1. MICR 201 Microbiology for Health Related Sciences
Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010
Chapter 24: Infections of the central nervous system

2. Why is this chapter important?
Infections that affect the central nervous system (CNS) can be catastrophic and potentially lethal.
Neurons do not regenerate, hence loss of neurons due to infection leads to permanent damage.

3. MENINGITIS, ENCEPHALITIS, BRAIN ABSCESS IN GENERAL
Map for chapter 24
MENINGITIS, ENCEPHALITIS, BRAIN ABSCESS IN GENERAL

4. The human nervous system

5. Anatomy of the CNS CNS has two major parts
Brain
Spinal cord
Both surrounded by three layers of connective tissue – meninges.
Cerebrospinal fluid is found in the subarachnoid space.
The brain and spinal cord are protected from the body by the blood-brain barrier.
Protects against infectious disease
Some pathogens can pass through the blood- brain barrier

6. Effects of edema on the brain
Inflammation is one of the first and most formidable responses.
Always causes swelling
No room for swelling in the CNS.
Danger of brain herniation
Normal
Edema

7. Effects of infection on brain function
Infection can also affect proper brain function through:
Acidosis
Hypoxia
Destruction of neurons
Effects of infection can be profound and irreversible.
Blood-brain barrier can make it difficult to treat CNS infections.

8. Spread of microorganisms into the brain
Skull or backbone fractures
Medical procedures
Along peripheral nerves
Rabies virus, Herpes simplex virus
Blood or lymph
Infection originates from another body site
Neisseria meningitidis, Streptococcus pneumoniae
Must cross blood-brain barrier (capillaries)

9. The meninges and cerebrospinal fluid (CSF)
CSF is obtained by lumbar puncture
Used for diagnoses of meningitis and other CNS disorders
Never refrigerate CSF for culture

10. http://doctorgrasshopper. files. wordpress

11. Main types of infections of the nervous system
Meningitis
Inflammation of meninges
Headaches, stiff neck, light sensitivity, vomiting
Encephalitis
Inflammation of the brain
Mental disturbance, altered consciousness, seizures
Abscess
Focal symptoms depending on the location of the abscess
Often polymicrobial, anaerobes, amoeba

12. Bacterial meningitis Fever, headache, stiff neck, light sensitivity
Followed by nausea and vomiting
May progress to convulsions and coma
Bacterial meningitis can be severe and cause:
Brain damage
Hearing loss
Learning disability
Diagnostics with CSF
Neutrophil exudate
Low glucose
Latex agglutination for selected microorganisms
Culture
Important to know type of bacterium
Antibiotic therapy can prevent its spread.
Cephalosporines
Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Listeria monocytogenes
Escherichia coli
Streptococcus agalactiae
newborns

13. Waterhouse-Friderichsen Syndrome
Neisseria meningitidis sepsis
Septic Shock and bleeding into adrenal gland
Petechial skin lesions (bleeding into skin)
Death within 12 – 48 hours

14. Viral meningitis Most common cause of aseptic meningitis
Lymphocytic pleocytosis in CSF
Viral meningitis is generally less severe:
Fever less elevated
Usually resolves without treatment.
90% of cases caused by enterovirus
Also herpesvirus and mumps virus.

15. Fungal meningitis: Cryptococcus neoformans
Soil fungus associated with pigeon and chicken dropping (soil enriched for growth of fungus)
Transmitted by the respiratory route; spreads through blood to the CNS
Capsule
Mortality up to 30%
AIDS patients
Treatment: amphotericin B and flucytosine

16. Encephalitis Infection of the brain
Fever, head aches, chills and altered consciousness
Abnormal EEG, MRI

17. Viral encephalitis Western and Eastern equine Virus, West Nile Virus
Edema in right temporal lobe
Most common is arboviral encephalitis (transmitted by arthropods)
Western and Eastern equine Virus, West Nile Virus
Seasonal occurrence
Subclinical to severe symptoms including death
Herpes Virus 2 encephalitis
33 y old female patient presented with agitation, confusion, mutism, and fever

18. Amoeba meningoencephalitis
Free living amoeba found in fresh water
Infection during swimming
Entry via nasal mucosa and ascension into brain via olfactory nerve
Naegleri fowleri infection has near 100% fatality rate
Acantamoeba infection has better prognosis

19. Brain abscess
Cerebellar abscess in CT

20. Tetanus Many bacteria cause meningitis.
Increased cranial pressure and inflammation
Tetanus and botulism infections affect the CNS in different ways.
Produce exotoxins with an affinity for CNS tissue
Antibiotic therapy is ineffective once the exotoxin has been produced.

21. Specific diseases of the central nervous System
Tetanus
Poliomyelitis
Rabies
Trypansomiasis
Prion diseases (Chapter 8)

22. Tetanus Tetanus is caused by Clostridium tetani.
Gram-positive
Anaerobic
Rod shaped
Produces terminal endospores
Commonly found in soil
Spores enter tissue and germinate
Vegetative bacteria produce a neurotoxin call tetanospasmin or tetanus toxin

23. Tetanus toxin
Toxin enters the presynaptic terminals of the lower motor neurons.
From there, it gets into the CNS.
Toxin acts at the anterior horn cells in the spinal cord.
Blocks postsynaptic inhibition of the spinal motor reflexes
Produces spasmodic contraction of the muscles
Occur locally at first
May extend up and down the spinal cord

24. Tetanus Incubation period can vary between 4 days and several weeks.
The shorter the incubation period, the more severe the infection.
Tetanus leads to systemic muscle spasms.
Masseter muscle of the jaw usually first to be affected.
Mouth cannot be opened (sometimes called lockjaw)
Muscles for respiration and swallowing can eventually be compromised.
Severe cases can suffer from opisthotonus (head and heels move toward each other)
Death results from exhaustion and respiratory failure.
Mortality for untreated tetanus is %.

25. Tetanus ophistotonus

26. Tetanus treatment
Antibiotics are not effective once toxin is produced.
Neutralization of the toxin with human tetanus immunoglobulin is important.
Additional supportive measures are:
Maintenance of a dark, quiet environment
Sedation
Provision of an adequate airway for breathing
Vaccination with toxoid

27. Rabies Transmitted by animal bite
Virus multiplies in skeletal muscles, then brain cells causing encephalitis
Initial symptoms may include muscle spasms of the mouth and pharynx and hydrophobia, saliva overproduction
Develops into acute fatal encephalitis
Furious rabies: animals are restless then highly excitable
Paralytic rabies: animals seem unaware of surroundings
Pre-exposure prophylaxis: Vaccine
Post-exposure treatment: Vaccine + immune globulin

28. Rabies infection pathway

29. Polio Condition first known as infantile paralysis
Risk of paralysis actually increases with age.
Essentially nonexistent in most modern countries
There is an effective vaccine.
Still a major problem in developing countries.
Virus is an enterovirus with an affinity for the CNS.
Normally crosses the blood-brain barrier
Can also use axons or the perineural sheath of the peripheral nervous system
Motor neurons are particularly vulnerable.

30. Polio Various levels of neuronal destruction cause:
Necrosis of neural tissue
Infiltration by mononuclear cells, primarily lymphocytes
90% of poliomyelitis infections are very mild and subclinical.
Three types of polio infection:
Abortive poliomyelitis
Nonparalytic poliomyelitis (aseptic meningitis)
Paralytic poliomyelitis

31. Paralytic poliomyelitis
Occurs in 2% of persons infected
Characterized by asymmetric flaccid paralysis
Extent varies from case to case
Temporarily damaged neurons can regain function
Recovery can take six months
Paralysis persisting after this period is permanent

32. Polio vaccines Polio vaccine essentially wiped out this infection.
Two types of vaccine:
Inactive form – developed by Jonas Salk
Live attenuated form – developed by Albert Sabin

33. Success of poliomyelitis vaccination

34. Trypanosomiasis Protozoa Transmitted by tsetse fly Undulating membrane
Live in body fluids
Escape immune system by changing a surface protein (encoded by ~ different genes)
Enter brain and cause encephalitis
Sleeping disease
Fatal within years if left untreated

35. Chapter 24 key concepts
Central nervous system infections can be very dangerous and require immediate and aggressive therapy.
The central nervous system has a blood–brain barrier to prevent access of blood borne pathogens.
Pathogens that can move from the blood to the cerebrospinal fluid cause meningitis.
Most central nervous system infections result from bacteremia or viremia.
Many viruses have an affinity for the central nervous system.

36. Chapter 24 key concepts
Viral infection of the central nervous system can be acute or persistent.
Acute viral CNS infections include rabies, polio, and encephalitis.
Persistent viral infections include measles and rubella.
Prions cause persistent central nervous system infections.
Fungal infections of the central nervous system are primarily opportunistic and occur in immunocompromised individuals.
Parasitic infections of the central nervous system are usually caused by free-living amebas.

37. Final Examination – Wednesday, June 12, 2013
10:45am – 1:15pm
Lecture, Chapter End Self Study Questions
100 Multiple Choice Questions: 2 points each x 100 = 200 points
~65%: Chapters 14-26
~35%: Chapters 1-13
Please bring Scantron and No. 2 pencil

38. CORRECTION – Chapter Question
Chapter 22 Infections of the Digestive System
1. The most common source of gastrointestinal infection in the developed world is
A. Salmonella
B. Shigella
C. Escherichia
D. Campylobacter
E. Staphylococcus aureus
Correct answer is D. Campylobacter