Viral meningitis and myelitis

Question 1

Viral meningitis

Answer 1

Viral meningitis, inflammation of subarachnoid space due to viral etiology. It is the second most common type of meningitis, next to acute bacterial meningitis. However, it is often less severe than bacterial meningitis and has a better prognosis

Question 2

Agents of viral meningitis

Answer 2

1. Enteroviruses: >85%
   ™2. Herpesviruses, including HSV, VZV, EBV
   ™3. Arboviruses: especially in people having travel history
   ™4. LCM virus:
   people with history of contact with rodent
   ™5. Other causes: Mumps virus, measles virus, influenza virus and HIV.

Question 3

CSF analysis on viral meningitis

Answer 3

1. Normal or slightly elevated protein level (20–80 mg/dL)
   ™2. Normal glucose level (except CMV)
   ™3. Normal or mildly elevated CSF pressure (100–350 mm H2O)
   ™4. Cell count is typically 25–500/μL, (except LCM virus and mumps)
   ™5. Pleocytosis: Lymphocytes predominant (except first 48 h of illness in West Nile virus,…)
   6.™ Organisms are not seen on Gram staining of CSF

Question 4

Lab diagnosis of viral meningitis

Answer 4

1. CSF analysis
2. Molecular methods
3. Viral culture: low sensitivity
4. Antibody detection: for less prevalent
5. Oligoclonal GABA globulin bands

Question 5

BioFire FilmArray for meningitis diagnosis

Answer 5

™ BioFire FilmArray is an automated nested multiplex PCR that can simultaneously detect 14 common agents of meningitis in CSF, which includes agents of:
pyogenic and viral meningitis.
It is extremely sensitive and specific, with a turnaround time of 1 hour

Question 6

Viral culture as lab diagnosis

Answer 6

The sensitivity of CSF cultures for the diagnosis of viral meningitis is generally poor.
However, isolation of enteroviruses from stool is not diagnostic as it may also result from residual fecal shedding from a previous infection

Question 7

Antibody detection for viral meningitis lab diagnosis

Answer 7

Antibody detection is important for the diagnosis of less prevalent arboviruses such as West Nile virus
However it is of less useful for viruses that have a high seroprevalence in the general population, such as HSV and VZV.

Question 8

Treatment of viral meningitis

Answer 8

Treatment of almost all cases of viral meningitis is primarily symptomatic, which includes analgesics, antipyretics, antiemetics and fluid and electrolyte replacement.
Antivirals may be useful for certain viral agents:
1.‰ Oral or intravenous acyclovir may be useful in patients with meningitis caused by HSV-1 or 2 and in cases of severe EBV or VZV infection
2.‰ Patients with HIV meningitis should receive highly active ART

Question 9

Non-polio enterovirus infections

basics like occurrence

Answer 9

M/C cause of viral meningitis,
™• sporadic or occur in clusters
•™ Although cases can occur throughout the year, affecting any age, but majority occur in the summer and ⛈, especially in children
•™ eg., include Coxsackieviruses, echoviruses, parechoviruses and Enterovirus 71.

Question 10

Agents causing viral meningitis

examples

Answer 10

1. Coxsackie viruses
2. Echo viruses
3. Parechoviruses
4. Enterovirus 71
5. Herpesvirus:
   HSV, VZV, EBV
6. Arboviruses
7. HIV
8. Mumps
9. Lymphocytic choriomeningitis (LCM)

Question 11

Taxonomy of picornaviridae

Answer 11

1. Enteroviruses: by feco-oral route, but do not cause any intestinal manifestations:
   • Polioviruses
   •„ Coxsackieviruses, echoviruses, parechoviruses and Enterovirus 71
2. Rhinoviruses comprise of >100 antigenic types. They are transmitted by respiratory route and cause common cold

Question 12

Coxsackie viruses

clinical manifestations

Answer 12

1. Aseptic meningitis:
   2.™ Herpangina:
   severe febrile vesicular pharyngitis by group A viruses (type 2–6, 8, 10)
   3.™ Hand-foot-and-mouth disease
   4.™ Pleurodynia (Bornholm disease or epidemic myalgia)
2. Cardiac
3. Respiratory
4. Acute hemorrhagic conjunctivitis
5. Generalised disease of infants
6. Pancreatitis

Question 13

Aseptic meningitis and coxsackie virus

Answer 13

It is caused by all types of group B coxsackieviruses and by many group A coxsackieviruses (M/C A7 and A9)

Question 14

Hand-foot-and-mouth disease

Answer 14

Oral and pharyngeal ulcerations and vesicular rashes of the palms and soles which heal without crusting. It is particularly associate with coxsackievirus A16

Question 15

Pleurodynia, also known as Bornholm disease or epidemic myalgia

Answer 15

It is caused by coxsackie B viruses.

It is characterized by fever and abrupt onset of stabbing chest pain

Question 16

Acute hemorrhagic conjunctivitis

Answer 16

• By coxsackievirus A24 and enterovirus 70
• Self-limiting subconjunctival hemorrhage.
• Incubation period: 1 day.
• Complete recovery within 8–10 days
„• caused epidemics among adults, during 1969–71 in Africa and Southeast Asia

Question 17

Lab diagnosis of coxsackie viruses

Answer 17

Specimen: throat swabs, stool, CSF,…
™1. Isolation of the virus:
•„ Intracerebral inoculation into suckling mice (obsolete now):
 Coxsackie-A produce flaccid paralysis
 Coxsackie-B produce spastic paralysis.
•„ Inoculating into tissue culture: Cytopathic effect within 5–14 days.
™2. PCR (e.g. VP1 gene) rapid, more sensitive and serotype-specific
™3. Serology to detect neutralizing antibodies.

Question 18

Echoviruses

Answer 18

Echoviruses (enteric cytopathogenic human orphan viruses) infect humans by feco-oral route.
Echoviruses are typed into serotypes 1–33 but not all cause human illness
™ They are associated with aseptic meningitis, encephalitis, rashes, common cold, and ocular disease
™ They can cause outbreaks in summer especially among children.

Question 19

Parechoviruses

Answer 19

Serotype 1 and 2 were previously classified as echoviruses 22 and 23 respectively
• Their capsid consists of three viral proteins (in contrast to four proteins in most picornaviruses)
• They have been rarely associated with aseptic meningitis, respiratory and neonatal diseases

Question 20

Enterovirus 71

Answer 20

Enterovirus 71 has caused large epidemic of meningitis in Southeast Asia.
• also cause encephalitis, hand-foot-and-mouth disease, herpangina (similar to coxsackieviruses) and paralysis resembling poliomyelitis

Question 21

Herpesvirus Meningitis

Answer 21

Common agents are herpes simplex viruses, varicella-zoster virus (VZV) and Epstein-Barr virus (EBV)
™• Rare causes include CMV and human herpesvirus

Question 22

HSV Meningitis

Answer 22

2nd M/C cause of viral meningitis
• Adults are commonly affected than children.
•™ HSV-2 is a more frequent cause of meningitis than HSV-1 (but in HSV encephalitis, HSV-1 is M/C)
•™ History of genital herpes is important as HSV meningitis can occur in ~25–35% of women and ~10–15% of men at the time of an initial episode of genital herpes.

Question 23

Mollaret meningitis

HSV meningitis

Answer 23

HSV typically produces a chronic recurrent lymhocytic meningitis
• It is characterized by repeated episodes of meningitis, typically lasting two to five days occcurring weeks to years apart.
• It can also be caused by EBV

Question 24

Neurological manifestations caused by HSV include:

Answer 24

1. Mollaret meningitis
2. HSV encephalitis: M/CC of acute sporadic viral encephalitis
   ™3. Bell’s palsy: HSV-1 and 2 are one of the M/CC
   ™4. Autonomous system involvement (sacral region): common
   numbness, tingling of the buttock areas, urinary retention, constipation, and impotence
   ™5. Transverse myelitis: rare
   rapidly progressive symmetric paralysis of the lower extremities
   6.™ Guillain-Barré syndrome
   7.™ Peripheral nervous system involvement

Question 25

Arboviral Meningitis

Answer 25

1. West Nile virus: in Americas, Africa, West Asia; by Culex
   ™2. Saint Louis encephalitis virus: in US, by Culex
   ™3. Tick-borne encephalitis viruses such as Powassan virus or Colorado tick fever virus
   4.™ California encephalitis virus: in US, by Aedes
2. Non-encephalitic arboviruses which can cause meningitis are Zika virus (Brazil) and Oropouche virus

Question 26

HIV Meningitis

Answer 26

Meningitis in HIV infection may occur:
1. Following primary infection in 5-10% of cases
2. Less commonly at later stages of illness.
• Cranial nerve palsies especially involving cranial nerves V, VII, or VIII, are more common in HIV meningitis than in other viral infections

Question 27

Mumps Meningitis

Answer 27

1. May occur secondary to parotitis
2. In about 10% of cases, patients may directly develop meningitis without an underlying history of parotitis (atypical mumps).
   Mumps meningitis is more common in the late winter ❄️ or early spring, especially in unvaccinated children with a male preponderance.

Question 28

LCM Virus Meningitis

Answer 28

Lymphocytic choriomeningitis (LCM) virus affects people with history of contact with rodent droppings or urine. 
Some patients have an associated rash, pulmonary infiltrates, alopecia, parotitis, orchitis, or myopericarditis.

Question 29

Viral myelitis

types

Answer 29

1. Gray matter myelitis:
   • infections of the anterior horn of the spinal cord;
   • acute flaccid paralysis
   •„ M/C by poliovirus, enteroviruses and arboviruses .
   2.™ Transverse myelitis or leukomyelitis, or white matter myelitis:
   • from direct viral invasion or via immune-mediated mechanisms
   • by the herpesviruses and influenza virus, rarely HIV and HTLV.

Question 30

Poliovirus

structure

Answer 30

Poliovirus and other picornaviruses are simple in structure,
• very small (28–30 nm size) and non-enveloped.
•™ spherical shaped and icosahedral symmetry
•™ Capsid is composed of 60 subunits, each consisting of four viral proteins (VP1-VP4), except parechoviruses (have three proteins)
•™ have ss positive sense linear RNA

Question 31

Wild Poliovirus (WPV)

Answer 31

There are three wild poliovirus strains: WPV1, WPV2 and WPV3.
™ All three strains are identical, similar manifestations and severity of illness, ™but genetically and immunologically distinct (differ from each other in VP1 region) ➡️ type-specific antibodies and not cross-protective ➡️ each strain need to be eradicated individually
™ Currently all the natural cases are caused by WPV1. Others are eradicated

Question 32

Poliovirus pathogenesis

Answer 32

1. Transmission: feco-oral (M/C) (respiratory droplets or by conjunctival contact)
2. Multiply locally: intestinal epithelial cells, submucosal lymphoid tissues, tonsils and Peyer’s patches
3. Entry: mediated by binding to CD155 receptors on host cell
4. Spread to CNS/spinal cord:
   „ Hematogenous spread (M/C)
5. Site of action: motor nerve ending. i.e, anterior horn cells
6. Neuron degeneration:
   Earliest change in neuron is the degeneration of Nissl body

Question 33

Advantage of IPV

Answer 33

1. IPV is much safer than OPV, safer even in immunocompromised people
   „2. It does not cause vaccine-associated paralytic polio (VAPP)
   „3. It is more stable, does not require stringent storage conditions.

Question 34

Disadvantages of IPV

Answer 34

1. It does not provide herd immunity: Being inactivated vaccine, it cannot spread by feco-oral route
   2.„ It is not useful during epidemics; as there is no community protection. Instead, it can precipitate paralysis
   „3. It does not induce mucosal IgA production, hence, the local immunity is absent
   „4. It is relatively expensive than OPV