Lecture 2: Infections of the Central Nervous System Flashcards
Where does the cerebral spinal fluid act as a shock absorber?
Between the pia mater and arachnoid
(circulating around the brain and spinal cord)
What are the 3 connective tissues surrounding the brain?
Pia mater
Arachnoid
Dura mater
What is meningitis classified by?
Inflammation of the connective tissue layers surrounding the brain
What are capillaries throughout the body made of?
Endothelial cells
In the brain where are the endothelial cells packed more tightly together to produce tight junctions?
Sub arachnoid and perivascular space
What is known as the blood-brain barrier?
Sub arachnoid and perivascular space
What substances can pass the blood-brain barrier?
Lipid solubility - oxygen, carbon dioxide, ethanol, steroid hormones
Specific transport systems - sugars, amino acid
Why does the brain loose the arm of the immune response?
Antibodies are too large to cross the blood-brain barrier
Many antibodies are unable to pass the barrier due to their size
What are the common human flora associated with meningitis?
Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
What are all the bacteria associated with meningitis?
Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Escherichia coli
Streptococcus agalactiae
Listeria monocytogenes
Staphylococcus aureus
What are the pathogenic and host factors associated with meningitis?
Bacterial pathogenic factors:
Capsule - polysaccharide capsule
Adhesins - stick to endothelial surface
Host factors:
Cytokines
Selectins on endothelial surface
Integrins on neutrophils
How does bacterial invasion of meningitis occur to the cerebral spinal fluid (CSF)?
Bacteria adhere to capillary wall and enter CSF in low numbers
Local macrophages are stimulated by bacterial breakdown products and TNF and IL-I are produced
(fragments released = cytokine production)
TNF and IL-I initiate expression of selectin molecules on the endothelial cell surface.
Endothelial cell IL-8 causes neutrophils to express integrins
Neutrophils adhere to endothelium and enter CSF - breakdown of blood-brain barrier allows entry of albumin
CSF now contains bacteria, neutrophils and protein in significant quantities
What can pneumococci do to allow entry through the pharynx?
Pneumococci can switch capsule production on/ off
Makes it difficult for the pathogen to adhere
What does IL-I do in bacterial invasion of meningitis in the CSF?
Initiates expression on endothelial cells
What does IL-8 do in bacterial invasion of meningitis in the CSF?
They drive the expression of integrins on neutrophils
What does integrin do in bacterial invasion of meningitis in the CSF?
Causes cell-to-cell adhesion
How is a brain abscess diagnosed?
Fever
Headache
Vomiting
Photophobia
Rash
Abnormal behaviour
How is a brain abscess diagnosed?
(4 ways)
Lumbar puncture (needle into spine to extract for dialysis)
Computed tomography (generates 3D image from large series of 2D x-ray images)
Microbiologically - analysis of pus of CSF by microscope
Biochemistry - 3 samples of CSF
How is a brain abscess caused?
Infection of the brain tissue
Inflammatory response over several days forming abscess
Zone of swelling compressing the brain
How is a brain abscess diagnosed through biochemistry?
3 samples of CSF collected:
Protein analysis
Glucose determination
Microbiology
What are the distinguishing features of tuberculous?
Increased WCC
90% monocytes/ lymphocytes
Very high protein
Decreased glucose
What are the distinguishing features of viral meningitis?
Increased WCC (lower than bacterial)
95% lymphocytes
Protein: normal or increased
Glucose: normal
What are the distinguishing features of bacterial meningitis?
WCC - very very high
95% neutrophils
Protein increased
Glucose - massive decrease
What the basic parameters of WCC, protein & glucose in the blood?
WCC: <5/uL
Protein: <450 mg/L
Glucose: >40% blood
How is tetanus diagnosed?
Clinical symptoms and a medical history that shows no tetanus immunization
What are the signs of tetanus?
Trismus/ lockjaw - neck stiffness
Difficulty in swallowing
Elevated temperature, sweating, elevated blood pressure episodic rapid heart rate
Spasms
What gram is tetanus toxin?
Gram positive
What is the mode of action of tetanus toxin?
Acts internally as an endopeptidase cleaving the synaptic vesicle protein synaptovrevin.
Local failure of neuromuscular transmission can occur.
Affects spinal inhibitory neurons irreversibly where GABA and glycine are neurotransmitters
What is tetanus toxin coded by?
Coded by a plasmid
How is botulism diagnosed?
Demonstrates the botulinum toxin in patients serum or stool
Injecting serum or stool into mice and looking for signs of botulism that can be blocked by specific antisera
What is the botulism mode of action?
Toxin in ingested food is absorbed by the duodenum and enters the blood
Affects the neurotransmitter release of Ach
(end up flaccid so muscles cannot work)
What is Gullian-Barre syndrome?
Response to foreign antigens that are mis-targeted to host nerve tissues instead
Autoimmune disease triggered by previous infection
How is Guillain-Barre syndrome diagnosed?
Depends on typical clinical findings
Done by discounting
Rapidly evolving flaccid paralysis
Absence of fever
What are the targets in Guillain-Barre syndrome?
Gangliosides
What percentage of patients with Guillain-Barre syndrome have a history of acute infection? What are the further division of infection?
75% (within the past 1-4 weeks)
20-30% - Campylobacter jejuni
20-30% cytomegalovirus or Epstein-Barr virus
How is meningitis treated with Streptococcus pneumoniae infection?
Penicillin-sensitive: Penicillin G
Penicillin-intermediate: Ceftriaxone or cefotaxime
Penicillin-resistant: Ceftriaxone or cefotaxime and vancomycin
How is meningitis treated with Haemophilus influenzae infection?
Ceftriaxone or cefotaxime
How is meningitis treated with Neisseria meningitidis infection?
Penicillin-sensitive: Penicillin G or ampicillin
Penicillin-resistant: ceftriaxone or cefotaxime
Prophylaxis for close contacts
How is meningitis treated with gram negative bacilli infection?
Ceftriaxone or cefotaxime
How is meningitis treated with Listeria monocytogenes infection?
3-week course of IV ampicillin +gentamicin
How is meningitis treated with Streptococcus agalactiae infection?
Penicillin G or ampicillin
How is meningitis treated with Staphylococcus aureus infection?
Methicillin-sensitive = nafcillin
Methicillin-resistant = vancomycin
How is viral meningitis treated?
Patients with mild cases - only cause flu-like symptoms
Fluids, bed rest
Possibly anticonvulsants
Corticosteroids to reduce brain inflammation
How is a brain abscess treated?
Lowering increased intracranial pressure (osmotic diuretics & steroids, hyperventilating)
Intravenous antibiotics
Surgical aspiration or removal of brain abscess
How is mild tetanus infection treated?
5000 units tetanus immunoglobulin IV or IM
Metronidazole 500mg IV for 10 days
Diazepam (5-20mg per day)
Tetanus vaccination
How is severe tetanus infection treated?
Admission into intensive care
Tracheostomy - mechanical ventilation
Magnesium
How is Botulism infection treated?
Inducing passive immunity (anti toxin immunoglobulin)
Remove contaminated food
Wounds treated
Antibiotics (aminoglycosides or clindamycin)
How is Guillain-Barre syndrome treated?
Supportive care with monitoring of all vital functions
80% complete recovery
5-10% recover with severe motor disability
2-3% fatalities
