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15. Central Nervous System Pathology > 4. CNS infections > Flashcards

4. CNS infections Flashcards

1
Q

Routes of infection

A
  1. Direct implantation
    - Trauma
    - Meningomyelocele
  2. Local extension
    - Sinusitis
    - Otitis media
    - Dental caries
  3. Hematogenous spread
    - Septicaemia
    - Infective emboli (e.g. from infective endocarditis)
    - Facial infections (retrograde venous spread through anastomoses with veins of face)
  4. Transport along peripheral nervous system
    - Rabies virus
    - Herpes simplex virus
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2
Q

Pattern of involvement of microbes

A

Coverings:

  1. Extra-/subdural abscess: Bacteria
  2. Meningits: Bacteria, Fungi, Viruses

Brain parenchyma:

  1. Cerebral abscess: Bacterial, Fungi
  2. Encephalitis: Viruses, Prions

Both:
Meningo-encephalitis: Viruses

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3
Q

Types of clinical presentations from CNS infections

A
  1. Subdural empyema & Extradural abscess
  2. Meningitis
  3. Cerebral abscess
  4. Encephalitis
  5. Specific pathogen-related CNS infections
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4
Q

Subdural empyema

A

Direct implantation or local extension (usually bacteria)

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5
Q

Clinical features of subdural empyema

A
  1. Spinal tap: similar to that of cerebral abscess

2. Local symptoms, meningitis symptoms

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6
Q

Complications of subdural empyema

A

Thrombophlebitis of bridging veins leading to cerebral infarction

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7
Q

Treatment of subdural empyema

A

surgical drainage

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8
Q

Extradural abscess

A

Direct implantation or local extension (usually bacteria)

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9
Q

Complications of extradural abscess

A

In the case of a spinal cord epidural infection, it may cause spinal compression, constituting a neurosurgical emergency

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10
Q

Definition of meningitis

A

Inflammation of the meninges & CSF within the subarachnoid space

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11
Q

Causes of meningitis

A
  1. Acute bacterial meningitis
  2. Aseptic meningitis
  3. Tuberculous meningitis
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12
Q

Causes of acute bacterial meningitis

A
  1. Neonate:
    - Escherichia coli
    - Listeria monocytogenes
    - Group B Streptococci
    → empiric treatment: ampicillin + gentamicin
  2. Child < 5 years old
    - Streptococcus pneumoniae
    - Haemophilus influenzae
    - Neisseria meningitidis
    → empiric treatment: ceftriaxone
  3. Adolescent
    - Neisseria meningitidis
    → empiric treatment: ceftriaxone
  4. Adult
    - Neisseria meningitidis
    - Streptococcus pneumoniae
    → empiric treatment: ceftriaxone
  5. Elderly & Immunocompromised
    - Streptococcus pneumoniae
    - Haemophilus influenzae
    - Neisseria menigitidis
    - Listeria monocytogenes
    → empiric treatment: ceftriaxone + ampicillin
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13
Q

Aseptic Meningitis

A
  1. Usually viral (enteroviruses such as echovirus & coxsackievirus)
  2. Commonly causes concomitant encephalitis (viral
    meningoencephalitis)
  3. Often self-limiting
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14
Q

Tuberculous Meningitis

A
  1. Mycobacterium tuberculosis
  2. Causes a chronic meningitis often affecting the base
    of the brain
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15
Q

Morphology of tuberculous meningitis

A

Gross appearance:

i) Gelatinous exudate in subarachnoid space often at base of brain
ii) White granules (tubercles) scattered all over meninges

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16
Q

Complications of tuberculous meningitis

A
  1. obliterative endarteritis of arteries in subarachnoid space (leading to cerebral ischemia & infarct)
  2. fibrous adhesive arachnoiditis (leading to cranial nerve palsies & hydrocephalus)
  3. tuberculoma (producing space-occupying symptoms)
  • May cause concomitant encephalitis (tuberculous meningoencephalitis)
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17
Q

Clinical presentation of meningitis

A
  1. Headache, fever, malaise
  2. Photophobia
  3. Neck stiffness
  4. Kernig’s sign (leg bent at the knee & hip at 90
    degrees, with subsequent extension being painful)
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18
Q

Pathological effects & complications of meningitis

A
  1. Cerebral infarction (due to thrombophlebitis)
  2. Meningeal fibrosis
    - May lead to hydrocephalus
  3. Cranial nerve palsies
    - Especially TB as it affects base of brain
  4. Raised intracranial pressure
  5. Mental retardation (in children)
  6. Waterhouse-Friderichsen Syndrome
    - Hemorrhagic adrenalitis resulting from meningitis-related septicaemia
    - Most often occurring with meningococcal or pneumococcal meningitis
19
Q

Causes of cerebral abscess

A
  1. Routes of spread
    - Single abscess (direct implantation, local extension)
    - Multiple abscesses (hematogenous spread; predisposing factors include infective endocarditis, congenital right-to-left cardiac shunts, chronic pulmonary sepsis – bronchiectasis, immunosuppression)
  2. Causative organisms (usually bacteria)
    - Streptococci
    - Staphylococcus aureus
    - Bacteroides spp.
    - Escherichia coli
20
Q

Clinical features of cerebral abscess

A
  1. Swinging fever
  2. Signs of raised ICP
  3. Focal deficits
21
Q

Complications of cerebral abscess

A
  1. Cerebral herniation

2. Abscess rupture leading to venous sinus thrombosis & meningitis

22
Q

Types of encephalitis

A
  1. Acute encephalitis
  2. Delayed/subacute encephalitis
  3. Prion disease
23
Q

Causes of acute encephalitis

A
  1. Often involves meninges concomitantly: acute meningoencephalitis
  2. Causative viruses: HSV, measles, CMV, HIV
  3. Fetal nervous system: CMV, rubella
24
Q

Causes of delayed/subacute encephalitis

A
  1. Subacute sclerosing panencephalitis: measles
  2. Progressive multifocal leukoencephalopathy: JC virus
  3. Reactivation disease: VZV
25
Causes of prion disease
Single abscess (direct implantation, local extension)
26
CNS targets of specific viruses (Neurons & glia)
1. HSV 1 (predilection for temporal lobe; characteristic Cowdry type A intranuclear inclusions) 2. Rabies virus (characteristic negri body – intracellular eosinophilic bodies found in pyramidal neurons of hippocampus or Purkinje cells of cerebellum) 3. Measles virus 4. CMV (also infects endothelial cells)
27
CNS targets of specific viruses (motor neurons)
1. Poliovirus (spinal cord motor neurons, leading to flaccid paralysis & hyporeflexia) 2. Enteroviruses
28
CNS targets of specific viruses (Dorsal root ganglia)
VZV
29
CNS targets of specific viruses (oligodendrocytes)
JC virus
30
CNS targets of specific viruses (microglia)
HIV
31
Types of Specific Viral Infections
1. Subacute Sclerosis Panencephalitis (SSPE) 2. Progressive Multifocal Leukoencephalopathy (PML) 3. HIV Infection
32
Subacute Sclerosis Panencephalitis (SSPE)
1. Caused by altered measles virus 2. Persistent but non-productive infection 3. Occurs in children or young adults months to years after acute measles infection 4. Presents with cognitive decline, spasticity & seizures 5. Histologically: widespread gliosis, myelin degeneration, intranuclear viral inclusions within oligodendrocytes & neurons
33
Progressive Multifocal Leukoencephalopathy (PML)
1. Caused by JC virus (papovirus) infection of oligodendrocytes resulting in demyelination 2. Occurs mainly in immunocompromised patients 3. Presents with progressive neurologic deficits 4. Histologically: areas of pallor in white matter (cerebrum, cerebellum, brainstem), atypical oligodendrocytes with viral inclusions, bizarre astrocytes
34
HIV Infection
1. Direct effects of HIV on CNS: aseptic meningoencephalitis (histologically: multinucleated giant cells, microglial nodules, perivascular lymphocyte cuffing) 2. Effects on spinal cord: vacuolar myelopathy of posterior columns & corticospinal tracts ('holes' in myelin sheath & macrophage infiltration) 3. Associated pathological conditions: opportunistic CNS infections (toxoplasmosis, CMV, aspergillosis, cryptococcosis, PML), lymphomas
35
Specific Pathogen-related CNS Infections
1. Neurosyphilis 2. Fungal infections 3. Parasitic infections 4. Prion disease
36
Neurosyphilis
1. Meningovascular syphilis - Granulomatous meningitis involving base of brain & more variably the cerebral convexities & spinal meninges - Subintimal vessel thickening 2. General paresis of the insane - Diffuse cortical microglial infiltrate, gliosis & iron deposits - Insidious progressive mental deficits associated with mood alterations that eventually terminate in dementia 3. Tabes dorsalis - Demyelination of the posterior columns - Loss of joint position sense: ataxia - Loss of pain perception: Charcot joints, skin damage - Other sensory disturbances: lightning pains, absence of deep tendon reflexes
37
Fungal infections
Usually occurs in immunocompromised patients
38
Causative organisms in fungal infections
1. Candida albicans 2. Cryptococcus neoformans 3. Aspergillus fumigates 4. Mucor 5. Histoplasma capsulatum
39
Pathological effects & complications of fungal infections
1. Vasculitis & thrombosis (leading to hemorrhage & cerebral infarction) 2. Meningitis (especially Cryptococcus neoformans) 3. Parenchymal invasion → abscesses & granulomas (Candida albicans, Cryptococcus neoformans)
40
Parasitic infections
Protozoal: 1. Malaria 2. Toxoplasma - Typically produces abscesses in cerebral cortex (grey-white junction or deep grey nuclei) - Can find tachyzoites & bradyzoites at periphery of necrotic foci - Ring enhancing lesions in MRI 3. Naegleria fowleri (Primary amoebic meningoencephalitis) 4. Trypanosoma Helminthic 1. Echinococcus 2. Taenia solium (neurocysticercosis)
41
Pathogenesis of prion disease
1. Mode of transmission: genetic (familial, sporadic contaminated transplant tissue, food ingestion) 2. Prion protein (PrP) undergoes conformational change from alpha helix to beta pleated sheet which enables it to resist digestion 3. PrP also induces protein misfiling in normal cells
42
Morphology of prion disease
1. Grossly: almost normal 2. Histologically: - Spongiform transformation of cerebral cortex & deep grey matter - Neuronal loss - Reactive gliosis - Amyloid deposits & plaques
43
Different spectrum of prion disease
1. Creutzfeldt-Jakob disease 2. Variant CJD (mad cow disease) 3. Gerstmann-Straussler-Scheinker syndrome 4. Fatal familial insomnia

15. Central Nervous System Pathology (8 decks)

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