Chpt.22.

Chapter 22: Diseases of the Nervous System

The Nervous System is divided into 2 divisions

1. The central nervous system (CNS) is the brain and the spinal cord

2. The peripheral nervous system (PNS) – all the nerves that branch off the brain and spinal cord

CNS

The brain and SC are covered with 3 membranes called meninges pg 644

1. Outer membrane = dura mater

2. Middle membrane = arachnoid mater

3. Inner membrane = pia matera. Between the pia and arachnoid mater is the

subarachnoid space wh/ contains the cerebral spinal fluid

CNS

1. The restricted permeability of blood vessels in the brain is called the blood-brain barrier

a. It prohibits most microbes from passing into the CNS

b. It also prohibits most drugs and antibiotics from passing into the CNS too

CNS

Inflammation of the meninges = meningitis

Inflammation of the brain = encephalitis

Inflammation of the brain and meninges = meningoencephalitis

Meningitis

Meningitis can be caused by bacteria, viruses, fungi, and protozoa

Bacterial meningitis is more severe than viral meningitis

1. Sx = fever, pounding HA, stiff neck, nausea, vomiting, convulsions, death

2. Dx = spinal tap to check the CSF, gram stain and culture the organism, check for increased # of WBCs

3. Tx = start with broad spectrum Abs and shift tx if needed after the dx

Meningitis

3 bacteria cause 70% of cases and 70% of deaths

1. Haemophilus influenzae (type b) Meningitis

a. Haemophilus influenzae – aerobic, gram neg rods, common microbiota of the throat

b. Transmitted by close contact and nose and throat discharges

c. Healthy adults can be carriers (reservoirs) for the bacterium

Meningitis

1. 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

Meningitis

2. Meningococcal meningitisa. Neisseria meningitidis – aerobic, gram neg, diplococcus with a capsule - virulenceb. the most serious form of acute meningitis – without tx 80% mortalityc. 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

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

Meningitis

3. Pneumococcal meningitisa. Streptococcus pneumoniae – G + cocci that appear end to end (diplococcus), encapsulated, alpha hemolytic on blood agarb. 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

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

Meningitis

• Differential dx: 3 bacterial meningitisHaemophilus influenza – G neg, tiny rod

Neisseria meningitidis – G neg coccus, rash that doesn’t fade

Streptococcus pneumoniae – G pos diplococcus, alpha hemolytic

Listeriosis

1. Listeria monocytogenes – small G + rods that are named for the proliferation of monocytes in affected animals

2. Disease may occur as:a. listeric meningitis – HAs, stiff neck, delirium, comab. blood disease accompanied by a high # of monocytesc. infection of the uterus with flu-like sxs, if women is pg the fetus may abort or be stillborn – 60% infant mortality

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 animals5. It is transmitted mainly by food such as cold cuts and

soft cheesea. is one of the few pathogens that can grow at

refrigerator temperatures6. Pregnant women are at risk and are cautioned not to eat

soft, unpasturized cheeses7. Dx: culture pathogen from blood or CSF8. Tx: Abs – Penicillin G – 1st choice

Tetanus (lockjaw)

1. Clostridium tetani – G +, spore forming, anaerobic rod found in the soil

2. Transmission by soil contaminated puncture wound – thorn, animal bite

a. spores enter the wound and revert to multiplying bacilli that produce the 2nd most powerful toxin known to science

1) neurotoxin = tetanospasm exotoxin

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 spine6. Death is due to paralysis of respiratory ms and

respiratory arrest

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

Botulism

1. Clostridium botulinum – spore forming, anaerobic, G + rod, found in the soil

2. Produces the most potent exotoxin known

a. 1 oz. of toxin can kill all the people of the US

Botulism

3. Three major forms of botulisma. food – borne in children and adults

caused by ingestion of preformed toxins1) improperly home canned non acidic foods2) nausea and vomiting precede the neurological sxs3) the neurotoxin inhibit the release

of acetylcholine = a neurotransmitter that signals ms contraction

Botulism

3. a. food – borne4) 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 failureb. 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

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

Leprosy (Hansen’s Disease)

1. Mycobacterium leprae – acid fast roda. Generation time = 12 days

b. Can’t be cultured in lab media so was grown in armadillos, now grown in the foot pads of mice

c. Prefers, outer cooler parts of the body

d. Eventually invades the peripheral nerves where it causes nerve damage


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


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


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

Viral diseases of the nervous system

Poliomyelitis (polio) is an acute viral infection of the CNS that can cause neuromuscular paralysis

1. Poliovirus is a small RNA virus of the Genus Enterovirus

2. Transmission is fecal oral route through food or water contaminated with feces that contain the virus

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

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

poliomyelitis

Signs and symptoms2. 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

Poliomyelitis

Diagnosis 1. Suspected when epidemics of

neuromuscular disease occur in summer in temperate climates

2. RNA fingerprinting to see if is wild strain or vaccine strain

3. Isolation of virus from feces or throat secretions

a. cell cultures inoculated – look for CPE

Poliomyelitis

Prevention and tx1. Alleviate pain, artificial ventilation2. 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

Rabies

1. Rabies is a zoonotic disease characterized by fatal encephalitis

2. Causative agent – genus Lyssavirus in the family Rhabdoviridiae

a. bullet shaped single stranded RNA virus

3. Highest mortality rate of any human disease once sxs have materialized

a. few people have recovered from active case of rabies

Rabies

4. Transmission and Epidemiologya. occurs in most warm blooded animalsb. 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 animalc. several cases transmitted through transplanted body tissue esp. corneas

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 – 1st 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)

Rabies

5. Signs and symptoms d. paralytic form – px not hyperactive but paralyzed, disoriented, stupore. 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 CSFb. After death – microscopic studies of brain tissue show neuron cells w/ intracytoplasmic inclusions called Negri bodies, fluorescent Ab test on brain tissue

Rabies

7. Prevention and Txa. 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

b. Vaccinate domestic and wild animals

Arboviral encephalitis

1. Arboviral encephalitis is caused by mosquito-borne viruses

a. Encephalitis = acute inflammation of the brainb. Arbo is short for arthropod borne

2. Caused by a series of RNA viruses3. 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

4. There are many forms of the disease and many vectors

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

Fungal Diseases of the Nervous System

Cryptococcosis 1. Cryptococcus neoformans – yeast like

fungi2. Transmission is associated with

inhalation of dried yeast cells from pigeon (and chicken) droppings

a. Usually in urban areas

3. Initial infection of lungs and is usually subclinical and resolves rapidly

Fungal Diseases of the Nervous System

Cryptococcosis3. 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

Protozoan Disease of the Nervous System

African Trypanosomiasis = sleeping sickness

1. 2 subspecies of Trypanosoma brucei infect humans

a. When introduced into the blood stream the protozoa invade the brain tissue causing a coma like condition

African Trypanosomiasis

2. Trypanosoma brucei gambiense – West African trypanosomiasisa. few sx for weeks or monthsb. sx = fever, HA, deterioration of CNSc. without tx – coma and death

3. Trypanosoma brucei rhodesiense - East African trypanosomiasisa. humans and domestic animals become acutely illb. sx within a few daysc. death within a few weeks or months


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 stageb. 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


5. Virulence factor – when the host starts producing IgM Abs to the trypanosome the trypanosome changes it’s surface Ags making the existing IgM ineffectivea. 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 CSF7. Prevention = vector control – release sterile

males

Trypanosome in blood smear

Tse Tse Fly

Amebic Meningoencephalitis

Caused by 2 species of protozoa1. Primary amebic meningoencephalitis

a. Pathogen = Naegleria fowlerib. World wide, few cases in USc. Transmitted by swimming in ponds, streams usually

to childrend. Initially infects the nasal mucosa and later

penetrates the brain and proliferatese. Fatality rate nearly 100% within days after sx

appearf. Dx is made at autopsy

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

Nervous System Diseases caused by prions

1. Long incubation times (years)

2. CNS damage slowly progressive, spongiform degeneration of the brain

3. Transmission is direct contact with infected tissue

4. Dx = biopsy or image of brain

5. Tx = none


Sheep scrapie

1. Animal scrapes itself against fences and wall until it is raw

2. Animal gradually loses motor control and dies

3. Can be passed to another animal experimentally by injection of infected brain tissue


Creutzfeldt-Jakob Disease (CJD) – rare human disease similar to scrapie

1. Often occurs in families suggesting a genetic component

2. Can be transmitted by corneal transplants, injection of growth hormone from human tissue

3. Boiling, radiation, autoclaving are not reliable for destroying prions

4. New Guinea tribes suffered from spongiform encephalopathy disease called kuru

a. Transmitted by cannibalism – eat brain


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

Chpt.22.

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