Viral Meningitis

Question 1

Definition of viral meningitis

Answer 1

Viral meningitis is inflammation of the meninges caused by a variety of different viruses and is the most common cause of aseptic meningitis.

Question 2

Epidemiology of viral meningitis

Answer 2

One of the most common infections of the CNS. Viral meningitis affects all ages but is most commonly diagnosed in children. Males appear to be affected more commonly than females. Arboviruses are responsible for a substantial proportion of non-enteroviral viral meningitis.

Question 3

Etiology of viral meningitis

Answer 3

Human enteroviruses are the most common cause of viral meningitis. Herpes viruses cause a spectrum of CNS disease including meningitis, myelitis and encephalitis. Herpes Simplex Virus 1(HSV1) is the most common cause of viral encephalitis in the western world. HSV2 is more commonly associated with viral meningitis which may occur during primary infection or with shingles but may occur without any rash.

Question 4

Pathophysiology of viral meningitis

Answer 4

Enteroviruses are spread by the faecal oral route. Non-polio enteroviruses and arboviruses initially replicate outside the CNS in tissues such as muscle, liver and the respiratory or GI tracts and then reach the CNS by haematogenous spread. Viral penetration of the BBB occurs by either infection or endothelial cells or of migrating leukocytes. Once within CNS, viruses spread through the subarachnoid space leading to meningitis and may go on to infect neurons and glial cells leading to encephalitis or myelitis. The cellular immune response to viral infection of the CNS leads to the accumulation of lymphocytes within the CSF and the release of inflammatory cytokines such as interleukin 6 and TNF. The inflammatory response increases the permeability the BBB and allows the diffusion of circulating immunoglobulins into the CSF.

Question 5

Risk factors of Viral meningitis

Answer 5

Risk factors:
Strong:
Infants and young children → enteroviral meningitis most commonly affects this age group. Symptoms in children generally abate within 1 week, adults may have a more prolonged clinical course
Young adults and older people → herpes simple virus follows a bimodal age distribution with infection in young adults as a result of primary exposure and in older adults as a result of waning immunity
Summer and autumn → in temperate regions enteroviral meningitis shows a marked seasonality with more cases seen in summer and autumn
Exposure to mosquito or tick vector → infections with arboviruses are more common when contact with the mosquito or tick vectors are more likely
Unvaccinated for mumps → meningitis is a common manifestation of mumps occurring in up to 10% of cases.

Weak:
Use of swimming pools and ponds
Immunosuppression
Exposure to rodents

Question 6

Hx and Exam of viral meningitis

Answer 6

Hx and Exam:
Key Diagnostic factors:
Presence of risk factors 
Headache 
Nausea and vomiting
Photophobia 
Neck stiffness
Fever

Other diagnostic factors:
Rash

Uncommon:
Kernig’s sign - when the patient is lying with thigh flexed on the abdomen, the leg cannot be completely extended

Brudzinski’s sign : when patients neck is flexed (after ruling out cervical trauma or injury), flexion of the knees and hips is produced: when the lower extremity of one side is passively flexed, a similar movement is seen in the opposite extremity

Question 7

Investigations for viral meningitis

Answer 7

1. CSF microscopy→ in viral meningitis: CSF WBC coin is typically >5cells/mm^3 but may be normal. A CSF WBC count >5 cells/mm^3 has a sensitivity of 90% for the diagnosis of viral meningitis. Result: WBC >5 cells/mm^3 for children and adults and >20cells/mm^3 for neonates
2. CSF gram stain → negative in viral meningitis, positive CS gram stain indicates bacterial meningitis. Result: negative gram stain
3. CSF bacterial culture → should be negative in viral meningitis. Result: negative
4. CSF protein → typically normal or mildly elevated: >0.45g/L in 50% and >1g/L in 16%. Result: normal or elevated
5. CSF glucose → low CSF glucose is usually >0.5 of plasma glucose. Low CSF glucose is typically seen in bacterial, fungal and TB meningitis but may be seen in viral meningitis. Result: may be low
6. CT/MRI head scan → may be useful to exclude cerebral abscess. Result: unremarkable: may exclude abscess or bacterial meningitis

Question 8

Management of Viral Meningitis

Answer 8

Initial: possible bacterial meningitis

In infants aged <1month
1st line: antibiotic therapy : empiric abx therapy to cover group B streptococci, Listeria and coliforms. If the infant has been in a hospital nursery - add staphylococcus aureus cover.

infants aged ≥1 month, children, and adults aged ≤50 years
Antibiotic therapy - empiric abx therapy
Adjunct: dexamethasone

Adults aged >50years
1st line : abx therapy: empiric abx therapy
Adjunct: dexamethasone

Acute:
Confirmed viral agent, other than HSV, varicella zoster or CMV
1st line: supportive care

HSV or varicella zoster confirmed causative agent Treatment course 7-10 days
1st line: antiviral therapy plus supportive care

Primary:
Acyclovir - children and adults : 10mg/kg IV Q8H, neonates may require higher doses, consult specialist for further guidance on dose
OR
Valaciclovir: children: consult specialist for guidance on dose; adults: 1g orally Q8H

Secondary:
Foscarnet: children - consult with specialist
Adults : 40mg/kg IV Q8H
→ used in aciclovir resistant herpes simplex

CMV confirmed causative agent:Treatment course 7-10 days
1st line: antiviral therapy plus supportive care

Primary options:
Ganciclovir: children- consult specialist
Adults: 5mg/kg IV Q12H

OR
Valganciclovir: children - consult specialist
Adults: 900mg Q12H

Secondary options:
Foscarnet: children - consult with specialist
Adults : 60 mg/kg IV Q8H

Tertiary options:
Cidofovir: children - consult specialist
Adults: 5mg/kg IV once weekly

Ongoing : recurrent viral meningitis
1st line: consideration of antiviral therapy