1. Dr. Mohammed Alorjani, MD. EBP.
Pathology of
Nervous System (I) -3
2016
Dr. Mohammed Alorjani, MD. EBP.

2. INFECTIONS OF CNS

3. IMPORTANT FACTORS
Route: Hematogenous (most common), Direct (trauma & iatrogenic…), Local extension from adjacent focus, e.g. air sinuses & congenital malformations, Peripheral nerves
Agent: Bacteria, Viruses, Fungi, Parasites,
or immune process
Normal or immunocompromised host

4. SITES of INFECTIONS
Epidural & Subdural infections
Meningitis
Cerebral abscess
Encephalitis, mainly viral

5. Epidural & Subdural Infections:
Staph., Strep., Gram neg. bacilli, Mixed.
Direct local spread
Epidural Localized space occupying lesion
Subdural empyema  Spreading infection & ↑ICP
Involvement of subdural vessels may lead to cerebral cortical thrombophlebitis and arteritis  infarction

6. Meningitis: Inflammation of leptomeninges & CSF
1- Acute Bacterial Meningitis:
- Neonates: Group B Streptococci & E. coli
-  6M: H. influenza, S. pneumoniae
- Adolescents & young adults: N. meningitidis
- Elderly: S. pneumoniae & L.monocytogenes
- Shunt operations: Staphylococci

7. Clinical picture:
Fever, headache, vomiting, photophobia, neck rigidity.
In N. meningitidis, may be accompanied
by skin rash & complicated by septicemic
shock
Waterhouse Friderichsen Syndrome
C.S.F. findings:
↑Pressure, ↑Protein, ↓sugar, numerous
neutrophils, demonstrable bacteria

8. Morphology: Exudate in subarachnoid space, especially
around base, full of neutrophils & organisms
Severely congested meningeal vessels,
surrounded by neutrophils
Sometimes superficial cerebritis & ventriculitis
Abscesses may occur
May show phlebitis, venous occlusion &
hemorrhagic infarction of underlying brain.

9. PURULENT (BACTERIAL) MENINGITIS

10. Thick exudate over base of brain in pyogenic meningitis

11. PURULENT MENINGITIS

12. 2- Acute Aseptic Meningitis (Viral Meningitis):
Enterovirus, echovirus, coxackie & mumps v. EBV, HIV
Hematogenous spread
Mild self-limiting often seasonal
Brain edema, mild mononuclear cell infiltration of meninges & superficial brain cortex
CSF is clear, slight protein, normal sugar,  lymphocytes

13. ASEPTIC (VIRAL) MENINGITIS

14. 3. CHRONIC Meningitis/meningo- encephalits
TB, brain and meninges
SYPHILIS, gummas in brain
LYME DISEASE (Neuro-borreliosis)
transmitted by ticks.
aseptic meningitis
facial nerve palsies
polyneuropathies
mild encephalopathy. 14

15. Chronic Meningitis:
1- Tuberculous Meningitis:
Hematogenous spread from lung → brain
Direct spread from Tuberculous vertebra
Result: meningitis or tuberculoma

16. Morphology:
Thick cheesy exudate, thick meninges,
tubercles on surface.
( Caseating Granulomas)
Basal cisterns & sulci most affected
May show obliterative endarteritis &
infarction
CSF: Protein, lymphocytes, sugar N or 

17. TUBERCULOMA 17

18. 2- Neurosyphilis: caused by spirochete (T. pallidum)
Meningovascular syphilis: Meningeal chronic
infection with obliterative endarteritis & cerebral gummas. – usually base of brain
Plasma cells characteristically in lesions
Paretic neurosyphilis: Invasion of frontal lobe by spirochetes, loss of neurons & proliferation of microglia (ROD CELLS) & gliosis ± granular ependymitis
Result: progressive mental deficits, mood alteration → severe dementia – General Paresis of the Insane (GPI)

19. Involves spinal cord → damage to sensory nerves in dorsal columns:
Tabes Dorsalis:
Involves spinal cord → damage to sensory nerves in dorsal columns:
loss of pain sensation and joint position sense & locomotor ataxia → skin and joint damage (Charcot joints), characteristic "lightning pains” & absence of deep tendon reflexes
Acute syphilitic meningitis:
HIV infected patients who have ↑risk for neurosyphilis & may develop severe rapidly progressive disease

20. Complications of Bacterial Meningitis
1- Obstructive hydrocephalus
2- Cerebral infarction
3- Cerebral abscess
4- Epilepsy
5- Cranial nerve palsy
6- Deafness
** Prognosis depends on rapidity of proper antibiotic therapy

21. Parenchymal Infections:
Localized: abscess, tuberculoma,
toxoplasmosis, parasites
Diffuse: encephalitis, usually viral

22. Brain Abscess: Usually bacterial but may be fungal Direct implantation
Local extension: from paranasal sinusitis, mastoiditis & middle ear infection 
Frontal or temporal lobes
Hematogenous route: usually with predisposing conditions...
May be multiple

23. Morphology:
Localized suppuration & liquefactive necrosis, surrounded by granulation tissue, reactive astrocytes & severe edema leading to  ICP.
Later Fibrous capsule & gliosis
CSF: protein, cells, normal sugar
Complications:
Meningitis, Venous sinus thrombosis, Ventriculitis, Focal neurological defects, epilepsy.

24. PURULENT CEREBRAL ABSCESS

25. VIRAL Encephalitis ARBO VIRUSES (West Nile, Equines,… etc) HSV1 & HSV2
Herpes Zoster
CMV
POLIO
RABIES
HIV
Progressive Multifocal Leukoencephalopathy (JC)
Subacute Sclerosing Panencephalitis (Measles) 25

26. May be sporadic in healthy subjects
May only affect immunocompromised
subjects
Some are selective to the CNS while
others affect other tissues

27. VIRAL ENCEPHALITIS & MYELITIS:
Sporadic infection: HSV encephalitis
Latent infections: Herpes Zoster
Neurotropic: Poliovirus, Rabies
Antenatal: CMV, Rubella
Immune deficiency:
HIV, CMV, PML, Herpes Zoster
Some systemic viral infections do not infect the CNS, but initiate immune mechanisms in CNS e.g. Influenza virus

28. Some viruses have selective sites:
CMV -Ventricles
HSV -Temporal lobe & orbital frontal area
Polio - Anterior horn cells of spinal cord
Herpes Zoster - Thoracic dorsal root
ganglia

29. Features common to most viral infections:
1- Perivascular mononuclear infiltrate
2- Cell lysis, neuronophagia
3- Microglial nodules
4- Nuclear or cytoplasmic inclusions
e.g. Cytoplasmic negri bodies in rabies,
nuclear inclusions in CMV …etc.

30. Microglia showing neuronophagia

31. Perivascular cuffs of lymphocytes
Microglial nodules

32. Eosinophilic Negri body of Rabies, also basophilic inclusions of CMV32

33. 1- Herpes Simplex Virus type 1 & 2
Normal host: children or adults
Hemorrhagic necrotizing inflammation in temporal lobe & orbital gyri of frontal lobe
HSV-2 in adults may cause meningitis
All common features of viral encephalitis seen with eosinophilic intranuclear viral inclusions (Cowdry type A) in neurons & glial cells.

34. HERPES ENCEPHALITIS

35. 2- Varicella –Zoster Virus (Herpes-Zoster)
Chicken pox in children but latent infection in dorsal root ganglia in adults
Self-limited skin eruption along a dorsal nerve dermatome (Shingles) or Postherpetic Neuralgia
In immunosuppressed patients, may show acute encephalitis.
Lesion is typical of viral infection
± granulomatous arteritis & infarction

36. 3- Cytomegalovirus (CMV)
AIDS patients: subacute encephalitis any region & any cell but mainly ependymal & subependymal cells.
There is hemorrhagic periventricular necrosis with large cytoplasmic & intranuclear inclusions
Fetus: intrauterine infection.
Changes similar to above + brain destruction, microcephaly & calcification

37. 4- Rabies Severe often fatal, encephalitis
bite of a canine or others
ascending along peripheral nerve from bite, incubation period may last months
Neuronal degeneration and inflammatory reaction, most severe in
midbrain, & floor of 4th. Ventricle
Presence of Negri bodies: cytoplasmic, eosinophilic inclusions in pyramidal neurons of the hippocampus & Purkinje cells of cerebellum

39. 5- Poliovirus Enterovirus causing mild gastroenteritis
Involvement of CNS in the non-immunised
Acute:
mononuclear cell perivascular cuffs and neuronophagia of the anterior horn motor neurons of the spinal cord
Chronic:
Atrophy of the anterior (motor) spinal roots, and neurogenic atrophy of denervated muscle. Postpolio syndrome
Rare cases develop paralysis of respiratory muscles

40. 6- Human Immunodeficiency Virus (HIV)
At least 60% of AIDS pts. develop CNS dis.
Early: aseptic viral meningitis in 10%
Chronic HIV: Meningoencephalitis:
Progressive → HIV encephalopathy, affecting motor control, memory, incontinence
Commonest cause of dementia in the young (HAND)
Demyelination: Vacuolar myelopathy affecting spinal cord nerve tracts.

41. Pathology:
Mainly white matter & basal ganglia,
& spinal cord.
Demyelination, microglial nodules with
multinucleated giant cells …
Brain atrophy

43. 43

44. 7- JC virus →PML (Progressive Multifocal Leukoencephalopathy)
Caused by JC virus (a polyomavirus) exposure during childhood
AIDS patients & other immunosuppressed patients
Infect oligodendrocytes: Enlarged nuclei with inclusions. Large astrocytes are also seen. RESULT:
Progressive demyelination of white matter

46. PRION DISEASES SPONGIFORM ENCEPHALOPATHIES:
Caused by prion variants not containing RNA nor DNA
TRANSMISSIBLE FATAL Disease, NO Rx
Prion proteins are present in normal brains ( PrP)
Abnormal folding (mutation) of PrP →
(PrPsc ) → (PrPsc, PrPsc, PrPsc …etc)
Mutation can be sporadic, familial or iatrogenic acquired via infected material

48. Include a variety of conditions:
* Kuru
* Creutzfeldt-Jacob Disease
* ‘New Variant’ CJD
* Fatal Familial Insomnia
* Scrapie in sheep
* Bovine spongiform encephalopathy (Mad
Cow Disease)

49. CJD (Creutzfeldt-Jakob)
1 per million incidence, 7th decade
Sporadic cases, not epidemic
Iatrogenic Transmitted ! Contaminated material
Familial cases well documented – PRNP mutation (15%)
Rapidly progressive dementia
FATAL, no treatment known, like ALL prion diseases
CJ has also been called JC, but the term “JC” makes it confusable with the JC polyoma virus, so CJ-D is probably the politically correct term 49

50. Creutzfeldt-Jacob Disease:
Rapidly progressive
Usually older people
Younger in familial cases
Variant CJD = Mad Cow Disease
usually acquired through cattle & recently, blood transfusion.

51. Pathology:
Multifocal spongiform transformation of cortex & deep grey matter→ multiple cysts, most in caudate & putamen.
No inflammatory response.
Microscopic findings:
Neuronal loss
Gliosis
Atrophy
Amyloid deposits may be present (v.CJD)

53. Hence the term “spongiform.”53

54. FUNGAL ENCEPHALITIS:
Candida, Cryptoccocus, Aspergillus, & Mucor
Normal or Immunocompromised patient sp. Cryptoccocus
Hematogenous or direct spread
Diabetics with ketoacidosis are especially prone to Mucormycotic infection from nose or sinuses
AIDS patients are prone to cryptococcal
meningoencephalitis

55. Blood vessel invasion with hemorrhagic infarction especially found in Aspergillus
Morphology of fungal infections:
Microabscesses in brain or poorly formed granulomas ± meningitis.
Fungi can be demonstrated by PAS or Silver stain

56. OPPORTUNISTIC INFECTIONS Fungal cerebritis: Aspergillus

57. OPPORTUNISTIC INFECTIONS Fungal cerebritis: Aspergillus

58. Other infections: Cerebral Toxoplasmosis:
occurs in immuno-compromised patients
(AIDS), produces small, usually multiple, abscesses & necrotic foci which contain
toxoplasma pseudocysts in microglial
nodules

59. Toxoplasma Pseudocyst

60. Amebic meningoencephalitis

61. Cysticercosis: Tapeworm Tenia Solium
Man is the intermediate host: Ova are ingested  Larvae  Cysts
Anywhere in the body !
Mass lesion
Death  intense inflammation & eosinophils

62. Echinococcosis: Echinococcus granulosus Tapeworm
Hydatid Cyst

63. Hydatid Cyst Wall