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

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.

Why is this chapter important?

Map for chapter 24

MENINGITIS, ENCEPHALITIS, BRAIN ABSCESS IN GENERAL

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The human nervous system

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

Anatomy of the CNS

Inflammation is one of the first and most formidable responses.◦ Always causes swelling

No room for swelling in the CNS. Danger of brain herniation

Effects of edema on the brain

Normal Edema

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.

Effects of infection on brain function

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)

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Spread of microorganisms into the brain

CSF is obtained by lumbar puncture

Used for diagnoses of meningitis and other CNS disorders

Never refrigerate CSF for culture

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The meninges and cerebrospinal fluid (CSF)

10http://doctorgrasshopper.files.wordpress.com/2010/01/lots-of-lumbar-puncture-pics.jpg

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

Main types of infections of the nervous system

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

Bacterial meningitis

Streptococcus pneumoniaeHaemophilus influenzaeNeisseria meningitidisListeria monocytogenesEscherichia coliStreptococcus agalactiae

newborns

Neisseria meningitidis sepsis

Septic Shock and bleeding into adrenal gland

Petechial skin lesions (bleeding into skin)

Death within 12 – 48 hours

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Waterhouse-Friderichsen Syndrome

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.

Viral meningitis

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

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Fungal meningitis: Cryptococcus neoformans

Infection of the brain

Fever, head aches, chills and altered consciousness

Abnormal EEG, MRI

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Encephalitis

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

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Viral encephalitisEdema in right temporal lobe

33 y old female patient presented with agitation, confusion, mutism, and fever

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

Amoeba meningoencephalitis

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Brain abscess

Cerebellar abscess in CT

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.

Tetanus

Tetanus Poliomyelitis Rabies Trypansomiasis Prion diseases (Chapter 8)

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Specific diseases of the central nervous System

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

Tetanus

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

Tetanus toxin

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 15 - 60%.

Tetanus

Tetanus ophistotonus

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

Tetanus treatment

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

Rabies

Rabies infection pathway

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.

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

Polio

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

Paralytic poliomyelitis

Polio vaccine essentially wiped out this infection.

Two types of vaccine:◦ Inactive form – developed by Jonas Salk◦ Live attenuated form – developed by Albert Sabin

Polio vaccines

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Success of poliomyelitis vaccination

Protozoa Transmitted by

tsetse fly Undulating

membrane Live in body fluids Escape immune

system by changing a surface protein (encoded by ~ 1000 different genes)

Enter brain and cause encephalitis◦ Sleeping disease◦ Fatal within 2- 3

years if left untreated

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Trypanosomiasis

http://www.cdc.gov/parasites/sleepingsickness/

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.

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.

Chapter 24 key concepts

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

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