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
2
Q
Encephalitis
A
- Inflammation of the brain
- Headache, fever, halluications, coma, death
- Caused by acute infection or complication of latent disease
3
Q
Most common cause of viral encephalitis
A
- Enterovirus
- HSV
- Rabies
- Arboviruses
4
Q
Myelitis
A
- Inflammation of the spinal cord
- When both brain and spinal cord are involved, condition is called encephalomyelitis
5
Q
Meningoencephalitis
A
Encephalitis with meningitis
6
Q
Occludins and claudins
A
Form very tight junctions between epithelial cells at blood brain barrier
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
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)
9
Q
Two main viruses causing fatal encephalitis
A
- HSV
- Arbovirus
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
11
Q
5 groups of enteroviruses
A
- Poliovirus
- Coxsackie group A
- Coxsackie group B
- Echovirus
- Enterovirus
12
Q
Enterovirus 71
A
- Mild disease in adults and children
- Outbreaks associated with meningitis and encephalitis under 5 yo
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
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)
15
Q
Cells that poliovirus infect
A
Mucosal cells in oropharynx and intestine
16
Q
Polio infections
A
- Short-term with mild viraemia (non-specific symptoms)
- If viraemia persists, virus spreads to spinal cord and brain
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
