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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_186_библиотеки_им_акад_М_И_Перельмана

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b.
2ormoreback-to-backseizureswithoutreturntobaselineinbetween.
2. Although it is generally believed that it takes approximately 30 minutes for ongoing generalized convulsive seizure activity to pose significantriskoflong-term brain damage, itishighlyunlikelythatseizureactivitywillspontaneouslyceaseonceit has persistedfor5 minutes,andthus—atthe5-minutemark—itisnecessarytodiagnosestatusandtreatit.
3. Nonconvulsivestatusepilepticus(NCSE).NCSEisjustwhatitsoundslike:prolongedseizureactivity(inthiscase,thethresholdisat least10minutes)without prominent (or any)associatedmotoractivity.This ismostoftenseen incriticallyill patients—patients with severesepsis,acuteneurologicinsults,orpatientswhoarepost-cardiacarrest—andshouldalwaysbeconsideredwhentheseverysick patients are “not wakingup”despite adequate medicalmanagement.Thediagnosis, asyoucan imagine,relies almost exclusively on EEG,butneitherdiagnosingnortreatingNCSEisstraightforward.ItisthereforeimportanttoknowthatNCSEexistsandtohavealow thresholdforEEGmonitoringwhenpersistentlypoororfluctuatingmentalstatusisotherwiseunexplained.
Box6.10GeneralizedVersusFocalConvulsiveStatusEpilepticus
Whenpeopletalkaboutconvulsivestatusepilepticus,whattheytypicallymeanis generalizedconvulsivestatusepilepticus,thatis,shakingoftheentirebody.Butconvulsive statuscanalsobefocal—forexample,prolongedshakingofonearmoroneleg.Focal motorstatuswithoutimpairedconsciousness(alsoknownasEpilepsiaPartialisContinua) isnearlyalwaysduetoanunderlyingfocalbrainlesion.Itisnotanemergencyinthesame waythatgeneralizedconvulsivestatusis:itcan,infact,lastfordays,months,orevenyears withoutanyevidenceofbraindamage.Itcanalsobenotoriouslydifficulttotreat,andoften requiresabalancebetweensymptommanagement(reducingtheshakingtoatolerable level)andmedicationsideeffects(primarilyavoidingover-sedationcausedbytoomany AEDs).
Thetreatmentalgorithmforgeneralizedconvulsivestatusepilepticusisstraightforwardandeffective. Memorizethis.Itiseasytopanicwhenconfrontedwithapatientinconvulsivestatus,butifyouknowthis algorithm,youwon’thesitatebeforejumpingintoaction.
1.  First line: Benzodiazepines. Options include IV lorazepam, midazolam, anddiazepam. These act rapidly butcan cause significant respiratorydepressionandcanthereforeonlybegivenuptocertaindosesinordertoavoidintubation.
2. Secondline:Youhaveseveraloptions,allofwhichareequallyefficacious.Decidewhichwaytogobasedonsideeffectprofile.
a.
IV levetiracetam. The dosehas to be adjusted to the patient’s renalfunction, but otherwise, levetiracetam has no significant, immediateadverseeffectsthatyouneedtoworryabout.
b.
IVvalproate.Avoidinpregnantpatients,orinpatientswithknownthrombocytopeniaorliverdysfunction.
c.
IV phenytoin. Avoid in patients with known cardiac arrhythmias, or who are currently hemodynamically unstable. If it is available,you should giveIV fosphenytoininsteadofphenytoin: itisaprodrugofphenytoinandcanbeinfusedupto3xfaster withlessriskofthrombophlebitisorcardiacarrhythmias.
d.
IVlacosamide.Lacosimideisaneweragentandhaslesssupportingevidencethanthemedicationsabove.Thusfar,however,it seemstobeequallyaseffectiveandisanothersecond-lineoption.Avoidthisdruginpatientswithknowncardiacarrhythmias.
3. Thirdline:Chooseasecondoptionfromtheabovelist.Ifyou’vegivenlevetiracetamwithoutresponse,forinstance,tryvalproate.
4.  Fourth line:Sedate and intubate. At this point, youare essentially attempting to temporarily shutdown—andhopefully reset—the brain.Midazolamandpropofoldripsarethemostcommonlyusedtherapies.Pentobarbitalandketamineareotheroptions.
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Box6.11
Youmightwonderwhyphenytoin—anarrow-spectrumantiepilepticmedication—isusedto treatgeneralizedstatus.Justasmostfirst-timeunprovokedseizuresinadultsarefocal­onsetseizuresthathavesecondarilygeneralized,mostcasesofstatusinadultsarealso focal-onsetseizureswithsecondarygeneralization.
Box6.12ImagingChangesAssociatedWithStatusEpilepticus
Asidefromidentifyingunderlyingstructurallesions,anMRIcanrevealabnormalitiesdueto ongoingseizureactivityitself.LeptomeningealenhancementaswellasareasofT2 hyperintensityonfluid-attenuatedinversionrecovery(FLAIR)sequencesanddiffusion restrictionondiffusion-weightedimaging(DWI)sequencesarecommon(mostoftenseenin cortical,thalamic,anddeeplimbicstructuressuchasthehippocampus)andarebelievedto berelatedtoseizure-inducedcellularedema.
Anexampleofpost-statuschangesondiffusion-weightedMRI,showingpredominantlyleft-sided hyperintensity(arrows)alongthecorticalrim(referredtocolloquiallyasthecorticalribbon)that comprisestheoutermostlayerofthebrain.ModifiedfromBillerJ,EspayA.PracticalNeurologyVisual Review.2nded.WoltersKluwer;2013.
Box6.13RefractoryandSuper-RefractoryStatusEpilepticus
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Refractorystatusepilepticusisdefinedasongoingseizureactivitydespitefirst-lineand second-linetreatment.Super-refractorystatusepilepticusisstatusepilepticusthathasnot respondedtoanesthetictherapy.
PsychogenicNonepilepticSeizures(PNES)
Previouslycalledpseudoseizures,PNESareparoxysmaleventsthatclinicallyresembleepileptic seizuresbuthavenoEEGcorrelate;thatistosay,ifapersonexperiencesapsychogenicseizurewhile hookeduptoanEEG,theEEGwillbenormalwithoutanyepileptiformactivity.
Clinically,PNESmaysometimescloselyresembletrueseizureactivity(i.e.,relativelybrief,rhythmic, nonsuppressiblestereotypedmovements)orsometimesnot(lastingmuchlonger—often15to20minutes —nonrhythmic,nonstereotyped,andsuppressible).PNEStendtobecharacterizedbyasynchronous, erraticmovementsthatstartandstop;associatedbackarchingandcryingarecommon.Nomatterhow manyepilepticandnonepilepticseizuresyouhaveseen,however,itisimportanttoremainhumble.True epilepticseizuresoriginatinginthefrontallobe,forinstance,canappear“psychogenic”withbizarre bicyclingofthelegsorotherhypermotorbehaviors,andcaneasilybemistakenforpsychogenicevents. Youmaysuspectnonepilepticseizures,but—withrelativelyfewexceptions—youcannotknowforsure unlessyoucaptureanepisodeonEEG.
PatientswithPNESoftenhavearelativeorclosefriendwithepilepsy.Manypatientsexperienceboth epilepticandnonepilepticseizures.Ahistoryofsexualabuseiscommon,asareothercomorbid psychiatricconditions.
Explainingthisdiagnosistothepatientcanbechallengingbutiscriticallyimportant.Thelonger patientsbelievetheyhave—andaretreatedfor—trueepilepsy,theworsetheirprognosisforrecovery fromPNES.Emphasizingtheseriousnessofthisdiagnosisisoftenhelpful.Althoughtheseeventsmaynot beepilepticinnature,theyarejustas“real”asepilepticseizures,andcanhaveseriousanddebilitating consequences(e.g.,leadingtomultiplehospitaladmissions,evenunnecessaryintubations,aswellas causingunderstandableanxietyandexacerbatingothermentalhealthdisorders)ifnotappropriately managed.
Referraltopsychotherapyand—ifneeded—graduallypeelingoffpreviouslystartedantiepileptic medications,arethemainstaysoftreatment.Ifdiagnosedearly,theprognosisisgood.
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YourPatient’sFollow-up:Carltonpresentedwithaleftgazepreferenceandright-sided
weaknessafterbeingfounddownonthegroundbyEMS,withreportedfull-bodyshaking priortoEMSarrival.ShortlyafterhisarrivaltotheED,youactivateastrokecode.CTofthe headandCTangiogramarebothunremarkable.Asyouaretryingtogatherinformation regardinghishistoryandpotentialcandidacyforthrombolytictherapywithtPA—because youcannotyetruleoutastroke—youareabletoreachhiswifeonthephone,whotellsyou thathehashadseizuressincehewasachild.Shedoesnotknowwhatantiepileptic medicationhetakesorifhehasbeentakingitbutdoestellyouthathehasbeensickforthe pastfewdayswithhighfeversandchills.Onre-examination,younotethathisgaze preferencehasresolved.Hestillseemstobeslightlyweakerontherightthantheleft,but heisgraduallywakingup,andaftersomepromptingisabletotellyouhisnameandhis birthday.
Althoughyoustillcannotknowforsurethathehasnothadanischemicevent,hisexaminationis rapidlyimproving;besidesthesubtleweaknessofhisrightarm,hisexaminationisnownon-focaland thusyoudecide,appropriately,todefertPA.AnMRIperformedseveralhourslaterisnormal,without evidenceofacuteischemia.Thepatient,nowfullyawake,isabletotellyouthathenormallytakes levetiracetamtwiceadaybutmissed2dosesinthelast2daysbecausehewasfeelingsoill.Youcounsel himontheimportanceofmedicationadherence,loadhimwithlevetiracetamtobumpuphisleveland
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dischargehimhome,withstrictprecautionstoreturntothehospitalifhehasanotherseizure.
Younowknow:
1. Generalizedseizuresincludegeneralizedtonic-clonic, tonic,clonic, myoclonic,atonic,andabsenceseizures.Focalseizuresaredivided intothosewithimpairedawarenessandthosewithretainedawareness. Focalseizureswithimpairedawareness(previouslyknownas complexpartialseizures)arethemostcommontypeofseizureinadultswithepilepsy.
2. It can be surprisingly difficult to distinguish the postictal state from stroke in the acute setting. Performing a careful neurologic examinationand quickly obtainingrelevantcollateralinformationis essential.Sometimes,ifyou stillare notsure andthe patienthas persistentandsignificantneurologicdeficits,treatingthatpatientasifheorsheishavingastrokeisimperative.
3. Therearemanyantiepilepticmedications,nooneofwhichhasbeenshowntobesignificantlysuperiortoanyother.Approximatelyone­third of patients with epilepsy are drug-resistant and should be referred to comprehensive epilepsy centers and considered for nonpharmacologictherapies,suchasdietmodificationsandepilepsysurgery.
4. Notalltypesofstatusepilepticusaretrueemergencies.Generalizedconvulsivestatusisanemergencyandmustberapidlyrecognized andtreated.Focal convulsivestatus, alsoknown asEpilepsiaPartialisContinua,isnotanemergencyandcangoonfordays, months, andevenyearswithoutsignificantbraindamage.
5. Nonconvulsive statusismost frequentlyseenanddiagnosedincriticallyill patientswithpersistentlypooror fluctuatingmentalstatus. Rapiddiagnosis(viaEEG)andtreatmentcanoftenhelpwithpatientprognostication.
6. Psychogenicnonepilepticseizures arecommon,particularlyamongpatientswith close friendsorfamilywithepilepsy,andthosewitha historyofothercomorbidpsychiatricconditionsorsexualabuse. PNEScanbedifficulttodistinguishfromepilepticseizures;diagnosis often requires prolonged monitoring to capture an episode while the patient is hooked up to an EEG. With early diagnosis and appropriatemanagement,theprognosisisgood.
1
Theterm“symptomatic”heresimplymeansthattheconditionhascausedaseizure,henceitis“symptomatic.”
2
Notethedistinctionbetweenacute,symptomaticconditionsandremote,symptomaticconditions.
3
Therearecaveatstothisrule.Forexample,apatientwithapriorstrokecanhavenonepilepticseizures.AndanabnormalEEG—assumingit isn’tperformedduringtheevent—doesnotnecessarilymeantheeventitselfwasatrueseizure.Don’tworryifallthisdoesn’tmakeperfect sensetoyounow;itwillbytheendofthechapter.Thepointisthat,aswithanydiagnosis,don’tforgettouseyourclinicaljudgment!
4
No,youarenotsuddenlyreadingathrillerbyDanBrown,andyes,thisisreallythetermusedbyneurologiststomeanthesignsor manifestationsofaseizure.
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7NeurocognitiveDisordersandDementia
Inthischapter,youwilllearn:
1. How to distinguish the cognitive changes of normal aging from those of mild cognitive impairment(MCI)anddementia
2. To distinguish among the most common types of dementia, including Alzheimer disease (AD),vasculardementia,anddementiawithLewybodies(DLB),amongothers
3. Howtoscreenforreversiblecausesofdementia
4. Whattreatmentsareavailabletohelpourpatientswithdementia
CASE7
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YourPatient:Aaron,a65-year-oldphysicsprofessor,comestoseeyoubecauseof
concernsabouthismemory.Workisgoingfine,butonacoupleofoccasionshehas forgottenwhereheparkedhiscarandmorethanonceduringalecturehehasforgottenthe nameofoneofhisstudents.Oneothertimeheforgotthenameoftheengineerwhowasthe founderofthescienceofthermodynamics(SadiCarnot,forthoseofyouwhoare interested).Heisonnomedicationsanddeniesthatheisdepressed.Hisfatherwas diagnosedwithAlzheimerdementiainhisseventies,andAaronisafraidheisshowingthe firstsignsofdementia.Shouldhebeevaluated,andifso,how?
CognitiveImpairment
Thereisabroadspectrumofcognitivefunctionthatweregardasnormal.Ourabilitiesinthemany differentmodalitiesofintelligencevaryfrompersontoperson,andthankgoodnessforthat;afterall,a worldofalllawyersoraccountantsorevenhealthcareproviderswouldbeaverylimitedandboring placeindeed.
Thereisalsoaspectrumofnormalcognitivedeclineasweage:memory,executivefunction, processingspeed,andword-findingtypicallyalldecline,varyinginhowmuchandhowfasteach modalityregressesfromindividualtoindividual(thegoodnews:othercognitivefunctions,suchas readingandverbalreasoning,oftenimprovewithage).Withnormalaging,mostofthesechangesareslow andsubtleanddonotimpactourworkorsocialinteractions.Attheotherextreme,thereisdementia—not apartofnormalaging—inwhichdailyactivitiesbecomesignificantlyimpaired.Betweennormalaging anddementia,thereissomethingcalledmildcognitiveimpairment(MCI).
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Onesimplifiedviewofhowcognitiondeclineswithaging.
Beforewediveintothedetailsofthemultipletypesofdementia,herearesomeusefuldefinitionsto helpyoukeepthingsstraight.
Dementia.Sowhatexactlydowemeanwhenweusethetermdementia?Whencognitivedeclineimpairs apatient’sabilitytofunctionindependently,thatpatienthascrossedoverthevague,ill-definedgrayline thatseparatesMCI(seethenextpage)fromdementia1.Itisalinethatiscrossedtoooften:aboutonein sevenindividualsovertheageof70carriesthediagnosisofdementia,andbyage90thatnumberis greaterthanoneinthree.Dementiaisoneoftheleadingcausesofdeathanddisabilityworldwide,and becauseofoursteadilyagingpopulation,itsprevalenceisexpectedtoincreaseasmuchasthreefoldby
2050.
Patientswithdementiawillshowadeclineinatleastoneofthefollowingdomains:
Memoryandlearning Executivefunctioning (organizationalskillssuchasplanningandproblem-solving,self-control and moralreasoning) Language(wordfinding,fluencyandcomprehension) Socialcognition(socially-appropriateinsightandemotions) Complexattention(theabilitytomaintainandmanipulateinformation,andtheabilitytostayontask despitedistraction) Perceptual motor function (ability to use one’s sensory and motor skills to interact with the environment)
Box7.1DementiaVersusDelirium
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Dementiatendstopresentinsidiouslyandisbothprogressiveandirreversible,whereas deliriumpresentsacutely,withawaxing-and-waningcourseandoftenreversibleetiology.For acomprehensivediscussionofdeliriumandencephalopathy,seeChapter15.
Alzheimerdementia(AD),vasculardementia,dementiawithLewybodies(DLB),frontotemporal dementia(FTD),andpriondisease(suchasCreutzfeldt-Jakobdisease)areallimportanttypesof dementiathatwillbediscussedindepthlaterinthischapter.
MildCognitiveImpairment(MCI).Estimatesvary,butMCIaffectsasmanyasoneintenpeopleupto age69,andnearlytwointenuptoage74.FifteenpercentofpatientswithMCIovertheageof65willgo ontodevelopovertdementiawithin2years;thisstatisticcanunnerveeventhemoststoicalamongyour patients,soremembertoemphasizetothemthatthismeansthat85%ofpeoplewithMCIwillnot progresstodementiaduringthatperiod.
ThesimplestdefinitionofMCIiscognitiveimpairmentthatdoesnotfullymeetthediagnostic criteriafordementia;inotherwords,cognitiveimpairmentthatdoesnotsignificantlyimpairactivitiesof dailyliving.Everyone’sbaselineisdifferent,soitisimportantnottomakethediagnosisofMCIunless thereisadeclinefromthepatient’sownparticularbaseline.
DistinguishingMCIfromthecognitivechangesthataccompanynormalagingislargelybasedon clinicaljudgment,relyinginnosmallpartonthepatient’sown(andthepatient’sfamily’s,friends’,and colleagues’)assessment.Symptomsthatsuggestsomethingmorethannormalagingisgoingoninclude:
Gettinglostinfamiliarplaces Forgettingrecentevents Demonstrating a declining ability to comprehend things that previously were within the patient’s grasp Exhibitingadeclineinexecutivefunctionssuchasplanningandorganizing Experiencingbehavioralchanges,rangingfromapathytoaggression
ShouldYouScreenforCognitiveImpairment?.Routinescreeningoftheolderpopulationisnot recommendedbymost(althoughnotall)currentguidelines,primarilybecausethereisnoevidencethatit improvesmeaningfulclinicaloutcomes.Wecurrentlydonothavemuchinthewayofevidence-based methodstoslowcognitivedeclinebeyondthesamelifestylerecommendations—healthydiet,exercise, etc—wewouldmaketoanypatient.Thedataonphysicalexercise,however,arestartingtoget interesting,withpreliminaryevidenceshowingthatitcandelaytheprogressionfromMCItodementia.
HowtoAssessCognitiveImpairment.Testingisappropriateifandwhenyoususpectyourpatientmay becognitivelyimpaired,andvarioustoolsforcognitiveassessmentareavailable.Some,whichcanbe doneinyouroffice,arequickandeasy,whereasothersrequirereferraltoaspecialtycenterandaremore involved(oftenrequiringawholeday’ssessionofcognitivetestingdonebyaneuropsychologist).The utilityoftestingliesmoreinproviding“objective”evidenceofthediagnosisandthetrajectoryofthe illnesstoconcernedpatientsandfamilymembersthaninguidingtherapyandimprovingclinical outcomes.Thevalidatedin-officetestseachtakeonlyafewminutestoperformandincludetheMini­MentalStateexamination,theMini-Cog,theMontrealCognitiveAssessment,andthe8-ItemAscertain Dementia.
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