Neuroinfec*ons

A.  Localiza*on§  Meningi*s-inflamma*onofmeninges§  Encephali*s-braininflamma*on§  Myeli*s-spinalcordonflamma*on

B.  E*ology§  Bacterial§  Viral§  Fungal§  Parasi*c§  Priondiseases

C.Accordingtocerebro-spinalfluidcharacter§  Purulent§  Non-purulent

Classifica*on

Bacterial

•  Pneumococci-Streptococcuspneumoniae-Gram-posi*vebacteria

•  Meningococci-Neisseriameningi*dis-Gramnega*vebacteria

•  Haemophilusinfluenzae•  Mycobacteriumtuberculosis•  Borreliabugdoferi

S.pneumoniae,H.influenza-carriersinthenasalcavity

bacteriemia

seedingofthebacteriatodifferentloca*ons,thisgivesriseto:

SepsisPurulentmeing*sDisseminatedpneumonia

Symptomsofbacterialmeningi*s/encephali*s

•  headache•  nausea•  vomi*ng•  photophobia•  highbodytemperature•  disordersofconsciousness•  petechiae•  convulsions•  symptomsofcranialnervedamageandfocalbraindamage

Brainabscess

•  E*ology:staphylococci,streptococci,baccillianaerobicbacteria

•  Secondarytosomepurulentinflamma*on-nasalsinuses,middleear,infectedfracturesoftheskull.

Symptoms

•  headache,signsoffocalbraininjurydependingontheloca*on,

•  diagnos*ctests:computedtomography,magne*cresonanceimagingofthebrain

•  Treatment:surgerywithsimultaneousan*bio*ctherapy

Tuberculousmeningi*s(Mycobacterium

tuberculosis)

•  Sourceofinfec*on:asickman•  Therouteofinfec*on:blood-derivedmostlyfromtheprimaryfocusinthelungs,lymphnodesororgantuberculosis

•  Rareincidence•  Peoplewithimmunodeficiency.

SymptomsProdromalstage:•  increasedbodytemperature•  chills•  weakness•  nightsweats•  headaches•  nausea•  vomi*ngDevelopedstageofthedisease:•  symptomsofmeningi*s•  damagetothecranialnerves•  focalsymptoms•  rarelyseizures

Lymedisease•  Neuroboreliosis–bacteria-Borreliaspirochete,thesymptomsofnervoussysteminvolvementmayoccuratanystageofthedisease(early/late)

•  Radiculopathy,mononeuropathies•  Meningi*s•  Encephali*s•  CranialnervepalsiesSymptoms:•  asymptoma*cinfec*on•  mildasep*cmeningi*s•  headache,photophobia,necks*ffness,fever

Viral

•  Enteroviruses-polio,echo,coxsackie•  Paramyxoviruses-mumpsvirus,measles•  HerpesViruses-HSVtype1and2,CMV,Epstein-Barrvirus

•  Tick-borneencephali*s(TBE)virus•  Rabiesvirus

•  Subtypesof*ck-borneencephali*s(TBE):•  European•  Siberian•  Far-east

•  Mortality infec*on subtype of the Far East - 15-20%, theremaining1-4%

•  10-12000newcasesofTBEintheworldeachyear

•  AccordingtotheNa*onal Ins*tuteofHygiene inPoland,theaverage annual incidence of approx. 0.7-0.9 /100 000 -approx.260cases

Epidemiology-TBE

TBEvirus•  TBEistypicallycharacterizedbyabiphasiccourse:

–  PhaseI:non-specificflu-likesymptomsandthelatencyperiod–  PhaseII:meningi*s,meningi*sandencephali*s,orinflamma*onofmeninges,

brainandspinalcord

•  Pa*entswitTBEviralinfec*on:•  30%donotdevelopclinicalsignsandsymptoms•  30%-50%experienceonly1phaseofthedisease•  30%ofpa*entsdevelop2phase-CNSac*vity.

•  M>F•  allagegroups•  Moresevereintheelderly•  Even46%ofpa*entsinthePhase2TBEdevelopinglatecomplica*ons

•  The diagnosis of TBE is only on the basis of signs andsymptomswhichmaybeeasilyoverlooked.

•  In children with neurological symptoms, residing in areasendemic forTBEvirus->serological tests for thepresenceofan*-TBE.

2phaseofTBEviralinfec*on-symptoms

•  Fever,whosevalueocenexceeds40°C.•  Meningi*saccompaniedmainlyheadache,nausea,

vomi*ng,dizzinessandnecks*ffness.•  Encephalomenigi*sisaccompaniedmainlycerebellarsigns

andsymptoms,whichusuallybelongsataxia.•  Otherneurologicalsymptoms-meningealsigns,confusion,

convulsions,slurredspeech,tremors.•  Paralysisofthespinalnerveswasobservedin11-15%of

pa*ents.•  Occurenceparesisoflimbsinpa*entswithinflamma*onof

themeninges,thebrainandspinalcord,upperlimbsaremoreaffectedthenlower

•  Seizuresarerare

LaboratorytestsSignsofinfec*oninbloodserum•  Leukocytosis,whichismuchhigherthanotherformsofviral

meningi*s(6600-14600/mm3)•  ElevatedESR(upto100mm/hr.)•  ElevatedCRPCerebrospinalfluid(CSF)•  RarelytheviruscanonlybedetectedinasampleofCSF,notin

blood•  Pleocytosis(predominanceoflymphocytes)to5000/mm3,higher

numberofrod-shapedgranulocytes(60%-70%)thenlimphocytes(30%-40%)

•  Protein50-200mg/dl•  Increasedra*oofalbuminintheCSFtoalbuminserum-

impairmentoftheblood-CSFtransfer

•  ThediagnosisofTBE-detec*onofspecifican*bodies•  Typically,IgMandIgGan*bodiesarepresentinthefirst

serumsampleswhenthesymptomsfromtheCNSappear•  ItisraretodetectonlyIgMan*bodiesinthefirstserum

sample.Inthiscase-repeatthetest.ThepresenceofIgMan*bodiesisnotenoughtoestablishthediagnosis.

•  Afewdayslater,IgMandIgGan*bodiesaredetectedintheCSF.

•  IgMan*bodiescanbedetectedinserumforseveralmonths.

•  IgGan*bodiespersistforthelife*meofthepa*ent.

TBEinchildrenTBEinchildrenhaslessseverecoursethaninolderpa*ents,but•  about20%-30%oftheaffectedchildrendevelop

encephalomeningits•  about25%developlong-termdisturbanceinafen*onand

concentra*ondeficits•  about2%sufferfrompermanentconsequencesof

neurologicaldiseaseLong-termconsequencesofTBEinfec*oninchildrenareunknown,whichunderlinestheimportanceofanaccuratediagnosis.

§  Ataxia, confusion, double vision, urinary reten*on and mildlimbparesis

§  Quadriplegia,coexis*ngparalysisoftherespiratorymuscles,dysphagia,dysarthria

Long-termsymptomsofTBE

TBEtreatment•  Theresultsofthelaboratorytestsdidnotaffectthe

treatment-areusedtodis*nguishbetweentheTBEandtheotherinfec*ons

•  TBEinfec*on-noan*viraltreatment.•  treatment-onlysymptoma*c:

–  maintainingfluidandelectrolytebalance–  ensureadequatesupplyofcalories–  analgesicsandan*pyre*cs–  administra*onofan*convulsantdrugs-ifnecessary–  useofphysiotherapyinfectedlimbsinordertopreventmuscle

atrophy–  useIGV-goodresults

•  Themosteffec*vepreven*onofTBEvaccina*on

TBEvirusvaccina*onThetwovaccines:•  Encepur•  FSMEImmunInjectStandardscheme:•  Idoseof0.5ml•  IIdose-0.5ml,acer1-3months•  IIIdose-0.5ml,9-12monthsacertheseconddoseShortenscheme:•  Idoseof0.5ml•  Theseconddoseonday70.5ml•  IIIdoseof0.5mlin21days•  Revaccina*onevery3-5years

CSFexamina*onCellnumber Celltype protein glucose

normal <5 limphocytes <45mg% >40mg%

purulent >200 granulocytes abovenormal <normal

purulent <200 limphocytes normalor>normal

normal

tuberculosis <200

limphocytes

>normal

<normaltuberculosis

Symptomsofpurulentmeningi*sinadults

– headache,nausea,vomi*ng– photophobia,hypersensi*vitytosounds– anxietythenprogressivelossofconsciousness,confusion,coma

– abnormalrhythmofsleepandwakefulness–  thephysicalexamina*on:necks*ffnessandposi*vesignsofmeningealsyndrome(Brudziński,Kernig)

MeningealsignsBrudzińskisign:Neck:thepa*entlyingonhisback->neckflexion->limbsflexioninthekneeandhipjointsSymphyseal:pressureonthepubicsymphysiselicitsareflexflexionofthehipandknee,andabduc*onofthelegKernigsign:posi*vewhenthethighisflexedatthehipandkneeat90degreeangles,andsubsequentextensioninthekneeispainful(leadingtoresistance)

NuchalrigidityistheinabilitytoflextheneckforwardduetorigidityoftheneckmusclesAmosssign:indica*onofpainfulflexionofthespineinwhichitisnecessarytosupportasilngposi*onbyextendingthearmsbehindthetorsoandplacingitsweightonthehands.

Meningealsigns

•  meningealsymptomsusuallyareabsent•  tenseandarchedfrontfontanelle•  hyperacusisskin•  anxiety•  groans•  convulsions

Symptomsofpurulentmeningi*sininfants

Viralmeningi*sencephali*s

•  thesummermonthsandearlyfall•  relatetoyoungpeopleupto40yearsofage•  veryrareininfants•  usuallymild,withoutpermanentsequelae•  some*mesaccompaniedbyinflamma*onofthebrain(encephalomeningi*s,meningoencephali*s)

Viralencephali*s-e*ology

•  Virusesoriginallyneurotrophic:rabiesvirus,arboviruses(exo*cencephali*svirus)

•  Infec*ousdiseasescomplicatedbyencephali*s:measles,mumps,rubella,chickenpox,shingles,flu

•  Otheradenoviruses,rotaviruses,enteroviruses•  Encephali*scausedbytheherpessimplexviruses:– Herpe*cencephali*s– Herpessimplexencephali*s(HSE)

CSFfluidinviralencepali*s

•  changesasinlymphocy*cmeningi*s•  inuntreatedHSEmortalityrateof60-80%,recoverywithoutresidual2.5%ofpa*ents

•  drugofchoice:acyclovir(Zovirax)10mg/kg.every8hours

Bacterialmeningi*s

•  Life-threa*ngcondi*on-shouldbetreatedassoonaspossible

•  Beforetreatment:1.Lumbarpuncture-ifthereisnocontraindica*ons–cytologicalandbiochemicaltests,latextests,directprepara*on,culture,PCR•  2.Bloodtest-to2tubeswith2differents*tchesforculture

•  latextests,PCR.

Actualdiagnos*cguidelines

Fromthefirstcontactwiththedoctortogiveempiricaltherapyis*me<3hours

inthecaseofmeningococcale*ologyfor30minutes.

An*bio*cs-giveni.v.,maximumdoses(limitedpenetra*onintotheCNS).

Fortheempiricaltherapyatleasttwoan*bio*cs

RecommendedtreatmentAge Etiology Antibiotics

Infants Perinatal infections

E.coli, Streptococcus agalactiae, Listeria monocytogenes,Klebsiella sp, and others, Gram minus intestinal bacilli

Ampicilin and Cefotaksym or Ampicilin and aminoglikozyd

Infants- nosocomial infections Streptoccoci, Gram minus intestinal bacilli , Pseudomonas aeruginosa

Ceftazidim and vancomicin

Infants 1-3 mo Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae and some pathogens from infants group

Cefotaxim or ceftriaxon and vanconicin, sometimes ampicilin

3 mo- 5mo Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae

Cefotaxim or ceftriaxon and vanconicin

5-50 yr Neisseria meningitidis, Streptococcus pneumoniae

Cefotaxim or ceftriaxon and vanconicin

>50yr Neisseria meningitidis, Streptococcus pneumoniae Streptococcus agalactiae, Listeria monocytogenes Haemophilus influenzae

Cefotaxim or ceftriaxon and vanconicin and ampicilin

TimeofstandardtreatmentBacteria Duration Neisseria meningitidis 7 days Haemophilus influenzae typ b 7-10 days Streptococcus pneumoniae 10-14 days Streptococcus agalactiae 14-21 days Staphylococcus aureus 14 days Listeria monocytogenes, Pseudomonas aeruginosa, Gram minus intestinal bacilli

>21 days

Unknown etiology 10-14days

Viralencephalomeningi*s

•  Treatment-infec*onscausedbyvirusesofherpes:acyclovir(Zovirax)10mg/kg/doseevery8hours

•  Ininfec*onsCMVganciclovir(Cymevene)5mg/kg/doseevery12hours

•  Drugsan*oedematous:•  20%Mannitol200ml(children10ml/kg/day)every8-12hours,Dexamethasone8mg(children0.6-1mg/kg/day)every6-8hours

•  An*convulsants(Luminal,Relanium)•  An*-inflammatory,an*pyre*c

Supervisionofdiagnosisandtreatmentneuroinfec*ons

•  KORUN-Na*onalReferenceCentreforBacterialInfec*onsoftheCentralNervousSystem

•  KORLD-Na*onalReferenceCentreforAn*microbialSuscep*bilityTes*ng