L11 – Infections of the Nervous System: Viral Infections Flashcards

1
Q

3 pathogenesis pathways for viral CNS diseases?

A

1) Delayed/ acoompanying inflammatory reactions
2) Direct cytolytic infection and neruonal damage
3) Post-infectious syndromes and demyelination

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2
Q

Explain how viral CNS infection can cause demyelination.

A

virus replicates outside CNS&raquo_space; cross-reacting immune response to myelin / dysregulation of immune response&raquo_space; demyelination of CNS

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3
Q

Typical temporal features of viral CNS infection?

A

 Biphasic illness
 CNS symptoms follow 2-12 days after initial illness

Presentation may be acute, subacute, or chronic

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4
Q

Relate the terms given to infection of different parts of the CNS.

A
  • Brain = encephalitis;
  • Meninges = meningitis
  • Spinal cord = myelitis;
  • Peripheral nerves = neuritis / neuropathy

Many viral infections may involve more than one site e.g. meningo-encephalitis.

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5
Q

List 5 clinical symptoms and signs of viral CNS infection.

A

1) Meningeal irritation: Neck stiffness, Kernig’s and Brudzinski’s sign
2) Encephalopathic signs: Alternation of consciousness, fits and seizures
3) Increased ICP: headache, vomiting
4) Focal neurological signs: paralysis, aphonic
5) Systemic signs: fever, lethargy

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6
Q

Compare between pyogenic, viral and TB/ Fungal meningitis: appearance of CSF?

A

Pyogenic: Turbid
Viral: Clear/ sl. turbid
TB/ Fungal: Clear/ sl. turbid

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7
Q

Compare between pyogenic, viral and TB/ Fungal meningitis: Total cells and predominant WBC.

A

Pyogenic: >500, PMN
Viral: <500, lymphocytic
TB/ Fungal: <500, lymphocytic

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8
Q

Compare between pyogenic, viral and TB/ Fungal meningitis: Protein and glucose

A

Pyogenic: Very low glucose, Very high protein
Viral: Normal glucose, high protein
TB/ Fungal: low glucose, very high protein

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9
Q

Compare between pyogenic, viral and TB/ Fungal meningitis: Gram stain and acid-fast stain

A

Pyogenic: 65 to 95%
Viral: -ve
TB/ Fungal: -ve, TB acid-fast stain only

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10
Q

Viral isolation from CSF is good or poor for which type of CNS infections?

A

Good isolation: Viral meningitis
Poor isolation: viral encephalitis, Post-infectious encephalitis (doesnt penetrate BBB)

Isolation rate best, early in illness

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11
Q

PCR of CSF is used for Dx of which viral CNS infections.

A

–herpes simplex encephalitis.
–CMV encephalitis / myelitis.
–VZV encephalitis /meningitis/ myelitis.
–more sensitive than culture in diagnosis of enterovirus.

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12
Q

List all diagnostic tests used for viral CNS infections?

A

Throat swab (mumps, enteroviruses)

Stool sample (enterovirus)

PCR of CSF (HSV, CMV, VZV, enterovirus)

CSF serology

Brain biopsy

Blood serology

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13
Q

List all serological tests for dx of viral CNS infections?

A
  • Rising Ab titre (paired sera): Flu A/B, VZV, HSV, entero, mycoplasma, (mumps, measles)
  • IgM Ab (single sera): JEV, EBV, (CMV)
  • Intra-thecal (in CSF) antibody synthesis (late presentation)
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14
Q

Why is serology for enterovirus not indicated in viral CNS infections?

A

problem of many serotypes and no common antigen

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15
Q

List common and less common viruses that cause viral meningitis

A

1) Common:
– Enteroviruses (ECHO, Coxsackie A/B).(summer months)
– H.simplex type 2 (genital herpes)

2) Less common:
– Mumps (immunisation has made less common)
– Lymphocytic choriomeningitis (LCM) (assn. with rodents)
– HIV seroconversion illness

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16
Q

Properties of enteroviruses: family, genetic material? Is their protective immunity the same?

A

Family Picornaviruses.

RNA viruses
Single +ve stranded,
non-enveloped

share a few common antigens, but protective immunity is type specific

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17
Q

List 7 clinically significant enteroviruses?

A
Polio 
Cox A
Cox B 
ECHO
EV 68, 70, 71
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18
Q

Hand foot and mouth disease is caused by which viruses?

A

Enterovirus: Cox A (A16), EV71

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19
Q

Which enteroviruses can cause asymptomatic infection?

A

All types

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20
Q

List some general symptoms caused by most enterovirus infections?

A
  • Asymptomatic
  • Fever, rash
  • Flaccid paralysis **
  • Meningitis
  • Carditis
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21
Q

Conjunctivitis is caused by which enterovirus subtypes?

A
  • Cox A (A24)

- EV70

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22
Q

Herpangina is caused by which enterovirus subtype? *small, blister-like ulcers on the roof of the mouth and in the back of the throat. *

A

Cox A

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23
Q

URTI is caused by which enterovirus subtype?

A

Cox A
Cox B
ECHO

24
Q

Enterovirus infection has a biphasic seasonality. True or false?

A

False

Enteroviruses have a summer seasonality

25
Q

HSV meningitis is usually caused by? Both sex affected equally or not?

A

herpes simplex type 2, but genital lesions may not be seen

> 30% females, 11% males with primary genital HSV have meningitic involvement

26
Q

HSV meningitis requires urgent medical attention. True or False?

A

Self-limited (2-3 days: unlike HSV encephalitis)

27
Q

List common and less common viruses that cause viral encephalitis?

A

Common:
– Herpes simplex type 1 (HSV 2 in neonates)
– Enteroviruses
– Varicella-zoster virus •

Less common:
– Febrile exanthems (measles, rubella, HHV-6)
– Arboviruses (eg.Japanese encephalitis) (travel in last 3 weeks).
– Other: EBV, influenza, mumps, adenovirus, HIV, LCM. RABIES

28
Q

2 routes of spread of HSV into brain?

A
  • May follow primary infection or reactivation.
  • Entry into CNS via

– a) spread along olfactory nerve (from nasopharynx) – affects frontal lobe

– b) reactivation from trigeminal ganglion - innervates pia mater – infection of brain

29
Q

Explain how HSV can become latent?

A

Primary infection: mild pharyngitis, fever(, genital herpes)

> > viral transit up peripheral nerve

> > latent virus in neuron in dorsal root ganglion (spinal cord)

30
Q

What can trigger HSV reactivation?

A

trigger factors (e.g. fever, physical trauma, stress, hormonal balance, age, immunosupression)

31
Q

Area of brain most affected by HSV encephalitis?

A

Characteristically in:

  • Temporal lobe; or
  • Orbital surface of frontal lobe

May also involve:

  • Adjacent frontal / parietal / occipital lobes
  • Cingulate gyri
32
Q

List some general symptoms of Herpes encephalitis?

A

General: altered consciousness; headache; seizures; vomiting; memory loss, fever

33
Q

List some clinical findings of Herpes encephalitis? (think neruonal damage effects, which part of brain?)

A
personality change; 
dysphasia; 
autonomic dysfunction; ataxia; 
hemiparesis (weakness of one entire side of the body)
seizures; 
cranial nerve deficits.
34
Q

Typical CSF findings of Herpes encephalitis?

A
CSF findings: 
 High Protein >40mg/dL
 Normal CSF:blood glucose ratio: 95% 
 WBC pleocytosis (lymphocytes)
  High RBC >50:
35
Q

List the lab tests used to dx herpes encephalitis and lab tests that are not useful?

A

Useful: HSV DNA detection by PCR in CSF; Intrathecal CSF antibody may confirm diagnosis

Not useful: rarely cultured from the CSF; Isolating HSV in throat / mouth, serology in blood

36
Q

Why Isolating HSV in the throat / mouth is of little significance?

A

– may be reactivation of latent virus unconnected with the CNS
– Approx 1% of healthy persons have HSV isolated from mouth)

37
Q

HSV DNA detection by PCR in CSF may still be detectable up to 7 days after start of acyclovir. True or False

A

True

38
Q

Herpes meningitis is not life treatening, but Herpes encephalitis is. True or False?

A

True

39
Q

Consequence of untreated herpes encephalitis?

A
  • Life threatening, medical emergency

* If untreated, mortality is 70%. Many survivors have permanent brain damage

40
Q

Course of action if Herpes encephalitis is suspected?

A
  • Start treatment on clinical suspicion, while waiting for CSF PCR result
  • Early treatment with i.v. acyclovir is life and function saving: Use 14 - 21 days therapy to prevent relapse
41
Q

Locality, reservoir, transmission, host and vector of JEV?

A
  • Common in South China, southeast Asia
  • animal reservoir/ host =water birds & pigs
  • Vector = mosquitoes associated with rice field
  • Human infection = end-host (no human- human transmission)
42
Q

Sequalae and prevention of JEV?

A

Most infections = asymptomatic (90-95%)

Symptomatic: Mortality = 10-30%; Many of the survivors have permanent brain damage

Prevention: vaccine available for endemic areas

43
Q

List viruses that can cause myelitis/ Neuropathy?

A

• Enteroviruses (EV71, Polio, other) • VZV, • EBV, • CMV, • exanthems, • mumps, • HSV 2 • Japanese encephalitis • Zika (Guillain Barre syndrome)

44
Q

Pathogenesis of Varicella-zoster virus? (think primary and reactivation infections)

A

1) Primary infection: chickenpox > viral transit up peripheral nerve > latent virus in neuron in dorsal root ganglion (spinal cord)
2) Recurrence: trigger factors (e.g. fever, physical trauma, stress, hormonal balance, age, immunosuppression) > reactivation of virus in neuron > viral transit down peripheral nerve (usually unilateral) > shingles / skin lesions (affect dermatome)

45
Q

VZV CNS infection may not cause skin lesions. True or false?

A

True

Skin lesions may precede or follow CNS disease.

or completely absent - “zoster sine herpete

46
Q

What is the consequence of VZV reactivation in an AIDS patient’s brain?

A

 Chronic progressive encephalitis
 Ventriculitis
 40% have no rash

47
Q

Which enteroviruses can cause flaccid paralysis?

A

All types

Especially Polio, EV71, EV68

48
Q

Which 5 viruses cause CNS infection most in immunocompromised patients?

A

1) Cytomegalovirus: encephalitis, cranial nerve palsies, poly-radiculopathy, neuritis, pneumonia, gastrointestinal
2) VZV: myelitis, encephalitis (acute / chronic progressive), radiculitis, ventriculitis
3) JC virus: progressive multifocal leukoencephalopathy
4) HIV
5) Chronic enteroviral meningo-encephalitis in agammaglobulinaemics

49
Q

Family, reservoir, transmission of Rabies?

A

Rhabdovirus family

Animal reservoir: Dogs mainly, cats, other mammals (e.g. fox, wolves, jackals, mongoose etc)

Animal saliva = infectious if introduced on mucosal surface / broken skin

Human-human transmission = unknown

50
Q

Local incidence of rabies?

A

In Hong Kong: Last local human case 1981; last animal rabies 1987.

Common in neighboring countries

Imported cases seen

Exposure of dog bites overseas needs to be managed

51
Q

Pathogenesis of rabies? 4 steps (think at the infectious site, travel to CNS, effects on brain, descending infections)

A
  1. Virus inoculation&raquo_space; replicates in striated muscle at the site of the bite&raquo_space; acetylcholine receptor serves as virus receptor&raquo_space; enters sensory nerve endings (peripheral nervous system) via stretch spindles
  2. Carried by axonal transport (passive ascent) to spinal cord&raquo_space; replication in dorsal ganglion
  3. Replication in brain (brain stem, cerebellum, other structures)&raquo_space; encephalitis
  4. Descending infection (exam): virus travels down peripheral nerves via sensory, autonomic nervous system to salivary glands (virus present in saliva), skin, muscle, retina, cornea, nasal mucosa, other organs
52
Q

How does the site of bite affect the time span of rabies infection to reach brain?

A

 Bites on the face: virus has less distance to travel =usually shorter incubation period

 Bite on leg: longer (e.g. 1 year)

53
Q

Inoculation, symptoms and signs of rabies (incl. furious and paralytic rabies)?

A

 Incubation: usually 20-90 days, may be >1 year

 Prodromal: non-specific, onset of itching at site of healed bite wound

 Furious rabies (hyperreflexia):

  • Hydrophobia (muscle of swallowing goes into spasm, scared of water)
  • Aerophobia (wind causes spasm)
  • Meningo-encephalitis

 Paralytic rabies: paralysis begins in bitten limb and spreads

54
Q

Dx of rabies CNS infection?

A

 Viral antigen by immunofluorescence (also skin biopsy, corneal scrap)

 Inclusion bodies (pink-staining Negri bodies)

55
Q

Course of action after rabies bite?

A

• No treatment once symptoms appear - fatal

• Prevention: Management of dog bite:
– Good wound toilet, aggressive washing, use local anaesthesia if needed. Avoid suturing. Manage tetanus risk (tetanus vaccine may be needed).

– Assess rabies risk

  • Post exposure prophylaxis by immunization
56
Q

What are the 4 criteria for assessment of rabies risk?

A

1) What animal? Rabies only affects mammals (dogs, cats)
2) Where? Endemic area/ travel history/ imported case
3) Behavior of animal? unprovoked bite, paralysis, increased salivation, other bites?

4) Animal alive or not?
Alive after 7 days = exclude rabies; Dead = examine animal brain for antigens and inclusion bodies

57
Q

Compare active and passive immunization for Rabies?

A

Active = Human diploid cell vaccine (killed vaccine); Immunisation course can be aborted

Passive = human rabies immunoglobulin
Local: infiltrate bite wounds thouroughly
Systemic: inject any remainder intra-muscularly