L10 – Pathology of CNS Infection

Question 1

Cause and typical organisms that cause bacterial meningitis in infants (2mo)

Answer 1

 Metastatic (intestinal tract)
 Direct invasion (birth canal)

 Escherichia coli
 Group B streptococci

Question 2

Cause and typical organisms that cause bacterial meningitis in Children (2mo - 5y)

Answer 2

Metastatic (oropharynx >> cribiform plate >> olfactory bulb >> brain)
Otitis media (>> mastoid sinus >> brain)

 Haemophilus influenzae
 Neisseria meningitidis
 Streptococcus pneumoniae

Question 3

Cause and typical organisms that cause bacterial meningitis in young adults?

Answer 3

Metastatic (oropharynx)

 Neisseria meningitidis (epidemics)
 Streptococcus pneumonia

Question 4

Cause and typical organisms that cause bacterial meningitis in all ages?

Answer 4

Direct invasion (e.g. head trauma from road accident)

 Staphylococci
 Group A Streptococci
 Streptococcus pneumoniae
 Pseudomonas aeruginosa

Question 5

Which part of the brain is affected in bacterial meningitis?

Answer 5

• Pus in subarachnoid space
• Prominent over vertex, base of brain + Accumulate in gyri

_ May spread to ventricles, infiltrate choroid plexus, extend over posterior aspect of spinal cord

Question 6

Microscopic appearance of subarachnoid space in bacterial meningitis?

Answer 6

subarachnoid space filled with polymorphs and later lymphocytes, plasma cells and macrophages

Causative organism +ve gram stain

Question 7

Gross pathological changes seen in subarachnoid space in bacterial meningitis?

Answer 7

 Petechial haemorrhages
 Focal infarction
 Small abscesses within white matter
 Inflammatory reaction: vasodilatation, congested blood vessels

Question 8

Late gross pathological changes in bacterial meningitis?

Answer 8

Organisation of inflammatory exudate:

1) Fibrosis: entrapment / scarring cause cranial nerve palsies (6th, 7th, 8th, optic nerves)
2) Thickening of meninges
3) Obliteration of subarachnoid space: granulation tissue cause adhesion between pia and arachnoid

Question 9

Complications of late bacterial meningitis?

Answer 9

• Hydrocephalus (obliterated subarachnoid space, exacerbate CN palsy)
• Septic thrombosis/ septicaemia of cerebral vessels in the subarachnoid space&raquo_space; cerebral infarction
• Direct infection/ infarction of parenchyma&raquo_space; epilepsy, mental retardation or focal neurological disorders such as hemiplegia and spasticity

Question 10

Initial Pathological changes seen in Intracerebral abscesses?

Answer 10

initial acute inflammation with polymorph infiltration, tissue necrosis with pus formation

= Cerebritis

Question 11

List 3 sites and 3 routes for intracerebral abscesses?

Answer 11

Sites:
 Epidural
 Subdural
 Intracerebral

Routes:
 Adjacent sepsis
 Direct penetrating injuries
 Hematogenous, e.g.: Infective endocarditis or Lung abscess

Question 12

Late pathological changes seen in Intracerebral abscesses?

Answer 12

 Fibrous capsule develops slowly around the nidus of infection and liquidative necrosis

 Abscess gradually increases in size and ruptures into ventricle / at brain surface

 Cerebral herniations

 Surrounding brain develops gliosis

Question 13

Most common clinical manifestation of intracerebral abscesses?

Answer 13

70% survivors develop epilepsy during the following 10 years

Question 14

What pathogens should be suspected if CSF sample is bacteriologic culture negative/ aspectic meningitis?

Answer 14

 Viral 
 Partially treated bacterial (e.g. antibiotics or fever) 
 Leptospirosis 
 Fungal 
 Mycobacterial

Question 15

2 diff. forms of TB meningitis?

Answer 15

Tuberculous meningitis and tuberculomas

Question 16

TB meningitis is secondary to which conditions? Can it arise as a primary cause?

Answer 16

 Miliary tuberculosis
 Active pulmonary tuberculosis
 Tuberculosis of the spine

No, always secondary to tuberculosis elsewhere in the body

Question 17

Which part of the brain is most affected by TB meningitis?

Answer 17

• Granulomatous inflammation most abundant in the basal part of brain
• Small granulomas in the pia-arachnoid (extensive fibrosis = obliteration of subarachnoid space)

Question 18

Pathological changes seen in TB meningitis?

Answer 18

1) Thick gelatinous exudate around granuloma = lymphocytes, plasma cells, macrophages and caseous material.
2) Granuloma formation = central caseous necrosis bordered by epithelioid histiocytes + Langhan’s giant cells + lymphocytes and fibrosis
3) fibrosis with extensive obliteration of the subarachnoid space

Question 19

What stain is used for TB meningitis?

Answer 19

Microscopy: acid-fast bacilli by Ziehl-Neelsen staining

Question 20

Complications of TB meningitis? What if brain parenchyma is also involved?

Answer 20

1) obstructs CSF flow in subarachnoid space = hydrocephalus
2) Inflammation, fibrosis damage cranial nerves = multiple cranial nerve palsy
3) Direct parenchyma infection
4) Endarteritis obliteran (intimal proliferation + luminal narrowing of cerebral arteries = superficial infarcts in adjacent brain tissue)

Question 21

Long term clinical manifestations of TBM?

Answer 21

 Focal neurological deficits
 Epilepsy
 Mental retardation

Question 22

Define tuberculoma?

Answer 22

encapsulated caseous mass in brain (may present as space-occupying lesions)

SIngle or multiple

Question 23

Lumbar puncture is not used against which type of meningitis?

Answer 23

Tuberculomas

Question 24

Complications of tuberculoma?

Answer 24

 Obstructs CSF flow (if near ventricles)

 Raises intracranial pressure

Question 25

2 reasons why TB meningitis or tuberculoma is difficult to dx?

Answer 25

1) Depends heavily on CSF examination, but can rarely identify the bacilli in CSF smears
2) Long culture time (6 weeks vs. medical emergency)

Question 26

What investigations are useful in TB meningitis dx apart from LP?

Answer 26

1) Find active tuberculosis in other parts of the body (e.g. lungs)
2) brain biopsy (e.g. during shunting procedure for treatment of hydrocephalus)

Question 27

Gross pathological changes seen in Fungal meningitis?

Answer 27

1) meninges are thickened, opalescent and contain mucoid exudate
2) Small cysts up to 3mm in diameter are found in the cortex or deeper down

Question 28

Histological changes seen in Fungal meningitis?

Answer 28

1) inflammatory infiltrate containing abundant polymorphs and also occasional granulomas resembling those seen in tuberculosis
2) spherical yeast organism with a thick mucoid capsule can be demonstrated by special staining

Question 29

Which yeast pathogens are typical of fungal meningitis, which are rarer?

Answer 29

Ususally cryptococcus neoformans

Candida albicans, Aspergillus and Actinomyces may rarely cause meningitis, seen in immunocompromised

Question 30

What staining is used to delineate fungal meningitis from another form of meningitis that resembles it?

Answer 30

Always use fungal cap stain i.e. Indian stain preparation of CSF
+
PAS/ ZN stain to delineate TB meningitis

Question 31

Ddx of Viral encephalitis if the temporal lobes are involves vs if the anterior horn cells of spinal cord is involved?

Answer 31

temporal lobes are mainly involved in herpes simplex encephalitis

poliomyelitis the damage occurs in the anterior horn cells of the spinal cord.

Question 32

Pathological changes seen in viral meningitis?

Answer 32

Infiltration of the leptomeninges by mononuclear cells

perivascular lymphocytic cuffing in the superficial layers of the cerebral cortex.

Question 33

Viral meningitis is usually self limiting. True or False

Answer 33

True

Except for encephalomeningitis

Question 34

Explain how viruses cause neurological diseases? Pathways?

Answer 34

1) Cytopathic effect from direct invasion of the CNS

2) Accompanying or delayed immunological response to virus invasion (e.g. post-viral encephalitis, polyneuropathy)

Question 35

4 Pathological changes seen in viral encephalitis?

Answer 35

1) Lymphocytic cuffing, plasma cell infiltration (often restricted to perivascular regions, meninges)
2) Widespread proliferation of microglial cells, microglial stars
3) Neuronophagia: Microglia, macrophages ingest infected, dead neurons
4) Viral inclusions within glia and neurons `

Question 36

How to detect viral inclusions in viral encephalitis?

Answer 36

electron microscopy, immuno-flourescence and immunoperoxidase staining.

Question 37

5 classes of viruses that cause viral meningitis?

Answer 37

1) Neurotrophic virus
2) Slow viruses
3) Congenital viral infection
4) Perivenous encephalomyelitis
5) Human immunodeficiency virus

Others: MS, Reye’s syndrome

Question 38

Give some examples of neurotrophic viruses that cause viral encephalitis?

Answer 38

poliovirus, rabies, herpes simplex

Question 39

Give some examples of congenital viral infections that cause viral encephalitis?

Answer 39

Cytomegalovirus: interferes with brain development, microcephaly, Owl’s eye inclusions

Rubella (immunization)

Question 40

Give 2 examples of Perivenous encephalomyelitis ?

Answer 40

Autoimmune attack on brain and spinal cord ususally triggered by viral infection

1) Postinfection / postvaccinal encephalomyelitis
2) Acute necrotizing hemorrhagic leukoencephalitis

Question 41

What is post-infectious encephalitis? Histological feature?

Answer 41

follow vaccination, measles, varicella or influenza virus infection

1) widespread small foci of perivascular tissue destruction (myelin is destroyed most)
2) Plaques of demyelination found around vessels with lymphocytic cuffing
3) Astrocytic proliferation is seen at later stage, leaving perivascular gliosis.

Question 42

List 4 protozoal and parasitic infections of the CNS.

Answer 42

Amoebic meningoencephalitis - Amoeba

Cerebral toxoplasmosis = Toxoplasma

Cerebral malaria - Malaria

Cysticerosis (larval cysts of the tapeworm Taenia solium)

Question 43

Expected CSF analysis results of Bacterial meningitis?

Answer 43

> 2000 polymorphs

High protein

Very Low glucose

Question 44

Expected CSF analysis results of TB meningitis/ tuberculoma?

Answer 44

 Initially >200 polymorphs
 Later 100-1000 lymphocytes

Very high protein
low glucose

Question 45

Expected CSF analysis results of Viral meningitis?

Answer 45

 Initially <100 polymorphs  Later >1000 lymphocytes

Elevated protein (not as high as TB or bacterial)

Normal/ Reduced glucose (not as low as TB or bacterial)

Question 46

Expected CSF analysis results of Viral encephalitis*** (not meningitis) ?

Answer 46

 Initially <100 polymorphs
 Later <500 lymphocytes** different from meningitis**

Elevated protein (not as high as TB or bacterial)

normal Reduced glucose (not as low as TB or bacterial)