1. CNS Infections

2. Infection of CNS coverings Dura – pachymeningitis Leptomeninges - leptomeningitis Infections of neural tissue Brain – encephalitis Spinal cord – myelitis Ventricles - ventriculitis

3. CNS Infections Pachymeningitis Sources  Direct spread from chronic suppurative infections of sinuses, ear, mastoid or compound fracture Manifestations  Usually localised +/- overlying osteomyelitis Extradural abscess Subdural empyaema Spinal epidural abscess.

4. CNS Infections Leptomeningitis (commonly purulent) Sources  Haematogenous (most common)  Direct from adjacent inflammatory lesion  ? Through cribriform plate  Iatrogenic eg. spinal tap Microbiology

5. CNS Infections Pathology Gross  Swollen, congested brain (acute inflammation)  Purulent CSF (filling sulci & basal cisterns) Micro  Purulent exudate in subarachnoid space, extending into perivascular spaces  Some cortical oedema +/- degeneration in chronic cases

6. Brain & Cord: Purulent meningitis

7. Brain: Purulent meningitis

13. Spinal cord: Purulent meningitis

14. CNS Infections Acute lymphocytic meningitis Causes  Viruses: ECHO, Coxsackie, Herpes simples II, E-B virus. Manifestations  Similar to bacterial meningitis – less severe  Gross: acute inflammation, clear CSF  Micro: lymphocytic cellular exudate in CSF and subarachnoid space

15. CNS Infections Chronic meningitis Causes  Mycobacterium tuberculosis - TB  Treponema pallidum – syphilis  Brucella – brucellosis  Fungi – Candida, Cryptococcus, Histopasma  Protozoa – Toxoplasma, Amoebae Micro:  Largely mononuclear inflammation with granulomas

16. Brain: Tuberculous meningitis.

17. Brain: Tuberculous meningitis

18. Tuberculous meningitis

19. CNS Infection Chronic meningitis Complications  Obstructive hydrocephalus  Focal infarctions/microinfarcts due to endarteritis oblitrerans  Formation of intracranial mass  Cranial nerve palsies

20. CNS Infections Infections associated with formation of intracranial mass Tuberculosis – tuberculoma Syphilis – gumma Amoebiasis – amoeboma Aspergillosis – aspergilloma, Crryptococcosis - toruloma. Parasites – cysticercosis, hydatid cyst.

21. Tuberculoma

22. Brain: Toruloma

23. CNS Infections CNS syphilis (tertiary) Meningoencephalitis (meningovascular syphilis) Gumma General paresis of the insane (GPI) – focal infarcts, atrophy and dementia Tabes dorsalis.

24. CNS syphilis

25. Brain: Syphilis

26. CNS Infections Cerebral abscess Sources  Direct spread (sinusitis, mastoiditis)  Haematogenous. Manifestations  Mass effect  Complications: spread into ventricles or subarachnoid space – ventriculitis or meningitis

27. CNS Infections Cerebral abscess Pathology  Localised suppuration  Surrounding pyogenic membrane  Surrounding brain: Oedema – vasogenic Inflammatory infiltrate rich in plasma cells and lymphocytes. Gliosis – astrocytes mainly.

28. CNS: Abscess

29. Cerebral abscess

31. Brain: cerebellar abscess.

32. Encephalitis Primary encephalitis Acute/subacute viral infections Persistent viral infections Slow viral infections Secondary encephalitis Post-infectious encephalomyelitis

33. CNS Infections Primary viral encephalitis  Herpesviruses – HSV 1 and 2  Enteroviruses – Poliovirus  Arboviruses  Rabiesvirus  Persistent virus infections (SSPE, PMLE)  HIV-1 infection

34. Encephalitis Primary encephalitis – morphology Gross  Focal/generalised inflammation +/- necrosis Micro  Mononuclear inflammatory infiltrate with perivascular extension (lyphocytes, plasma cells)  Neuronal destruction + neuronophagia  Proliferation of microglia – rod cells  Reactive gliosis – astrocytosis  Inclusion bodies  Demyelination.

35. Viral encephalitis: Preferred sites for various viruses

36. Brain: Encephalitis

37. Viral encephalitis: Histological lesions

38. Viral encephalitis: Neuronophagia

39. Encephalitis: Perivascular infiltrate

40. Encephalitis: Types of inclusion bodies

41. CNS infection: Rabies

42. Brain: Herpes simplex encephalitis

43. Brain: Herpes encephalitis: vessel necrosis + inflam. cells

44. Encephalitis: Intranuclear inclusions

45. CNS: Poliomyelitis

46. Encephalitis Primary encephalitis Persistent viral encephalitis  Subacute sclerosing panencephalitis (SSPE) Chronic infection Result of measles virus infection Affects older children Brain shows loss of myelin + gliosis + perivascular lymphocytic infiltration CSF contains high titres of measles antibody and viral antigen Expression of aberrant T-cell response to presence of virus in brain.

47. Encephalitis Primary encephalitis Slow virus infections  Progressive multifocal leucoencephalopathy (PMLE) Infection by papovavirus group (JC virus) In immunosuppressed patients (HD, chemotherapy for malignancies) Focal demyelination in white matter, basal ganglia Gitter cells in affected areas + atypical astrocytes + abnormal oligodendrocytes (contain virions as inclusions)

48. Brain: Progressive multifocal leukoencephalopathy

49. Encephalitis Secondary encephalitis  Bacterial eg Brucella  Spirochaetal eg Treponema  Rickettsial eg. Borrelia  Parasitic Protozoa – Toxoplasma, Plasmodium, Trypanosoma Metazoa – Schistosoma, Cysticercus, Hydatid.  Viral eg Mumps, Yellow fever

50. Encephalitis Postinfectious encephalomyelitis  Measles  Rubella  Varicella-Zoster  Vaccinia  Influenza  Variola.

51. CNS Changes in HIV Infection Aseptic meningitis 1-2 weeks after seroconversion in 10%. HIV 1 antibodies in CSF. Meningoencephalitis Gross  Diffuse cortical atrophy Micro  Chronic inflammation, focal necrosis + gliosis, endarteritis, microglial nodules +/- giant cells, multifocal/diffuse demyelination + gliosis

52. CNS Changes in HIV Infection Vacuolar myelopathy (20-30%) Similar to subacute combined degeneration Immunosuppression (not due to HIV) Inflammatory myopathy Muscle fibre necrosis + phagocytosis Interstitial infiltration with HIV-positive macrophages

53. CNS Changes in HIV Infection Cranial and peripheral neuropathies Acute & chronic demyelinating polyneuropathy Distal symmetrical polyneuropathy Polyradiculopathy Mononeuritis multiplex Sensory neuropathy due to ganglioneuritis (rare)

54. CNS in Childhood AIDS Neurological manifestations in 1 year: Microcephaly + mental retardation + delay of motor development Micro: Calcification in basal ganglia or deep cortical white matter (blood vessels) Foci of tissue destruction in grey/white matter Loss or delay in myelination Opportunistic CNS infections (rare in children)