Lec 23 - Viral infections of the CNS

Question 1

List the components of the meninges

Answer 1

Dura matter, arachnoid and pia matter and subarachnoid space

Question 2

Describe the structure of the blood brain barrier

Answer 2

• Endothelial cells of blood vessels
• Pericytes and astrocytes on top of endothelium
• Tight junctions = occludin, claudin, JAM and ESAM proteins

Question 3

What are the 3 pathways viruses can get through the blood-brain barrier? What viruses use each method?

Answer 3

1. Paracellular pathway = uses junction proteins eg HSV, SARS-CoV-2, WNV
2. Transcellular pathway = thru endothelial cells eg HIV
3. Trojan horse mechanism = infect immune cells that pass eg SARS-CoV-2, WNV

Question 4

Define aseptic meningitis and list the symptoms

Answer 4

Inflammation of meninges with no bacterial growth on CSF
Symptoms = fever, vomiting, meningism
Meningism = photophobia, headache, neck stiffness

Question 5

What are the causes of aseptic meningitis and what are the serological signs and tests to distinguish it?

Answer 5

Causes = uncommon complications of common systemic infections esp enteroviruses
Signs = high mononuclear count in CSF
Tests = normal CSF pressure, mod WBC count, lymphocytes, elevated proteins, normal CSF-serum glucose ratio

Question 6

Define encephalitis and what are the 2 combination types?

Answer 6

Inflammation/infection of brain
Combinations = encephalomyelitis (SC) and meningoencephalitis (meninges)

Question 7

What are the causes and symptoms of encephalitis?

Answer 7

Causes = acute or latent infection by enteroviruses, HSV, rabies and arboviruses
Symptoms = headache, fever, confusion, drowsiness, convulsions, seizures, hallucinations, memory loss, coma, death

Question 8

What is acute flaccid paralysis? Describe the cause and pathology

Answer 8

Acute onset of paralysis in 1+ limbs
Cause = anterior horn infection of motor neuron bodies by polio and enterovirus 71
Pathology = muscle atrophy and loss of function

Question 9

Describe the severity of CNS viruses

Answer 9

• Enteroviruses = mild
• Mumps and LCM = mild but worse than enteroviruses
• Arboviruses = severe
• HSV = fatal

Question 10

Describe the classification and main groups of enteroviruses

Answer 10

Non-enveloped, (+) ssRNA, Picornaviridae
72+ serotypes
Groups
1. Poliovirus
2. Coxsackie group A
3. Coxsackie group B
4. Echovirus
5. Enterovirus

Question 11

How are enteroviruses transmitted and what do they result in?

Answer 11

Transmission = hand to mouth contact
Results = respiratory infections, conjunctivitis, hand-foot-mouth disease, paralysis, meningitis and encephalitis

Question 12

Describe the classification, transmission and result of poliovirus infection

Answer 12

Classification = non-enveloped, (+) ssRNA, 3 serotypes
Transmission = faecal oral route
Poliomyelitis = acute enteroviral infection of SC that can cause neuromuscular paralysis

Question 13

Describe the pathology of poliovirus that allows it to infect the CNS

Answer 13

• Viraemia persists and spreads to CNS
• Infect then invade nervous tissue = flaccid paralysis
• Post polio syndrome (PPS) = progressive muscle deterioration until death

Question 14

What are the 3 cycles of JEV transmission? Where in the world is it found?

Answer 14

Found in Asia and very north of Australia
1. Natural cycle = aquatic birds and Culex mozzies
2. Amplifying cycle = domestic animals eg pigs and mozzies
3. Humans = dead end hosts

Question 15

How is JEV thought to cross the blood brain barrier? What are the symptoms and signs?

Answer 15

Trojan horse method
Symptoms = acute encephalitis with headache, high fever, stiff neck, stupor, convulsions, seizures, paralysis, coma, death
Signs = encephalitis with T cells, monocytes and macrophages

Question 16

What are the 2 complications of JEV infection?

Answer 16

In utero infection possible = abortion
Neuropsychiatric symptoms in 45-70% of survivors

Question 17

What are the results of HSV infection? What CNS infection is generally associated with HSV?

Answer 17

• Acute gingivostomatitis, herpes labialis, herpetic whitlow, ocular herpes, genital herpes, neonatal herpes, meningitis, encephalitis
• 10% of all encephalitis cases

Question 18

What is the classification and transmission of rabies?

Answer 18

Enveloped (-) ssRNA, bullet-shaped, Rhabdoviridae
Transmission = aerosols, salivary contamination of mucous membranes, bite from infected animal

Question 19

Describe the cycle of rabies infection

Answer 19

1. Reps in muscle
2. Peripheral nerves at site to CNS by retrograde axon flow (avoids immune)
3. Reps in salivary gland

Question 20

What are the 4 clinical phases of rabies infection? How do patients die of rabies?

Answer 20

1. Prodromal = fever, nausea, vomiting, headache, fatigue, pain/burning/itching at site
2. Furious = agitation, disorientation, seizures, twitching, hydrophobia
3. Dumb = paralysis, disoriented, stupor
4. Progression to coma = 100% death from inflammatory effect

Question 21

What is the typical sign of rabies infection?

Answer 21

Negri bodies

Question 22

What are some of the conditions included in HIV associated neurocognitive disorders (HANDs)?

Answer 22

AIDS dementia complex in brain, vacuolar myelopathy in SC, peripheral neuropathy in nerves, acute/chronic meningitis

Question 23

Why is it difficult to treat HIV in CNS?

Answer 23

Blood brain barrier blocking drugs and neurotoxicity of antiretrovirals

Question 24

What are the 2 mechanisms of HANDs?

Answer 24

1. Infected macrophages/microglial cells = neurotoxic viral proteins = astrocyte activation = increased glutamate = neuron injury and disrupted synapses
2. Systemic inflammation and microbial products = microglial activation and increased chemokines/cytokines = neuron injury