CNS Infection Flashcards
What are two methods through which a microbe can affect CNS function directly?
- Invasion of the brain parenchyma (e.g. viral encephalitis, cerebral abscess)
- Invasion of supporting structures of the brain (e.g. VZV large-vessel vasculopathy)
How can a microbe affect CNS function indirectly?
▪️ Immune-mediated damage
▪️ Infection triggering metabolic catastrophes
▪️ Toxin-mediated
▪️ Consequence of systemic sepsis
Why are common infections rarely neurovirulent?
▪️ 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)
How do CNS infections cause damage?
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)
What is the gold standard for proving a bug is the cause of disease?
Demonstrate presence of bug in CNS or bug-specific CFS immune response (e.g., antibodies, localised response to CNS)
What are the main acute neuroinfection syndromes?
▪️ Meningitis
▪️ Ventriculitis
▪️ Encephalitis
▪️ Myelitis etc
What are the main subacute and chronic neuroinfection syndromes?
▪️ Subacute sclerosing panencephalitis (following measles)
▪️ PML (JC virus, often with HIV)
▪️ HIV dementia
▪️ Tropical spastic paraparesis
What are the three key components of neurological formulation for the diagnosis of neurological infection?
▪️ Anatomy
▪️ Pathogenic mechanism
▪️ Aetiology - why this person from this place at this time
What factors may be contraindicative of lumbar puncture for investigating suspected infection?
▪️ Reduced level of consciousness
▪️ Focal signs
▪️ Immunosuppression
▪️ Papilledema
▪️ Anticoagulation/bleeding disorder
What are the main CSF tests?
▪️ 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
What can you look for in the bedside diagnosis of acute encephalitis?
Fever, altered consciousness, seizures
▪️ Age
▪️ Focal and lateralising neurology
▪️ Sporadic vs epidemic
▪️ Animals and vectors
▪️ Immunocompetance
What virus shows the most seasonal dependence?
Enterovirus (e.g., polio) - increase in summer
What are the most common causes of acute viral encephalitis in the UK?
▪️ HSV 1 and 2
▪️ VZV
▪️ Enteroviruses (e.g., polio, hep A)
What investigations can we use to diagnose acute encephalitis?
▪️ Imaging
▪️ EEG
▪️ CSF analysis via LP
What is the likelihood of HSE if the MRI is normal 72 hours after infection?
Highly unlikely
What brain areas are most affected by HSE?
▪️ Temporal lobes
▪️ Orbitofrontal cortex
What EEG signs might be seen in HSE and what does this suggest?
▪️ Temporal Periodic Lateralised Epileptiform Discharges (PLEDs)
▪️ Suggestive of severe illness with poor prognosis
What lab tests can we use to diagnose HSE?
▪️ 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
How do you treat HSE?
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
What are the most common causes of acute infectious meningitis?
Viral - usually benign, symptomatic relief
▪️ Enterovirus
▪️ HSV 2
▪️ Mumps
Bacterial - high morbidity and mortality
▪️ Meningococcus (younger people)
▪️ Pneumococcus (older people)
What are the main symptoms of acute infectious meningitis?
▪️ Headache
▪️ Fever
▪️ Meningismus - stiff neck, reaction to light, headache
What are some of the risk factors for pneumococcal meningitis?
▪️ Age - younger or older
▪️ Under functioning spleen
▪️ Alcoholism/malnutrition
▪️ Chronic disease
▪️ Head injury at base of skull - direct access to meninges
How does pneumococcal infection reach the brain?
▪️ Through blood stream/lungs/respiratory tract (haematogenous)
▪️ Direct entry with injury
How do we investigate pneumococcal meningitis?
▪️ Blood cultures
▪️ EDTA blood for PCR
▪️ CSF
How do we treat pneumococcal meningitis?
▪️ 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?
What is the prognosis of pneumococcal meningitis?
▪️ Mortality up to 30% without steroids
▪️ 30-50% neurological sequelae
What are emerging infections?
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)
