Challenges in viral CNS infections [encephalitis]

Transcription

1 Challenges in viral CNS infections [encephalitis] PIGS Training Course 2013 Basel November 8, 2013 Christoph Aebi

2 Definition Encephalitis is defined as a syndrome of neurological dysfunction caused by inflammation of the brain parenchyma a) caused by infection (direct or indirect)* b) caused by non-infectious processes *indirect, e.g. post-infectious encephalitis, ADEM etc.

3 Measles Koplik spots rash face rash trunk

4 Epidemiology Highly variable (age, geographic area, immunization rates, epidemics ) Europe: Incidence ,8 / in children. HSV encephalitis: 2-4 per % of identifiable causes are HSV, VZV, EBV, enteroviruses and TBE. Jmor et al. Virol J 2001;5:1; Whitley RJ et al. Semin in Pediatr Infect Dis 2005;16:17

5 History Consider in particular Current or recent influenza-like illness Rash Travel history Recent vaccination Animal contact Exposure to arthropods Immunocompromized state (HIV?)* *all patients with suspected encephalitis need HIV r/o

6 Non-specific rashes Adenovirus Enterovirus (ECHO)

7 Example: Hand-foot-mouth disease HSV-I Enterovirus

8 Clinical manifestations Fever (very common). Mental abnormalities (consciousness, behavioural etc.). New onset of seizures.* Focal neurologic signs. * More likely if cortex is affected, which is more likely infectious, than subcortical white matter disease (ADEM etc.)

9 Kneen r et al. J Infect 2012;64:449

10 Useful algorithm by the British Infection Association (BIA) Kneen r et al. J Infect 2012;64:449

11 Etiology Viruses HSV1 & 2 VZV EBV CMV HHV 6,7 Enteroviruses (incl polio, EV71) Flaviviruses (TBE) Rabies Measles, mumps, respiratory viruses etc. Bacteria and other organisms Mycoplasma pneumoniae Rickettsiae Coxiella burnetti Bartonella henseae Listeria monocytogenes Borrelia burgdorferi Malaria Cryptcoccocus neoformans Trypanosoma spp. Amebic meningoencephalitis

12 Course of fever in TBE Biphasic fever also reported for -HSV - enteroviruses Feigin & Cherry; Textbook of Pediatric Infectious Diseases, 2010

13 TBE cases 2013 in Switzerland Total unter 6 Jahren Gesamtzahl Fälle Fälle unter 6 Jahren Since 01/01/ : : Erkrankungsjahr

14 TBE endemic areas in Switzerland BAG,

15 Clinical hints and caveats Agent HSV VZV manifestations may be mild Consider 3 different manifestations

16 Varicella Seroprevalence in CH 100 VZV Seroprevalence (%) Age (years) Vaccine 2001;19:3097

17 VZV encephalitis (1) Post-infective immune mediated cerebellitis (2) Acute infective viral encephalitis. (3) Arterial ischemic stroke Berger TM et al. Pediatr Infect Dis 2000;19:653

18 Clinical hints and caveats Agent HSV VZV EBV Respiratory agents manifestations may be mild. Consider 3 different manifestations. without clinical munonuclosis; mostly adolescents. CNS disease preceding or without respiratory signs- M. pneumoniae may present with brainstem encephalitis. Influenza Various manifestations: ADEM, ANE. Enterovirus may present with brainstem encephalitis, myelitis (EV 71). May present with hemorrhagic conjuncitivits (EV70) TBE may present as poliomyelitis-like disease. Measles 3 different manifestations. - post-infectious (ADEM) - infectious in immunocompromised hosts - SSPE in immunocompetent hosts

19 Diagnostic work-up 1. LP 2. Imaging (MRI, CT) 3. Additional micro tests 4. Call neuro 5. EEG* *note: PLEDS are not specific for HSV

20 CSF interpretation of routine data

21 Studies on CSF (in addition to routine) All patients HSV-1 / HSV-2 PCR VZV PCR EBV PCR Enterovirus PCR TBE serum abx upon indication EBV/CMV (especially in the immunocompromised) HHV-6, HHV-7 (in all severe cases) Adeno, influenza, rotavirus measles, mumps Parvovirus B19 Other (depending on travel/exposure, etc.) Blood serologies or other body fluid tests may be helpful VZV, CMV, enteroviruses, PB19, adeno, influenza, other respiratory viruses Measles, mumps, etc.

22 Indications for MRI (1) All patients should receive MRI (with diffusion weighted imaging) within post admission (2) Superior sensitivity for HSV vs. CT [90% sens p 48 h in Gyrus cinguli, medial temporal lobe]. (3) Superior sensitivity in VZV [large vessel vasculitis or multifocal leukoencephalopathy] (4) Enterovirusus: generalized parenchymal destruction; brain stem involvement Gilden DH et al. N Engl J Med 2000;342:1245; Bitnun A et al, Clin Infect Dis 2001;32:1674

23 Treatment Kneen r et al. J Infect 2012;64:449

24 Evidence for acyclovir in HSV encephalitis Nucleoside analogue with antiviral activity against HSV. Reduces case-fatality rate (70 to 20%). Should be started within 6-48 h of admission. CSF PCR remains positive up to 7-10 d post starting therapy. Relapse common if duration of therapy is < 14 d (up to 30%). Some evidence that relapses are most common between 3 months and 12 yrs of age. Tunkel AR et al. Clin Infect Dis 2008;47:303; Ito Y et al. Clin Infect Dis 2000;30:185 Thomson C et al. Arch Dis Child 2001, epub

25 When to stop acyclovir? Case confirmed: s. above Case not confirmed STOP acyclovir if a) PCR negative on 2 occasions within hours PLUS MRI not characteristic OR b) PCR negative once > 72 hours after onset of symptoms PLUS LP normal PLUS MRI normal. Tyler KL. Rev Neurol Dis 2004;1:169

26 Evidence for acyclovir in VZV encephalitis No hard evidence Entity Cerebellitis Acute encephalitis Therapy No antiviral therapy Acyclovir 15 mg/kg/dose q8h for 14 days Stroke Acyclovir (duration???) Steroids (duration???)

27 Subacute and chronic encephalitis Typically managed primarily by neurologists Role of ID specialist bring up differentials Immunocompromized Measles (inclusion body) VZV (multifocal) CMV HSV-2 Enterovirus JC/BK (PML) HIV immunocompetent JC/BK (PML) Measles (SSPE)

28 The returning traveller THINK MALARIA Think TB, typhoid encephalopathy, trypanosomiasis Think amebic meningoencephalitis Consider viruses Viral encephalitis in children returning from abroad Dengue Rabies Japanese encephalitis West Nile and other flaviviruses Area Endemic areas worldwide Indian subcontinent et al. Southeast asia where the bugs fly

29 Dengue endemic areas

30 JE endemic areas

31 Encephalitis - PREVENT Stay out of risk areas! Immunize with MMR(V) Immunize against TBE (Encepur, FSME-Immun ) Immunize against rabies (Rabipur, Tollwut-Mérieux ) Immunize against JapE (Ixiaro ) Immunize against polio for endemic areas (Poliorix ) and immunize against Influenza!

32 Encephalitis - PREVENT Genetic counselling of families with infant with HSV encephalitis?

33 TBE- immunization rates < 16 yrs (3 doses) BAG,

34 Poliomyelitis

35 Encephalitis TREAT THE TREATABLE HSV, VZV Acyclovir CMV, HHV Gancicovir, Foscarnet Enterovirus consider IVIG, [pleconaril] Adeno consider cidofovir, [ribavirin] ALL REQUIRE EARLY ONSET NEUROREHABILITATION

36 THANK YOU!