• Separates blood cells from the myelin that surrounds nerve cells
  • Capillary walls that are normally "leaky" in all other parts of the body are constructed very tightly within the brain
  • Pinocytosis (process by which liquid or very small molecules move into a cell) through the capillary walls is impossible, although gases such as oxygen and extremely small molecules can move through
  • The only way for a substance to move from the blood into the brain is either attached to lipids or some special carrier molecule
• Is present in all vertebrate brains and is laid down during the first trimester of fetal development

1. Trauma
   • Skull/backbone fracture
   • Medical procedures
2. Altered permeability of blood-brain barrier
   • Inflammation
   • Bloodstream and lymphatic system are the conduits
3. Meningitis and encephalitis are the result

• Inflammation of the meninges
• Symptoms are fever, headache, and a stiff neck
  • Nuchal rigidity (stiff neck)
  • Brudzinki's - flexing the patient's neck causes flexion of hip and knee
  • Kernig's - flexing the patient's hip 90 degrees then extending the knee causes pain
• Caused by viruses, bacteria, fungi, and protozoa
  • Viruses are most common cause and cause a mild disease, especially in children under one
  • To develop bacterial meningitis, the invading organism must reach the subarachnoid space
    • This is usually through the blood, from the upper respiratory tract where the initial colonization has occurred
    • Less frequently, there is direct spread from an adjacent focus (middle ear infection, sinus infection, etc.)

1. First month of life: E. coli and Group B Streptococcus; L. monocytogenes
2. Between 1 and 2 months: Group B Streptococcus
3. After 2 months: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis
   • Recall that these 3 have a capsule
   • They adhere and colonize the nasopharynx of healthy children (normal flora)
     • It is thought that a concurrent viral infection predisposes these children to bacterial penetration of the nasopharynx epithelium and, thus, entry into the blood
     • Once in the bloodstream, the capsule enables the bacteria to resist phagocytosis
     • The bacteremic phase allows penetration of the CSF
     • The released endotoxin is the major pathogenic component, causing inflammatory mediators to be released (TNF, prostaglandins, leukotrienes)
     • The end result is damage to the blood-brain barrier (vasculitis), brain edema, impaired cerebral flow, and neuron injury

• Aerobic, Gram negative
• Normal throat flora
• Also causes pneumonia, epiglottitis, otitis media
• Has a capsule
  • Most virulent bacterium has type b capsule antigen
    • Called Hib
• Do not confuse with influenzae virus
  • Was named H. influenzae because thought to be cause of influenza pandemics of 1890
  • Was actually cause of secondary infections following virus infection
• Hib meningitis occurs mostly in children under 4
  • Hib vaccination starts at 2 months
  • Before vaccine, this was most common meningitis for kids

• Gram positive, diplococcus
• Normal throat flora
• Also causes pneumonia and otitis media
• Its capsule is most important element in pathogenicity
• S. pneumoniae meningitis occurs most commonly in children under 4 and in hospitalized elderly

• Gram negative, aerobic diplococcus
• Normal throat flora in some
• Most commonly occurs in children under two
• Outbreaks observed in closed populations
  1. Military barracks
  2. Schools
  3. Camps
  4. Institutions
• Three major serotypes
  1. A: epidemics in Africa, China, Middle East
  2. B: associated with sporadic cases
  3. C: common in US
• Encapsulated

• Gram positive rod; zoonotic
• Causes listeriosis
  • Mild, symptomless disease in healthy adults
  • In immunosuppressed, pregnant, or similarly compromised people, has a special affinity for colonization in CNS and placenta
    • Meningitis and spontaneous abortions occur
    • If baby is born, it may be septic or have meningitis
• Often foodborne
  • Dairy products
• Ingested by phagocytic cells where it proliferates
  • Has ability to move directly from 1 macrophage to next

• Causes tetanus
• Obligate anaerobe
• Endospore forming
• Gram positive rod
• Common in soil contaminated with animal fecal wastes
• Neurotoxin enters CNS via peripheral nerves/blood
  • Blocks the relaxation pathway of opposing muscle, such that both sets of muscles contract, resulting in muscle spasms
  • Bacteria do not move beyond infection site
  • No inflammation

• Causes botulism
• Obligate anaerobe
• Endospore forming
• Gram positive rod
• Found in soil and freshwater sediments
• Ingestion of endospores is only harmful in infants
  • Adult intestinal flora do not allow C. botulinum to colonize
• In anaerobic environments, microbes grow and produce an exotoxin specific for synaptic end of nerve
  • Blocks release of acetylcholine, necessary for nerve impulse transmission
  • Flaccid paralysis occurs

• Causes leprosy, AKA Hansen's Disease
• Acid fast rod
• Grows in PNS and skin cells
  • Has never been grown in artificial media
• Armadillos are a reservoir
• Long generation time of 12 days
• Microbe prefers outer, cooler parts of body
• Occurs in 2 forms
  1. Tuberculoid (neural)
     • Characterized by regions of skin that have lost sensation, surrounded by nodules
  2. Lepromatous
     • Skin cells are infected, and disfiguring nodules form all over body
     • Peripheral nerves are attacked by bacteria, leading to loss of feeling and protective withdrawal reflexes
     • Deformation of hand into clawed form; necrosis
• People who develop disease probably have a specific defect of cell-mediated immunity
• Untreated, Hansen’s Disease leads to disfigurements and social ostracism
• Sensory and motor loss, especially in limbs and face, are common
  • Afflicted areas are exposed to injury and infection, resulting in characteristic deformities

1. Poliomyelitis
2. Rabies
3. Arboviral encephalits

• Infection is initiated by ingestion of virus
  • Multiplies in throat and small intestine
  • From lymph nodes, enters blood, causing a viremia
  • Most cases stop here
    • Sometimes, virus penetrates walls of capillaries and enters CNS
    • Virus has affinity for motor nerve cells in upper spinal cord and multiplies here
      • Cells die; paralysis results
• Sabin vaccine: attenuated (live) virus
• Salk vaccine: inactivated virus

• Fatal encephalitis
• Incubation period is prolonged (50 days-6 years)
  • Long enough that immunity can be developed from a post-exposure vaccination
    • Series of antirabies vaccine and immune globulin injections
• Virus multiplies in skeletal and connective tissue
  • Remains localized here for months
• Then, it enters and moves along peripheral nerves to CNS, 15-100 mm/day
  • Once in PNS, not accessible to immune system until CNS begins to be destroyed

• Arboviruses are mosquito-borne viruses that cause encephalitis
  • Arthropod-borne virus = arbovirus
• Sentinel animals are tested periodically for antibodies
• Symptoms range from mild to severe
  • Chills, headache, fever
  • Mental confusion and coma
• Eastern equine encephalitis
• Western equine encephalitis
• St. Louis encephalitis
• West Nile virus
• Japanese B encephalitis

• Cryptococcus neoformans
• Cryptococcosis is disease
  • Initially an infection of lungs
  • May spread through blood to brain and meninges
  • Chronic, progressive, fatal meningitis

1. Trypanosomiasis
   • Tsetse fly is vector
   • Trypanosomes move from blood into CSF
   • Symptoms include decrease in physical activity/mental acuity, leading to coma/death
2. Naegleria Meninoencephalitis
   • Amoeba infecting nasal mucosa and proliferating in brain
   • Fatality 100%

1. Sheep scrapie
2. Creutzfeld-Jakob disease (CJD)
3. Bovine spongiform encephalopathy (BSE)
4. Bovine variant
5. Prion:
   • Aberrant form of a normal protein found on on nerve cell membranes that is heat and sterilization resistant
   • This altered form has the same sequence of amino acids
     • It differs in its conformation ("pleated" rather than helical)
     • This altered form is catalytic and "self-propagating," causing other normal forms of protein to change into the aberrant form
     • Because this form is very resistant to breakdown, it builds up, causing a "spongiform" type of damage in the brain

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