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MICR3320 > 23 - Viral Infections of CNS > Flashcards

23 - Viral Infections of CNS Flashcards

1
Q

Aseptic meningitis

A
  • Not caused by pyogenic bacteria
  • Inflammation of the meninges
  • Viral infection most common cause
  • Fever, meningism, vomiting
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2
Q

Encephalitis

A
  • Inflammation of the brain
  • Headache, fever, halluications, coma, death
  • Caused by acute infection or complication of latent disease
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3
Q

Most common cause of viral encephalitis

A
  • Enterovirus
  • HSV
  • Rabies
  • Arboviruses
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4
Q

Myelitis

A
  • Inflammation of the spinal cord
  • When both brain and spinal cord are involved, condition is called encephalomyelitis
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5
Q

Meningoencephalitis

A

Encephalitis with meningitis

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6
Q

Occludins and claudins

A

Form very tight junctions between epithelial cells at blood brain barrier

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7
Q

Acute flaccid paralysis (AFP)

A
  • Acute onset of flaccid paralysis in one or more limbs
  • Caused by anterior horn cell infection with wild or vaccine polio virus
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8
Q

Pathways viruses use to get through blood brain barrier

A
  • Paracellular pathway (between cells)
  • Transcellular pathway (through cells)
  • “trojan horse” mechanism (use immune cells)
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9
Q

Two main viruses causing fatal encephalitis

A
  • HSV
  • Arbovirus
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10
Q

Enteroviruses

A
  • Non enveloped +ssRNA
  • Picornaviridae
  • 5 main groups
  • Hand to mouth contact transmission
  • Responsible for respiratory infections, conjunctivitis and hand-foot mouth disease
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11
Q

5 groups of enteroviruses

A
  • Poliovirus
  • Coxsackie group A
  • Coxsackie group B
  • Echovirus
  • Enterovirus
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12
Q

Enterovirus 71

A
  • Mild disease in adults and children
  • Outbreaks associated with meningitis and encephalitis under 5 yo
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13
Q

Poliovirus

A
  • Non-enveloped, (+) ssRNA linear genome
  • 3 serotypes (2 and 3 eradicated)
  • Faecal oral route or contaminated food or water
  • Resistant to acid (survives in stomach)
  • Multiples in intestine, can enter CNS
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14
Q

Poliomyelitis (polio)

A
  • Acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis
  • 1 in 200 infections leads to irreversible paralysis (death when breathing muscles become immobilised)
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15
Q

Cells that poliovirus infect

A

Mucosal cells in oropharynx and intestine

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16
Q

Polio infections

A
  • Short-term with mild viraemia (non-specific symptoms)
  • If viraemia persists, virus spreads to spinal cord and brain
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17
Q

Post polio syndrome

A
  • Progressive muscle deterioration
  • Occurs in 25-50% of patients infected with polioviruses in childhood
18
Q

Three groups of arboviruses

A
  • Flaviviridae
  • Togaviridae
  • Bunyaviridae
19
Q

Examples of Flaviviridae

A
  • Yellow fever
  • Dengue
  • JVEV
  • MVEV
  • West Nile
20
Q

Examples of Togaviridae (alphavirus genus)

A
  • CHIKV
  • O’nyongnyong
  • Ross river
  • Sindbis
  • Barmah forrest
  • Eastern and western equine encephalitis
21
Q

Examples of Bunyaviridae

A
  • La crosse encephalitis
  • Crimean Congo haemorrhagic fever virus (Nairovirus)
  • Rift valley fever virus (Phlebovirus)
  • Hantavirus Pulmonary Syndrome (Hantavirus)
22
Q

JVEV transmission

A
  • Transmitted naturally between aquatic birds by
    Culex mosquitoes (like west nile)
  • Pigs and humans dead end hosts
23
Q

JVEV pathogenesis

A
  • Spread of JVEV to CNS can be prevented by neutralizing antibodies
  • Enter CNS via blood (trojan horse mechanism)
24
Q

JVEV clinical signs

A
  • Acute encephalitis
  • Headache, fever
  • Paralysis, seizures, coma, death
  • Neuropsychiatric sequelae in survivors
  • In utero abortion
  • 30% mortality rate
25
Q

HSV

A
  • Enveloped, ds DNA genome
  • Genital, ocular, neonatal herpes
  • 10% of encephalitis (majority cases reactivation)
  • Herpetic whitlow
26
Q

VZV

A
  • Varicella Zoster Virus
  • Enveloped, ds DNA genome
  • Herpesviridae
  • Encephalitis in immunocompromised patients
27
Q

Varicella

A
  • Chickenpox
  • Primary infection
  • Self-limiting disease of children
  • Morbidity and mortality in other age groups
28
Q

Herpes zoster

A
  • Shingles
  • Reactivation of VZV in sensory nerve ganglia (dorsal root)
  • Most often in elderly
29
Q

Rabies

A
  • Enveloped, (-) ssRNA, bullet-shaped virus
  • Rhabdoviridae
  • Spread by bite from infected animal
  • Virus replicates first in muscle
  • Binds to acetylcholine receptors at neuromuscular junction
  • Moves along peripheral nerves to CNS via retrograde flow in axons
  • Once virus enters the nerves it is not accessible to the host immune defences
  • Replication in motor neurons of spinal cord, and rapid scent to brain
  • Infection of brain
30
Q

Clinical phases of rabies

A
  • Prodromal phase (fever, nausea, vomiting)
  • Furious phase (agitation, twitching)
  • Dumb phase (paralysed)
  • Progression to coma phase (die of inflammation)
31
Q

Histopathologic feature of rabies

A

Negri bodies

32
Q

Rabies vaccine

A
  • Recombinant antigen
  • Can be given post-exposure protection, if given before symptoms
    arise (2 weeks to 2 year incubation)
33
Q

HIV

A
  • HIV enters the nervous system early, may immediate cause symptoms, or anytime during lifetime
  • Easily crosses the blood-brain barrier
  • Sustained viral replication and high viral load is associated with brain tissue inflammation, permanent cell death
34
Q

What can primary HIV disease lead to

A
  • AIDS dementia complex (brain)
  • Vacuolar Myelopathy (spinal cord)
  • Peripheral neuropathy (nerve)
  • Meningitis (acute or chronic)
35
Q

HAND

A
  • HIV associated Neurocognitive Disorders
  • Neuroinflammation
  • Poor CNS penetration of antiretrovirals
  • Blood brain barrier repelling drugs
  • Neurotoxicity of antivirals
36
Q

HAND mechanisms

A
  • HIV-infected macrophages and microglial cells release neurotoxic viral proteins.
  • These viral proteins trigger astrocyte activation.
37
Q

what does astrocyte activation result in

A
  • Increased glutamate release.
  • Reduced glutamate uptake.
38
Q

What do elevated extracellular glutamate levels cause

A
  • Neuronal bioenergetic disturbances.
  • Aberrant synapto dendritic pruning.
  • Neuronal injury.
39
Q

What does systemic inflammation and microbial translocation products lead to

A
  • Microglial activation.
  • Increased production of chemokines and cytokines.
  • Further contribution to neuronal injury.
40
Q

Immunosuppression caused by HIV

A

Lead to opportunistic infections

41
Q

HAART

A
  • Highly active retroviral therapy
  • Do not easily cross
    into the brain in laboratory studies
  • However, HIV-infected individuals may show increased permeability of the BBB
  • HAART usually reduces viral load both in the periphery and in the CNS
  • Reduction of viral load in the CNS is associated with reduced cognitive symptoms
42
Q

HIV anti retroviral therapy

A

Transmission reduced to almost zero when viral load is undetectable for less than 6 months

MICR3320 (25 decks)

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