Viral CNS Infections

Question 1

Routes of Infection

Answer 1

1. hematogenous spread -> perivascular cuffing w/ sensitized T cells, B cells, macrophages
   a. infect/transverse BBB
   b. directly infect glial cells -> infect neurons
   c. “trojan horse” - infection of myeloid, lymphoid, or leukocytes which then cross the BBB via diapedesis, transmigration, extravasation
2. retrograde axoplasmic flow (think herpes or rabies virus) from a peripheral nerve

Question 2

Aseptic Meningitis - Causes

Answer 2

1. 90% Enterovirus - Coxsackie, Echovirus
   * summer and early fall
2. Mumps Virus
   * spring, unvaccinated!
3. Lymphocytic Choriomeningitis Virus (LCM)
   * zoonotic - urine of infected mice, guinea pigs, hampsters
4. HSV-2
   * during primary genital infection
5. HIV
   * during initial infection

Question 3

Meningoencephalitis/Encephalitis - Causes

Answer 3

1. HSV
2. Rabies Virus
3. Arboviruses

Question 4

Alpha HSV - Route of Infection

Answer 4

(HSV-1, VZV, PRV)

1. retrograde infection of pseudounipolar sensory neurons of PNS ganglia
2. latency
3. reactivation and anterograde spread

Question 5

RABV and Poliovirus - Route of Infection

Answer 5

RABV and Poliovirus

1. replication in muscle
2. infection of nerve cell @ NMJ
3. retrograde spread via neuromuscular junctions

Question 6

HSV, VSV, BDV, InfA, HeV - Route of Infection

Answer 6

several viruses may infect receptor neurons in nasal olfactory epithelium and spread anterograde to CNS (only 1 synapse away!)

Question 7

Common Causes of CNS Viral Infections

Answer 7

Enteroviruses* (mst common cause, all age groups)

Mumps/Measles* (many complications)

HSV-1/2

VZV, CMV

Arboviruses

Rabies

HIV

Question 8

Mumps/Measles - Complications

Answer 8

• acute disseminated encephalomyelitis (ADEM)
• measles inclusion body encephalitis (MIBE)
• subacute sclerosing panencephalitis (SSPE)
  
  • many years after infection

Question 9

Clinical Manifestations -

Viral Meningitis v. Viral Encephalitis

Answer 9

Viral Meningitis

• fever, vomiting, headache, nuchal rigidity, photophobia

Viral Encephalitis

• fever, vomiting, headache, nuchal rigidity, photophobia + alterations in consciousness, confusion, seizures, paralysis, changes in sensation or vision

Question 10

Viral v Bacterial?

Answer 10

Symptoms

• Viral - headache, fever, vomiting
• Bacterial - headache, fever

CSF Examination

• Viral
  
  • WBCs = 2-2000/mm3 (elevated)
  • protein = near normal
  • *negative gm stain and culture
• Bacterial
  
  • WBCs = 1000-5000/mm3 (very elevated)
  • protein = elevated
  • usually a positive gm stain and culture

New techniques - CSF IgM titers (acute!) and PCR. In chronic infections, pathogen-specific IgG in CSF > serum.

Question 11

Enterovirus - Examples and Pathogenesis

Answer 11

Enterovirus = +ssRNA

• rhino, echo, coxsackie, polio, HepA

The target tissue determines the predominant disease!

• brain = polio, coxsackie
• meninges = polio, coxsackie, echo

Question 12

Polio - Morphology

Answer 12

Picornaviruses

• ss+RNA, the RNA is infectious!
• non-enveloped, icosahedral

Three Serotypes (1, 2, and 3)

• global distribution
• humans are the only susceptible host

Infection is via fecal/oral route.

Question 13

Polio - Vaccine

Answer 13

SalK (IPV)

• formalin inactivated (Killed) vaccine
• induces systemic serum Ab levels but NOT mucosal immunity…given in multiple doses
• used in US due to reversion of live attenuated virus

Sabin (OPV)

• oral, attenuated (live) vaccine, attenuated for all three serotypes
• induces mucosal IgA response as well as sysemic immunity
• used in vaccination campaigns in developing nations bc can be given in one dose