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Question 1

Astrocytes

Answer 1

 Respond by ↑number & size in gliosis
 Commonest reactive change is Gliosis
Gemistocytes:
 Swollen reactive astrocytes with acidophilic cytoplasm
 ↑ Glial fibrillary acid protein (GFAP)
 May lead to Fibrillary astrocytes
 In chronic conditions such as brain tumors
Rosenthal fibers:
 Aggregates of thick eosinophilic astrocytic fibers  In old gliosis or some low grade glial tumors

Question 2

Oligodendrocytes

Answer 2

 Synthesis & maintenance of myelin
 Deranged in demyelinating diseases
 Inclusions in specific viral infections – PML (JC virus)

Question 3

Ependymal cells

Answer 3

 Line the ventricles and detoxify CSF
 Ependymal Granulations
 Areas in ventricles of sloughed ependymal lining
 Could be normal or pathologic (ventriculitis)
 Inclusions characteristic of CMV

Question 4

Microglia

Answer 4

(Scavengers of the brain)
 Macrophages in infarction: (Gitter cells)
 Elongated cells in syphilis: (Rod cells)
 Aggregates of microglia around injured cells: (Microglial nodules)
 Aggregate around dead neurons: (Neuronophagia)

Question 5

CNS infections Routes of infection

Answer 5

 Hematogenous (most common)
 Direct (trauma & iatrogenic)
 Local extension from adjacent focus (air sinuses & congenital malformations, peripheral nerves)

Question 6

Epidural & Subdural Infections:

Answer 6

 Staph, Strep, Gram negative bacilli, Mixed
 Direct local spread
Epidural abscess
 Arise from an adjacent infection: sinusitis or osteomyelitis
 Produces localized space occupying lesion
 Subdural empyema  Mass effect & ↑ICP
 Subdural vessels → cerebral cortical thrombophlebitis  infarction

Question 7

Aseptic (Viral) Meningitis:

Answer 7

 Hematogenous spread
 Mild self-limiting often seasonal
 Brain edema, mild mononuclear infiltrate (meninges & superficial cortex)  CSF is clear, slight protein, normal sugar,  lymphocytes

Question 8

Acute Pyogenic (Bacterial) Meningitis
Neonates 
Adolescents and young adults 
Elderly 
Clinical picture 
CSF findings
Morphology

Answer 8

 Neonates: Group B Streptococci & E. coli
 Adolescents & young adults: N. meningitidis
 Elderly: S. pneumoniae & L.monocytogenes
Clinical picture:
 Fever, headache, vomiting, photophobia, neck rigidity
 N. meningitides: skin rash & complicated by septicemic shock & Waterhouse Friderichsen Syndrome (Adrenal hemorrhage and failure)

CSF findings: ↑Pressure, ↑Protein, ↓Sugar, ↑Neutrophils and bacteria

Morphology:
 Exudate in subarachnoid space (around base) = neutrophils & MOs
 Severely congested meningeal vessels, surrounded by neutrophils
 Sometimes focal cerebritis & ventriculitis & abscesses may occur
 May show phlebitis, venous occlusion & hemorrhagic infarction

Question 9

Chronic Meningitis/meningo-encephalitis

Answer 9

 TB: brain and meninges

 Syphilis: gummas in brain (meningovascular neurosyphilis)

Question 10

Lyme disease (Neuro-borreliosis) transmitted by ticks

Answer 10

 Aseptic meningitis
 Facial nerve palsies
 Polyneuropathies
 Mild encephalopathy

Question 11

Tuberculous Meningitis:

Answer 11

 Hematogenous spread from lung → brain
 Direct spread from Tuberculous vertebra (Pott’s disease)  Result: meningitis or tuberculoma
 Thick cheesy exudate & thick meninges
 Caseating Granulomas
 Basal cisterns & sulci most affected
 May show obliterative endarteritis & infarction
 CSF: high Protein, high lymphocytes, sugar N or low

Question 12

Neurosyphilis:

Answer 12

caused by spirochete (T. pallidum)

Meningovascular neurosyphilis
Paretic neurosyphilis
Tabes dorsalis
Acute syphilitic meningitis

Question 13

Meningovascular neurosyphilis:

Answer 13

 Meningeal chronic infection
 Obliterative endarteritis & cerebral gummas
 Usually at the base of the brain
 Plasma cells characteristically high in lesions

Question 14

Paretic neurosyphilis:

Answer 14

 Invasion of frontal lobe by spirochetes
 Loss of neurons & proliferation of microglia (Rod cells)
 Gliosis ± granular ependymitis
 Progressive mental deficits, mood alteration → severe dementia

Question 15

Tabes dorsalis

Answer 15

Involves SC → 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

Question 16

Acute syphilitic meningitis:

Answer 16

 HIV infected patients who have ↑risk for neurosyphilis

 May develop severe rapidly progressive disease

Question 17

Complications of Bacterial Meningitis

Answer 17

 Obstructive hydrocephalus 
 Cerebral infarction
 Cerebral abscess
 Epilepsy
 Cranial nerve palsy 
 Deafness

Question 18

Prognosis depends on

Answer 18

rapidity of proper antibiotic therapy

Question 19

Parenchymal Infections:

Answer 19

 Localized: abscess, tuberculoma, toxoplasmosis, parasites

 Diffuse: encephalitis, usually viral

Question 20

Brain Abscess:

Answer 20

 Usually bacterial
 Direct implantation
 Local extension from paranasal sinusitis, mastoiditis & middle ear
infection -> Frontal or temporal lobes
 Hematogenous: usually with predisposing conditions (may be multiple)
Morphology:
 Localized suppuration & liquefactive necrosis
 Surrounded by granulation tissue, reactive astrocytes
 Severe edema leading to high ICP
 Later Fibrous capsule & gliosis
CSF: high protein, high cells, normal sugar
Complications:
 Meningitis
 Venous sinus thrombosis
 Ventriculitis
 high ICP

Question 21

Fungal encephalitis:

Answer 21

 Candida, Cryptoccocus, Aspergillus, & Mucor
 Normal or Immunocompromised patient esp. Cryptoccocus
 Hematogenous or direct spread
 Diabetics with ketoacidosis are especially prone to Mucormycotic
infection from nose or sinuses
 Candida albicans produces multiple micro-abscesses +/- granuloma
 AIDS patients are prone to cryptococcal meningoencephalitis
 Blood vessel invasion with hemorrhagic infarction found in Aspergillus
Morphology of fungal infections:
 Microabscesses in brain or poorly formed granulomas ± meningitis.
 Fungi can be demonstrated by PAS or Silver stain

Question 22

Viral encephalitis

Answer 22

• Sporadic infection: HSV encephalitis
• Latent infections: VZV
• Neurotropic: Poliovirus, Rabies
• Antenatal: CMV, Rubella
• Immune deficiency: HIV, CMV, PML, VZV
• Some systemic viral infections do not infect the CNS, but initiate immune
  mechanisms in CNS (Influenza virus)

Question 23

Some viruses have selective sites:

Answer 23

 CMV - Ventricles
 HSV - Temporal lobe & orbital frontal area
 Polio - Anterior horn cells of spinal cord
 VZV - Thoracic dorsal root ganglia

Question 24

Features common to most viral infections:

Answer 24

 Perivascular mononuclear infiltrate
 Cell lysis & neuronophagia
 Microglial nodules
 Nuclear or cytoplasmic inclusions (Cytoplasmic negri bodies in rabies, nuclear inclusions in CMV)

Question 25

Herpes Simplex Virus type 1 & 2

Answer 25

- Normal host: children or adults - Hemorrhagic necrotizing inflammation - In temporal lobe & orbital gyri of frontal lobe - HSV-2 in adults may cause meningitis - Eosinophilic intranuclear viral inclusions (Cowdry type A) in neurons & glia

Question 26

Varicella–Zoster Virus (Herpes-Zoster)

Answer 26

- Chicken pox in children but latent infection in dorsal root ganglia in adults - Self-limited skin rash along dermatome (Shingles) or Post-herpetic neuralgia - In immunosuppressed patients, may show acute encephalitis - Lesion is typical of viral infection ± granulomatous arteritis & infarction

Question 27

Cytomegalovirus (CMV) AIDS patients:

Answer 27

 Subacute encephalitis any region & any cell  Mainly ependymal & subependymal cells  Hemorrhagic periventricular necrosis  Large cytoplasmic & intranuclear inclusions

Question 28

Cytomegalovirus (CMV) Fetus

Answer 28

``` intrauterine infection  Changes similar to above  Brain destruction  Microcephaly  Calcification ```

Question 29

Rabies

Answer 29

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

Question 30

Poliovirus

Answer 30

- Enterovirus causing mild gastroenteritis - Involvement of CNS in the non-immunised - Acute:  Mononuclear cell perivascular cuffs  Neuronophagia of the anterior motor neurons of the spinal cord - Chronic:  Atrophy of the anterior (motor) spinal roots -> paralytic poliomyelitis or Postpolio syndrome (>20 yrs)  Rare cases develop paralysis of respiratory muscles

Question 31

CJD (Creutzfeldt-Jakob)

Answer 31

 1 per million incidence, 7th decade  Sporadic cases, not epidemic  Iatrogenic (Transmitted by Contaminated material)  Familial cases well documented – PRNP mutation (15%)  Rapidly progressive dementia  FATAL, no treatment known