oftheleftortho-phoriceyeandadditionalparesisoftheleftsuperiorobliquemuscle.Decreasedanklejerks,distalhypesthesiaandimpairedvibrationsensewereattributedtodiabeticneuropathy.CSFproteinwasincreased(154mg/dl;IgG:13-2mg/dl,nooligoclonalbandsofIgG).CTwasnormal.Aftertwoweeks,abductionparesisofthelefteyehadimprovedto400.Patient6A75yearoldwomanwhohadexperiencedtypeIIdiabetesandarterialhypertensionforfouryearsdevelopedviolentheadachewithbifron-talaccentuationduringthenight.Thenextmorningshenoticeddiplopiaandunsteadinessofgait.Onexaminationabductionoftheortho-phoricrighteyewaslimitedto20°andtherewasadductionnystagmusonthelefteye.Tandemwalkingwasunsteadywithatendencytofalltotheright.Theanklejerkswerebilaterallydecreased.CSFwasnormal.CTscanwasnormalincludingthinsectionsofthebrainstem.Aftertwoweeksabductionparesisoftherighteyehadimprovedto30°.Patient7A73yearoldmanwitharterialhypertensionforfiveyearsandtypeIIdiabetesforsixmonthssuddenlynoteddiplopia.Examinationshowedslightesotropia(2°)andlimitedabduc-tion(to20°)oftherighteyeonlateralgazeandduringocularcephalicreflex.Therewasadductionnystagmusofthelefteye.Tandemwalkingwasunsteadywithatendencytofalltotheright.Therewasapredominantlysensoryneuropathywithbilaterallydecreasedkneejerks,lossofanklejerks,distalhypalgesia,andimpairedvibrationsense.CSFproteinwasslightlyincreased(57-4mg/dl).Theclinicalconditionhadcompletelyrecoveredafterthreemonths.Patient8A74yearoldwomanwithtypeIIdiabetesfor20yearsnoticedsuddendiplopiawhenlookingtotheright.Onexaminationabductionoftherightorthophoriceyewasrestrictedto200.Bilaterallydecreasedanklejerksandimpairedvibrationsenseattheankleswereattributedtodiabeticneuropathy.Aftertwoweeksabduc-tionoftherighteyehadimprovedto50°.MethodsHorizontaleyemovementswererecordedseparatelyforeacheye.Surfaceelectrodeswereplacedneartheouterandinnercanthioftheeyesandaboveandbelowtherighteyeforblinkartifactdetection.Thebandwidthoftherecor-dingsystemwas0-40Hz.Allsignalsweredocumentedbyalinearinkjetwriterusingpaperspeedsof10and100mm/s.Voluntaryhorizontalsaccadesweretriggeredbyfollowingalightspotprojectedonascreen1-2minfrontofthepatient.Targetjumpsof20,30and400totheleftorrightfromtheprimarypositionwereusedatrandomintervals.Peakvelocitiesofsixsaccadesof30°toeithersidewereevaluated.Thenormalrangeof300abductionsaccadesin40controlswas320to640°/s.Interoculardifferencesdidnotexceed35°/s.Themasseterreflex(MassR)waselicitedbyabrisktaponthepatient'sjawusingareflexhammer.Therecordingwastriggeredatthemomentofthemechanicaltapbyasignalfromapiezo-electricelementmountedintheham-mer.TheMassRwasrecordedusingsurfaceelectrodeswiththerecordingelectrodeplacedoverthebellyofthemassetermuscle(25mmabovethemarginofthemandible)andthereferenceoverthejugularboneatthelateraledgeoftheorbit.Tensuccessiveeventswereaveraged.Theresponseswereconsideredabnormalusingoneormoreofthefollowingcriteria:1)Unilateralorbilaterallosswithrecoveryatre-examination;2)Unilateralorbilateraldelayabovetheagerelatedmean+2-5SD;3)Righttoleftdifferenceof0-5msormore.In30controlsolderthan40yearsthenormalvaluewas7-6msand2-5SDwas1-3ms.Themeanrighttoleftdifferencewas0-15msand2-5SDwas0-3ms.ThecriteriaforMassRimprovementatre-examinationwereareappearanceofthecompletelyorpartially(�4in10trials)abolishedresponsesandshorteningoflatencyby�08mis.Theblinkreflex(BR)waselicitedbystimulatingthesupraorbitalnerveoneithersideusingrectangularstimuliof0-1msdura-tion,constantcurrentof25mAandintervalsof10s.Responsesfromtheorbicularisoculimuscleswererecordedbysurfaceelectrodeswiththerecordingelectrodeplacedinferiortothelowerlidhalfwaybetweentheinnerandouteredgeoftheorbit.Fiveconsecutiveeventswereevaluated.Theipsilateralandcon-tralateralR2componentswerewithinnormallimitsinallourpatients.ThecriteriaofanabnormalRIresponsewere:1)UnilaterallossofRI;2)Unilateralorbilateraldelayabovetheagerelatedmean+2-5SD;3)Righttoleftdifferenceof1-3msormore.In30controlsolderthan40yearsthenormalvaluewas10-7msand2.5SDwas0-8ms.Themeanrighttoleftdifferencewas05msand2-5SDwas0-7ms.ThecriterionforBR-RIimprovementwasshorteningofthelatencyby�1-3ms.Forbrainstemauditoryevokedpotentials(BAEP)rarefactionandcondensationclicksof70dBaboveclickhearingthresholdwitharepetitionrateof10/sweredeliveredmon-aurally.Responseswererecordedbysurfaceelectrodeswiththerecordingelectrodeplacedoverthemastoidandthereferenceoverthevertex.Latenciesweredeterminedfrom1000averagedresponses.ResultsTheeightpatientsinthisseriesshowedabduc-tionparesiswithresidualmovementsof10-106 107InternuclearophthalmoplegiaofabductionFigure1Electro-oculogramofpatient2showingadductionparesiswithhypermetricabductionsaccadesandadductionnystagmusonthelefteye.Saccadeswereperformedfromtheprimarypositiontotherightattargetjumpsof200(A)and40°(B).(r:righteye;H:lefteye).20Or40Or0JLAIB0-ls400.Clinically,thedisorderwasbilateral,thoughasymmetrical,inone(patient4)andunilateralintheremainingseven.Thepareticeyewasorthophoricinpatients1,3,4(righteye),5,6,and8andslightlyesotropic(2-3°)inpatients2,4(lefteye),and7.Adductionnystagmusonthecontralateraleyewasclin-icallyobservedinpatients2,4(lefteye),6and7.Electro-oculography(EOG)confirmedtheclinicalfindings(fig1)andadditionallyrevealedadductionnystagmusontheeyecon-tralateraltothelateralrectusparesisinpatient4(righteye),fig2.InfourofthesevenpatientswithclinicallyunilateralabductionparesisEOGdemonstratedadditionalslowingofabductionsaccadesofthecontralateraleye(patients5,6,7,8)(fig3,4).Velocitieswerebetween290and380°/swithinteroculardifferencesof140to170°/scomparedwithadductionsaccadesoftheoppositeeye.Thiswasassociatedwithadductionnystagmusinthreepatients'7(fig3,4).Thusadductionnystagmusonthecontralateraleyewasseeninone(patient2)ofthreepatientswithstrictlyunilateralabductionparesis.Bilateralasym-metricalabductionparesiswasassociatedwithbilateraladductionnystagmusinthree(patients4,6,7)andwithunilateraladductionFigure2Electro-oculogramofpatient4showingasymmetricalbilateralabductionparesiswithbilateraladductionnystagmus.Saccadeswereperformedfromtheprimarypositiontotheright(A)andleft(B)attargetjumpsof30°.(r:righteye;l:lefteye).30r0ro0A30°l~~~~~~~~~~~~~~~~~~~~~~r5~~~~~30°rA~~~~~~30orBFigure3Electro-oculogramofpatient7showingasymmetricalbilateralabductionparesiswithbilateraladductionnystagmus.Saccadeswereperformedfromtheprimarypositiontotheright(A)andleft(B)attargetjumpsof300.(r:righteye;H:lefteye).nystagmusinone(patient5).Nonystagmuswasseeninone(patient8).Patient1withunilateralabductionparesishadanadditionalparalysisofupwardanddownwardgazeandofconvergence.Additionalunilateralsuperiorobliqueparesiswasobservedinpatient3withunilateralabductionparesisonthepareticeyeandinpatient5withasymmetricalbilateralabductionparesisonthemoreseverelyaffectedeye.MassRabnormalitieswereobservedinallpatientsinthisseries(table).Thosewithunilateralabductionparesis(patients1,2,3)hadunilateralMassRabnormalitiesipsilateraltothepareticeye.Fouroffivepatients(5,6,7,8)withasymmetricalbilateralabductionparesisshowedbilateralMassRchanges.Theyweremorepronouncedipsilateraltothemoreseverelyaffectedeyeinpatient6,andinpatient8,theinitiallybilateralMassRabnormalitychangedintoaunilateralone,whichwasipsilateraltothemoreseverelyaffectedeyeatre-examination.TheMassRwasunilaterallyabnormalipsilateraltothemoreseverelyaffec-tedeyeinpatient4.TheBR-RIwasunilaterallyabnormalin4patients(1,3,4,8)(table).Changeswereipsilateraltothepareticeyeinpatient1and3withunilateralabductionparesisandipsilateraltothemoreseverelyaffectedeyeinpatient4and8withasymmetricalbilateralabductionparesis.BAEPwavesItoVwerenormalinallpatients.Abductionparesisrecovered(patients1,2,3,30rAls301rB1IFigure4Electro-oculogramofpatient6showingasymmetricalbilateralabductionparesiswithbilateraladductionnystagmus.Saccadeswereperformedfromtheprimarypositiontotheright(A)andleft(B)attargetjumpsof30¢.(r:righteye;l:lefteye).Brr Thomke,Hopf,KramerTableAlterationsofthemasseterreflexandtheR,componentoftheblinkreflexinthreepatients(1,2,3)withunilateralandfive(4,5,6,7,8)withasymmetricalbilateralabductionparesis.MasseterreflexBlinkreflexR,Latency(ms)Latency(ms)PatientRightLeftRightLeft18-9*(7)82(10)11-4*9-4after3weeks8-0(8)8-2(10)10-010028-9*(7)8-2(8)10.210-6after3months80(9)79(10)37-9(10)9.3*(7)11-012.5*after2weeks81(10)85(10)11-111.8*4-*(0)8.6(8)12-7*103after6months8.3(10)86(10)11210-6512-4(5)10-2(7)11.5110after2weeks94(7)9-2(9)6-*(1)80(4)10210-4after2weeks81(6)79(9)793(8)9-6(7)11211.3after3months8-5(10)85(10)8-(0)-(0)13-2*113after2weeks-*(0)73(9)11.8*115(Abnormalresponsesaregiveninboldprint;*indicatesabnormalitiesipsilateraltothepareticeyeinunilateralandipsilateraltothemoreseverelyaffectedeyeinasymmetricalbilateralabductionparesis;formasseterreflex,thenumbersofresponsesobtainedoutof10trialsaregiveninbrackets)4,andonthelessseverelyaffectedeyeinpatients5,6,7,8)orimproved(onthemoreseverelyaffectedeyeinpatients5,6,7,8)withrecovery(patients1,2,4,6,7)orimprovement(patients3,5,7)ofMassRandBR-R,findings.DiscussionInallpatientsperipheralcausesofMassRimpairmentwereexcludedclinicallybyabsenceofmassetermuscleparesis,sensorydisturbanceofthebranchesofthe5thnerveandcornealrefleximpairment.Undersuchconditions,aMassRabnormalityhastobeattributedtoanipsilateralupperpontineormesencephaliclesion.'213AssociatedMassRandBR-RIabnormalitiesindicateanipsilateralrostralpontinelesion.'415SuprasegmentallesionshavenotbeenreportedsofartoinfluencetheMassRandBR-Rl.Thusthefindingsinourpatientsareinfavourofarostralpontineand/ormesencephaliclesionipsilateraltotheabductionparesis.Improvementornor-malisationofabductionparesiswasalwaysassociatedwithimprovementornormalisationoftheelectrophysiologicalfindings.Thisstronglyindicatesthatclinical,EOGandelec-trophysiologicalchangeswerecausedbythesamelesion.Alesionofthesixthcranialnerveasthecauseofabductionparesisinourpatientswasveryunlikelyastherewasnoelectro-physiologicalevidenceforamidpontineorlowerpontinelesionattheleveloftheinfranu-clearintrapontinecourseofthesixthnerve(normalipsilateralandcontralateralR2com-ponentsoftheBR,normalBAEPwavesItoIIIinallpatients).Electrophysiologicaltestingsuggeststhatthelesionislocatedipsilateraltotheabductionparesisattheupperponsormidbrainlevel.Thislocationwasevidentinpatient1fromparalysisofupwardanddownwardgazeandconvergence617andisconfirmedbypreviousobservations.Inafiveyearoldgirlwithbilateralslowingofabductionsaccadesandbilateraladductionnystagmus'anda66yearoldwomanwithbilateralabductionparesis,3upgazeparesisandcombinedupgazeandcon-vergencepareses,respectively,stronglyindicatedarostralmidbrainlesion.'617Bilateralabductionparesiswithupgazepalsywasobservedinmidbrainhaemorrhage'8andunilateralabductionparesiswithupgazeparalysisinipsilateralmeso-diencephalichaemorrhage.'9Themidbrainlocationwasobviousintwopatientswhodevelopedatran-sientipsilateralabductionparesisafterunilateralmesencephalotomy.20Wesuggestthatthemostprobablecauseofabductionparesisinourpatientsisimpairedinhibitionofthetonicrestingactivityoftheipsilateralmedialrectusmuscle.Impairedinhibitionofthetonicrestingactivityofantagonisticeyemusclesresultsinhorizontalandverticaleyemovementparesesdespitenormalactivationoftheagonists.2-23Theproposedlocationandpathophysiologicalexplanationisalsosupportedbytheobserva-tionofunilateralabductionparesiswithnormallateralrectusexcitationbutgrosslyimpairedmedialrectusinhibitioninapatientwithclinicalevidenceofanipsilateralmesence-phaliclesion(indicatedbyipsilateralconver-genceparesis).2'InhibitionofmedialrectusmotorneuronshasbeenattributedtoaninhibitoryactionofMLFfibres.24However,duringsaccadesandpursuiteyemovementsMLFfibreactivityisonlyassociatedwithcontraversiveeyemovements2425andnoMLFactivitywasrecor-dedipsilateraltotheabductingeye.2425PolaandRobinson24proposedthatinhibitoryMLFfibrescrossattheoculomotornucleusleveltocontralateralmedialrectusmotorneurons.Theabsenceofdemonstratedcrossingfibres2627andtheobservationofimpairedmedialrectusinhibitionontheeyeipsilateraltounilateralMLF�lesions2'0stronglycontradictsthishypothesis.DisynapticinhibitionofabducensnucleusmotorneuronsandinternuclearneuronsafterunilateralstimulationofthecontralateralPPRF31mediatedbyinhibitoryburstneuronsofthedorsomedialreticularformation,(whichreceiveafferentsfromtheipsilateralPPRFandprojecttocontralateralabducensnucleus,3233)wasthoughttoinvolvethetonicrestingactivityofantagonisticeyemusclesduringlateralgaze.'4Inhibitionofthelateralrectusmusclewasattributedtoinhibitionoflateralrectusmotorneuronsandmedialrectusinhibitionwasexplainedbyinhibitionofabducensnucleusinternuclearneuronscausinginhibi-tionoftheexcitatoryprojectionsoftheseneuronsviatheMLFtocontralateralmedialrectusmotorneurons("disfacilitation").34However,1)LossofexcitatoryMLFfibreactivitytomedialrectusmotorneuronswasneverfollowedbyreductionofthetonicrestingactivityofthemedialrectus�muscle;2'02)Unilateralstimulationofinhibitoryburstneuronscausedabductionoftheipsilateraleyeonlywhentheeyewasadducted(superimposedoncontinuousexcitationofmedialrectusmotorneuronsviatheMLF),butnotintheprimaryposition(whenthereisnoMLFfibre108 InternuclearophthalmoplegiaofabductionFigure5Hypothesisforahorizontalgazeinhibitorysystem(Thepatternofexcitationandinhibitionisshownforleftwardgaze.Blackarrows:excitation;whitearrows:inhibition;LE:lefteye;RE:righteye;LR:lateralrectus;MR:medialrectus;NVI:abducensnerve;VI:abducensnucleus;NIII:oculomotornerve;III:oculomotornucleus;PPRF:paramedianpontinereticularformation;MLF:mediallongitudinalfasciculus;PMLF:para-MLF;IBN:inhibitoryburstneurons)NVIactivity);'53)BilateralinterruptionoftheMLFandtheinhibitoryprojectionstotheabducensnucleicausesbilateralINOandbilaterallossoflateralrectusinhibitionbutonlymildimpair-mentofmedialrectusinhibition.22Thesefind-ingscontradicttheassumptionthattheMLFisaneuralpathwayformedialrectusinhibition.Inparticular,thelargelysparedmedialrec-tusinhibitionafterMLFdestruction22pointstotheexistenceofaseparateinhibitoryconnec-tionwhichwasidentifiedinexperimentalstudies.'637AfterbilateralMLFdestruction,unilateralstimulationofinhibitoryneuronsofthePPRFbetweenthefourthandsixthcranialnervenucleievokedmonosynapticinhibitorypotentialsinipsilateraloculomotornucleusneurons36andipsilateralmedialrectusmotorneurons.'7Fibredegenerationstudiesinrab-bits'6andprimates39andautoradiographicstudiesincats33andprimates26"'showedanuncrossedconnectionbetweenthePPRFandtheoculomotornucleusascendingadjacenttobutseparatefromtheMLF2639andapproach-ingmedialrectusmotorneurons.'"SuchfibresoriginatefromthesameneuronswithintheipsilateralPPRFwhichgenerateinhibitorymonosynapticpotentialstoipsilateralmedialrectusmotorneurons.4'Thisconnection,whichmaybecalledthepara-MLF,mostlikelymediatesmedialrectusinhibition.Onthebasisofthesedataweproposeamodifiedconceptoftheprenuclearorganisationofhorizontaleyemovements(fig5).Accordingly,abductionparesisisduetoimpairedinhibitionofmedialrectustonicrestingactivityfollowinginterrup-tionofthepara-MLF.Asmallischaemiclesionseemsmostlikelyinallourpatients.Patients2,4,5,6,7,8sufferedfromdiabetesandpatients6and7alsohadarterialhypertension;patient1hadarterialhypertensionandatrialfibrillationandpatient3wasaheavysmoker.Theregioninquestionissuppliedby:a)AfewlongarteriesoriginatingfromthebasilararterysupplyingtheMLFandterminatinginthepara-MLFregion;b)Afewsmallbranchesofthemedialcerebellararterysupplyingthemesencephalicnucleusofthetrigeminalnervewhichalsoterminateinthepara-MLFregion;c)Smallbranchesofthecolliculararteryapproachingthepara-MF4243Obviouslytheterritoryofthepara-MLF(fig6)formsawatershedzone.Circulatoryarrestofoneofthelongpenetratingarteriesofthebasilarartery,whichoftenshowanasymmetrictermination,43maycontributetoasymmetricalabductionparesisobservedinfivepatients(4,5,6,7,8).Also,acombinedlateralrectusandsuperiorobliquemuscleparesis(patient3,5)mayoccurfromasingleischaemicmidbrainlesion,sincethepara-MLF,thetrochlearnerveafteritscrossing,andthemesencephalicnucleusofthetrigeminalnervearecloselyrelatedatthatsite(44)(fig6).AbrainstemlesionwasnotshownbyCT(patients1,2,3,4,5,6)orMRI(patients3,4).However,suchlesionsarefrequentlytoosmalltobedetected,whichrecentlyhasbeenillus-tratedin11patientswithisolateddiabeticoculomotorpalsyduetomidbrainlesions.'3Thinnerslices(3mminsteadof10mminourpatients)andGadolinium-DTPA(notusedinourpatients)mayimprovethesensitivityofMRIinthiscondition.Inconclusion,weproposetheexistenceofanabductionparesisofprenuclearoriginonthebasisofclinicalandelectrophysiologicalfind-ingsindicatingarostralpontineormesence-phaliclesionineightpatients.Abductionparesisisduetoimpairedinhibitionofthetonicrestingactivityoftheipsilateralmedialrectusmuscleduringlateralgaze.SuchinhibitionistriggeredbythemonosynapticinhibitorypotentialsobservedinmedialrectusmotorneuronsafterunilateralstimulationofPPRFneurons.TheinhibitorypotentialsaremediatedbyanuncrossedconnectionbetweenthePPRFandtheoculomotornucleus.ThisconnectionascendingincloseproximitytotheMLFmaybecalledthepara-MLF.Sincethepara-MLFisaninternuclearconnectionthemovementdisorderresultingfromitsdamageisappropriatelytermedinternuclearophthal-moplegiaofabduction(INO-abd).Thediag-nosisofINO-abdshouldbeconsideredinpatientswithanincompleteabductionparesisandclinical,morphologicaland/orelectro-physiologicalevidenceofanipsilateralrostralpontineormesencephaliclesion.Orthophoriaintheprimarypositionasobservedinpatients1,3,4(righteye),5,6and8isexpectedinINO-abdbutoccursalsoinincompleteabducensnervepalsy.45Mild109 Thomke,Hopf,KramerFigure6Transversesectionthroughtheponto-mesencephalicbrainstem.(Accordingto(44),courseofthepara-MLFaccordingto(26,39).Thelevelsofthesectionareshownbythekeydiagramontheleft.(1)Mainsensorynucleusofthetrigeminalnerve;(2)Mesencephalicnucleusofthetrigeminalnerve(3)Motornucleusofthetrigeminalnerve;(4)PPRFNucleusreticularispontiscaudalis;(5)Mediallongitudinalfasciculus;(6)Genuofthefacialnerve;(7)Mesencephalictractofthetrigeminalnerve;(8)Motorpartofthetrigeminalnerve;(9)Sensorypartofthetrigeminalnerve;(10)PPRFNucleusreticularispontisoralis;(11)Decussationofthetrochlearnerves;(12)Trochlearnerve;(13)"Para"mediallongitudinalfasciculus;(14)trochlearnucleus;(15)oculomotornucleus;(16)oculomotornerve.esotropiaobservedinpatients2,4(lefteye)and7doesnotexcludeanINO-abd.InINOofadductionduetoimpairedprenuclearexcitatoryinputtomedialrectusmotorneurons,exotropiaofthepareticeyemayoccur.'8Byanalogy,mildesotropiainINO-abdisinterpretedintermsofanimpairedprenu-clearinhibitoryinputtomedialrectusmotorneurons.Alternatively,dysfunctionofver-genceneuronsmaycauseesotropiainmidbrainlesions.47Adductionnystagmusonthecon-tralateralwasseeninfiveofourpatients.ItisnotaconclusivesigninindividualpatientsindicatingINO-abdasitmayalsooccurinabducensnervepalsy.'8Diagnosticproblemsmayariseinpseudo-abducenspalsywithabductionparesisduetoabnormalconver-genceimpulsesonlateralgazedescribedinmidbraintegmentallesions.49Butthesepatientsshowmiosisonlateralgaze,49whichisnotafeatureofINO-abd.1LutzA.OberdieBahnenderBlickwendungundderenDissoziierung.(NebsteinesFallesvonOphthalnoplegiainternuclearisanteriorinverbindungmitDissoziierungderBogenginge).KlinMonatsblAugenheilkd1923;70:213-35.2LarmandeA-M.LaparalysiesupranucleaireduVI.(diteophthalmoplegieinternucleaireposterieure).Archd'Ophtalmol(Paris)1969;29:521-30.3SchiffterR.DieinternukleirenOphthalmoplegien.KlinischeAnalysevon25Krankheitsfaillen.Nervenarzt1975;46:116-27.4CollardM,EberAM,StreicherD,RohmerF.L'ophthalm-oplegieinternucleaireposterieure-existe-t-elle?Aproposdeonzeobservationsavecoculographie.RevNeurol1979;135:293-312.5TopilowHW.PosteriorinternuclearophthalmoplegiaofLutz.AnnOphthalmol1981;13:221-6.6BogousslavskyJ,RegliF,OstinelliB,RabinowiczT.Paresisoflateralgazealternatingwithso-calledposteriorinternu-clearophthalmoplegia.Apartialpontinereticularforma-tion-abducensnucleussyndrome.JNeurol1985;232:38-42.7KommerellG.Internuclearophthalmoplegiaofabduction.Isolatedimpairmentofphasicocularmotoractivityinsupranuclearlesions.ArchOphthalmol1975;93:531-4.8WalshFB,HoytWF.ClinicalNeuro-Ophthalmology,3rded,Vol1.Baltimore:WilliamsandWilkins,1969:239-43.9FineM,MacGlashanCB.Unilateralinternuclearophthal-moplegiaofvascularorigin.ArchOphthalmol1956;56:327-37.10HennV,BuittnerU,Buttner-EnneverJA.SupranukleareOrganisationderOkulomotorik-physiologischeundanatomischeGrundlagen.In:KommerellG,ed.Augen-bewegungsst6rungen.NeurophysiologieundKlinik.Muinchen:Bergmann1978:129-41.11RothsteinTL,AlvordEC.Posteriorinternuclearophthal-moplegia.Aclinicopathologicalstudy.ArchNeurol1971;24:191-202.12OngerboerdeVisserBW.Afferentlimbofthehumanjawreflex:electrophysiologicandanatomicstudy.Neurology1982;32:563-6.13HopfHC,GutmannL.Diabetic3rdnervepalsy:Evidenceforamesencephaliclesion.Neuriology1990;40:1041-5.14KimuraJ.Clinicaluseoftheelectricallyelictedblinkreflex.In:DesmedtJE,ed.Motorcontrolmechanismsinhealthanddisease.NewYork:RavenPress1983:773-86.15HopfHC,ThomkeF,GutmannL.Midbrainversuspontinemediallongitudinalfasciculuslesions.Theutilizationofmasseterandblinkreflexes.MuscleNerve1991;14:326-30.16Buttner-EnneverJA,CohenB,BaumgartnerG.Verticalgazeparalysisandtherostralinterstitialnucleusofthemediallongitudinalfasciculus.Brain1982;105:125-49.17Pierrot-DeseillignyC,ChainF,GrayF,SerdaruM,EscourelleR,LhernitteF.Parinaud'ssyndrome:electro-oculographicandanatomicanalysisofsixvascularcaseswithdeductionsaboutverticalgazeorganisationinthepremotorstructures.Brain1982;105:667-96.18WeisbergLA.Mesencephalichemorrhages:clinicalandcomputedtomographiccorrelations.Neurology1986;36:713-6.19KorneyS.BlickstorungenbeivascularenHerdendesmesodiencephalenObergangsgebietes.ArchPsychiatZgesNeurol1959;198:535-43.20NasholdBS,GillsJP.Ocularsignsfrombrainstimulationandlesions.ArchOpthalmol1967;77:609-18.21OrlowskiWJ,SlomskiP,WojtowiczS.Bielschowsky-Lutz-Cogansyndrome.AmJOphthalmol1965;59:416-30.22BurdeRM,LehmanRAW,Roper-HallG,BrooksJ,Kelt-nerJL.Experimentalinternuclearophthalmoplegia.BritJOphthalmol1977;61:233-9.23PinhasI,PinhasA,GoldhammerY,BrahamJ.Progressivesupranuclearpalsy:Electromyographicexaminationsofeyemuscles.ActaNeurolScandinav1978;58:304-8.110 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