Diseases of the Nervous System

Chapter 27
Nester 5th. Ed.
Components of the Nervous
System
 Central Nervous System(Figure 27.1 and 2)
• Brain
• Spinal cord
• Protective coverings
– Bones
– Meninges
– CSF in the Subarachnoid Space
 Peripheral Nervous System
Figure 26.1, Page
664
CNS Environment
 Well protected
• totally internal
 Organisms have trouble getting in
• probably by accident
• infect other areas much more easily
 No normal flora at all
Figure
Figure
Figure 26.2,
26.2 26.2,
Page 665
Page 664
Routes into the CNS
 Blood stream
• blood-brain barrier
– single layer of tightly packed capillary cells
– keeps out organisms, viruses or drugs
– can be breached by high concentrations of pathogen
or drug
• Infections of the face above the mouth
– infections of veins which communicate directly to
veins of the CNS
Routes into the CNS
 Nerves
– pathogens travel up nerve bundles
– axoplasmic flow
 Bones
• bones surround CNS particularly the brain
• pathogen must penetrate periosteum
• pathogen must get through the bone
• pathogens can get through from
– sinuses
– mastoids
– middle ear
Routes into the CNS
• Skull fractures
– non-healing injuries lead to recurring infections
– Fracture across the floor of the skull producing either
otorrhea or rhinorrhea
 Penetrating injuries
Types of Infections of the CNS
 Meningitis
 Encephalitis
 Localized brain abscess
Types of Meningitis
 Acute bacterial meningitis

 Acute viral meningitis

 Chronic meningitis
Acute Bacterial Meningitis
 Causative agents
• Varies with age (Figure 27.5)

• Recent changes due to immunizations (Figure

27.3)
Figure
26.5,
Page
667
 Figure 26.3, Page 666

Rates of serious Haemophilus influenzae disease per 100,000

children less than five US 1987 to 1998
Acute Bacterial Meningitis
 Common symptoms
• Begins with a mild cold
• Severe throbbing headache, nausea and
vomiting
• Fever
• Meningism
– Stiffness and pain in the neck and back
Acute Bacterial Meningitis
 Characteristics of CSF
• Pressure is increased
• CSF is cloudy (contains pus)
• Increased protein
• Decreased glucose
• Neutrophils present
• Bacteria can be found on staining the CSF
• Bacteria can be cultured
Acute Bacterial Meningitis-
Meningococcal Meningitis

 Organism - Neisseria meningitides

• 12 antigenic groups
– A, B, C, Y and W135
– diagnosis by Immunological techniques
• Gram (-) diplococci (Figure 26.7)
• Oxidase (+)
• Grows on ordinary blood agar or chocolate
Figure 26.7, Page 667
Meningococcal Meningitis -
Symptoms
 Mild cold followed by sudden onset of
• severe throbbing headache
• fever
• marked pain and stiffness of back and neck
 Progression to
• deafness
• altered consciousness
• coma
Acute Bacterial Meningitis
Meningococcal Meningitis -
 Petechial rash - Figure 26.6
• purplish spots
• from small hemorrhages
Meningococcal Meningitis -
Symptoms

 Shock
• leads to death within 24 hours
• usually progression is slower
– can still treat
Meningococcal Meningitis -
Pathogenesis
 Inflammation
• pus & clots cause brain swelling & infarcts
• flow of CSF obstructed
– pushes brain against skull
• damage to
– auditory nerves
– optic nerves
– motor nerves - paralysis
Meningococcal Meningitis -
Pathogenesis
 Endotoxin
• decreases blood pressure - shock
• hemorrhages - rash
• released in “showers” from meninges into
blood
– a reason why this disease can be rapidly fatal
Meningococcal Meningitis -
Epidemiology
 Usually in epidemics
 Occurs commonly in infants age 6-11 mths
 Also, often in children and adults
• especially at military bases and colleges
 High incidence during WW II in military
recruits crowded in barracks

Meningococcal disease in the US 1935 to 1998

Meningococcal Meningitis -
Epidemiology
 Usually in epidemics
 Occurs commonly in infants age 6-11 mths
 Also, often in children and adults
• especially at military bases and colleges
Meningococcal Meningitis -
Epidemiology

 Humans = reservoir and carrier

• isolated from 5-15% of normal people
 Most infections are of the nose and throat
Meningococcal Meningitis -
Epidemiology
 Frequency by different strains varies a lot
 Factors
• immunity of population to previously encountered
strains
• wide use of sulfa drugs producing resistance
– B & C were resistant to sulfa drugs before they were used
in 1935
• crowding
• transfer of virulence by transformation
Meningococcal Meningitis -
Prevention
 Opsonins to group antigens are protective
 Vaccine - capsule polysaccharide
• used to control epidemics
• people of high risk
 Vaccine for Group B polysaccharide is
being developed
• this is a poor antigen
Meningococcal Meningitis -
Treatment
 Prophylactic treatment
• rifampin
• strains from patients are more virulent
– treat close contacts
 Early cases before shock and brain injury
• penicillin
• chloramphenicol
 Mortality <10% with treatment
Other Bacterial Causes of Acute
Bacterial Meningitis
 Haemophilus influenzae
• before immunizations was the leading cause of
meningitis in infants 6-12 months of age
• 6 antigenic types (a-f)
– b is involved in the most serious cases
– antibody to the types is protective
Other Bacterial Causes of Acute
Bacterial Meningitis
 Haemophilus influenzae
• 1985 Vaccine
– b capsule polysaccharide
– for children >24 months
• 1987 Vaccine
– conjugate of b and diphtheria toxoid
– for children >18 months
• 1990 Vaccine
– newer conjugate
– for infants 2 months or greater
Other Bacterial Causes of Acute
Bacterial Meningitis- Listeriosis
 Organism- Listeria monocytogenes
 Foodborne disease that causes a small percentage
of meningitis
 Sometimes occurs in epidemics
 Details about the infection see Table 26.2
Acute viral meningitis
 More common cause of meningitis than bacteria
 Usually a benign, self-limited condition
 Does not require specific treatment
 Patients usually recover with no sequelae
 Infection often looks like bacterial meningitis
initially
 Other signs and symptoms depending on the
cause
Acute viral meningitis
 Characteristics of the CSF
• Pressure increased
• CSF is clear
• Mild increase in protein
• Glucose is normal
• Few cells present mainly monocytes
• No bacteria on staining and culturing
(abacterial, or aseptic meningitis)
Acute viral meningitis
 Causative organisms
• Coxsackie viruses
• Echoviruses
• Mumps
• Enteroviruses
 See Table 26.5 for details on this condition
Chronic Granulomatous
Meningitis
 Symptoms are insidious in onset
 Slight fever, intermittent headache,
dizziness and difficulty in thinking
 Symptoms get worse over weeks or months
 Vomiting, weight loss, stupor, seizures and
cranial nerve impairments occur
Chronic Granulomatous
Meningitis
 People who are most susceptible are the
immunocompromised
 May end up dying
 Causative agents
• Fungal diseases such as the Cryptococcus
• Mycobacterium tuberculosis
• Treponema pallidum
Cryptococcal
Meningoencephalitis
 Cryptococcus neoformans - old name
 Filobacidella neoformans - new name
• sexual reproductive form resembles a group of
pathogenic Basidiomycota
• small encapsulated yeast
• large capsule = virulence factor
– decreases phagocytosis
– decreases migration of leukocytes
– diffuses from yeast and binds to opsonins
Figure 26.16, Page 677
Cryptococcal
Meningoencephalitis
 Pathogenesis
• fungal spores are airborne in dust
• inhaled
• lung
– lung macrophages usually eliminate fungus
– no disease
– inefficient killing by macrophages leads to fungemia
– fungus disseminated via blood
Cryptococcal
Meningoencephalitis
 Pathogenesis
• Dissemination
– more likely when cellular immunity is depressed
– meninges and brain -
– most common sites
– skin
– bone
– etc.
Cryptococcal
Meningoencephalitis
 Pathogenesis
• meningoencephalitis
– inflammation of brain and meninges
– meninges thicken
– decreases flow of CSF
– increases pressure on the brain
– brain abscesses
Cryptococcal
Meningoencephalitis
 Epidemiology
• worldwide
• fungus in the soil, particularly associated with
pigeon droppings
• 0.2-0.9/100,000 of the population in healthy people
• 2 to 4 cases/1000 AIDS patients, one of the top 4
indicators of AIDS
• usually a first indicator of AIDS
Cryptococcal
Meningoencephalitis
 Treatment
• Amphotericin B
– doesn’t cross blood brain barrier
– can put tube through skull to lateral ventricle
• and Flucytosine
• or Itraconazole
• treatment succeeds 70% of the time, except in
AIDS patients because they lack T cell action
• without treatment death is almost 100%
Chronic Granulomatous Meningitis
 Mycobacterium tuberculosis
• Slender, rod –shaped bacterium that is acid fast. Gram
positive cell wall with addition of mycolic acid.
• Strict aerobe with a very long generation time
• Two phases of tuberculosis infection
– Primary infection
– Secondary or reactivation tuberculois
• Usually confined to the lungs, but may spread to other
organs
Figure 23-17,
Page 582
Chronic Granulomatous Meningitis

 Syphilis
• Causative agent is Treponema Pallidum
• Stages of the disease
– Primary – chancre at site of infection
– Secondary – associated with a spirochetemia,
Patient has a skin rash, fever and may have swollen
regional lymph nodes
– Tertiary- spirochetes are everywhere in nervous
system produce neurosyphilis which can include a
meningitis. (Meningovascular syphilis)
Neurosyphilis
Encephalitis
 Majority of causes of a diffuse involvement
of the brain substance are viruses
 Unlike viral meningitis, viral encephalitis is
a serious infection that often leads to death
 Those who survive are often left with
permanent neurological deficits, because
the viruses infect the cells of the CNS
Viral Encephalitis - all types
 Symptoms
• fever
• Headache and photophobia
• stiff neck
• disorientation
• seizures
• coma
• impairment of 1 or more motor or sensory nerves
Viral Encephalitis
 Symptoms
• most people recover but are left with permanent
impairment
– epilepsy
– paralysis
– deafness
– difficulty thinking
Viral Encephalitis
 Cases of viral encephalitis fall into one of
two groups
• Sporadic viral encephalitis
• Epidemic viral encephalitis
Sporadic Viral Encephalitis
 Sporadic disease - a disease that occurs at a
fairly constant low frequency in a given
population
 Encephalitis - inflammation of the brain
Sporadic Viral Encephalitis
 Causes
• Herpes simplex viruses - HSV-1 and HSV-2
– most common cause
– 1/2 cases are primary infections
– 1/2 cases are recurrences
• Mumps virus
• Measles virus
• Epstein-Barr virus - HHV-4
• Varicella-zoster - HHV-3
Sporadic Viral Encephalitis
 Causes
• Herpes simplex viruses - HSV-1 and HSV-2
– most common cause
– 1/2 cases are primary infections
– 1/2 cases are recurrences
• Mumps virus
• Measles virus
• Epstein-Barr virus - HHV-4
• Varicella-zoster - HHV-3
Sporadic Viral Encephalitis
 Causes
• Herpes simplex viruses - HSV-1 and HSV-2
– most common cause
– 1/2 cases are primary infections
– 1/2 cases are recurrences
• Mumps virus
• Measles virus
• Epstein-Barr virus - HHV-4
• Varicella-zoster - HHV-3
Sporadic Viral Encephalitis
 Causes
• Herpes simplex viruses - HSV-1 and HSV-2
– most common cause
– 1/2 cases are primary infections
– 1/2 cases are recurrences
• Mumps virus
• Measles virus
• Epstein-Barr virus - HHV-4
• Varicella-zoster - HHV-3
Sporadic Viral Encephalitis
 Causes
• Herpes simplex viruses - HSV-1 and HSV-2
– most common cause
– 1/2 cases are primary infections
– 1/2 cases are recurrences
• Mumps virus
• Measles virus
• Epstein-Barr virus - HHV-4
• Varicella-zoster - HHV-3
Sporadic Viral Encephalitis
 Causes
• Herpes simplex viruses - HSV-1 and HSV-2
– most common cause
– 1/2 cases are primary infections
– 1/2 cases are recurrences
• Mumps virus
• Measles virus
• Epstein-Barr virus - HHV-4
• Varicella-zoster - HHV-3
Epidemic Viral Encephalitis
 Arboviruses-ARthropod BOrne viruses
 Vectors insects
 Reservoirs are birds or animals
 Humans are infected accidentally
• when the natural host is reduced in number
• when the number of mosquitoes is high
Epidemic Viral Encephalitis
 All are enveloped, single-stranded RNA
viruses
 St. Louis, LaCrosse, EEE, JE, West Nile.
 See Table 26.6 for summary
Epidemic Viral Encephalitis
 Bunyavirus
• LaCrosse encephalitis virus
• California encephalitis virus
• vector = Aedes mosquito
– mosquitoes pass virus in their eggs to future
generations
• natural host = chipmunks, squirrels
• accidental host = human
• occurs in kids 4-14 years old
Epidemic Viral Encephalitis
 St. Louis encephalitis virus
• Flavi virus
• RNA
• vector = Culex mosquito
• natural host = birds and mammals
• accidental host = human
• occurs in people over 45 years old
Epidemic Viral Encephalitis
 West Nile Virus
• Vector – several types of mosquitoes in US
• Of people bitten 20% get neurological symptoms –
some are unusual
• Vision loss, muscle tremors, numbness
– Similar to stroke, polio and Parkinson’s symptoms
• In 2004, there were 2539 cases in the US & 100 deaths
• Currently in 2006, 1 confirmed human case in
Mississippi as of May 2
• Present in mosquitoes in 22 counties in Texas
• Most mild cases have fever as only symptom
West Nile Virus p 663 TEM
West Nile Virus - 1999
West Nile Virus 2000
West Nile Virus 2001
West Nile Virus 2002
West Nile Virus 2003
West Nile Virus 2004
West Nile Virus 2005
Poliomyelitis
 Picornaviridae
 Enterovirus
 Polio viruses 1, 2, 3
• small RNA viruses
Poliomyelitis
 Pathogenesis
• fecal oral transmission
• oral cavity cells infected including tonsils
• passes through stomach acid intact
• intestinal cells infected
• blood
• CNS
• motor nerves infected based on receptors
Poliomyelitis
 Abortive polio
• most common
• sore throat
• fever, malaise
• drowsiness, headache
• nausea, vomiting, constipation
• recover in a few days
Poliomyelitis
 Non-paralytic polio
• same symptoms as abortive
• plus stiffness and pain in neck and back
• aseptic meningitis
• lasts 2-10 days
• recover completely
Poliomyelitis
 Paralytic polio- spinal type
• may follow abortive or non-paralytic polio or
may occur alone
• pain and muscle spasms precede paralysis
• flaccid paralysis
• neuron damage and death
• muscles shrink
• bone development is impaired
Poliomyelitis
 Paralytic polio- bulbar type
• most serious
• involves medulla and the muscles for breathing
• some recovery occurs if the person survives the
acute disease
Poliomyelitis
 Epidemiology
• greatest impact on economically advanced
countries
– more epidemics with more paralytic polio
– affects all ages
– virus spreads in the population much later
• worldwide
– 450,000 cases/year
– 5-10 % mortality
Poliomyelitis
 Epidemiology
• underdeveloped countries
– poor sanitation
– almost everyone gets the virus early in life
– babies with maternal Ab get mild disease
– still become immune
– even 2-3 months after birth the cases are mild
 Southeast Asia (especially India) still has
out breaks of wild type polioviruses
Poliomyelitis
 Prevention
• pasteurization
• proper chlorination of drinking water
• vaccines
– Salk - original inactivated vaccine - 90% effective
– Sabin - oral live attenuated vaccine - 99% effective
– Problem - reversion
– polio occurs after first dose
– 1978 - killed purified vaccine - >90% effective
Polio cases for 06 September 2005 :
Global cases of poliovirus: 1163

Yemen (importation) 440

Nigeria (endemic) 389
Indonesia (importation) 231
India (endemic) 27
Sudan (re-established transmission) 26
Pakistan (endemic) 15
Ethiopia (importation) 15
Angola (importation) 7
Afghanistan (endemic) 4
Mali (importation) 3
Niger (endemic) 3
Chad (re-established transmission) 1
Poliomyelitis
 Prevention
• vaccines
– recommendations to avoid problem
– use the 1978 inactivated vaccine for the first dose
– follow this with the live attenuated
– non-immune parents get the 1978 inactivated vaccine
before the children get the oral vaccine
Poliomyelitis
 Post-polio syndrome
• 300,000 survivors in the U.S.
• occurs 15-50 years after polio
• no evidence for latent or persistent virus
• muscle pain, weakness and degeneration and loss of
function
• worst in those with most nerve damage
• neurons branched out to take over for killed neurons -
wear out from extra duty
Rabies
 Rhabdoviridae
• Rabies virus
– bullet shaped
– enveloped
– ss RNA
Rabies
 Incubation period
• usually 1-2 months
• can be a year or more
• depends on:
– dose of virus
– proximity of portal of entry to the brain
– virus strain
– concentration of virus receptors on host cells
– severity of wounds
Rabies
 Pathogenesis
• virus in saliva of rabid animal
– animal bites human
– local replication in muscle cells
– virus crosses neuromuscular junction
– attachment and penetration
– virus travels by axoplasmic flow
– eventually reaches the brain and replicates
Rabies
 Pathogenesis
– virus in brain travels through nerves to:
– salivary glands
– eyes
– fatty tissue under skin
– heart
– other organs
• virus in aerosols (of bat feces)
– enter lungs and move to the nerves and brain
– then out to other areas
Rabies
 Pathogenesis
• person to person transmission
– corneal transplants
– not an issue now since transplants are tested for
infectious agents
Rabies
 Symptoms
• earliest:
– headache, muscle aches, fatigue
– fever, sore throat, nausea
– tingling or twitching at the site of viral entry
• rapidly progress to:
– agitation, confusion, hallucinations
– encephalitis, seizures, increased sensitivity to light,
sound, and touch
Rabies
 Symptoms
– fever increases
– increased salivation
– hydrophobia
– painful muscle spasms of the throat and respiratory tract are
induced by swallowing or just seeing liquids
– seen in 1/2 of the cases
– coma
– death
– time from first symptoms to death is 4 days
Rabies
 Epidemiology
• widespread in animals
• U.S. - skunks, raccoons, bats, wolves, foxes,
coyotes, domestic animals
• dogs and cats not a problem since vaccine
• 1,000,000 dog bites a year - rabies is rare
• dog rabies is a problem in other countries
• immigrants come in with rabies from a dog
Primary Amoebic
Meningoencephalitis
 PAM
 Protozoan
• Naegleria fowleri
– one of few free living human pathogens
– 3 forms
– amoeba
– flagellate
– cyst
Primary Amoebic
Meningoencephalitis
 Pathogenesis
• org from soil contaminates warm fresh water
– with or without chlorine
• protozoan gets in the nose
– usually while swimming
• olfactory nerve
• across cribiform plate
• brain
Primary Amoebic
Meningoencephalitis
 Pathogenesis
• Nests of amoebas form in brain tissue
• Amoebas cause extensive hemorrhage
• Severe damage to cerebrum and cerebellum
• death occurs in about one week
Primary Amoebic
Meningoencephalitis
 Epidemiology
• usually in a hot dry summer
• water levels drop - tend to be muddy
• most often in children
– swim in shallow soil contaminated water
• states reporting cases frequently
– Texas, Oklahoma, Arizona
• amoeba can be in water tanks, wells and
refrigerator filters
Trypanosomiasis
 African sleeping sickness
 Protozoan
 Mastigophoran - moves with flagella
 Trypanosoma brucei
• rhodesiense - east Africa
• gambiense - central and west Africa
• vector = tsetse fly
Trypanosomiasis
 Pathogenesis
• protozoan in tsetse fly saliva
• fly bites human
• protozoan multiplies at skin bite site
• lymphatic vessels
• blood - parasitemia
• fever
• IgM produced
Trypanosomiasis
Lesion at the bite site
Trypanosomiasis
 Pathogenesis
• symptoms improve due to immune response
• protozoan changes its protein antigens
• new multiplication by changed organism
• parasitemia
• symptoms
• new immune response
• cycle - org can make hundreds of new Ags
Trypanosomes in the blood
Typranosomiasis
 Pathogenesis
• rhodesiense
– rapid progression of disease
– heart and brain invaded in 6 weeks
– death due to heart failure occurs in six month
• gambiense
– slower progression
– years before death
– damage also from immune complexes
Trypanosomiasis
 Symptoms
• incubation period is one week from bite
• tender nodule forms at bite site
• fever
• regional lymph nodes swell
• all resolves spontaneously
• recurrent fevers develop weeks to years later
– recurrences occur for months to years
Trypanosomiasis
 Symptoms
• CNS involvement
– gradual loss of interest in everything
– decreased activity
– indifference to food
– slurred speech
– coma
– death
Trypanosomiasis
 Epidemiology
• where tsetse fly is found
– within 15 degrees of the equator
• 10-20,000 new cases each year
– includes tourists
• reservoir
– rhodesiense - wild animals
– gambiense - humans
Epidemiology of African
Trypanosomiasis
Trypanosomiasis
 Prevention
• insect repellants
• protective clothing
• insecticides
• clearing brush (breeding)
Trypanosomiasis
 Treatment
• suramin works before CNS involvement
– I.V.
– itching, vomiting, nerve damage
• melarsoprol crosses blood brain barrier
– arsenic compound
– toxic
• difluoromethylornithine - new drug
American Trypanosomiasis
 Chagas’ disease
 Protozoan
 Mastigophoran - flagella
 Trypanosoma cruzi
American Trypanosomiasis
 Epidemiology
• Central and South America
• reservoir
– humans
– dogs and cats
– opossums
– armadillos
– animals are infected up to California and Maryland
South american
trypanosomiasis
American Trypanosomiasis
 Epidemiology
• vector
– reduviid bugs - assassin bugs
– triatomine bugs - bed bugs, kissing bugs
• leading cause of heart disease where the
organism is endemic
 Treatment
• none
Slow Virus Diseases
 ALL are eventually fatal
 SSPE
• Sub-acute Sclerosing PanEncephalitis
• 2-10 years after a symptomatic measles infection
• demyelination may be immunological
• virus also infects neurons
• may be due to a defective measles virus
Slow Virus Diseases
 SSPE (continued)
• Patients present with personality changes,
cognitive disorders and involuntary myoclonic-
type movements
• Death is within 1-2 years of onset of symptoms
• This has become rare in the United States due to
a decrease in measles infections, but it is seen in
other parts of the world where measles infections
are still common
Slow Virus Diseases
 Progressive Multifocal Leukoencephalopathy
• Known as PML for short
• Papovaviruses - JC and BK
• rare CNS complication of:
– AIDS due to HIV infection
– chronic leukemia
– Hodgkin’s disease
– lymphosarcoma
– other immunosuppressions
Slow Virus Diseases
 Progressive Multifocal Leukoencephalopathy
• Virus is common - 70-80 % of humans have Ab
• Characterized by virus infection of oligodendrocytes
with the presence of large atypical astrocytes
• Widespread focal demyelination of the white matter of
the brain
• Presents as an acute, rapidly progressive illness
associated with multiple neurological dysfunctions
• Mortality rate is high
Sub-acute Spongiform
Encephalopathies
 Unconventional infectious agents
• prions only contain protein, no genetic material
• confined to CNS
• fatal
• no inflammation
• no immune response
 Sporadic, but can be transmitted from an
infected individual
Sub-acute Spongiform
Encephalopathies
 Neuronal loss, demyelination and
spongiform change within the brain
 Animal forms of the disease
• Scrapie in sheep and goats
• Bovine spongiform encephalopathy in cows
(Mad cow disease)
• Wasting disease in deer and elk
Sub-acute Spongiform Viral
Encephalopathies
 In humans
• Usually seen in people > 50 years old
 Known diseases
• Kuru
• Creutzfeldt-Jakob Disease (CJD)
• Gerstman-Straussler-Scheinker disease
Sub-acute Spongiform Viral
Encephalopathies

 Kuru
• Found particularly in Papua, New Guinea
• Transmitted by eating the infected brains
• No longer occurs since cannibalism has ended
• Particularly affects the cerebellum presenting
first with a shivering tremor and unsteadiness
then with progressive dementia
Sub-acute Spongiform
Encephalopathies
Creutzfeldt-Jakob disease - CJD
• Most common of these diseases in humans
• World-wide has an incidence of 1 per million
• 2 types of CJD
– Sporadic form most common
– Variant form is associated with transmission from
mad cow disease
Sub-acute Spongiform
Encephalopathies
• Sporadic form of CJD
– Can be transmitted to surgeons, transplant and brain
surgery patients, human growth hormone
– Once symptoms develop the survival time is about 7
months
– Age of patient at presentation is usually over the age
of 50 years.
Sub-acute Spongiform
Encephalopathies

 Variant form of CJD

• Age at presentation is usually in the mid
twenties
• Associated with transmission from “Mad cow
disease”
• Progression of the disease is slower
Sub-acute Spongiform
Encephalopathies

 Gerstman-Straussler-Scheinker disease
• same as the sporadic form of CJD with a more
protracted course
Infections of the Peripheral
Nervous System
 Leprosy
 Botulinism
Leprosy - Hansen’s Disease
 1868 - first causal link of a bacterium to human
disease
 Aerobic, acid-fast rod
 Cannot grow on artificial media
 Use foot pad of mice , armadillos, monkeys
 Generation time of 12 days - very slow
 Only organism that likes the cooler peripheral
nerves
Leprosy-Symptoms
 Skin
• increased or decreased sensation
• increased or decreased pigmentation
• these lesions:
– increase in size and thicken
– lose hair
– lose sweating ability
– lose sensation
Types of Leprosy
 Two major types of leprosy depending on
whether the patient can produce cell-
mediated immunity or not
• Tuberculoid leprosy- patient has good cell
mediated immunity and produces localixed
granulomas
• Lepromatous leprosy the lesions are more
diffuse due to a lack of cell mediated immunity
Tuberculoid Leprosy -
Pathogenesis
 Skin lesions
• localized, flat and red
• become larger with an irregular shape
• become indurated and elevated
• become hyper-pigmented at the rim and pale in
the center
Tuberculoid leprosy
Tuberculoid Leprosy -
Pathogenesis
 Major neuronal involvement
• granulomas form around nerves
– small nerves die
• nerve degeneration - Figure 26.9
– anesthesias
– skin ulcers and muscle atrophy
– trauma likely
– contractures, paralysis, auto-amputation
– paralysis of eyelid, keratitis, corneal ulceration
Tuberculoid Leprosy -
Pathogenesis
 People are usually non-infectious
• delayed type hypersensitivity
 Lepromin skin test positive
 Langhans cells
• giant cells
• nuclei in a circle or horseshoe shape
• in granulomas similar to those seen in TB
Lepromatous leprosy
Lepromatous Leprosy -
Pathogenesis
 Skin, peripheral nerves, anterior eye,upper
airways, testes, hands and feet
 Lepra cells (lipid laden macrophages)
• filled with acid-fast bacilli - Figure 27.10
 Skin lesion - hypo or hyper-anesthetic
• macular, papular, nodular
• face, ears, wrists, elbows, knees
• coalesce to form a leonine face
Lepramatous Leprosy -
Pathogenesis
 People are very infectious
• due to little to no immune response
• T-suppressor cells are in the lesions
• nasal secretions contain organisms
– secretions are transmitted
 Lepromin skin test negative
Lepromatous vs Tuberculoid leprosy
Leprosy - Epidemiology
 Person to person spread but usually needs
multiple exposures
 Mucous membranes or skin abrasions
 Very few exposed people get leprosy
 No animal reservoir
• although the 9 banded armadillo of LA has
organism that resembles very closely the human
bacterium
Leprosy - Treatment
 No vaccine yet
 Tuberculoid
• dapsone and rifampin together
• 6 months
 Lepromatous
• dapsone, rifampin, and clofazimine together
• 2 years
Botulinism
 Causative agent is Clostridium botulinum
• Anerobic, gram positive, spore-forming rod found in soil
• Found in contaminated food often home-canned foods or
sausages.
• Endospores germinate in food and produce an exotoxin
which affects the nervous system
• Incubation period is usually 12 to 36 hours
• Symptoms include blurred or double vision, weakness,
nausea, vomiting, diarrhea and skeletal muscle paralysis
• Problem of honey and infants
Tetanus AKA “Lock Jaw”
 Causative agent is Clostridium tetani
• Anaerobic, spore-forming, Gram-positive rod
 Can be found in contaminated wounds if the area
is anaerobic enough
 Pathological effects are due to the action of the
exotoxin produced by the vegetative cells
 Average incidence of tetanus by age in the
population (Figure 27.11)