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

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Follow-uponYourPatient:AlthoughAaron’spresentationdidnotringanyimmediatealarm
bells,youuseoneofthequickin-officementalstatusevaluationsanddiscoverheappearsto havemildcognitiveimpairment.Youassurehimhedoesnothavedementia.Youlethim knowthatthereisnomedicationcurrentlyavailabletoreducehisriskofprogression,buthe readilyagreestoyourrecommendationsforahealthylifestyle—dailyexerciseinparticular. Hewillcomebacktoseeyouregularlytomonitorhiscognitivestatus.
Younowknow:
1. Thereis afine linethatseparates thecognitivechangesofnormalagingwith thoseofmildcognitiveimpairment;mentalstatustesting canbehelpfultodistinguishbetweenthetwo.
2. Importanttypesof dementia include Alzheimer disease (profoundmemory loss), vascular dementia (progresses in stepwise fashion), dementia with Lewy bodies (parkinsonism and often visual hallucinations), frontotemporal dementia (behavioral and personality changes)andCreutzfeldt-Jakobdisease(rapidprogression).
3. Always rule out reversible causes of dementia, such as depression, alcoholism, Hashimoto thyroiditis, vitamin B12 deficiency, and normalpressurehydrocephalus.
1
TheDiagnosticandStatisticalManualofMentalDisorders(DSM)IVandVusethetermmajorneurocognitivedisordertorefertowhat
ismorecolloquiallyknownasdementia.
2
SeeChapter13foracomprehensivereviewofParkinsondisease.
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8Meningitis,Encephalitis,andOther InfectiousDiseasesoftheNervousSystem
Inthischapter,youwilllearn:
1. Thedifferencebetweenmeningitisandencephalitis
2. Theclinicalpresentation,causes,andmanagementofmeningitis
3. Theclinicalpresentation,causes,andmanagementofencephalitis
4. TheneurologiccomplicationsofHIVinfection,neurosyphilis,andLymedisease
5. WhatweknowsofarabouttheneurologicmanifestationsofCOVID-19
6. Thepresentationandmanagementofbrainabscesses
CASE8
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YourPatient:Amir,a33-year-oldmanagementconsultant,comestoseeyouwithasevere
headachethatbeganjustafewhoursago,associatedwithphotophobiaandchills.Hehasa historyofmigraineheadaches,butthisheadacheisfarmoreseverethanhisusual migraines.Youmeasureatemperatureof103.2°Fanddemonstratemarkednuchalrigidity (astiffneck)onhisexamination.Thereisnoobviousrash.Therearenofocalneurologic abnormalities.Heislethargicbutnotdisoriented.Whatisyourimmediatenextstepinhis management:doyouorderaCTorMRI,performalumbarpunctureforCSFanalysis,or starthimonempiricantimicrobialtherapyrightaway?
Encephalitisreferstoinflammationofthebrainparenchyma.Meningitisreferstoinflammationofthe meninges.Theyaretraditionallydistinguishedfromeachotherbythepresenceofneurologicimpairment (encephalitis)orthepreservationofnormalneurologicfunction(meningitis).
Becauseencephalitis,unlikemeningitis,affectsthebrainparenchyma,itcancausefocalneurologic deficits,includingalteredmentalstatus(mostcommonly),hemiparesis,hemisensoryloss,andlanguage impairment.
Ontheotherhand,althoughmeningitiscancausealteredmentalstatus,mostoftenthisisasecondary phenomenonthatcanbeattributedtoacombinationoflethargyandpain(rememberthat,unlikethebrain
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parenchyma,themeningesarepainsensitive).Cerebralfunctionisotherwisenormal.Theclassic syndromeassociatedwithmeningitisistheresultofmeningealirritationandistermed,aptlyenough, meningismus:acombinationofstiffneck,headache,andphotophobia.
Itisnotuncommonformeningitisandencephalitistocoexisttosomedegree(meningoencephalitis). Meningitis,forinstance,canpresentwithfocalneurologicdeficitsasaresultofinvolvementofthe nearbybraincortexandspinalcord.However,forpurposesofclarityinsortingoutthedifferential diagnoses,itisagoodideatomaintainthefollowingdistinction:
Fever+focalneurologicdeficits=encephalitis Fever+meningismus+nofocalneurologicdeficits=meningitis
Warning:wearegoingtopokeseveralholesinthiscategorizationaswemakeourwaythroughthis chapter.Butthinkingaboutmeningitisandencephalitisinthiswayprovidesasolidframeworkfor understandinginfectiousdiseasesofthecentralnervoussystem.
Meningitis
IntheUnitedStates,themajorityofadultcasesofmeningitis(andencephalitis,too)arecausedby viruses.Viralmeningitisisrelativelybenign.Althoughtheseviralinfectionsareoftenveryunpleasantand canbedebilitating,thevastmajorityofpatientsmakeacompleterecovery.Fewerthan1in5casesof meningitisarecausedbybacteria,butthesecanbesodeadlysoquicklythatitisappropriatethatwefirst turnourattentiontothem.
BacterialMeningitis
Bacterialmeningitisisamedicalemergency.Althoughthereareothercausesofmeningitisbesides bacterialinfection(we’vejustmentionedthatviralmeningitisismorecommon,and,asyouwillshortly see,therearenumerousotherinfectiousandnoninfectiousetiologies),patientswhopresentlikeAmir withfever,headache,nuchalrigidity,photophobia,and/orconfusionhavebacterialmeningitisuntil provenotherwise.Yourfirststepistostarttreatmentimmediately,beforeyouproceedwithanyfurther evaluation.
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Suspectedbacterialmeningitisshouldbetreatedasamedicalemergency.
ClinicalPresentation.Mostpatientswithbacterialmeningitislookverysick.Theclassicpresentation consistsoffever,nuchalrigidity,photophobia,andalteredmentalstatus.Patientswhodonothaveatleast oneoftheseclassicsymptomsalmostcertainlydonothavebacterialmeningitis.Ontheotherhand,fewer thanhalfofpatientswithbacterialmeningitispresentwiththefullsymptomcomplex.Especiallyin infants,1theelderlyandimmunosuppressedpatients,oneormoreofthesesymptomsisoftenmutedor absentaltogether.Headacheisactuallythemostcommonpresentingsymptomofbacterialmeningitis (reportedbyapproximately80%ofpatients),followedbyfeverandnuchalrigidity.Thequalityand locationoftheheadachepainarevariableandcannotbeusedtohelpguidediagnosis.
Box8.1BrudzinskiandKernigSigns
Nuchalrigidityreflectsunderlyinginflammationofthepain-sensitivepiaandarachnoid
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meningesaroundthespinalrootsandnerves.Movementoftheneckisverypainful,so patientsattempttoholdtheirneckasstillaspossible.Ifduringyourexaminationyoutryto forceneckflexion,patientswillflextheirkneesandhips;thisiscalledtheBrudzinskisign. Forcingpatientstoextendonekneewiththethighatarightangletothetrunkwillcausepain inthebackandhamstrings,afindingtermedtheKernigsign.Whenpositiveintheright clinicalsetting,thesetestsarehighlyspecificformeningitis.However,theyarenotsensitive, thatis,theirabsencecannotbeusedtoruleoutthediagnosis.
ElicitingtheBrudzinskiandKernigsigns.
Otherfeaturesofbacterialmeningitiscaninclude:
Nauseaandvomiting Seizures Coma Focal neurologic signs (we’re poking holes in the standard definition already)—most commonly these arecranialnerveabnormalitiesduetoinflammatory exudatethatcrossesthepialbarrierand compressesthenerves Rash—meningococcalmeningitis,whichcarriesaparticularlypoorprognosis,isoftenaccompanied byatransientandrapidlyprogressivemaculopapularrash
CausesofBacterialMeningitis.Bacteriacanfindtheirwayintothesubarachnoidspaceeitherby hematogenousspread(bacteremia)orbydirectextensionfromalocalsiteofinfection,suchasacute sinusitisorotitismedia.Differentagegroupsareaffectedbydifferentorganisms(seetable),butinadults themostcommoncausesofbacterialmeningitisare:
1. Streptococcuspneumoniae(akapneumococcus)
2. Neisseriameningitidis(akameningococcus)
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TheMostCommonPathogensandTheirTreatment,byAgeGroup
Age MostCommonPathogens EmpiricTreatment
<1month GroupBStreptococcus(GBS),E.coli(+otherentericgram-negativerods),listeria Ampicillin+cefotaxime 1–23months GBS,E.coli,S.pneumoniae,N.meningitidis,H.flu Vancomycin+ceftriaxone 2–50years S.pneumoniae,N.meningitidis Vancomycin+ceftriaxone >50years S.pneumoniae,N.meningitidis,listeria,aerobicgram-negativerods(pseudomonas) Vancomycin+ceftriaxone+ampicillin
GBS,groupBstreptococcus.
Box8.2MeningococcalandPneumococcalVaccines
RoutinevaccinationagainsttheAandCmeningococcalserogroupshasledtoamarked declineinmeningococcalinfection,andvaccinationagainsttheBserogroupisnowavailable aswell.Pneumococcalvaccinationisnowrecommendedroutinelyforadults65yearsand olderaswellasforthoseatriskofinvasivedisease,thatis,thosewithacochlearimplant, CSFleak,orapriorhistoryofinvasivepneumococcaldisease,andhasdecreasedthe incidenceofinvasivepneumococcalinfection.
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Fulminantrashinapatientwithmeningococcemia.(ReprintedfromScheldMW,WhitleyRJ,MarraCM. InfectionsoftheCentralNervousSystem.4thed.LippincottWilliams&Wilkens;2004.)
S.pneumoniae,agram-positivediplococcus,isthemostcommoncauseofbacterialmeningitisin adults.Thisbacterialinfectionmorecommonlycausespneumonia(henceitsname),andmanypatients withmeningitisalsohaveevidenceofpneumonia.Ofimportance,however,theabsenceofpneumonia doesnotprecludethediagnosisofS.pneumoniaemeningitis.
N.meningitidis,agram-negativediplococcus,isthesecondmostcommoncause.Meningitiscaused byN.meningitidisisuniqueinthatitoftenpresentswithdevastatingsuddenness,progressingrapidly overjustafewhours.Itshouldbesuspectedimmediatelyinapatientwhopresentswiththeclassic nonblanchingmaculopapularrash(seeabove),whichcanbeseeninabout50%ofpatientsatthetimeof presentation.Complicationscanincludeshock,whichcancauseadrenalinfarctionandadrenal insufficiency(knownasWaterhouse-Friderichsensyndrome);disseminatedintravascularcoagulation; heartfailure;andpurpurafulminans(diffusecutaneousbleedingandnecrosis).
TheincidenceofmeningitiscausedbyHaemophilusinfluenzae,agram-negativerod,hasdeclined dramaticallyintheUnitedStatesandotherdevelopednationssincetheearly1990sbecauseof
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widespreadchildhoodvaccinationagainstH.flutypeb(knownasHib,themostvirulentstrainand,ofthe typeablestrains,themostlikelytocauseinvasivedisease).Worldwide,however,H.fluremainsoneof themostcommoncausesofmeningitis.Childrenlessthan5yearsofagearemostlikelytobeaffected.
Listeriamonocytogenes,agram-positiverod,causesabout5%to8%ofcasesofbacterialmeningitis andoccursmostlyinneonates,pregnantwomen,adultsover50yearsandimmunocompromisedpatients. Itisprimarilyafoodborneillness(mostoftenacquiredfromcontaminatedandunpasteurizedmilkor cheese).Meningoencephalitisisactuallymorecommonthanmeningitisalone,andthecoursecanrange frommild(feverwithsubtlementalstatuschanges)tofulminant,resultingincomaordeath.
Lesscommonbacterialcausesincludestreptococci(groupAstreptococcalinfectioncanbeseen followingbasilarskullfracture;groupBstreptococcalinfectionpredominantlyaffectsneonatesand infants),aswellasstaphylococciandaerobicgram-negativebacteria(S.aureusandpseudomonascan beassociatedwithpenetratingskulltraumaorneurosurgery;immunocompromisedpatientsareat increasedriskofpseudomonasmeningitis).Escherichiacolimostoftenaffectsneonatesasaresultof exposureduringvaginaldelivery.
Diagnosis.Patientswithsuspectedbacterialmeningitisshouldhaveacompletebloodcountandblood culturesdrawnimmediately.Ifpossible,bloodculturesshouldbeobtainedbeforeinitiatingantibiotic therapy;theyarepositiveinamajorityofcasesofbacterialmeningitis.However,thekeytodiagnosisisa lumbarpunctureforcerebrospinalfluid(CSF)analysis.Ifthelumbarpunctureis,forwhateverreason, contraindicatedordelayed,antibiotictherapyshouldnotbedelayed,becauseanydelayintreatmentcan befatal.
CSFanalysisallowsyouto(1)quicklydistinguishbacterialfromviralandothercausesofmeningitis, (2)immediatelyidentifytheorganismiftheGramstainispositive,2and(3)sendoffdefinitiveteststo pindownthepreciseetiologyandantibioticsusceptibilityofthecausativeorganism.
CSFFindingsAssociatedWithMeningitis
OpeningPressure PredominantCellType Protein Glucose
Bacterial ↑ Polymorphonuclearleukocytes ↑ ↓ Fungal ↑ Lymphocytes ↑ ↓ Viral ↑ornormal Lymphocytes ↑ornormal normal
TheessentialCSFteststoorderinclude:
acellcountanddifferential glucoseandproteinlevels aGramstain cultures(bacterial,viraland,ifthepatientisimmunocompromisedorhasotherriskfactors,fungal) andpolymerasechainreaction(PCR)testing(bothviralandbacterial)
ACToftheheadisindicatedbeforeperformingalumbarpunctureonlyifthereisconcernfor increasedintracranialpressure,whichcouldleadtoherniationwhenCSFiswithdrawnduringthelumbar puncture.Suspectincreasedintracranialpressureif:
1. thereareany neurologicabnormalitiesonexamination(papilledemaspecificallyisindicative ofelevatedintracranialpressure,butany focalityonexaminationispotentiallyconcerningforaconcomitantoralternativediagnosis,includingintracranialabscessorothermass lesion);
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2. thepatientexperiencedaseizure;or
3. thepatientisimmunocompromised.
Treatment.Onemoretime:ifyoususpectbacterialmeningitis,donotdelaytreatmenttopursueyour diagnosticevaluation.Empiricantibiotictherapyinadultsusuallyconsistsofathird-generation
cephalosporin(ceftriaxone)combinedwithvancomycin(seeTableonpage207).Ampicillinshouldbe addedinolderorimmunocompromisedpatientstoprovidecoverageforlisteria.Therapycanbeadjusted oncetheactualpathogenhasbeenidentifiedandantibioticresistancepatternshavebeenassessed.
Intravenous(IV)dexamethasoneshouldalsobegivenforsuspectedorprovenpneumococcalmeningitis (nobenefithasbeenfoundforothercausesofbacterialmeningitis)andcontinuedonlyifgram-positive diplococci(i.e.,pneumococci)areconfirmedonGramstain.Althoughitisunclearifcorticosteroids decreasemortalityinpatientswithpneumococcalmeningitis,theydoappeartoimproveneurologic outcomesandreducetheriskofhearingloss.IVhydrationmayalsoreduceneurologicsequelae.
IVacyclovirisalsooftenaddedempiricallybecauseoftheoverlapintheclinicalpresentationof herpessimplexvirus(HSV)meningitis/encephalitis(seebelow,andpage216)andbacterialmeningitis. OnceHSVinfectionisruledout,acyclovircanbestopped.
Prognosis.Despitemoderntechniquesofdiagnosisandtoday’spowerfulantibiotics,about25%of patientshospitalizedwithbacterialmeningitisstilldie,andmanywhosurvivehaveresidualhearingloss, seizures,cognitiveimpairment,orotherfocalneurologicdeficits.Oneimportantriskfactorformortality thatweshouldbeabletokeepimprovingisdelayininitiatingantibiotictherapy.
OtherCausesofMeningitis
Wecangroupthemanyothercausesofmeningitisintothosethatareinfectiousandthosethatarenot.In eithercase,routinebacterialculturesinCSFwillbenegative.TheresultingCSFprofileisoftentermed asepticmeningitis(i.e.,culture-negativemeningitis).
Infectious(Viral)Causes.Viralmeningitisistheleadingcauseofasepticmeningitis.Symptomstendto befarlessseverethanthoseseenwithbacterialmeningitis.Themostcommonviralcausesinclude:
Enteroviruses (including echovirus, coxsackie virus, and other nonpolio enteroviruses). In the UnitedStates,theseinfectionsusuallyoccurinthe summermonths.Patientsalmostalwaysrecover completely,althoughsymptomssuchasheadacheandfatiguecanpersistformonths. Herpesviruses.Unlikeherpesencephalitis(seepage216),whichisalmostalwayscausedbyHSV­1,meningitisis mostoftencausedbyHSV-2.Genitallesionsareoftenpresent.Patientsaretreated with IV acyclovir, although the benefitremains unclear.HSV-1, varicella-zoster virus (VZV) and cytomegaloviruscanalsocausemeningitis,usuallyinimmunocompromisedpatients. HIV. HIV meningitis tends to presentatthe time ofinitial seroconversion and typicallyresolves withouttreatment. Mosquito-borneinfections.Inrecentyearsanumberofmosquito-borneinfectionshavesurfacedin the United States. Chief among them is West Nile virus. This particular virus can also cause encephalitisoracuteflaccidparalysis(seepage217). Mumps.BeforetheMMRvaccinewasintroduced,mumpswasoneofthemostcommoncausesof aseptic meningitis. Today, because of the increasing numbers of children who are not being vaccinated, the incidence is again rising. Meningitis remains the most frequent extrasalivary,
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