CNS Infection

Question 1

What are two methods through which a microbe can affect CNS function directly?

Answer 1

1. Invasion of the brain parenchyma (e.g. viral encephalitis, cerebral abscess)
2. Invasion of supporting structures of the brain (e.g. VZV large-vessel vasculopathy)

Question 2

How can a microbe affect CNS function indirectly?

Answer 2

▪️ Immune-mediated damage
▪️ Infection triggering metabolic catastrophes
▪️ Toxin-mediated
▪️ Consequence of systemic sepsis

Question 3

Why are common infections rarely neurovirulent?

Answer 3

▪️ Infectious dose/load of organism not great enough
▪️ Host innate and adaptive immune response
▪️ Neurovirulent features of organism (BUT very small genetic changes in organism can change this)

Question 4

How do CNS infections cause damage?

Answer 4

Vicious cycle:
▪️ Invasion causes inflammatory response (e.g., BBB breakdown, cytokine release)
▪️ Raised intracranial pressure and oedema (vasogenic, interstitial, cytotoxic)
▪️ Direct neuronal injury (necrosis or apoptosis)

Question 5

What is the gold standard for proving a bug is the cause of disease?

Answer 5

Demonstrate presence of bug in CNS or bug-specific CFS immune response (e.g., antibodies, localised response to CNS)

Question 6

What are the main acute neuroinfection syndromes?

Answer 6

▪️ Meningitis
▪️ Ventriculitis
▪️ Encephalitis
▪️ Myelitis etc

Question 7

What are the main subacute and chronic neuroinfection syndromes?

Answer 7

▪️ Subacute sclerosing panencephalitis (following measles)
▪️ PML (JC virus, often with HIV)
▪️ HIV dementia
▪️ Tropical spastic paraparesis

Question 8

What are the three key components of neurological formulation for the diagnosis of neurological infection?

Answer 8

▪️ Anatomy
▪️ Pathogenic mechanism
▪️ Aetiology - why this person from this place at this time

Question 9

What factors may be contraindicative of lumbar puncture for investigating suspected infection?

Answer 9

▪️ Reduced level of consciousness
▪️ Focal signs
▪️ Immunosuppression
▪️ Papilledema
▪️ Anticoagulation/bleeding disorder

Question 10

What are the main CSF tests?

Answer 10

▪️ Cell count and cytology
▪️ Gram stain (look for bacteria)
▪️ Antigen detection
▪️ Microbial culture
▪️ CSF/plasma glucose of lactate - if CSF is less than third of blood = bacteria
▪️ Nucleic acid detection
▪️ CSF antibody tests

Question 11

What can you look for in the bedside diagnosis of acute encephalitis?

Answer 11

Fever, altered consciousness, seizures
▪️ Age
▪️ Focal and lateralising neurology
▪️ Sporadic vs epidemic
▪️ Animals and vectors
▪️ Immunocompetance

Question 12

What virus shows the most seasonal dependence?

Answer 12

Enterovirus (e.g., polio) - increase in summer

Question 13

What are the most common causes of acute viral encephalitis in the UK?

Answer 13

▪️ HSV 1 and 2
▪️ VZV
▪️ Enteroviruses (e.g., polio, hep A)

Question 14

What investigations can we use to diagnose acute encephalitis?

Answer 14

▪️ Imaging
▪️ EEG
▪️ CSF analysis via LP

Question 15

What is the likelihood of HSE if the MRI is normal 72 hours after infection?

Answer 15

Highly unlikely

Question 16

What brain areas are most affected by HSE?

Answer 16

▪️ Temporal lobes
▪️ Orbitofrontal cortex

Question 17

What EEG signs might be seen in HSE and what does this suggest?

Answer 17

▪️ Temporal Periodic Lateralised Epileptiform Discharges (PLEDs)
▪️ Suggestive of severe illness with poor prognosis

Question 18

What lab tests can we use to diagnose HSE?

Answer 18

▪️ PCR of CSF - highly sensitive and specific at right times BUT can be negative very early or late on
▪️ CSF antibody studies - positive 7-10 days into illness
▪️ Brain biopsy - gold standard

Question 19

How do you treat HSE?

Answer 19

IV aciclovir
▪️ Complete inhibitor of viral DNA polymerase stopping reproduction
▪️ Probably for 2-3 weeks but unclear
▪️ Earlier the better!
▪️ Relapse particularly common in paediatrics

Question 20

What are the most common causes of acute infectious meningitis?

Answer 20

Viral - usually benign, symptomatic relief
▪️ Enterovirus
▪️ HSV 2
▪️ Mumps

Bacterial - high morbidity and mortality
▪️ Meningococcus (younger people)
▪️ Pneumococcus (older people)

Question 21

What are the main symptoms of acute infectious meningitis?

Answer 21

▪️ Headache
▪️ Fever
▪️ Meningismus - stiff neck, reaction to light, headache

Question 22

What are some of the risk factors for pneumococcal meningitis?

Answer 22

▪️ Age - younger or older
▪️ Under functioning spleen
▪️ Alcoholism/malnutrition
▪️ Chronic disease
▪️ Head injury at base of skull - direct access to meninges

Question 23

How does pneumococcal infection reach the brain?

Answer 23

▪️ Through blood stream/lungs/respiratory tract (haematogenous)
▪️ Direct entry with injury

Question 24

How do we investigate pneumococcal meningitis?

Answer 24

▪️ Blood cultures
▪️ EDTA blood for PCR
▪️ CSF

Question 25

How do we treat pneumococcal meningitis?

Answer 25

▪️ High dose of IV antibiotics ASAP - preferably with bactericidal action
▪️ Steroids (either before or with first antibiotics) (e.g., dexamethasone 6 hourly for 4 days)

BUT steroids only beneficial in resource rich countries?

Question 26

What is the prognosis of pneumococcal meningitis?

Answer 26

▪️ Mortality up to 30% without steroids
▪️ 30-50% neurological sequelae

Question 27

What are emerging infections?

Answer 27

Infectious diseases that have either:
▪️ Not previously been recognised by medical science (e.g., COVID-19)
▪️ Jumped species barrier (e.g., bird flu)
▪️ Translocated to discrete geographical areas where not previously found (e.g., West Nile in Australia)