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Encephalitis:
1. Einführung(Symptome,ErregerübersichtundpathophysiologischeProzesse)
2. EncephalitisdurchdirektenVirusbefalldesZNS(Bsp.Herpessimplex)
3. GleicherErregeraberverschiedenepathogenetischeMechanismen(Bsp.Masern)
4. ImmunologischbedingteEncephalitiden: Auslöser?(Viren,andereMechanismen)
5. WennderSpaziergangdurchdenWaldgefährlichwird:durchInsektenübertrageneEncephalitis(Bsp.Zeckenencephalitis)
Vortragsübersicht
ViraleInfektedesZNSWegederNeuroinvasion:
- Neuraler Wege Rabies VirusHerpes simplex VirusVaricella-Zoster Virus
- Olfaktorischer Weg Herpes simplexArboviren
- Hämatogener Weg EnterovirenCytomegalievirusEpstein Barr VirusMumps, MasernAdenoviren, FilovirenLymphocytäre ChoriomeningitisArboviren, HIV, HTLV
ViraleEncephalitis
Hauptsymptome:- Bewusstseinsstörungen- FokaleneurologischeAusfälle- EpileptischeAnfälle- Übelkeit,Erbrechen- Temperaturinstabilität- ev.Diabetesinsipidus- ev.inadaequate ADH– Sekretion- ev.HirnstammbeteiligungmitAtaxie,Hirnnervenausfällen,Nystagmus,pyramidalenSymptomen
Prodromi:- Fieber- Kopfschmerzen- Merkfähigkeitsstörungen
Krankheitspektrum undTherapieeinigerneurotroper VirenErreger Encephalitis Myelitis Vaskulitis Therapie(Evidenzstärke)
Adenovirus + + - -
HSV-1 + + + Aciclovir (Ia),Famciclovir,Foscarnet (Ib)
VZV + + + Aciclovir (1a)
EBV + + + Ganciclovir (V)
CMV + + Foscarnet,Ganciclovir (Ib)
HHV6 + + + Foscarnet (V)
Parvovirus B19 + + +
FSME + +
Mumps-Virus + + +
Masern-VirusSSPE
++
Ribavirin (V)Inosiplex +aIFN (Ib)
Echo-/Rotavirus + +
InfluenzaA + + + Amantadine (V)
Encephalitis
Erreger(Virus)
Ak gegenneuraleMembranproteine
undJonenkanäle
Tumore+andereendogene
Immunmechanismen
PersistenzMutation
desErregers
Pathogenese
Symptome:- Bewusstseinsstörungen 96 -100%- Fieber 78 - 95%- Kopfschmerzen und Meningismus 74 - 81%- Epileptische Anfälle 59 - 67%- Persönlichkeits-, Verhaltensstörungen 68 - 87%- Fokale neurologische Ausfälle 26 - 79%- Ein Teil der Patienten
mit Operculum Syndrom(Gesichtslähmung, Dysarthrie und Dysphagie)
mit Choreathetosemit Klüver-Bucy Syndrom (fehlende Empathie und Angstreaktion,
orale Automatismen)- Aphasie, Sprechstörungen 12 - 65%- Meningismus 13 - 38%
Herpessimplex Encephalitis
Gnann JWundWhitley RJ2017
HerpesEncephalitisDiagnostische Untersuchungen:1. Liquor: Zellzahl, Granulocyten < Lymphocyten
+ Erythrocyten (abnorm > 95%)Liquoreiweiss é > 80%Antikörper auf HSVPCR auf Herpesviren (gold standard)sensitiv 98% und spezifisch 94%Cave! falsch negativ Resultate währendden ersten Krankheitstagen, LP nach 3 – 4 Tagen wiederholen
2. EEG: sensitiv aber nicht spezifisch3. MRI: sensitiv mit Signal Anhebung
(T2, DWI und Flair)4. Hirnbiopsie nur in Ausnahmesituationen
Liquorbefunde beiHerpessimplex Encephalitis
CSF is very insensitive, with HSV detected by culture in fewerthan 5% of patients with biopsy-proven HSE.
The diagnostic test of choice for HSE is demonstrationof HSV DNA in CSF using a polymerase chain reaction(PCR) assay [61–63]. In HSE caused by HSV-1, the sensi-tivity of PCR is estimated to be 98% with specificity 94–99%. The Simplexa™ HSV-1 and 2 Direct kit (FocusDiagnostics) is FDA-approved for detection of HSVDNA in CSF [64]. However, many laboratories continueto utilize PCR assays that were developed in-house andmay have variable sensitivity and specificity. Use of type-specific primers allows discrimination between HSV-1 andHSV-2. CSF positive for HSV-2 by PCR is indicative ofeither HSE caused by HSV-2 (rare) or HSV-2 meningitis(more common), although the two syndromes are usuallyclinically distinguishable.
PCR is usually positive within 24 h of symptom onset andremains positive during the first week of acyclovir therapy.Negative CSF PCR has been reported in HSE patients whowere tested very early in their clinical course [65, 66]. If theclinical presentation is strongly suggestive of HSE, but theinitial CSF PCR is negative, acyclovir therapy should be
continued and the patient should undergo a second lumbarpuncture; the PCR is usually positive when the patient isretested. False-negative PCR results may also occur as a resultof a suboptimal assay or due to the presence of an inhibitorysubstances in CSF (e.g., blood). False positive results are rare,but occasionally occur (as with any PCR-based assay), mostlikely due to laboratory cross-contamination.
The duration of PCR positivity in the setting of acyclovirtherapy has not been well-defined but is at least 7 days [62].After 10–14 days of acyclovir therapy, the HSV DNA in CSFwill usually become undetectable (although detection of HSVDNA beyond 2 weeks has been described) [62, 67]. Thismeans that there is a wide window for repeat PCR testing ifthe original CSF is negative, even if acyclovir therapy hasbeen initiated. A longer duration of CSF PCR positivity hascorrelated with poor outcome in some reports [68].
The availability of PCR has largely eliminated the need forbrain biopsy, which was previously the definitive diagnostictest. Brain biopsy may still be necessary in unusual caseswhen the clinical and radiographic evidence suggest HSE,but the PCR is repeatedly negative. HSV can be identified inbiopsied brain tissue by PCR, viral culture, in situ hybridiza-tion, or immunohistochemical staining. Assays for detectionof HSV antigens and anti-HSV antibodies in CSF have beendescribed but have been replaced by PCR. These tests mayoccasionally be useful as an alternative to brain biopsy inunusual cases where HSE is strongly suspected, but the PCRis nondiagnostic [69, 70].
Quantitative PCRmethodology has been utilized in a smallnumber of HSE cases and demonstrates a decline in CSF viralload over the course of acyclovir therapy [30, 67, 71].Whether the magnitude of the CSF viral load predicts out-come is uncertain. Several investigators have found no corre-lation between quantitation of HSV DNA in CSF and severityof clinical disease and prognosis [67, 68, 72–74]. Other stud-ies have demonstrated a positive correlation between higherCSF viral load and poorer clinical outcome [71, 75].
Table 2 Cerebrospinal fluid findings in patients with herpes simplexencephalitis
Laboratory test Typical finding
Leukocytes 25–75/mm3 (range 0–>500)
Percent lymphocytes 75–90% (range 60–98%)
Glucose 60–75 mg/dL (about 25% of patients will haveCSF glucose <50% of serum glucose level)
Protein 65–85 mg/dL (about 60–70% of patients willhave elevated CSF protein)
Not every finding was reported for every patient. Compiled from 302reported HSE cases [16–19, 77, 139]
Table 1 Presenting signs andsymptoms in patients with herpessimplex encephalitis
Finding Percentage of patients Reported range
Fever 80% 70–97%
Confusion/disorientation 72% 54–81%
Personality changes/behavioral disturbances 59% 42–92%
Headache 58% 42–70%
Altered mental status/impaired consciousness 58% 54–100%
Seizures 54% 35–65%
Focal neurological deficits 41% 26–79%
Nausea and vomiting 40% 19–46%
Aphasia/altered speech 40% 12–65%
Coma 33% 4–48%
Meningismus 28% 13–38%
Not every finding was reported for every patient. Compiled from 388 reported HSE cases [16–20, 77, 139, 140]
13 Page 4 of 12 Curr Infect Dis Rep (2017) 19: 13
Gnann JWundWhitley RJ2017
Herpes simplex Encephalitis:Therapie
Acyclovir 20mg/kg/8h während 21 TagenCave! Bei kürzerer Therapiedauer
Rezidivgefahr!!
Acyclovir + Corticosteroide Þ bessere Resultate?nur Einzelfälle, keine prospektive Studie,erfolgreich bei erhöhtem IKD
(Kamel S. et al: J Neurol Neurosurg Psychiatr 2005Gnaham J.W. und Whitley RJ: Curr Infect Dis Rep 2017)
HerpessimplexEncephalitis:Outcome
Normal 62 (42%)Geschädigt:Mittelschwer 45 (29%)Schwer 33 (23%)Exitus 9 ( 6%)
Hsieh et al 2007Elbers et al 2007Lahat et al 1999Ito et al 2000Uren et al 1993Wang et al 1994Kimura et al 1992
HSV Infektion im ZNS
CytokineChemokine Aktiviert durch Gliazellen
Neuroimmunantwort
Sekundäre Schädigung
RezidivnachHSVEncephalitisVirusbedingtesRezidivderHSE
NichtVirusbedingtePost-HSE
ZeitpunktdesHSERezidivs
Variabel 4-6WochennachHSEBeginn
NeurologischeSymptome FokaleneurologischeAusfälle,epileptischeAnfälle,Verhaltensstörungen
Kinder:AbnormeBewegungen(Choreathetose,Ballismus)Adoleszente:Verhaltensstörungen
HSVPCRimLiquor positiv negativNeuenekrotischeLäsionenimMRI
ja nein,ev.Befallderweissen Substanz
AnsprechenaufantiviraleTherapie
ja nein
Aetiologie HSV Infektion Autoimmun,NMDARoderDR2Antikörper,
Armangue Tetal:Curr Opin Neurol 2014
ungenügendesAnsprechenaufantiviraleTherapie+klinischeZeicheneinerNMDAREncephalitis?
BestimmungderNMDAR-Ak imSerumundLiquorHSVPCRimLiquor+/- imBlut
ErneutHSVTherapie(Acyclovir)
„Firstline“Immuntherapie:IVIGoderPlasmapherese
HSVKontrolle(PCR)+Monitorisierung derNMDAR–AKTiter
„Secondline“Immuntherapie:Steroide+/- Rituximab +/- CyclophosphamidKontrollenHSV(PCR)undNMDAR-Ak Titer
TherapieschemafürRezidivnachHSEoderprolongiertemHSEVerlauf
0714211369136912
Tage
MasernNeurologischeKomplikationen
PIE
Exanthem
Masernvirus-infektion
ME: MasernencephalitisPIE: PostinfektiöseEncephalitisMIBE: MasernEinschlusskörperchen
(inclusion body)EncephalitisSSPE: Subakutesklerosierende
PanencephalitisMIBE
Monate
SSPE
Jahre
ME
Praevalenz:Akute primäre Masernencephalitis 1 : 1000Akute Postmasernencephalitis 1 : 1000Akute Postvaccinationsencephalitis 1 : 1000000Masern Einschlusskörperchen Encephalitis 1 : ?Akute disseminierte Encephalomyelitis (ADEM) 1 : 1000ADEM nach MMR Impfung 1-2 : 100000 Subakute sklerosierende Panencephalitis (SSPE) 1 : 25000SSPE nach Masern bei Kindern < 2 Jahre 1 : 5000SSPE nach Masernimpfung < 1 : 1000000Letalität:Akute Masernencephalitis 15 - 20%Akute Postmasernencephalitis 5 – 25%Masern Einschlusskörperchen Encephalitis 75%SSPE > 90%
NeurologischeKomplikationenvonMasern
NeurologischeKomplikationenvonMasernKlinik,EEG,Bildgebung
PrimäreMasern-encephalitis
Akutepost-infektiöseMasernenc.
Einschluss-körperchenEncephalitis
SSPE
Voraus-setzungZeitspanne
AktiveMasern Masernvor1– 6Monaten
Immundefekt,innerhalb1JahresnachMasern
M. währenderster2LJ,3– 20JahrenachM
Klinik Fieber,Kopf-schmerzen,Epi-Anfälle, mentaleStörungen,Ausschlag
allg.Schwäche,mentaleStörungenSensibilitätsstö-rungen
mentaleStö-rungen,refraktäreEpi-Anfälle,MotorischeAusfälle
Verhaltensstö-rung, Demenz,Myoklonienprogredient
EEG DiffusDeltaw.fokaleod.gene-ralisierte Epi-Entladungen
normaloderunspezifischabnorm
DiffuseDeltaw.fokaleodergene-ralisierte Epi-entladungen
PeriodischeKomplexe,Burstsuppression.
MRI T2fokaleHyper-intensitäten,Hirnoedem
T2multifokaleHyperintensitätHirn+RM
normal,OedemspäterAtrophien,Ventrikulomegalie
FokaleLeuko-dystrophie,diffusekortikaleAtrophie
NeurologischeKomplikationenvonMasernLaborbefunde
PrimäreMasern-encephalitis
Akutepost-infektiöseMasernenc.
Einschluss-körperchenEncephalitis
SSPE
Masernvirus nachweisbar nichtnachweisbar
nachweisbarpersistierend
defekter Masern-Virus
Masern-AkimSerum
+/- + ++, Titeransteigend
+++
Masern-AkimLiquor
+/- + ++, Titeransteigend
+++.
MyelinbasischesProtein
keines +++ keines keines
Liquorbefund(Zellen,Eiweiss,Glucose)
LymphocytenéEiweisséGlucose normal
LymphocytenéEiweisséGlucosenormal
normal normal
MasernEinschlusskörperchen Encephalitis
- PatientenmitImmundefizienz (z.B.beilymphatischerLeukämieoderandernmalignenTumoren)
- AuftretennachMasernundMasernimpfung,aberauchohneersichtlichenGrund
- NurgeringesExanthemwegengestörterT-ZellFunktion- Hauptsymptome:EpileptischeAnfälle(fokalodergeneralisiert,meistTherapieresistent),Bewusstseins- undVerhaltensstörungen
- Gelegentlich:fokalemotorischeAusfälle,visuelleSymptomeinklusivekortikaleErblindungundDysphagie
- Diagnose:PCRaufMasernviren- Prognose:Mortalitätca.75%
Stadium KlinischeSymptome
StadiumI Persönlichkeitsveränderungen,Schulprobleme,Verhaltensstörungen
StadiumII Massive,häufigerepetitivemyoklonischeZuckungen,epileptischeAnfälleundDemenz
StadiumIII Rigor,extrapyramidaleSymptome,progressiveAbnahmederAnsprechbarkeit
StadiumIV AkinetischerMutismus,vegetativerZustand,Coma,autonomeStörungen
Subakutesklerosiende Panencephalitis(SSPE)KlinischeStadien
AkutedisseminierteEncephalomyelitis (ADEM)KlinischeSymptomeundLiquorbefunde
UnspezifischeProdromi:- Kopfschmerzen,Myalgien,leichtesFieberundÜbelkeitFokaleneurologischeAusfälle:- Hemiparese,Tetraparese,seltenAphasie- AtaxieVeränderungendesmentalenStatus:- Schläfrigkeit,StuporundComaWeitereSymptome:- HirnnervenAusfälleundN.opticus neuritis- SymptomeeinerMyelopathie- unwillkürlicheBewegungen
Liquor:- Lymphocytäre Pleocytose,Protein↑,- oligoklonale Bandenin0-29%nachweisbar
Infectious agents associated with ADEM
normal and lipid-ladenmacrophages are not seen (Poweret al., 1993). However, rare cases of HIV encephalopathypresenting as an ADEM-like illness, with demyelinationand relative sparing of axons, have been reported (Joneset al., 1988; Gray et al., 1991; von Giesen et al., 1994).HTLV-I infection causes slowly progressive myelopathyand is associated with demyelination, but through a dif-ferent mechanism than ADEM. HTLV-I does not infectoligodendrocytes or neurons but preferentially infectsCD4þ and CD8þ T cells, which, when activated by thevirus, could lead to demyelination (Hollsberg, 1997;Kannian et al., 2012). It may also infect microglia, whichmay become activated and release cytokines toxic tomyelin (Hollsberg, 1997).
Other forms of encephalitis that may also causedemyelination but distinct from ADEM include sub-acute sclerosing panencephalitis, a chronic progressivemeasles infection of the brain, rubella panencephalitis,varicella-zoster virus (VZV) encephalitis, and humanherpesvirus-6 (HHV-6). In panencephalitis caused byrubella, prominent white-matter changes with axonalfragmentation are seen (Townsend et al., 1975, 1976).VZV encephalitis in AIDS patients can produce demye-lination. In addition to inflammatory demyelination,
VZV may also directly infect oligodendrocytes, sinceviral inclusion bodies can be seen in these cells (Grayet al., 1991, 1994; Amlie-Lefond et al., 1995). HHV-6can produce demyelination also by directly infectingoligodendrocytes (De Bolle et al., 2005). HHV-6 is alsoone of several hypothesized etiologic agents for MS(Challoner et al., 1995).
Another form of demyelinating disease seen inHIV isprogressive multifocal leukoencephalopathy (PML),which is caused by infection of oligodendrocytes bythe JC virus, a polyomavirus. PML is seen underconditions that impair immunity, such as acquiredimmunodeficiency syndrome (AIDS), posttransplant,lymphoma, and autoimmune diseases receiving treat-ment with chemotherapy or immunomodulators suchas natalizumab, rituximab, or efalizumab (Carsonet al., 2009). PML lesions usually occur in the deep whitematter and are typically solitary, but they can rarely bemultifocal (Astrom et al., 1958). Also, cortical demyelin-ation from PML has been described (Sweeney et al.,1994; Shintaku et al., 2000;Moll et al., 2008). The frontaland parieto-occipital regions are usually affected, butdeep graymatter, brainstem, cerebellum, and spinal cordcan be involved (von Einsiedel et al., 1993; Bienfait et al.,1998; Kastrup et al., 2002; Bernal-Cano et al., 2007). Thedemyelinating lesions seen in PML lack inflammatoryreaction and necrosis, but have accompanying reactiveastrocytes and oligodendroglial nuclear inclusions(Astrom and Stoner, 1994; Aksamit, 2006). However,upon immune reconstitution, as may occur in AIDSpatients after highly active antiretroviral therapy or inautoimmune diseases once immunosuppression isstopped, PML lesions once containing little inflamma-tion now develop intense inflammatory reaction withedema and necrosis (Tan et al., 2009). This immunereconstitution inflammatory syndrome can producediffuse white-matter changes, as seen on magnetic res-onance imaging (MRI), even in areas initially devoidof any pathology, for example in MS after cessationof natalizumab therapy (Tan et al., 2011; Gheuenset al., 2012).
PATHOGENESIS
The pathogenesis of ADEMhasmost resemblance to theanimal model experimental autoimmune encephalomy-elitis (EAE), which is an acute demyelinating diseaseinduced by immunization of animals with myelin proteinproducts (Rivers et al., 1933). After immunization withCNS antigens emulsified in Freund’s complete adjuvant,animal recipients present with amonophasic illness caus-ing tetraparesis and incontinence. Histologic analysisshows inflammatory demyelinating lesions typically inthe spinal cord and in some animal strains in the brain.
Table 35.1
Infectious agents associated with acute disseminatedencephalomyelitis
Viruses Vaccinations Bacterial
Measles Measles StreptococcusMumps Mumps Borrelia
burgdorferiRubella Rubella LegionellaCoxsackie Rabies
(Semple-type)Mycoplasmapneumoniae
Coronavirus Tetanus SalmonellaHerpes (HSV, HHV-6,VZV, EBV, CMV)
Oral polio Rickettsiarickettsii
Influenza A and B Influenza ChlamydiaHepatitis A and B Pertussis CampylobacterHTLV-1 Hepatitis B LeptospiraHIV Japanese
encephalitisvirus
Dengue virus Tick-borneencephalitis
Smallpox Yellow fever
Adapted from Garg (2003); Bennetto and Scolding (2004); Menge
et al. (2005); Tenembaum et al. (2007).
HSV, herpes simplex virus; HHV, human herpesvirus; VZV, varicella-zoster virus; EBV, Epstein–Barr virus; CMV, cytomegalovirus; HTLV-
1,humanT-lymphotropicvirus-1;HIV,human immunodeficiencyvirus.
706 A. JAVED AND O. KHAN
AkutedisseminierteEncephalomyelitisTherapie
1. Acyclovir 20mg/kg/d(meistinitialeingesetztwegendiagnostischerUnsicherheit)
2. Cortison20– 30mg/kg/Tagwährend3-5TagenoderDexamethason 1mg/kg/Tag
3. IVIg 2g/kgüber5Tage4. Plasmapherese,wennkeinAnsprechenaufSteroide
5. WennkeinAnsprechenaufTh 1– 4:Cyclophosphamid und/oderMitoxantron
Fig. 9. Distribution of I. ricinus, mapped as points according to the coordinates of the site of collection. This differs from map in Fig. 8 in which actual coordinates ofcollections, instead of the complete administrative divisions, are included as ‘‘positive’’ to the tick, allowing a finer mapping of the tick’s range. It is observed that thedistribution of I. ricinus in western Palearctic is larger than the distribution of TBEV. Map originally published by Estrada-Peña et al. (2013a,b,c,d).
Fig. 10. Schematic cycle of transmission of the tick-borne encephalitis flavivirus. It shows the importance of some species of rodents on which the larva and nymph may feedtogether, that may produce a back-transmission of the virus from the infected nymphs to the co-feeding larvae, without systemic circulation of the virus in the host. The largehosts for adults are necessary only for the completion of the life cycle of the tick, but have been not reported as important in the transmission of the virus in the nature. Thecourse of the tick life cycle is indicated by blue arrows. The possible transmission of the virus between ticks and mammals or directly between ticks is marked by red arrows.Figure prepared with material originally created by Alex McAuley.
116 A. Estrada-Peña, J. de la Fuente / Antiviral Research 108 (2014) 104–128
LebenszyklusderZeckeÜbertragungsmöglichkeitendesFSMEVirusaufdenMenschen
Estrada-PenaAundDelaFuente J2014
InfizierteHuftiere
NachZeckenstichInfizierungderLangerhanszellen derHaut→ InfektionderLymphknoten(Lymphocyten und
Makrophagen→ Virämie Phase→InfektiondesNS
ZielzellenimNS:EpithelzellenderHirnhäute,Purkinjezellen,motorischeKerneimHirnstammundRM,NeuroneimThalamus,Diencephalen undMesencephalon(Neuronenzerstörung)
PathogenesederZeckenencephalitits
KlinikderFSME:
• NachInkubationszeitvonca 10TagenSymptomeeinerSommergrippe:Fieber,Kopfschmerzen,HustenundgastrointestinaleBeschwerden
• SpontanerRückgangderSymptome• EinigeTagespätererneuterFieberanstieg:• 50%isolierteMeningitis• 40%Meningiencephalitis• 10%Myelitis
SymptomebeiFrühsommerMeningoencephalitis
Meningitis Encephalitis Myelitis
Allgemeinsymptome AZ↓Fieber AZ↓Fieber AZ↓Fieber
Häufig Kopfschmerzen Bewusstsein↓(Sopor,Coma)Bewusstseinveränderung(Delir, Halluzinationen)KognitionsstörungenAtaxie,Paresen
SchlaffeParesenMiktions-störungen
Gelegentlich NeuritisderHirnnerven
Tremor,mimischesBeben,zentraleAtemstörungen,Dysphagie,epileptischeAnfälle
SpasmenderBlasenmuskulatur,Schmerzen(RumpfundExtremitäten)
KaiserR.2016
CME
Abb. 28 FSME-RisikogebieteinDeutschland,StandMai2015([20];Grafik:Pfitzer;mitfreundl.Genehmigung,www.zecken.de). FSME Frühsommermeningoenzephalitis
Erwachsenen ca. 10-mal seltener auftreten [28, 29, 32, 34, 41, 42, 49, 50, 51, 52, 53, 54, 55, 56,57]. Letale Verläufe sind bei Kindern und Jugendlichen eine absolute Ausnahme.
Das jüngste Kind mit einer FSME-Virusinfektion war 17 Tage alt [50]. Klinisch imponiertezunächst ein Anfall mit nachfolgender Hemiparese, die sich nach 2Monaten nicht zurückgebildethatte. Die Magnetresonanztomographie (MRT) des Gehirns zeigte zunächst ein Hirnödem dergesamten linken Hemisphäre und nach 2 Monaten eine Atrophie in diesem Bereich. Klinisch botder Säugling fokale Anfälle, der weitere Verlauf ist nicht bekannt.
Doppelinfektionenmit dem FSME-Virus und Borrelia burgdorferi s. l. verlaufen meist schwer-wiegend [58, 59].
Diagnostik
Die Diagnose der FSME stützt sich auf:4 eine Exposition in einem Risikogebiet,4 einen Zeckenstich innerhalb der letzten 1 bis 3 Wochen (fakultativ),4 die klinische Symptomatik mit Kopfschmerzen, Fieber und ggf. neurologischen Funktionsstö-
rungen,4 einen entzündlichen Liquorbefund sowie4 den Nachweis FSME-spezifischer Immunglobulin-M(IgM)- und IgG-Antikörper im Serum,4 den Nachweis eines erhöhten FSME-spezifischen Antikörperindexes im Liquor (bei Unsicher-
heiten).
Der Nervenarzt 6 · 2016 671
FSMEDiagnose