CNS INFECTION

1. CNS INFECTION FM Brett MD., FRCPath

2. ORGANISMS~ PATHOGENIC - cause disease in every individual ~ OPPORTUNISTIC – Affect people with lower resistance

3. CNS INFECTION Development and outcome depends on Organism nature route of entry dose HostAnatomical defenses - skull, meninges Physiological - immune defense mechanisms

4. Bacteria Entry into the cranial cavity Haematogenous -distant foci e.g lung Local spread -Skull - middle ear, nasal sinus, osteomyelitis Abnormal routes - Trauma -fractures Surgery - shunts Congenital sinus

5. BACTERIAL INFECTIONSDepending on their virulence/pathogenicity bacteria can induce: • Purulent lesions • Cellular inflammatory reactions with giant cells • Inflammatory oedema caused by toxins and other inflammatory • substances released by bacterial secretions or lysis, in the absence of bacterial replication

6. PYOGENIC INFECTION1. BONE – EPIDURAL – usually spinal sec to osteomyelitis • DURA MATER - SUB DURAL - sec to sinusitis, otitis etc. • ARACHNOID – SUBARACHNOID – sec to haematogenous spread of bacteria • 4. PIA - INTRAPARENCHYMAL - abscess

7. SUBDURAL

8. Three organisms responsible for acute • meningitis in childhood or adult life • Meningococcus • Haemophilus influenza • Pneumococcus

9. Bacterial meningitis

10. Bacterial meningitis

11. Complications of acute meningitis • in the neonate • Obstructive hydrocephalus • Cavitating lesions in the white matter

12. Meningococcus Nasopharynx Blood Bacteraemia Septicaemia Chronic Meningitis Endotoxic shock immune complexes acute meningitis DIC arthritis, vasculitis

13. CSF

16. Complications of bacterial meningitis • Acute inflammation of adjacent structures • Organisation of inflammatory structures

17. Organisation of inflammatory exudate Impedes flow of CSF into venous sinuses Obstructs CSF outflow from IV ventricle

19. A twelve year review of central nervous system bacterial abscesses: presentation and aetiology. Roche M, Humphreys H, Smyth E, Phillips J et al Clin Mic & Inf 2003;9:803-14 1988-2000 163 patients

20. Cerebral abscess ~ Mean age – 35.2 ~ P/C – headaches, pyrexia, altered mental state (depends on site, number, and +/- secondary cerebral lesion) ~ Site – frontal lobe commonest ~ Majority – associated with sinusitis, mastoiditis 20% no source ~ Bacteria isolated from 73%. Polymicrobial – 17.7% ~ Anaerobes – 13.6% ~ 9.8% died ~ 11% developed epilepsy

21. Cerebral abscess Predisposing conditions Local – otitis media, sinusitis, trauma Systemic ~ chronic lung disease ~ cyanotic congenital heart disease ~ transplants ~ immunosupression

22. Parenchymal abscess formation ~ Early cerebritis (days 1-3) ~ Late cerebritis (days 4-9) ~ Early capsule formation (days 10-13) ~ Late capsule formation (days 14 onward)

25. AIMS OF TREATMENT ~ Eliminate infectious process ~ Reduce mass effect within cranial cavity – thus reduce secondary injury ~ Treat infections

26. Tuberculous meningitis Usually M Tuberculosis More commonly associated with documented history of tuberculosis exposure in children than adults

27. CSF

28. Syphylis • Asymptomatic CNS involvement • Syphylitic meningitis – 1-2 yrs • meningovascular syphylis – 7yrs • parenchymatous neurosyphylis • gummatous neurosyphylis

29. 1 syphylis – spirochaete dissemination – chancre 2nd – haematogenous dissemination - rash, adenopathy, 3 – CVS, CNS, gumma Latent – lasts mths – yrs. Pts may progress straight to the stage of latent syphylis without developing secondary syphylis

30. Syphylis I syphylis – spirochaete dissemination – chancre 2nd – haematogenous dissemination - rash, adenopathy, 3 – CVS, CNS, gumma Latent – lasts mths – yrs. Pts may progress straight to the stage of latent syphylis without developing secondary syphylis

31. Neurosarcoidosis ~ Chronic granulomatous disease of unknown aetiology ~ CNS involved in 5%. CNS disease often accompanied by PNS disease ~ Usually base of the brain ~ Facial nerve palsy common. May develop deafness, vertigo, ataxia, DI, hypopituitrism

32. Acute viral infections • Aseptic meningitis • Poliomyelitis • Herpesvirus - HSV, VCZ, EBV, cytomegalo, HHV6 • Rubella • Rabies

33. Aseptic meningitis-common causes • Echovirus • Coxsachie B virus • Coxsachie A virus • HSV-2 • Mumps • Measles • Adenovirus

34. CSF

35. Poliomyelitis Precentral gyrus Reticular formation Motor nuclei of pons and medulla Ant horn cells of spinal cord

36. HERPESVIRUS INFECTIONS DNA VIRUSES - include HSV1, HSV2, EBV, CMV and HHV6 HSE Encephalitis Focal neurologic signs Mortality 25-50%

37. HSE - oral labial vesicles - retrograde axonal spread – trigeminal ganglion- (latency) Reactivation (spontaneously, trauma, UV light, systemic disease) Entry of HSV-1 into CNS – olfactory nerves Reactivation of latent virus in trigeminal nerve Reactivation from temporal lobes

39. Chronic viral infectionsprogress over mths - years SSPE– follows exposure to measles virus Age of onset – 5-15 yrs prognosis poor PML- JC virus affects immunosupressed individuals demyelination

40. HIV ~ First recognised in USA in 1981 ~ Widely distributed worldwide ~ 30 million currently infected ~ 9000 infections daily - > 50% sub-saharan Africa ~ USA and western Europe – homosexual, and IVDA ~ Elsewhere heterosexual ~ Small proportion perinatal or breast feeding ~ Organ donors, blood etc

41. HIV – retrovirus ~ Infects cells carrying CD4 antigen i.e CD4+ T helper cells and monocytes/macrophages ~ This leads to a) cell mediated immunodeficiency – AIDS b) invasion of CNS by macrophage/monocytes ~ CNS disease – infection by virus - opportunistic infections - Lymphomas - HIV asssociated systemic disease affecting CNS e.g metabolic, cvs etc. - complications of treatment

42. Commonest processes identified prior to HAART ~ Cryptococcus ~ Toxoplasmosis ~ PML~ HIVE~ HIVL ~ Cytomegalovirus infection ~ Vacuolar myelopathy ~ CNS Lymphoma By and large did not have bacterial infections

49. Commonest causes of a cerebral mass in a patient with HIV Toxoplasmosis CNS lymphoma Tuberculoma PML CMV Lesion not related to HIV - glioma