02-10-23 - Infections of the CNS Flashcards
Learning outcomes
- Explain how infection of the central nervous system occurs
- List the different causes of meningitis
- Identify hosts with particular susceptibility to different causes of meningitis
- Differentiate between bacterial and viral meningitis
- Explain how meningitis is treated and prevented
- Explain the role of specific virulence factors in the pathogenesis of meningitis
- Identify the common infective causes of encephalitis.
- List the different types of transmissible spongiform encephalopathies.
Case study
- Case study
1) Clinical history:
* A 3 year old boy, is admitted to hospital with a 2 day history of lethargy, irritability and poor feeding.
2) Examination:
* He is pyrexial and drowsy
* There has 2-3 purplish-red lesions on the trunk and extremities, which the parents say were not present when he was examined by their GP.
* There is no neck stiffness but his right arm is painful with no history of trauma
3) What are you most worried about?
* Meningococcal disease
* May present with meningitis, sepsis or both – bacteria can cause infection in the CNS and cause sepsis, which can spread in the bloodstream and disseminate throughout the body
* Meningococcal sepsis can present with petechial/purpuric rash (little dark spots, with non-blanching rash), purpura filimans and gangrene
4) Mortality:
* 5-15% from meningococcal meningitis 40+% from meningococcal sepsis
* 40+% from meningococcal sepsis
How often does are there complication in survivors of those with meningococcal meningitis?
What are 7 complications of meningitis?
What are 4 complications of sepsis?
- There are complications in survivors of those with meningococcal meningitis in 20% of cases
- 7 complications of meningitis:
1) Seizures
2) Hearing difficulties
3) Other cranial nerve problems
4) Focal paralysis
5) Hydrocephalus
6) Intellectual disability
7) Ataxia - 4 complications of sepsis:
1) Limb amputations
2) Arthritis and join pain
3) Skin necrosis and scarring
4) Organ dysfunction: liver, kidney, adrenal glands
What is meningitis and encephalitis?
- Meningitis is inflammation of the meninges
- Encephalitis is the inflammation of the brain parenchyma
What is sepsis?
How does it affect the organs?
What can sepsis progress to?
- Sepsis is a serious condition in which the body responds improperly to an infection (dysregulated host response to infection), normally in the context of bacteraemia spreading to organs
- The infection-fighting processes turn on the body, causing the organs to work poorly.
- Sepsis may progress to septic shock.
- This is a dramatic drop in blood pressure that can damage the lungs, kidneys, liver and other organs.
What does the BBB consist of?
What occurs when it is breached by infectious agents?
Where is the Blood-CSF barrier located?
What occurs when it is breached by infectious agents?
What are 3 ways microbes can spread around the CNS?
- The BBB consists of tightly packed endothelial cells line the blood vessels in the brain mechanically supported by thin basement membrane.
- Breach by infectious agents causes encephalitis.
- Blood- cerebrospinal spinal fluid (CSF) barrier is a similar barrier at arachnoid membrane and in ventricles.
- Breach by infectious agents causes meningitis
- 3 ways microbes can spread around the CNS:
1) Sinuses
2) Otitis media
3) Skull fracture
What occurs when these barriers are breached?
What are 3 ways these barriers can be breached?
- On rare occasions pathogens can traverse these barriers resulting in a typical inflammatory response associated with infection.
- 3 ways these barriers can be breached:
1) Growing across & infecting cells comprising barrier
2) Passive transfer in intracellular vacuoles
3) Carriage across in infected white blood cells
What are 3 causes of meningitis?
- 3 causes of meningitis:
1) Infection
2) Auto-immune disease
3) Malignancy
Most common infection agents for meningitis (in picture):
* Bacteria (4)
* Viruses (5)
* Fungi (1)
* Protozoa (3)
How can causative organisms for meningitis vary in different age groups?
Where is the main causative organism for meningitis in neonates?
What are the main meningitis causing organisms in the following groups (in picture):
1) Neonates
2) <5 years old
3) Young adults
4) Older
5) Immunosuppressed
- The main causative organisms of bacterial meningitis vary by age and other risk factors
- The main cause of sepsis in neonates is bacterial and pick up if the baby is delivered through the mother’s birth canal
- Main meningitis causing organisms in various groups (in picture)
What are 4 dangers of early onset neonatal meningitis?
What are 3 dangers of late onset neonatal meningitis?
- 4 dangers of early onset (<3days) neonatal meningitis:
1) Infected by heavily colonised mother
2) Premature rupture of membranes
3) Preterm delivery
4) 60% fatality rate - 3 dangers of late onset neonatal meningitis:
1) Lack of maternal antibody
2) Poor hygiene in nursery
3) 20% fatality rate
Bacterial meningitis pathogens: Neisseria meningitidis.
What kind of bacterium is this?
What species’ does it infect?
Where is its normal microbiota?
How does transmission occur?
How many different serotypes are there? How do they differ?
How many pathogenic serogroups are there?
How can meningococcal meningitis be prevented?
- Bacterial meningitis pathogens: Neisseria meningitidis
- Gram negative Intracellular diplococci
- Only infects humans
- Normal microbiota in nasopharynx
- Transmission by droplet spread or direct contact from carriers
- At least 12 serotypes - different in polysaccharide antigens
- 5 pathogenic serogroups strains – A, B, C, W135, Y
- Meningococcal meningitis is vaccine preventable
Bacterial meningitis pathogens: Haemophilus influenzae.
What type of bacterium is this?
How many serotypes are known to cause disease?
What is the most virulent strain?
How can H influenzae be prevented?
- Bacterial meningitis pathogens: Haemophilus influenzae
- Gram-negative coccobacilli
- Six capsular serotypes (a-f) known to cause disease
- Most virulent strain is H. influenzae type b (Hib)
- H influenzae meningitis is vaccine preventable
Bacterial meningitis pathogens: Streptococcus pneumoniae.
What type of bacterium is this?
Where is its normal microbiota?
How many bacterial serotypes are there?
What is it a common cause of?
What 3 other conditions does Streptococcus pneumoniae also cause?
How can Invasive pneumococcal disease be prevented?
- Bacterial meningitis pathogens: Streptococcus pneumoniae
- Gram positive diplococci
- Normal microbiota in nasopharynx
- There are over 90 bacterial serotypes
- Common cause of meningitis in young children and adults with specific risk factors (e.g. older, diabetic, alcohol excess, asplenic)
- 3 other conditions Streptococcus pneumoniae also causes:
1) Pneumonia
2) Otitis media
3) Bloodstream infections - Invasive pneumococcal disease is vaccine preventable
How are asplenic patients treated differently to protect against capsulated organisms?
- Vaccinate asplenic patients against capsulated organisms (N meningitidis, H influenzae b, S pneumoniae)
Describe the presence/absence of the following symptoms in septicaemia and meningitis (in picture):
1) Fever and or vomiting
2) Severe headache
3) Limb/joint/muscle pain
4) Cold hands and feet/shivering
5) Pale or mottled skin
6) Breathing fast/breathless
7) Rash
8) Stiff neck
9) Dislike of bright lights
10) Verly sleep/vacant/difficult to wake
11) Confused/delirious
12) Seizures (fits)
What level/space are lumbar punctures performed at?
What are 3 important things to remember when performing a lumbar puncture?
- In lumbar punctures, the spinal needle can be safely inserted into the subarachnoid space at the L3-4 or L4-5 interspace (between vertebrae), since this is well below the termination of the spinal cord in most patients.
- 3 important things to remember when performing a lumbar puncture:
1) Measure the opening pressure (pressure of CSF coming out)
2) Take matched blood and CSF glucose samples
3) Collect enough fluid (and some to spare!)
Describe the typical CSF findings by main pathogen classes of infective meningitis (in picture):
1) Normal
2) Bacterial
3) Viral
4) TB
5) Fungal
What are the 9 main reasons for delaying or omitting a lumbar puncture in a case of suspected infective meningitis?
- 9 main reasons for delaying or omitting a lumbar puncture in a case of suspected infective meningitis:
1) Risk of bleeding
2) Focal neurology suggesting a mass lesion in the brain
3) Signs of severe sepsis or rapidly evolving rash
4) Respiratory or cardiac compromise
5) Anticoagulant therapy/known thrombocytopaenia (abnormally low platelets)
6) Infection at the site of LP
7) Presence of papilledema
8) Continuous or uncontrolled seizures
9) GC2<12
Describe the treatment of bacterial meningitis caused by the following organisms:
1) Suspected meningococcal infection
2) Suspected meningococcal infection
3) N. meningitidis
4) H. influenzae
5) Strep. Pneumoniae
6) Group B Streptococcus
7) Gram negative bacilli
8) L. monocytogenes
9) M tuberculosis
What type of therapy is used in the context of meningitis?
What 5 antibiotics are used for meningitis depending on the causative organism?
What are steroids used for in these treatments?
- Treatment of bacterial meningitis caused by varying following organisms (in picture)
- Since meningitis is often an emergency, we need to utilise empirical therapy, which refers to antibiotics that are administered during the period prior to the receipt of blood culture and antibiotic susceptibility test results, whereas the term “definitive therapy” refers to the antibiotic therapy given subsequent to receipt of these results.
- 5 antibiotics are used for meningitis depending on the causative organism:
1) Cefotaxime (broad spectrum antibiotic)
2) Ceftriaxone (cephalosporin antibiotics)
3) Gentamicin (aminoglycoside antibiotics)
4) Amoxacillin (penicillin antibiotic)
5) Anti-TB antibiotics - Steroids, such as dexamethasone, are used to reduce inflammation in order to reduce long term pathologies
What 3 routine vaccinations are offered as prevention for bacterial meningitis?
What vaccines are offered against other neurological infections?
- 3 routine vaccinations offered as prevention for bacterial meningitis:
1) Haemophilus influenzae b
2) Pneumococcus
3) Meningococcus A,B,C, W, Y - Vaccines against other neurological infections include polio and tetanus
What is encephalitis?
What is the most common cause of encephalitis?
What are 5 less common causes of encephalitis?
What are 5 symptoms/signs of encephalitis?
What are the investigations for viral encephalitis?
How is it treated?
- Encephalitis is inflammation of the brain tissue
- The most common cause of encephalitis is HSV-1
- 5 less common causes of encephalitis:
1) VZV
2) HIV
3) Covid-19
4) Japanese encephalitis
5) West Nile Virus - 5 symptoms/signs of encephalitis:
1) Altered cerebration (thought process)
2) Confusion
3) Abnormal behaviour
4) Seizures
5) Fever - The investigations for encephalitis are similar to that of meningitis
- There will be typical findings for CSF, but temporal lobe changes on MRI scan (often the temporal lobe is affected)
- The treatment of encephalitis is high dose IV acyclovir (antiviral medication)
What are Immune-compromised patients at risk from?
What are 4 pathogens that can cause CNS infections in immune-compromised individuals?
- Immune-compromised patients (e.g., people with HIV, posttransplant) may be at risk from a wider range of pathogens)
- 4 pathogens that can cause CNS infections in immune-compromised individuals:
1) Toxoplasmosis gondii
2) Mycobacterium tuberculosis
3) Cryptococcus neoformans
4) Nocardiosis
What are Transmissible Spongiform Encephalopathies (TSEs)?
What are they caused by?
What are prions?
How do they affect proteins in the brain?
How fatal/rapidly progressing are prion diseases?
How do prion diseases affect nervous tissue?
What are prions resistant to?
What is the treatment for prion diseases?
What are 3 human prion diseases?
What are 2 animal prion diseases?
- Transmissible Spongiform Encephalopathies (TSEs) are rare neurodegenerative disorders
- The causative agents of TSEs are believed to be prions.
- The term “prions” refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain.
- The functions of these normal prion proteins are still not completely understood.
- The abnormal folding of the prion proteins leads to brain damage and the characteristic signs and symptoms of the disease.
- Prion diseases are usually rapidly progressive and always fatal.
- Prion diseases Cause vacuoles and plaques in nervous tissue
- Prions are highly resistant to heat, chemical agents and irradiation
- There is no treatment and no vaccine
- 2 human prion diseases:
1) Creutzfeldt-Jakob disease (CJD)
2) Variant Creutzfeldt-Jakob disease (vCJD) - 3 animal prion diseases
1) Bovine Spongiform Encephalopathy (BSE)
2) Kuru
3) Scrapie
