Chapter 22
Microbial Diseases
of the Nervous System
Structure and Function of the Nervous System
The central nervous system (CNS) consists of the brain and spinal cord. It is the control center that
picks up sensory information from the environment and, after interpreting it, sends out impulses to
coordinate body activities. The peripheral nervous system consists of all the nerves branching from the
brain and spinal cord. These nerves are the communication lines between the CNS and the body, and
the external environment. The skull protects the brain and the backbone protects the spinal cord; both
the brain and spinal cord are covered by the meninges (Figure 22.1). The meninges consist of the dura
Cerebrum
Skull bone
Skull bone
Subarachnoid
space
(cerebrospinal
fluid)
Dura mater
Arachnoid
mater
Cranial
meninges
Pia mater
Blood vessel
Cerebrum
Cerebellum
Spinal cord
Dura mater
Arachnoid
Spinal
mater
meninges
Pia mater
Subarachnoid space
Subarachnoid space
of spinal cord
FIGURE 22.1 The meninges and cerebrospinal fluid. The meninges, whether cranial or spinal, consist of three
layers: dura mater, arachnoid mater, and pia mater. Between the arachnoid mater and the pia mater is the subarachnoid space, in which cerebrospinal fluid circulates. Note how the cerebrospinal fluid is vulnerable to contamination by microbes carried in the blood that are able to penetrate the blood–brain barrier at the walls of the
blood vessels.
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mater (outermost layer), the arachnoid mater (middle layer), and the pia mater (innermost layer).
Cerebrospinal fluid circulates in the space between the pia mater and the arachnoid layers (subarachnoid
space). The blood–brain barrier consists of capillaries that permit certain substances to pass from the
blood to the brain but that prevent others from passing. Microorganisms can gain access to the CNS by
trauma (accidental, or medical procedures such as spinal taps). Also, microorganisms may enter by
movement along peripheral nerves or by the bloodstream and lymphatic system. An inflammation of
the meninges is meningitis; an inflammation of the brain is encephalitis. Antibiotics often are unable to
cross the blood–brain barrier.
Bacterial Diseases of the Nervous System
Bacterial Meningitis
The three major types of bacterial meningitis are meningococcal meningitis, caused by Neisseria meningitidis; pneumococcal meningitis, caused by Streptococcus pneumoniae; and Haemophilus influenzae meningitis. Nearly 50 other bacteria have been reported to cause meningitis, as can fungi, viruses, and protozoa.
Meningitis patients complain of headache and have symptoms of nausea and vomiting. This may proceed to convulsions, coma, and even death.
Haemophilus influenzae Meningitis.
Haemophilus influenzae type b, the main serological type of
medical importance, is an aerobic, gram-negative bacterium. It is often a member of the normal throat
flora. The name derives from the need for factors from lysed red blood cells and the erroneous idea at
one time that it was the cause of influenza. It is the most common cause of bacterial meningitis among
children under four years of age. The incidence has been decreasing since the introduction of a vaccine
(Hib vaccine).
Neisseria meningitidis (Meningococcal Meningitis). Meningococcal meningitis is caused by the
bacterium Neisseria meningitidis, an aerobic, gram-negative bacterium. It is a frequent inhabitant of the
throat behind the nose, and a throat infection can lead to bacteremia followed by meningitis. Symptoms
are thought to be due to endotoxins produced by the bacteria, which can also sometimes enter the bloodstream and cause serious tissue damage. The disease primarily affects the very young, with the highest
incidence in the first year. Serological group A causes widespread epidemics in Africa, China, and the
Middle East. In the United States group C predominates.
Streptococcus pneumoniae Meningitis (Pneumococcal Meningitis). Pneumococcal meningitis
is caused by Streptococcus pneumoniae, a common inhabitant of the nasopharyngeal system. About half
the cases are among children aged one month to four years. The mortality rate is high. A conjugated vaccine was recently introduced.
Diagnosis and Treatment of Bacterial Meningitis. Chemotherapy must be prompt; broadspectrum third-generation cephalosporins are the first choices. Diagnosis requires a sample of cerebrospinal fluid obtained by a spinal tap. Gram stains and cultures can be made. Serological tests such as
rapid latex agglutination tests are used.
Listeriosis. Listeria monocytogenes, the gram-positive rod causing listeriosis, is widely distributed,
mainly in animal feces. Listeriosis is a mild disease in most adults but is more serious in the immunosuppressed, including cancer patients. When infecting a pregnant woman it often causes abortion or serious damage or death to the fetus. The organism proliferates within phagocytic cells and grows at refrigeration temperatures. It is a major concern in the food industry.
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Tetanus
The cause of tetanus is an obligately anaerobic, endospore-forming, gram-positive rod, Clostridium
tetani. It is a common soil organism, particularly soil contaminated with animal fecal wastes. Growth of
C. tetani in wounds releases tetanospasmin, a neurotoxin that blocks the nerve pathway that signals
muscle relaxation. Spasms result as opposing muscle sets contract (spastic paralysis). Contraction of the
jaw muscles prevents opening of the mouth (lockjaw). In extreme cases the body bows backwards
(opisthotonos). Death from respiratory failure occurs in many cases. Most people in the United States
have been immunized by the tetanus toxoid included in the DTaP (diphtheria, tetanus, acellular pertussis) vaccine. A booster of toxoid may be given when a dangerous wound is received; this booster causes
the body to renew its immunity level in a rapid anamnestic response. If the patient has had no previous
immunity, toxoid may not cause a rapid enough appearance of antibodies, and a temporary immunity
can be provided by tetanus immune globulin (TIG) pooled from immunized humans.
Botulism
The cause of botulism is an obligately anaerobic, endospore-forming gram-positive bacterium,
Clostridium botulinum, found in soil and freshwater sediments. The exotoxin produced is a neurotoxin
that blocks the transmission of nerve impulses across the synapses, causing progressive flaccid paralysis.
Symptoms typically appear in a day or two. Most botulism results from attempts at preservation by
heat that fail to eliminate the C. botulinum endospore but provide anaerobic conditions for its growth.
There are several toxin types. Type A toxin is found mostly in the western United States. It is proteolytic and probably the most virulent. Type B toxin is less virulent, and both proteolytic and nonproteolytic strains occur. Type B is responsible for most outbreaks in the eastern United States and Europe.
Type E toxin is produced by a strain found in wet soils and sediments and often involves seafood. This
organism is nonproteolytic, its endospores are less heat-resistant, and the toxin can be produced at
refrigerator temperatures. The botulinal toxin is heat-labile; that is, it is destroyed by boiling. It is not
formed in acid foods below pH 4.7. Nitrates are included in some meat products to prevent bacterial
growth following germination of endospores. For treatment, antitoxins of trivalent ABE type are available, but they do not affect attached toxins. Toxin identification can be done by inoculating mice with
the suspected toxin; if the mice who survive the inoculation are protected by, for example, type A antitoxins, then the suspected toxin is considered to be type A. Wound botulism can occur from C. botulinum growth in wounds, and infant botulism may occur from growth in the infant GI tract, which is
rarely a factor in adults. Botulinum toxin has commercial uses. Injection of the toxin (Botox) at intervals
of a few months eliminates forehead wrinkles.
Leprosy
Leprosy, sometimes called Hansen’s disease for the person who first isolated the organism, is caused
by an acid-fast rod, Mycobacterium leprae. It is probably the only bacterium that grows primarily in the
peripheral nervous system. The microorganisms have not been grown on artificial media but can be
grown in armadillos. There are two main forms of leprosy. The tuberculoid (neural) form (roughly the
same as paucibacillary in the WHO system) is characterized by regions of the skin that have lost sensation and are surrounded by a border of nodules. The lepromin test, similar to the tuberculin test in
design, usually is positive for this form. In the lepromatous (progressive) form of leprosy (roughly the
same as multibacillary in the WHO system), skin cells are infected, and disfiguring nodules form over
the body. Mucous membranes of the nose (one sign is a lion-faced appearance) and the hands are particularly affected; the organism prefers cooler regions of the body. Progression to this stage of leprosy indicates a less-effective immune system.
Leprosy is not very contagious. Death is usually a result of complications from diseases such as
tuberculosis. Laboratory diagnosis is by identification of acid-fast rods in lesions. The sulfone drugs, such
as dapsone, are the most effective treatment. Rifampin and a fat-soluble dye, clofazimine, also are used.
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Viral Diseases of the Nervous System
Poliomyelitis
Poliomyelitis is informally called polio. Symptoms usually are a few days of headache, sore throat, and
fever; only a few cases are paralytic. The poliovirus occurs in three different serotypes. The primary
mode of transmission is ingestion of fecal-contaminated water. In paralytic cases, the virus penetrates
capillary walls and enters the CNS, where it displays a high affinity for nerve cells. The motor nerve cells
in the upper spinal cord, called the anterior horn cells, are particularly affected. In recent years, persons
who had polio as children have been showing signs of muscle weakness called post-polio syndrome.
The Salk vaccine (inactivated polio vaccine, IPV) uses viruses inactivated by formalin. This vaccine
requires a series of injections and periodic booster shots. The newer enhanced polio vaccine (E-IPV,
grown on human diploid cells) is available; it is often used for immunosuppressed individuals. The
Sabin vaccine (oral polio vaccine, OPV) contains three live attenuated strains. The immunity from this
vaccine resembles that acquired naturally, but on rare occasions the vaccine itself may cause the disease,
probably by a mutation to virulence. Diagnosis is usually based on isolation of the virus and observation of cytopathic effects on cell cultures.
Rabies
The rabies virus, a rhabdovirus with a bullet shape, is typically transmitted in the saliva of a biting
rabid animal. The virus travels along peripheral nerves to the CNS, where it produces encephalitis.
Symptoms include spasms of the muscles of the mouth and pharynx when swallowing liquids. This
painful reaction causes an aversion to water, which is the basis of the term hydrophobia (fear of water)
that is applied to rabies.
Animals with furious rabies are restless, snapping at anything. Some animals suffer from paralytic
rabies, in which there is only minimal excitability, although they may snap irritably if handled.
Laboratory diagnosis is usually made by a fluorescent antibody test. In early years, the Pasteur
treatment was standard for prevention of rabies in exposed individuals. The vaccination procedure consisted of injections of dried spinal cords of rabbits infected with rabies virus. Currently, treatment of
exposed people begins with the administration of human rabies immune globulin (RIG), followed by
active immunization. The latter is done with human diploid cell vaccines (HDCV) grown in human
diploid cell lines. HDCV is administered in five or six injections over a 28-day period. Indications for
antirabies treatment are unprovoked bites from dogs, cats, skunks, and similar animals. It also is possible to contract rabies by inhalation of aerosols of the virus.
Arboviral Encephalitis
Encephalitis, caused by viruses called arboviruses (arthropod-borne viruses) that are transmitted by a
mosquito, is common in the United States. Horses frequently are infected, accounting for terms such as
Eastern equine encephalitis (EEE) and Western equine encephalitis (WEE). St. Louis encephalitis
(SLE) and California encephalitis (CE), which do not infect horses, also occur. These diseases are summarized in Table 22.1. In the Far East, Japanese B encephalitis is a similar disease. All cause a percentage of neurological damage; however, EEE is the most severe in the United States, causing a high
incidence of brain damage, deafness, and similar neurological problems. It also has the highest mortality
rate. In 1999 an outbreak of West Nile virus occurred in the New York City area and has now become
endemic almost nationwide. Diagnosis is usually made by serological tests. Control of mosquitoes is an
essential preventive measure.
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261
TABLE 22.1
Types of Arboviral Encephalitis
Disease
Mosquito
Vector
Host
Animals
U.S.
Distribution
Eastern equine
encephalitis
(EEE)
Aedes, Culiseta
Birds, horses
East Coast
More severe even than WEE; affects
mostly young children and younger
adults; relatively uncommon in humans
Western equine
encephalitis (WEE)
Culex
Birds, horses
Western
United States
Severe disease; frequent neurological
damage, especially in infants.
St. Louis
encephalitis (SLE)
Culex
Birds
Throughout
country
Mostly urban outbreaks; affects mainly
adults over 40.
California
encephalitis (CE)
Aedes
Small
mammals
North-central
states, New
York State
West Nile (WNV)
Culex,
Aedes,
some
others
Primarily
birds, assorted
rodents, and
large animals
Throughout
country
Affects mostly 5–18 year age group in
rural or suburban areas; La Crosse strain
medically most important. Rarely fatal;
about 10% have neurological damage.
Symptoms vary from mild to severe.
Likelihood of severe neurological
symptoms and fatality increases
with age.
Comment
Fungal Disease of the Nervous System
Cryptococcus neoformans Meningitis (Cryptococcosis)
Cryptococcus neoformans is a yeastlike fungus widely distributed in soil, especially in soil enriched by
pigeon droppings. The disease cryptococcosis is thought to be transmitted by inhalation of dried
infected pigeon droppings. Often the disease does not proceed beyond an infection of the lungs, but it
may spread by the bloodstream to the brain and meninges. Laboratory diagnosis is by latex agglutination tests of cerebrospinal fluid. The drugs of choice for treatment are amphotericin B and flucytosine.
Protozoan Diseases of the Nervous System
African Trypanosomiasis
African trypanosomiasis is a disease caused by protozoa that affects the nervous system. The flagellates
Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense enter the body by a tsetse fly bite. Later
they move into the cerebrospinal fluid, where the resulting symptoms are responsible for the informal
name of sleeping sickness. Animals are reservoirs for the parasite. Human-to-human transmission by
bites of the insect vector is more likely with T. b. gambiense. T. b. rhodesiense causes a disease that is more
acute, running its course much more quickly. Suramin and pentamidine isethionate are used in
chemotherapy. A new drug, eflornithine, blocks an enzyme needed for proliferation. It is very effective
against T. b. gambiense but variable against T. b. rhodesiense.
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Naegleria Meningoencephalitis
An amoebic protozoan found in ponds and streams, Naegleria fowleri can infect the nasal mucosa and
from there reach and proliferate in the brain. The fatality rate of Naegleria meningoencephalitis is
nearly 100%.
Nervous System Diseases Thought
To Be Caused by Prions
There are a number of fatal diseases of the human central nervous system caused by prions. Sheep
scrapie is a typical prion disease. Creutzfeldt–Jakob disease and kuru are similar diseases in humans.
A current international public health concern is bovine spongiform encephalopathy (BSE), or mad cow
disease, which affects many herds of cattle in the British Isles. The agents causing these diseases are
unknown; they do not have any detectable nucleic acid, and one hypothesis is that they are composed
entirely of protein (prions). Chapter 13 has a further discussion of this subject.
Microbial Diseases of the Nervous System
Self-Tests
In the matching section, there is only one answer to each question; however, the lettered
options (a, b, c, etc.) may be used more than once or not at all.
I. Matching
1. A membrane layer covering the brain and spinal cord.
a. Meninges
2. A prion-caused disease.
b. Tetanus
3. Opisthotonos.
c. Rabies
4. Hansen’s disease.
d. Kuru
5. Human diploid cell vaccine is used in treatment.
e. Viroid
f. Leprosy
II. Matching
1. Innermost layer of the meninges.
a. Dura mater
2. Outermost layer of the meninges.
b. Ventricles
3. Middle layer of the meninges.
c. Subarachnoid space
d. Arachnoid
e. Pia mater
III. Matching
1. Formerly treated by the Pasteur treatment.
a. Rabies
2. Treated by human diploid cell vaccine after exposure.
b. Meningococcal meningitis
3. Caused by a bullet-shaped rhabdovirus.
c. Haemophilus influenzae
meningitis
4. Also known as hydrophobia.
d. Cryptococcosis
5. Thought to be transmitted by inhalation of the pathogen in
dried pigeon droppings.
e. Poliomyelitis
6. Caused by the bacterium Neisseria meningitidis.
f. Pneumococcal meningitis
7. Protozoan disease.
g. African trypanosomiasis
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IV. Matching
1. A prion-caused disease.
a. Creutzfeldt–Jakob disease
2. A mosquito-borne virus.
b. Meningococcal meningitis
3. The drugs of choice for treatment are amphotericin B and
flucytosine.
c. Listeriosis
4. Opposing muscles contract, causing spastic paralysis.
d. Cryptococcus neoformans
meningitis
5. Pathogen grows at refrigerator temperatures.
e. Tetanus
f. California encephalitis
V. Matching
1. Uses live viruses.
a. Salk polio vaccine
2. On rare occasions, the vaccine has caused the disease by a
mutation to virulence.
b. Sabin polio vaccine
VI. Matching
1. An amoebic protozoan found in ponds and streams that
causes a lethal brain infection.
2. Spread by the bite of a tsetse fly.
3. An important cause of bacterial meningitis.
a. Naegleria fowleri
b. Trypanosoma brucei gambiense
c. Cryptococcus neoformans
d. Streptococcus pneumoniae
4. The cause of African sleeping sickness.
VII. Matching
1. Probably the most virulent; the most common type in
western United States.
2. Outbreaks often involve seafoods; nonproteolytic.
3. Toxin can be produced at refrigerator temperatures.
a. Type A botulism
b. Type B botulism
c. Type E botulism
Microbial Diseases of the Nervous System
265
Fill in the Blanks
1. An infection of the brain is called
.
2. An infection of the meninges is called
.
3. The brain and the spinal cord comprise the
nervous system.
4. The nerves branching from the brain and spinal cord comprise the
nervous system.
5. The
consists of capillaries that permit certain substances, mostly
lipid-soluble, to pass from the blood to the brain but prevent other substances from passing.
6. The bacterium that causes
can be successfully grown in armadillos.
7. Of the several types of arthropod-borne encephalitis that occur in the United States, the most
severe in its effects is
.
8. The T in the DTaP vaccine stands for
.
9. The vaccine called Hib prevents meningitis caused by
10. The
.
fluid circulates in spaces within the brain (subarachnoid space).
11. A chemical sometimes added to foods to prevent the growth of Clostridium botulinum is
.
12. People with a less-effective cell-mediated immune system are more likely to develop the
form of leprosy.
13. The lepromatous (progressing) form of leprosy is roughly the same as
in the WHO system of naming.
Critical Thinking
1. The neurotoxin causing botulism results in a flaccid paralysis, while the neurotoxin causing tetanus
causes muscle spasms. Explain the difference.
2. Folklore associates the transmission of tetanus with rusty nails. Explain a rational basis for
this belief.
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3. In 1999 there was an outbreak in the New York City area of an arbovirus not previously known in
the United States, the West Nile virus. Health authorities are concerned that birds infected by the
virus might travel to warmer areas of the country. Explain this.
4. The Salk vaccine for polio, which uses a killed virus, is somewhat less effective in preventing the
disease, requires booster doses, and requires an unpleasant injection. However, it is now being recommended in place of the live, orally administered Sabin vaccine. Why?
5. People who have been infected with rabies may be able to develop immunity from a vaccination
given after exposure to the virus. Why is this possible?
Answers
Matching
I.
II.
III.
IV.
V.
VI.
VII.
1. a
1. e
1. a
1. a
1. b
1. a
1. a
2. d
2. a
2. a
2. f
2. b
2. b
2. c
3. b 4. f 5. c
3. d
3. a 4. a 5. d 6. b 7. g
3. d 4. e 5. c
3. d 4. b
3. c
Fill in the Blanks
1. encephalitis 2. meningitis 3. central 4. peripheral 5. blood–brain barrier 6. leprosy
7. Eastern equine 8. tetanus 9. Haemophilus influenzae type b 10. cerebrospinal 11. nitrate
12. lepromatous (progressive) 13. multibacillary
Critical Thinking
1. Botulism toxin prevents the movement of a signal along the nerve and the muscles never receive
signals to relax or contract. In normal operation, a nerve impulse initiates contraction of the muscle.
At the same time, an opposing muscle receives a signal to relax so as not to oppose the contraction.
The tetanus toxin blocks the relaxation pathway so that both opposing sets of muscles contract.
Microbial Diseases of the Nervous System
267
2. The endospore-forming bacterium that produces the tetanus neurotoxin is common in soil, where a
rusty nail might be found. If the nail is rusty, it is more likely to be contaminated with these bacteria
than a shiny, new nail. The bacterium is an obligate anaerobe and would grow well in a deep puncture wound such as would be caused by a nail.
3. Mosquitoes do not normally survive the winter in the area of the outbreak. The virus in infected
animals and humans is not likely to remain in the bloodstream for more than a very limited time.
Therefore, the disease is unlikely to become endemic in colder climates, for the same reason that
mosquito-borne diseases such as malaria and yellow fever are not usually found in these climates.
However, if infected birds migrate to warmer climates while still carrying the virus, mosquitoes that
survive the year around will feed on them, transmit it to other animals, and the disease will probably become endemic in that area.
4. The Sabin vaccine is easier and more pleasant to administer and provides a generally better immunity because it mimics an active infection. However, on rare occasions, it reverts to virulence and
causes polio. It has been decided recently that the advantages do not outweigh this risk.
5. The rabies virus has an unusually long incubation period. This makes it possible for a patient to
respond to vaccination and develop immunity to the virus during the incubation period.