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  • 1. Chapter 22: Diseases of the Nervous System
    • The Nervous System is divided into 2 divisions
    • The central nervous system (CNS) is the brain and the spinal cord
    • The peripheral nervous system (PNS) – all the nerves that branch off the brain and spinal cord
  • 2. CNS
    • The brain and SC are covered with 3 membranes called meninges pg 644
    • Outer membrane = dura mater
    • Middle membrane = arachnoid mater
    • Inner membrane = pia mater
      • a. Between the pia and arachnoid mater is the subarachnoid space wh/ contains the cerebral spinal fluid
  • 3. CNS
    • The restricted permeability of blood vessels in the brain is called the blood-brain barrier
      • It prohibits most microbes from passing into the CNS
      • It also prohibits most drugs and antibiotics from passing into the CNS too
  • 4. CNS
    • Inflammation of the meninges = meningitis
    • Inflammation of the brain = encephalitis
    • Inflammation of the brain and meninges = meningoencephalitis
  • 5. Meningitis
    • Meningitis can be caused by bacteria, viruses, fungi, and protozoa
    • Bacterial meningitis is more severe than viral meningitis
    • Sx = fever, pounding HA, stiff neck, nausea, vomiting, convulsions, death
    • Dx = spinal tap to check the CSF, gram stain and culture the organism, check for increased # of WBCs
    • Tx = start with broad spectrum Abs and shift tx if needed after the dx
  • 6. Meningitis
    • 3 bacteria cause 70% of cases and 70% of deaths
    • Haemophilus influenzae (type b) Meningitis
      • Haemophilus influenzae – aerobic, gram neg rods, common microbiota of the throat
      • Transmitted by close contact and nose and throat discharges
      • Healthy adults can be carriers (reservoirs) for the bacterium
  • 7. Meningitis
    • d. Pathogenicity is due to capsular type b antigens so it is called Hib
      • 1) Hib vaccine is responsible for the decline in cases
      • e. most cases are in children from 6 months (after mother’s Ab protection weakens) to 4 years
      • f. tends to occur as sporadic outbreaks in day care and families and not as epidemics in general population
  • 8. Meningitis
    • 2. Meningococcal meningitis
    • a. Neisseria meningitidis – aerobic, gram neg, diplococcus with a capsule - virulence
    • b. the most serious form of acute meningitis – without tx 80% mortality
    • c. transmission is through close contact with droplets and secretions
    • 1) the bacteria gain entry to the nasopharynx and can colonize and the host can be an asymptomatic carrier or they can cause a throat infection that can lead to bacteremia and eventually meningitis
  • 9. Meningitis
    • 2. Meningococcal meningitis
    • d. sxs begin as a flu like upper respiratory infection which spreads to the bloodstream and the bloodstream takes the bacteria to the meninges
    • 1) the sxs are caused by an endotoxin released into the circulation. The endotoxin causes the production of cytokines (WBCs) which damage blood vessels causing a rash that does not blanch (petechiae) on the trunk and appendages
    • e. meningococcus are associated epidemics in schools and the military
    • f. tx is intravenous antibiotics
    • g. A vaccine is available
  • 10. Meningitis
    • 3. Pneumococcal meningitis
    • a. Streptococcus pneumoniae – G + cocci that appear end to end (diplococcus), encapsulated, alpha hemolytic on blood agar
    • b. respiratory portal of entry and is a normal microbiota of the nasopharynx
    • 1) it can penetrate the respiratory mucosa and gain access to the bloodstream and enter the meninges
    • 2) 70% population are healthy carriers
  • 11. Meningitis
    • 3. Pneumococcal meningitis
    • c. now it is the leading cause of bacterial meningitis (since the Hib vaccine)
    • d. mortality rate children – 30%, elderly- 80%
    • e. vaccines are recommended for kids under 2 – side effect = < in otitis media
    • f. increasing #s of Ab resistant strains
  • 12. Meningitis
    • Differential dx: 3 bacterial meningitis
      • Haemophilus influenza – G neg, tiny rod
      • Neisseria meningitidis – G neg coccus, rash that doesn’t fade
      • Streptococcus pneumoniae – G pos diplococcus, alpha hemolytic
  • 13. Listeriosis
    • Listeria monocytogenes – small G + rods that are named for the proliferation of monocytes in affected animals
    • Disease may occur as:
      • a. listeric meningitis – HAs, stiff neck, delirium, coma
      • b. blood disease accompanied by a high # of monocytes
      • c. infection of the uterus with flu-like sxs, if women is pg the fetus may abort or be stillborn – 60% infant mortality
  • 14. Listeriosis
    • 3. Virulence factor – it is not destroyed and can proliferate in phagocytes
    • 4. Listeria is found in the soil and in the intestine of animals
    • 5. It is transmitted mainly by food such as cold cuts and soft cheese
    • a. is one of the few pathogens that can grow at refrigerator temperatures
    • 6. Pregnant women are at risk and are cautioned not to eat soft, unpasturized cheeses
    • 7. Dx: culture pathogen from blood or CSF
    • 8. Tx: Abs – Penicillin G – 1 st choice
  • 15. Tetanus (lockjaw)
    • Clostridium tetani – G +, spore forming, anaerobic rod found in the soil
    • Transmission by soil contaminated puncture wound – thorn, animal bite
      • a. spores enter the wound and revert to multiplying bacilli that produce the 2 nd most powerful toxin known to science
      • 1) neurotoxin = tetanospasm exotoxin
  • 16. Tetanus (lockjaw)
    • 3. The toxin acts by blocking the inhibition of muscle contraction.
    • 4. The toxin provokes sustained and uncontrolled opposing muscle contractions and spasms occur throughout the body = spastic paralysis
    • 5. The first sx is clenching of the jaw = trismus, followed by extreme arching of the back, flexion of arms and extension of legs
    • a. spasms can result in a fractured spine
    • 6. Death is due to paralysis of respiratory ms and respiratory arrest
  • 17. Tetanus (lockjaw)
    • 7. Tx = sedatives, muscle relaxants, px placed in dark, quiet room, penicillin to kill bacteria, tetanus antitoxin to neutralize toxin
    • 8. Prevention = tetanus toxoid vaccine, need booster every 10 years
    • a. a toxoid is an inactivated toxin that stimulates Ab production to inactivate the toxin
  • 18. Botulism
    • Clostridium botulinum – spore forming, anaerobic, G + rod, found in the soil
    • Produces the most potent exotoxin known
      • 1 oz. of toxin can kill all the people of the US
  • 19. Botulism
    • 3. Three major forms of botulism
    • a. food – borne in children and adults caused by ingestion of preformed toxins
    • 1) improperly home canned non acidic foods
    • 2) nausea and vomiting precede the neurological sxs
    • 3) the neurotoxin inhibit the release of acetylcholine = a neurotransmitter that signals ms contraction
  • 20. Botulism
    • 3. a. food – borne
    • 4) toxin results in flaccid paralysis – affects the muscles of the head first and include double vision, difficulty swallowing, dizziness and nausea – may die from respiratory and cardiac failure
    • b. Infant botulism – spores in raw honey
    • 1) immature state of neonate intestine and microbiota allow spores to germinate
    • 2) infants – floppy baby syndrome or flaccid paralysis
    • 3) children under 1 yr. shouldn’t eat honey
  • 21. Botulism
    • c. Wound botulism – spores enter wound or puncture , IV users
    • 1) sxs are similar to food borne botulism
    • 4. There are several different serological types of toxins with A,B and E associated with human disease and A being the most lethal
    • 5. Tx = large doses of antitoxin to neutralize the toxin, respirators for life support
    • 6. Botox – wrinkles, sweating, for excessive ms contraction conditions
    • 7. Potential bioterrorism weapon
  • 22. Leprosy (Hansen’s Disease)
    • Mycobacterium leprae – acid fast rod
      • Generation time = 12 days
      • Can’t be cultured in lab media so was grown in armadillos, now grown in the foot pads of mice
      • Prefers, outer cooler parts of the body
      • d. Eventually invades the peripheral nerves where it causes nerve damage
  • 23. Leprosy (Hansen’s Disease)
    • 2. Two main forms of leprosy
    • a. tuberculoid (neural) form – regions of the skin have lost sensation and are surrounded by a border of nodules
    • a. occurs in people with effective immune responses and sometimes resolves spontaneously
  • 24. Leprosy (Hansen’s Disease)
    • 2. Two main forms of leprosy
    • b. lepromatous or progressive form
    • 1) responsible for the disfigurement of the skin and bones
    • 2) px have the least effective cell mediated immune response and the disease has progressed from the tuberculoid stage
    • 3) shed large #s of bacteria in their nasal secretions and exudates of their lesions
  • 25. Leprosy (Hansen’s Disease)
    • 3. Leprosy isn’t very contagious, need intimate, prolonged contact
    • a. px can be made non-contagious in a few days with sulfone drugs so px are no longer segregated, 1870 – Molokai
    • b. incubation period is 3 – 6 years
    • 4. Dx = acid fast test, lepromin test
    • a. lepromin test = injection of killed M. leprae into the skin
    • b. a positive test indicates tuberculoid leprosy and a negative test indicates lepromatous leprosy
  • 26. Viral diseases of the nervous system
    • Poliomyelitis (polio) is an acute viral infection of the CNS that can cause neuromuscular paralysis
    • Poliovirus is a small RNA virus of the Genus Enterovirus
    • Transmission is fecal oral route through food or water contaminated with feces that contain the virus
  • 27. poliomyelitis
    • 3. Virus multiplies in the throat and small intestine causing sore throat and nausea and for 90% of the individuals the infection progresses no further
    • 4. In some cases the virus reaches the bloodstream by way of the lymph nodes causing viremia
    • 5. In about 1% of cases (viremia) the virus penetrates the capillary walls and enters the CNS and causes the paralytic form of poliomyelitis
  • 28. poliomyelitis
    • 6. Outbreaks are more pronounced during the summer and fall and polio is still endemic to parts of the developing world
    • Signs and symptoms
    • 1. non-paralytic – the majority are asymptomatic or mild sx ex. HA, sore throat, fever, nausea, myalgia
  • 29. poliomyelitis
    • Signs and symptoms
    • 2. Paralytic form
    • a. virus affects motor neurons in the spinal cord causing flaccid paralysis to ms of the tongue, face, neck and limbs
    • b. paralysis of the diaphragm may lead to death - iron lung
    • c. unused ms atrophy and severe deformities of trunk and limbs develop
    • d. sensory nerves are unaffected so crippled limbs are painful
  • 30. Poliomyelitis
    • Diagnosis
    • Suspected when epidemics of neuromuscular disease occur in summer in temperate climates
    • RNA fingerprinting to see if is wild strain or vaccine strain
    • Isolation of virus from feces or throat secretions
      • a. cell cultures inoculated – look for CPE
  • 31. Poliomyelitis
    • Prevention and tx
    • 1. Alleviate pain, artificial ventilation
    • 2. Vaccination with inactivated poliovirus vaccine – 1954 Jonas Salk
    • a. trivalent = combo of 3 serotypes of virus, Abs decline with time
    • b. now use enhanced inactivated vaccine in US
    • 3. Sabin oral vaccine – 1963 – trivalent attenuated virus – no longer used
    • a. can revert to wild type
  • 32. Rabies
    • Rabies is a zoonotic disease characterized by fatal encephalitis
    • Causative agent – genus Lyssavirus in the family Rhabdoviridiae
      • a. bullet shaped single stranded RNA virus
    • Highest mortality rate of any human disease once sxs have materialized
      • a. few people have recovered from active case of rabies
  • 33. Rabies
    • 4. Transmission and Epidemiology
    • a. occurs in most warm blooded animals
    • b. virus enters tissue through a skin wound contaminated with body fluids from an infected animal
    • 1) virus proliferates in PNS and moves towards the CNS
    • 2) virus has adapted and can grow in epidermal cells and then enter a peripheral nerve, so can contact by petting infected animal
    • c. several cases transmitted through transplanted body tissue esp. corneas
  • 34. Rabies
    • 5. Signs and symptoms
    • a. incubation period = 1-3 months, shorter if the wound is close to the brain (face, scalp, neck)
    • b. prodromal phase – fever, nausea, vomiting, HA, fatigue
    • c. furious rabies – 1 st signs = period of agitation, disorientation, seizures, twitching
        • 1) Spasms of the mouth and pharynx muscles lead to severe pain when swallowing which leads to hydrophobia (fear of H2O)
  • 35. Rabies
    • 5. Signs and symptoms
    • d. paralytic form – px not hyperactive but paralyzed, disoriented, stupor
    • e. both forms of rabies can lead to coma and death within days
    • 6. Dx
    • a. px alive – immunofluorescence studies for viral antigens detected in saliva, serum, or CSF
    • b. After death – microscopic studies of brain tissue show neuron cells w/ intracytoplasmic inclusions called Negri bodies, fluorescent Ab test on brain tissue
  • 36. Rabies
    • 7. Prevention and Tx
      • If contact with a rabid animal – px is given a series of antirabies vaccine and human rabies immune globulin injections to stop the spread of virus
      • Vaccinate domestic and wild animals
  • 37. Arboviral encephalitis
    • Arboviral encephalitis is caused by mosquito-borne viruses
      • Encephalitis = acute inflammation of the brain
      • Arbo is short for arthropod borne
    • Caused by a series of RNA viruses
    • Sxs are common to the different clinical types = chills, severe HA, sudden very high fever wh/ can progress to mental confusion, coma and rapid death
    • There are many forms of the disease and many vectors
  • 38. Arboviral encephalitis
    • 5. Birds are natural reservoirs of the virus and spread them during annual migrations
    • 6. Western and Eastern Equine encephalitis affects horses as well as humans
    • 7. West Nile Virus is an emerging virus that was reported in the US in 1999.
    • a. most cases are mild but polio like paralysis and encephalitis can cause death in elderly
    • 8. Dx is made by serological tests
  • 39. Fungal Diseases of the Nervous System
    • Cryptococcosis
    • Cryptococcus neoformans – yeast like fungi
    • Transmission is associated with inhalation of dried yeast cells from pigeon (and chicken) droppings
      • Usually in urban areas
    • Initial infection of lungs and is usually subclinical and resolves rapidly
  • 40. Fungal Diseases of the Nervous System
    • Cryptococcosis
    • 3. a. opportunistic to AIDS px and those on steroid tx
    • b. can spread to the blood and then the brain and meninges causing chronic meningitis wh/ is often progressive fatal if left untreated
    • 4. Dx = latex agglutination test to detect cryptococcal Ags in serum or CSF
    • 5. Tx = cocktail of Amphotericin B + flucytosine – still a 30 % mortality rate
  • 41. Protozoan Disease of the Nervous System
    • African Trypanosomiasis = sleeping sickness
    • 2 subspecies of Trypanosoma brucei infect humans
      • When introduced into the blood stream the protozoa invade the brain tissue causing a coma like condition
  • 42. African Trypanosomiasis
    • 2. Trypanosoma brucei gambiense – West African trypanosomiasis
    • a. few sx for weeks or months
    • b. sx = fever, HA, deterioration of CNS
    • c. without tx – coma and death
    • 3. Trypanosoma brucei rhodesiense - East African trypanosomiasis
    • a. humans and domestic animals become acutely ill
    • b. sx within a few days
    • c. death within a few weeks or months
  • 43. African Trypanosomiasis
    • 4. Transmission is by a bite of the tse tse fly – a vector who becomes infected with the protozoan Trypanosoma after biting an infected host (animal, human)
    • a. the trypanosome multiplies in the fly’s gut and migrates to the fly’s salivary glands where it develops into the infectious stage
    • b. the fly bites a new host and releases a fully formed stage of the parasite into the wound
    • 1) the pathogen moves into the lymphatics and blood
  • 44. African Trypanosomiasis
    • 5. Virulence factor – when the host starts producing IgM Abs to the trypanosome the trypanosome changes it’s surface Ags making the existing IgM ineffective
    • a. when the host makes new IgM Abs to the new trypanosome Ags it changes the Ag again (antigenic shift)
    • 6. Dx = microscopic exam of blood and CSF
    • 7. Prevention = vector control – release sterile males
  • 45. Trypanosome in blood smear
  • 46. Tse Tse Fly
  • 47. Amebic Meningoencephalitis
    • Caused by 2 species of protozoa
    • Primary amebic meningoencephalitis
      • Pathogen = Naegleria fowleri
      • World wide, few cases in US
      • Transmitted by swimming in ponds, streams usually to children
      • Initially infects the nasal mucosa and later penetrates the brain and proliferates
      • Fatality rate nearly 100% within days after sx appear
      • Dx is made at autopsy
  • 48. Amebic Meningoencephalitis
    • 2. Granulomatous amebic encephalitis
    • a. pathogen = Acanthamoeba sp.
    • b. transmission = direct contact
    • c. portal of entry = broken skin, conjunctiva
    • d. chronic, slowly progressive, fatal in weeks or months
    • e. multiple lesions (granulomas around amoeba) form in the brain, lungs
  • 49. Nervous System Diseases caused by prions
    • Long incubation times (years)
    • CNS damage slowly progressive, spongiform degeneration of the brain
    • Transmission is direct contact with infected tissue
    • Dx = biopsy or image of brain
    • Tx = none
  • 50. Nervous System Diseases caused by prions
    • Sheep scrapie
    • Animal scrapes itself against fences and wall until it is raw
    • Animal gradually loses motor control and dies
    • Can be passed to another animal experimentally by injection of infected brain tissue
  • 51. Nervous System Diseases caused by prions
    • Creutzfeldt-Jakob Disease (CJD) – rare human disease similar to scrapie
    • Often occurs in families suggesting a genetic component
    • Can be transmitted by corneal transplants, injection of growth hormone from human tissue
    • Boiling, radiation, autoclaving are not reliable for destroying prions
    • New Guinea tribes suffered from spongiform encephalopathy disease called kuru
      • Transmitted by cannibalism – eat brain
  • 52. Nervous System Diseases caused by prions
    • 5. Bovine spongiform encephalopathy (BSE)
    • a. aka Mad cow disease
    • b. US prohibits the use of meat from downer animals and the use of animal protein for feed supplements
    • c. disease can be passed to humans