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