Philippe G Jorens Department of Intensive Care Medicine University of Antwerp, UZA, Belgium

1. Philippe G JorensDepartment of Intensive Care MedicineUniversity of Antwerp, UZA, Belgium Meningitis-encephalitis 2004 With many thanks to P. Parizel, (neuro)radiology, UA, UZA

2. CASE REPORT… • viral prodrome several days: fever, headache, nausea, lethargy, myalgias • diffuse or focal syndromes: personality changes, decreased consciousness, stiff neck, confusion, convulsions, deafness, facial palsy

3. Meningitis-encephalitis • Meningitis encephalitis • Viral vs bacteriall • Meningoencephalitis • ADEM, encephalomyelitis • Myelitis, TM • cerebritis ...

4. Meningitis-encephalitis • Meningitis: leptomeningeal (photophobia, headache, stiff neck) • Only 50 % over 16 of age: triade

5. Encephalitis • (diffuse ) inflammation of the brain parenchyma • presents as diffuse and/or focal neuropsychological dysfunction, consciousness • Hemiplegia, hyperthermia, seizures • distinct from meningitis, although symptoms of meningeal inflammation may coexist

6. Intracranial infections Etiological agent

7. Meningitis-encephalitis: etiology • reactivation of the virus ( herpes simplex), sporadically • mosquitos or ticks (arbovirus) • animal bite (rabies) • immunocompromised ( varicella-zoster, CMV) • HIV

8. Encephalitis: etiology • hematogenous or spread along neural (rabies, HSV, VZV) and olfactory (herpes simplex) pathways) after entrance by the resp. tract ( influenza), gastronitestinal tract (poliovirus) or subcutaneous tissue (Rickettsia)

9. Etiology • Over 100 viruses nervous system infections • Epidemic and largely seasonal (Arbo and entero) • Summer, fall • Endemic (Herpes, Rabies)

10. Etiology- DNA • Poxviridae: variola, vaccinia • Herpesviridae: Simplex 1, 2, Varicella-zoster, CMV, EBV, Herpes 6,7 and 8 • Adenoviridae : Adenovirus • Papoviridae : Simian virus 40, JC • Hepadnaviridae: Hep B • Parvoviridae: Parvovirus B19

11. Etiology-RNA • Paramyxoviridae: parainfluenza, mumps, measles, RSV • Orthomyxoviridae: influenza • Rhabdoviridae: Rabies • Filoviridae: Ebola, Marburg, Bunyaviridae: California encephalitis, Hantavirus • Arenaviridae: lymphocytic choriomenigitis virus • Retroviridae: HTLV I and II, HIV I and II

12. Etiology: RNA (2) • Coronaviridae: coronavirus • Reoviridae: Reoviruses • Togaviridae: Rubella • Flaviviridae: St. Louis, Japanese encephalitis, Hep C • Picornaviridae: Polio, Coxsackie, Echo, entero, Hep A

13. New… • West Nile virus (New York) • Nipah virus (Malaysia) • Asia (enterovirus 71)

14. Encephalitis : incidence • 8-30/100000 year children, 5 adults • Herpes simplex : 0.2/100000 (neonatal: 2-3/10000) • arbovirus: only 10 % encephalitis • measles: - post-infectious (1/1000 persons): SSPE (1/100000 persons) • Japanese encephalitis: most common type outside US

15. Prognosis • 462 children, death 2.8 % , severely damaged 6.7 % (Rautonen et al, 1991) • HSV poor outcome (11.7 increased risk)

16. Viral meningitis • 10-year-old boy • Laboratory tests revealed CNS enterovirus infection, with clinical symptoms of meningitis. • CT -/+ C was normal. There was no abnormal meningeal thickening or enhancement.

17. Varicella meningo-encephalitis • 29-year-old man • Symmetric distribution of edema (subinsular, frontal and temporal opercular regions); hyperintensity in the lentiform and caudate nucleus on the right • Subtle meningeal enhancement is noted

18. Varicella • 1-3/10000 • Cases immunocompromised patient

19. CMV encephalitis  abscess • Immunocompromised 49-y-o woman (renal transplant) • Early stage: • edema • serpiginous and micronodular enhancement • Late stage (4 months later): abscess

20. Rabies • Encephalitis: 30000-70000 deaths/year • RNA Rhabdoviridae • Saliva, but also aerosol • Uniformely fatal disease, nervous tissue • Only 6 cases of survival after onset of clinical rabies • Prrexposure prophylaxis, expidious postexposure • Wild animals • Fluorescent material skin biopsy, serology …

21. Herpes simplex virus (type 1) encephalitis

22. Herpes simplex • Fatality : 30 -70 % • Type 1 (neonate: type II) • Prediliction inferior and medial temporal lobes • EEG

23. Intra-uterine CMV infectionTORCH

24. Enteroviruses • Coxsackie A and B, polio, echo, entero 68 and 71 • Good prognosis, except enterovirus 71: 1998 Taiwan outbreak • 129106 cases hand, fouth and mouth disease • 405 severe cases ( encephalitis, aseptic meningitis)

25. West Nile virus • 1999: New York City • 2002: 4156 human cases, 284 fatal 1937: Uganda • Birds (New York zoo …) • Enzootic cycle: birds, mosquitos • 2000: found in 14 mosquito species • Organ transplantation, blood transfusion

26. West Nile virus • Arbovirus: St Louis , Japanese • Incubation: 3-14 days • Flu like , Africa Middle east: rarely neurological • 1/150 infected: severe, meningitis, encephaltis, meningoencephalitis • Brain stem

27. Japanese encephalitis • 15000 deaths annually • Children, young adults • 1/3 die, 50 % survivors severe neurological deficit • Vaccination (97.5 % effective)

28. HIV • HIV: dementia • CMV, Varicella … • Progressive multifocal leukoencephalopathy • JC virus, human polyomavirus • Destruction oligodendrocytes • Middle cerebellar peduncle, HIV

29. Measles • Progressive postinfectious encephalitis • SSPE (subacute sclerosing panencephalitis) • Progressive dissemination of defective (noninfectious) viral replication

30. Encephalitis: morbidity • untreated herpes: mortality 50-75 %, treatment 20 % • varicella untreated: 15 %, 100 % immunosuppressed • sex: prediliction SSPE male (2-4)

31. BACTERIAL INFECTIONS • Pyogenic bacterial infections of the CNS most commonly cause: • focal cerebritis • abscess • meningitis • empyema (subdural or epidural).

32. Tuberculous meningitis (1) • CT+C in a 1-year-old girl with proven tuberculous meningitis • Hydrocephalus (communicating hydrocephalus) • Cisternal enhancement (thick gelatinous exudate) • Arterial involvement can result in thrombosis and infarction (MCA most commonly involved).

33. Subdural empyema with abscess • Thickening and enhancement of the falx cerebri • Incipient abscess formation • Mass effect and edema in the left cerebral hemisphere

34. Cerebritis • Axial TSE T2 • Axial FLAIR • Axial SE T1 + Gd • Coronal SE T1 + Gd

35. Tuberculoma • HIV-positive 46-year-old man. • Axial FLAIR (left) and T2-weighted (right) images show a hypointense nodular mass in the pons. There is perilesional edema.

36. Tuberculoma • HIV-positive 46-year-old man. • Gd-enhanced axial (left) and coronal (right) T1-weighted images reveal circumferential peripheral enhancement of the tuberculoma.

37. Cryptococcal-meningitis • 38-year-old-HIV-positive-woman • Diffuse meningeal enhancement (e.g. at the superior meningeal covering of the vermis. • No evidence of parenchymal disease in this patient.

38. Toxoplasma encephalitis • Proven toxoplasma encephalitis in a 28-year-old HIV+ man. • Bright nodules with ringlike enhancement in the left lentiform nucleus and in the head of the caudate nucleus. • Bifrontally on there is cortical and subcortical thickening and edema and meningeal enhancement.

39. Neurocysticercosis • 25-year-old-woman • Multiple nodular lesions with intensely enhancing peripheral rim and prominent perilesional edema • Several lesions demonstrate a hypointense center on both T1- and T2-weighted images due to calcification

40. II. Meningo-encephalitis

41. Case report • 34-year-old woman • Previous medical history is unremarkable • CC: • Progressive lethargy and somnolence • Evolution to deep coma over a 3-day time interval • Lumbar puncture: pneumococcal meningitis • MRI is requested to rule out parenchymal involvement

42. Meningo-encephalitis • Meningitis • Encephalitis • convulsions • focal neurological deficit • Necrotising vasculitis

43. Addendum ... physiopathogenesis

44. ADEM/ Demyelinating diseases • Myelin • CNS: produced by oligodendrocytes (glial cells) • Peripheral: Schwann cells

45. Myelin Demyelinating: destruction of existing myelin Dysmyelinating: abormal myelin (leukodystrofies)

46. Demyelinating diseases • Central nervous system • Multiple sclerosis • ADEM • Central pontine myelolysis • Leukoencephalopathy • Encephalitis

47. ADEM • Acute inflammatory and demyelinating multifocal disease of the brain and spinal cord • Days or weeks after infection (viral, streptococcal, vaccination) • Difficult to differentiate from MS

48. ADEM- Encephalomyelitis (1) • follows infection or vaccination, DD MS • infection: • Adenovirus, mumps, CMV, EBV, HIV 1 and II, herpes simplex, influenza A and B, measles, parainfluenza 1,2,3, RSV, Rubella, varicella, herpes 6, polio, hanta • vaccination: smallpox, rabies • mortality 5-30 % (Nasr et al, 2000)

49. ADEM

50. CASE HISTORY (1) • 3-year-old-child • no vaccination