Micro 4: CNS Infections and Meningitis Flashcards
Routes of pathogen entry into the CNS and examples
- Haematogenous (e.g. pneumococcus, meningococcus), 2. Direct implantation (e.g. trauma), 3. Local extension (e.g. from the ear), 4. PNS into CNS (e.g. rabies)
What is the most common route of entry of pathogens into the CNS?
Haematogenous
What are causes of aseptic meningitis?
Includes enterovirus and herpes (these also transfer by haematogenous spread)
Where does meningitis occur and what are the signs and symptoms?
Occurs in the meninges. Fever, headaches, stiff neck, usually some disturbance of brains function.
What are causative agents of meningitis?
Neisseria meningitides, Streptococcus pneumoniae, Haemophilus influenzae, TB, various viruses, Cryptococcus neoformans
Where does encephalitis occur and what are the signs and symptoms?
Occurs in the brain. Causes disturbance of brain function.
What are causative agents of encephalitis?
Rabies virus, arboviruses, Trypanosoma species, Prions, and amoeba
Where does myelitis occur and what are the signs and symptoms?
Occurs in the spinal cord. Signs and symptoms include disturbance of nerve transmission.
What are causative agents of myelitis?
Poliovirus
Where is neurotoxin found and what are the signs and symptoms?
CNS and PNS. Paralysis, rigid (tetanus) or flaccid (botulism).
What are causative agents of neurotoxin?
Clostridium tetani, Clostridium botulinum
What is the definition of meningitis?
Inflammatory process of the meninges and CSF.
What is meningoencephalitis?
This is inflammation of the meninges and brain parenchyma
What is neurological damage caused by?
Direct bacterial toxicity. Indirect inflammatory process and cytokine release and oedema (NOTE: oedema is a major problem because it occurs in a confined space). Shock, seizures and cerebral hypoperfusion.
What is the mortality for meningitis and what percentage have a neurological sequelae?
Mortality = 10%, neurological sequelae in 5% of meningitis survivors in the UK.
How is meningitis classified?
Acute (hours to days), Chronic (days to weeks), Aseptic (caused by viruses so there is no pus).
What organisms are the main cause of acute meningitis?
Neisseria meningitidis, Haemophilus influenza, Streptococcus pneumoniae
What are the three serotypes of N. meningitidis and what is the normal meningitis vaccine?
A, B and C. The normal meningitis vaccine is Meningitis C (although you can pay to get Men B).
Who is Streptococcus pneumoniae meningitis seen in?
Has a bimodal distribution (mainly in chldren/young people and elderly patients).
Haemophilus influenzae type B is not part of the UK immunisation schedule, true or false?
False
What are other organisms that may cause acute meningitis? And what are they key causes of?
Listeria monocytogenes (key cause of meningoencephalitis). Group B Streptococcus (can cause neonatal meningitis). Escherichia coli (biphasic - old people and neonates).
What are rare causes of meningitis?
TB, S Aureus, T pallidum and Cryptococcus neoformans
What organism is an infectious cause of childhood death in all countries?
Neisseria meningitidis
How is Neisseria meningitidis transmitted?
Transmitted from person-to-person, from asymptomatic carriers.
How is Neisseria meningitidis transmitted, how does it enter the body, and when does it cause infection?
From person-to-person, from asymptomatic carriers. Pathogenic strains are only found in about 1% of carriers. Enters the body through the nasopharyngeal mucosa in a susceptible individual. Causes infection in < 10 days.
The clinical spectrum in septicaemia is produced by FOUR processes, what are they?
- Capillary leak - albumin and other plasma proteins leads to hypovolaemia.
- Coagulopathy - leads to bleeding and thrombosis, endothelial injury results in platelet release reactions, the protein C pathway and plasma anticoagulants are affected.
- Metabolic derangement - particularly acidosis.
- Myocardial failure - and multi-organ failure
How may chronic meningitis (such as tuberculous meningitis) present?
CT scan of tuberculous meningitis may show enhancement in the basal cistern and meninges, with dilatation of the ventricles. Scans may also show tuberculous abscess in either left or right parietal region - note the enhancing thick-walled abscess.
What does TB meningitis have a similar presentation to?
Acute meningitis - fever headache and neck stiffness
Who is TB meningitis more common in?
Immunosuppressed patients
How long does it take for TB meningitis to present?
Takes weeks to present
What does TB meningitis involve?
Involves the meninges and basal cisterns of the brain and spinal cord.
What are complications of TB meningitis?
Tuberculous granulomas, tuberculous abscesses and cerebritis. There is also leptomeningeal enhancement (?). Chronic meningitis needs to be managed by specialists.
What is the most common infection of the CNS?
Aseptic meningitis
How does aseptic meningitis present?
Headache, stiff neck, photophobia. A non-specific rash may accompany these symptoms.
What are the most common organisms causing aseptic meningitis?
Coxsackie group B and echoviruses
Who does aseptic meningitis usually occur in and how is it treated?
Usually occurs in children < 1 year. Self-limiting disease that resolves in 1-2 weeks.
How is encephalitis transmitted?
Haematogenous - person-to-person or vectors (E.g. mosquitos, lice, ticks). Other viral causes of encephalitis.
What organisms cause encephalitis in children, in winter-spring?
Mumps
What organisms cause encephalitis in infants/children, in spring?
Measles, Varicella-zoster
Which organisms cause encephalitis in all ages, in summer-autumn?
Enteroviruses (Coxsackie A & B; echovirus; polio)
Which organism causes encephalitis in neonates and young adults, in summer-autumn?
Arboviruses
Which organisms cause encephalitis in infants and children in summer-autumn?
Western equine encephalitis and Eastern equine encephalitis
Which organism causes encephalitis in adults over 40 years old?
St Louis encephalitis
Which organism causes encephalitis in school-aged children, in summer-autumn?
California encephalitis
Which organism causes encephalitis in all ages, with no seasonal variation?
Rabies
Which organism causes encephalitis in children and young adults, with no seasonal variation?
Epstein-Barr virus/ cytomegaloviruses
Which ‘other’ organisms cause encephalitis in infants and children, with no seasonal variation?
Myxoviruses, paramyxoviruses and adenoviruses
Which organism cause encephalitis in adults, with no seasonal variation?
Herpes simplex (1&2)
Which organism is becoming the leading cause of encephalitis worldwide?
West Nile virus
How is West Nile virus transferred?
Mainly transferred by mosquitoes and birds. European birds tend to spend the winter in Southern Europe and Africa. West Nile Virus has spread across the USA.
What is an infectious, bacterial cause of encephalitis?
Listeria monocytogenes
Which organisms is amoebic encephalitis caused by?
Naegleria fowleri (Habitat - warm water). Acanthamoeba species and Balamuthia mandrillaris (Brain abscess, aseptic and chronic meningitis).
How does amoebic encephalitis spread?
Amoebae spread by direct extension (e.g. though the cribriform plates)
Which organism causes Toxoplasmosis?
Obligate intracellular protozoa parasite - Toxoplasma gonadii
How is Toxoplasmosis spread?
Spread via the oral, transplacental or organ transplant route.
Who does Toxoplasmosis cause severe infection in?
Immunocompromised patients
What organs does toxoplasmosis affect?
Grey and white matter of the brain, retinas, alveolar lining of the lungs, heart and skeletal muscle
What can brain abscesses (focal CNS infection) lead to?
They tend to cause death due to pressure-related issues
What is the pathophysiology of brain abscesses?
They tend to occur due to direct extension (e.g. otitis media, mastoiditis, paranasal sinuses). They can occasionally spread haematogenously (e.g. endocarditis).
What organisms may cause brain abscesses?
Streptococci (anaerobic and aerobic); Staphylococci (NOTE: staph and strep are common ENT pathogens); Gram-negative organisms (mainly in neonates); TB; fungi; parasites; Actinomyces and Nocardia species.
What is a common form of vertebral infection?
Pyogenic vertebral osteomyelitis is a common form of vertebral infection (e.g. staph and strep)
How does pyogenic vertebral osteomyelitis spread?
Can spread via direct open spinal trauma from infections in adjacent structures or it can spread haematogenously
If spinal infections / pyogenic vertebral osteomyelitis are left untreated, what can this lead to?
Permanent neurological deficits, significant spinal deformity and death
What are risk factors for spinal infections / pyogenic vertebral osteomyelitis?
Age, IV drug use, long-term systemic steroids, diabetes mellitus, organ transplantation, malnutrition, cancer.
How are CNS infections diagnosed?
MRI (better than CT in detecting parenchymal abnormalities such as abscesses and infarctions), CT scan (more readily available). Other useful tests: blood culture, throat swab, blood PCR, sputum culture, urine culture, CSF study?
What do CSF studies look at?
Colour/clarity, cell counts, chemistry (protein and glucose), stains (Gram, auramine (TB), India Ink (fungi)), cultures, with or without antigen screens, and PCR.
What would the appearance be in normal CSF vs. different types of meningitis?
Normal CSF: clear.
Purulent (bacterial) CSF: Turbid.
Aseptic (viral) meningitis: clear or slightly turbid.
Tuberculosis meningitis: clear or slightly turbid.
What cells (x 10^6/l) would be seen in normal CSF vs. different types of meningitis?
Normal: 0-5 leukocytes.
Purulent (bacterial) meningitis: 100-2000 polymorphs.
Aseptic (viral) meningitis: 15-500 lymphocytes.
Tuberculosis meningitis: 30-500 lymphocytes or some polymorphs.
What would Gram stain or antigen tests show in normal CSF vs. different types of meningitis?
Normal: negative results.
Purulent (bacterial) meningitis: positive results.
Aseptic (viral) meningitis: negative results.
Tuberculosis meningitis: negative results (scanty acid fast bacilli)
What level of protein would be found in normal CSF vs. different types of meningitis?
Normal: 0.15-0.4 g/l
Purulent (bacterial) meningitis: 0.5-3.0 g/l
Aseptic (viral) meningitis: 0.5-1.0 g/l
Tuberculosis meningitis: 1.0-6.0 g/;
What is the glucose level in normal CSF vs. different types of meningitis?
Normal: 2.2-3.3mmol/l, 60% of blood glucose level.
Purulent (bacterial) meningitis: 0-2.2 mmol/l.
Active (viral) meningitis: Normal.
Tuberculosis meningitis: 0-2.2 mmol/l.
A 20 year old woman presents with headache and neck stiffness. Gram stain purple-brown. Diplococci. What is the causative pathogen?
Streptococcus pneumoniae is a Gram-positive alpha-haemolytic diplococcus.
An 18 year old man presents with headache and neck stiffness. Gram stain pink. Lots of neutrophils are seen. What is the causative pathogen?
There are loads of neutrophils. There are Gram-negative diplococci which is mucousy with no haemolysis. This is meningococcus.
A 65 year old presents with headache and neck stiffness. Gram stain: purple-brown. Rod-shaped. What is the causative pathogen?
There are Gram-positive rods. This is Listeria monocytogenes.
A 45 year old presents with headache and neck stiffness. It is red and blue with Ziehl-Neelsen stain. What is the causative organism?
This is TB meningitis. This is likely to present with a chronic history. Ziehl-Neelsen stain shows RED and BLUE.
A 35 year old presents with headache and neck stiffness. The symptoms have lasted 3 days and he is an MSM. He also had a high opening pressure when doing the LP. This is India Ink stain. It appears like an orbit sort of structure.
What is the causative pathogen?
This is Cryptococcal meningitis. It appears like a orbit sort of structure - the yeast is in the middle and the capsule is around the outside. This feature along with a high opening pressure is pathognomonic of cryptococcal meningitis. It tends to occur in people who are immunocompromised (e.g. HIV).
What are 6 limitations of diagnostics?
- MRI oedema pattern and moderate mass effect cannot be differentiated from tumour or stroke or vasculitis in some patients
- Serology may not be useful in early stages of infection
- Difficulties obtaining sufficient CSF
- PCR techniques are expensive
- Methods to detect amoebic infections
- Availability of good laboratory technique
What are the time points in the decision-making process for treating CNS infections?*
Within 30 mins of patient contact, after 1-2 hours and at 24-48 hours
What data is available for decision-making in management of CNS infections?**
Clinical assessment, CSF analysis and CSF cultures
What is the generic therapy for meningitis?
Ceftriaxone 2g IV BD. If >50 years or immunocompromised, add amoxicillin 2g IV 4 hourly. Ceftriaxone is good at killing meningococcus, pneumococcus, haemophilus and E. coli
However, Ceftriaxone does NOT cover Listeria monocytogenes. This requires amoxicillin.
What is generic therapy for meningo-encephalitis?
Aciclovir 10mg/kg IV TDS. Ceftriaxone 2g IV BD. If >50 years or immunocompromised, add: amoxicillin 2g IV 4 hourly.
What is specific therapy for meningitis caused by S pneumoniae? **
Pen G 18-24 mu/d or Ampicillin 12g/d
What is specific therapy for N. meningitidis? **
Ceftriaxone 4 g/d or chloro 75-100 mg/kg/d
What is specific therapy for H. influenzae?**
Cefotaxime 12 gm/d or ceftriaxone 4g/d
What is specific therapy for Group B Strep.?**
Pen G 18-24 mu/d [plus aminoglycoside] or ampicillin 12g/d
What is specific therapy for Listeria?**
Ampicillin 12 g/d [plus aminoglycoside] or Pen G 18-24 mu/d
What is specific therapy for Gram negative bacilli?**
Cefotaxime 12g/d or ceftriaxone 4g/d
What is specific therapy for Pseudomonas?**
Meropenem 6g/d or ceftazidime 6g/d
What is the adjunctive therapy for meningitis?
Level of care required, corticosteroids (do NOT give them without speaking to a specialist, but it can be useful for cerebral oedema), repeat LP, public health.
