CNS Infections Flashcards

Question 1

Q

CNS

Routes of Entry

Answer

A

Hematogenous (most common)
- Invade across capillary endothelial cells
- Arterial circulation
- Retrograde venous spread via anastomoses with veins of the face
Choroid plexus
Direct implantation
- Trauma
- Congenital malformation (meningomyelocele)
Local extension
- Sinuses, teeth, vertebrae
Peripheral nervous system
- Spread along olfactory tracts, nerve ganglia
- Viruses = Herpes, rabies
Infected leukocytes

Question 2

Q

Meningitis

Definition

Answer

A

Inflammatory process of the leptomeninges and CSF within the subarachnoid space, usually caused by an infection.

Types:

Acute pyogenic - usually bacterial
Aseptic - usually acute or subacute viral
Chronic - usually tuberculous, spirochetal, or cryptococcal
Chemical – due to an irritant within the subarachnoid space

Question 3

Q

Meningitis

Acute vs Chronic

Answer

A

Acute
- Onset hours to days
- Can be caused by bacterial or viruses
  - Ex. Neisseria, Haemophilus
Chronic
- Onset over weeks
- Usually caused by fungi, Mycobacterium

Question 4

Q

Aseptic Meningitis

Answer

A

Clinical term: absence of organisms by bacterial culture in a pt with manifestations of meningitis.

Caused by viruses, fungi, unusual bacteria (Leptospira)
- Usually viral etiology
  - 80% of cases due to enteroviruses (Echo-, coxsackie-, polio-virus)
- May be bacterial, rickettsial, or autoimmune in origin
CSF characteristics:
- Low numbers of WBCs, mostly lymphocytes
- ↑ Proteins
- Normal glucose
- Usually do not see organisms in CSF
If viral ⇒ usually self-limiting
- Treat symptomatically

Question 5

Q

Septic Meningitis

Answer

A

“Pyogenic Meningitis”

Associated with bacterial infection
Purulent exudate in the subarachnoid space
May be acute (i.e. Neisseria, Haemophilus) or chronic (i.e. Mycobacterium)
CSF characteristics:
- High numbers of WBCs, mostly neutrophils
- ↑ Protein
- ↓ Glucose
- Organisms in CSF

Question 6

Q

CSF Characteristics

Comparison

Question 7

Q

Viral Mengingitis

Characteristics

Answer

A

Often perivascular lymphocytic cuffing
Microglial nodules around virally infected cells
Neuronophagia ⇒ microglial ingestion of infected neurons
Necrosis ⇒ severe viral infections
CSF:
- Cells: Monocytic, moderate increased
- Protein: Moderately increased
- Glucose: Normal

Question 8

Q

Viral Menigitis

Clinical Manifestations

Answer

A

Fever
Headache
Stiff neck
N/V
Photphobia
Somnolence
Rash

Question 9

Q

Picorna Viruses

Overview

Answer

A

Family of RNA viruses which include:

Enteroviruses (family) ⇒ meningitis, polio, heart infections
- Poliovirus types 1,2,3
- Coxsackie virus A and B
- Echovirus (Enteric cytopathic human orphan virus), types 1-34
- Enterovirus (species), types 68-71
Rhinoviruses ⇒ common cold

Question 10

Q

Picorna Viruses
General Characteristics

Answer

A

Small, naked ss-RNA viruses (Pico-RNA-virus), with ⊕ polarity

It does not carry an RNA dependent RNA polymerase
Virus genome serves as its own mRNA as well as the source of genetic information
Exhibits post-translational modification of its proteins by virus encoded proteolytic cleavages
Naked capsid structure ⇒ resistant to environment

Question 11

Q

Enteroviruses

Transmission I Epidemiology

Answer

A

Replication in respiratory and GI tract w/ shedding
- Shedding occurs in absence of clinical illness
Predominantly by fecal-oral route
- Hand to mouth
- Contaminated bodies of water
- Respiratory secretions can also transmit virus
No animal reservoirs
- Flies can mechanically transmit viruses (sewage and food)
Seasonal incidence ⇒ mainly late summer, early fall
Most common in young children and adolescents
Poor sanitation and crowded living condition promote transmission

Question 12

Q

Enteroviruses

Pathogenesis

Answer

A

Incubation usu. 7-10 days
Initial replication in epithelial and lymphoid cells of the pharynx (respiratory tract)
Seeds Peyer’s patches in the intestine
Can be recovered from the feces for ~ 1-2 months post-infection
Migrate into regional lymph nodes → bloodstream (viremia)
Blood → secondary or tertiary target organ(s) ⇒ presentation of classical disease syndrome
Cytolytic infection ⇒ replication causes direct damage to cells

Question 13

Q

Enteroviruses
Diagnosis

Answer

A

Based on clinical signs and symptoms
Supported by CSF finding (aseptic meningitis)
PCR assay for enteroviruses has good sensitivity and specificity (95%)
- May confirm dx within 24 hrs

Question 14

Q

Picornaviruses

Treatment

Answer

A

Supportive for immunocompetent
Pleconoril for infants and immunodeficient (enteroviruses only)
- ⊗ Viral attachment to host receptors
- ⊗ Uncoating of picornaviruses
- Must be given early

Question 15

Q

Enteroviruses

Infection Severity

Answer

A

Based on:

Infecting dose
Viral serotype
- Enterovirus 71 ⇒ polio-like syndrome
- Enteriovirus D68 ⇒ recent outbreak, polio-like
Pts age
- Coxsackie in infants under 1 mo
Health status

Question 16

Q

Poliovirus

Characteristics

Answer

A

Type of Picorna virus (naked ⊕-sense ssRNA)
3 important serotypes (types 1, 2, 3)
- All 3 included in trivalent vaccines
Causes a clinical spectrum of diseases

Question 17

Q

Polio

Epidemiology

Answer

A

Americas have been disease-free since 1994
Worldwide Incidence:
- 350,000 in 1988
- 1,604 in 2009
- ~900 in 2010
Worldwide vaccination
Persists in: Tajikistan (458), Pakistan, DR Congo, Congo, India

Question 18

Q

Poliovirus

Clinical Syndromes

Answer

A

Asymptomatic infection (90%)
- Limited to gut, oropharynx
Abortive poliomyelitis (5%)
- Flu-like symptoms, vomiting
Non-paralytic Polio (1-2%)
- Aseptic meningitis
Paralytic Polio (0.1 to 2%)
- Type 1 responsible for 85% of paralytic disease

Question 19

Q

Paralytic Polio

Answer

A

Infects upper and lower motor neurons
- Become chromatolytic and eventually die ⇒ neuronophagia
- Lymphocytic infiltration of the meninges and perivascular cuffing
- Microglial nodules around affected cells
Paralysis caused by destruction of cells in spinal cord (anterior horn cells, etc.), brain stem, and motor cortex
Result in asymmetric flaccid paralysis with no sensory loss

Question 20

Q

Bulbar Polio

Answer

A

Paralysis affecting the pharynx, vocal cords and diaphragm

Results in death if ventilatory support is not provided

Question 21

Q

Post-polio Syndrome

Answer

A

Occurs 30-40 yrs after polio infection
20-40% of original victims
Deterioation of muscles affected during initial infection
No virus present, no aberrant immune response

Question 22

Q

Poliovirus

Immune Response

Answer

A

Neutralizing serum IgG
- Prevents viremia
- Major role in blocking virus from entering CNS
Secretory IgA
- Prevents infection in OP and GI tract
CMI plays a role in resolution

Question 23

Q

Poliovirus

Vaccine

Answer

A

Two effective polio vaccines available today:

Sabin vaccine (OPV) ⇒ live attenuated organisms
- Was used in this country for many years but discontinued
- Still used in other countries where polio is endemic
- Lifelong immunity
- Induces natural immunity (i.e. IgA)
- Herd immunity
- Oral admin
- Risk to immunodeficient
- Risk of viral reversion
Salk vaccine (IPV) ⇒ killed virus
- Now used in the USA
- Need boosters
- IgG
- Need high community immunization levels
- IV admin
- Safe
- More expensive

Question 24

Q

Coxsackie Viruses

Answer

A

Common cause of aseptic meningitis

Two important groups:

Group A
- Hand, foot and mouth disease
- Herpangina ⇒ herpes-like vesicles in the buccal mucosa only
Group B
- Aseptic meningitis
- Also associated with myocardial and pericardial infections
- Usually in older children and adults
- Very severe in newborns
  - Febrile illness that progresses to heart failure

Question 25

Q

Hand, Foot, and Mouth (A16)

Disease

Answer

A

Most common in children under 5
Fever, ST, oral lesions that start as papules and become blisters
Palms and soles involved

Question 26

Q

Echovirus

Answer

A

Enteric Cytopathic Human Orphan Viruses

Types 1-34

Leading cause of viral meningitis
Typically associated with a petechial rash
Disease is usually self-limiting
Severity based on viral serotype, dose, pt status and age

Question 27

Q

Picornavirus

Summary

Question 28

Q

Encephalitis

Answer

A

Inflammation of the brain parenchyma with or without meningeal irritation
- Meningoencephalitis: Inflammation of the meninges and brain parenchyma
  - Usually has a viral etiology
Characterized by headache, fever, muscle aches/weakness, confusion, seizures, paralysis, LOC
Agents: HSV-1 and 2, Arboviruses, Naegleria, Rabies virus, Measles, Rubella

Question 29

Q

Herpes Simplex Encephalitis

Overview

Answer

A

Severe, devastating encephalomyelitis
Disease occurs throughout the year and in persons of all age groups
- 50% due to primary infection
- 50% due to recurrent infection
Dx w/ PCR of viral DNA from CSF
Acyclovir reduces morbidity and mortality
Histology: 3 M’s
- Multinucleation
- Margination of chromatin to the periphery of the nucleus
- Molding of the nuclei together

Question 30

Q

HSV Encephalitis

Children and Adults

Answer

A

HSV-1 in children and adults
Virus in trigeminal ganglion → temporal lobe via neurogenic pathways
Temporal lobe and base of the brain
Necrosis and hemorrhage
Antiviral agents may be helpful in acute therapy

Question 31

Q

HSV Encephalitis

Neonates

Answer

A

HSV-2 in neonates
Transmitted in birth canal of infected mother
- C-section reduces risk
CNS and systemic disease ⇒ High morbidity and mortality

Question 32

Q

Amoebic CNS Infection

Answer

A

Rare in North America
Rapidly fatal necrotizing encephalitis with Naegleria species (most common)
Chronic granulomatous meningoencephalitis with Acanthamoeba

Question 33

Q

Naegleria fowleri
General Characteristics

Answer

A

Protozoan parasite
3 developmental stages: cyst, flagellate and amoeboid (trophozoite) forms
Cyst form occurs under unfavorable conditions
Other forms are free living and thrive in warm freshwater

Question 34

Q

Naegleria fowleri

Lifecycle

Answer

A

3 developmental stages: cyst, flagellate and amoeboid (trophozoite) forms
Flagellate and trophozoites are free living and thrive in warm freshwater
Only trophozoites are infectious

Question 35

Q

Naegleria fowleri
Transmission and Epidemiology

Answer

A

Lives in very warm freshwater lakes mostly in southern states, hot springs and thermally polluted waters (powerplant runoff)
Found in sediment & disturbed by water activity
CNS entry through nose → cribriform plate and emissary veins
Travels along the olfactory nerve to the brain
Infections occur during the summer months
33 documented infections since 1996 with only 3 survivors

Question 36

Q

Naegleria fowleri
Clinical Manifestations

Answer

A

Early sx may include nasal congestion and loss of sense of smell
Symptoms of severe hemorrhagic, destructive meningo-panencephalitis occur 1 - 14 days after contact
- Includes headache, fever, nausea, vomiting and stiff neck
- Progress to seizures, loss of motor control and cognitive function
Infection is fulminant and progresses to death within 3-6 days
- 95% mortality

Question 37

Q

Naegleria fowleri
Diagnosis

Answer

A

ID organisms in brain on autopsy
A few cases have been dx early by the ID of trophozoites in CSF

Question 38

Q

Naegleria fowleri
Treatment and Prevention

Answer

A

Treatment:
- Only a few cases successfully treated with Amphotericin B
Prevention:
- Adequate chlorination of swimming water
- Avoid water related activities during period of high temp
- Hold the nose shut during water related activities in high-risk areas

Question 39

Q

Cysticercosis

Answer

A

Caused by Taenia solium (pork tapeworm)
Common in developing world
Man is the intermediate host for T. solium
Transmission and Pathogenesis:
- Fecal contamination of drinking water with eggs
- Larvae hatch and penetrate gut
- Disseminate in blood
- Cysts (cysticerci) develop in any organ
- Prefer brain, muscles, skin and heart
- In CNS become small, gliotic foci
Usually not lethal, but often neurologically symptomatic and can cause ↑ ICP
Seizure is common presentation
Treatable with anti-helminthics

Question 40

Q

Leptospira

Morphology and General Characteristics

Answer

A

Gram ⊖, obligate aerobe spirochete
Long and thin with hooks at one or both ends
Has periplasmic flagella ⇒ highly motile
Classified on the basis of specific antigens into 150 different strains called serovars
Easiest spirochete to grow ⇒ cultured on serum enriched media
Leptospirosis is usually a mild infection in both man and other animals
Common in Hawaii

Question 41

Q

Leptospira

Transmission & Pathogenesis

Answer

A

Contact with water, food or soil contaminated with urine of infected animals
Entry usually via ingestion or abrasions
Blood → kidney → urinary excretion

Question 42

Q

Leptospirosis

Clinical Manifestations

Answer

A

Disease ranges from subclinical to mild flu-like symptoms, meningitis or severe systemic disease
- Severity related to serovar of infecting strain
About 10% of individuals develop a highly fatal form known as Weil’s disease
- Characterized by jaundice, liver and kidney failure, vasculitis and myocarditis

Question 43

Q

Leptospirosis

Diagnosis

Answer

A

Serology, by microscopic agglutination

Cultures of blood, spinal fluid and urine

Question 44

Q

Leptospirosis
Immunity / Prevention

Answer

A

Due to bactericidal antibody and is serovar specific

Avoid exposure to contaminated water/animals

Question 45

Q

Arboviruses

Overview

Answer

A

Arthropod-borne virus ⇒ any virus transmitted by arthropod vectors

Infects vertebrates and invertebrates
Transmitted via bite of infected arthropod (mosquito)
Initiate persistent productive infection in salivary glands of small mammals, birds, and/or arthropods
Humans are usually dead-end hosts
Spring, Summer, early Fall
Aseptic meningitis to severe encephalitis that can cause serious morbidity and high mortality
CSF:
- Few lymphocytes
- ↑ Protein
- Normal glucose
Neuronal necrosis ⇒ neuronophagia

Question 46

Q

Arboviruses

Categories & Characteristics

Answer

A

Togaviruses (Alphaviruses): enveloped, ⊕-sense ssRNA
Flaviviruses: enveloped, ⊕-sense ssRNA, smaller than alphaviruses
Bunyaviruses: Enveloped, helical nucleocapsid, 3 segments of ⊖-sense ssRNA

Question 47

Q

Arboviruses

Transmission

Answer

A

Disease during summer months and rainy seasons
Viruses multiply in vertebrate and blood sucking insect hosts
- Extrinsic incubation period ⇒ time needed for virus to multiply in arthropod and achieve a concentration sufficient to infect and cause disease in humans
- Some insects maintain the virus in nature by transovarial transmission
Humans usu. dead-end host ⇒ insufficient viremia
- Exceptions include urban yellow fever and dengue
  - Humans can serve as reservoirs
  - Longer persistence of virus in blood and/or sequestration in the organs (West Nile infections)
  - Implications for blood banking and organ transplantation

Question 48

Q

Arboviruses

Pathogenesis

Answer

A

Replicates in endothelial cells, monocytes, and MΦ
Good inducers of Type I Interferons
- Flu-like sx initially
Spread to CNS via viremia
- IgG may block
- Delayed Ab response results in CNS disease

Question 49

Q

Arboviruses

Clinical Syndromes

Answer

A

Range of diseases:

Many infections are asymptomatic
Flu-like syndrome
- Fever with myalgias, arthralgias, and non-hemorrhagic rash
Encephalitis
- Fever, HA, AMS, seizures, coma
Hemorrhagic Fever ⇒ Dengue

Question 50

Q

Comparison of Selected Arboviruses

Question 51

Q

West Nile Virus

Overview

Answer

A

Flavivirus
Originated in Eastern Africa, Middle East
Reservoir: Wild birds
Vector: Mosquito

Question 52

Q

West Nile Virus

Clinical Disease

Answer

A

Asymptomatic (80%)
West Nile Fever (20%)
- Flu-like syndrome
West Nile meningitis or encephalitis (0.5%)
- Neuro-invasive
- May include muscle weakness and/or paralysis

Question 53

Q

West Nile Virus

Epidemiology

Answer

A

First seen in US in 1999
Highest incidence in AZ, NY, TX
Outbreaks usu. preceded by infection in the bird population
Risk factors:
- Immunocompromise
- Age – very old or very young
- Pregnancy
Median age
- Symptomatic disease 47 y/o
- Neuro-invasive disease > 75 y/o

Question 54

Q

West Nile Virus

Transmission

Answer

A

Mosquito bites
Transfusion and transplanted organ
- Seen in early 2,000s
- Red cross started screening blood in 2003
Intra-uterine / breastfeeding

Suggests longer viremia than other encephalitis viruses and/or sequestration in tissues of healthy individuals

Question 55

Q

West Nile Virus

Prevention

Answer

A

Spraying when mosquitos breed
Eliminating breeding sites (stagnant water)
Caution susceptible individuals to wear protective clothing or stay indoors during mosquito feeding times

Question 56

Q

Dengue Virus

Characteristics

Answer

A

Flavivirus family
- Enveloped, ⊕-sense ssRNA, smaller than alphaviruses
- Replicates in the cytoplasm
- Genome serves as mRNA
- Translation is the first step in replication
Reservoirs: monkeys and humans
Vector: urban mosquito (Aedes aegypti)
Four serotypes

Question 57

Q

Dengue Virus

Epidemiology

Answer

A

Tropical and subtropical areas
High density viremic population for transmission
- May be asymptomatic
- > 50% of world’s population at risk of infection
- 50-100 million cases of dengue fever each year

Question 58

Q

Dengue Fever

Answer

A

“Breakbone fever”

1° infection w/ Dengue virus

Clinical manifestations:
- High fever, chills, malaise
- Headache, retro-orbital pain
- Severe lumbosacral back and bone pain, myalgias
- Rash is frequently present
Runs its course in 5-7 days
Usually resolves without complications

Question 59

Q

Dengue Virus

Primary Infection Pathogenesis

Answer

A

Replicates 1° in vascular endothelium and monocytes or MΦ
Induces release of large quantities of cytokines
Viremia ⇒ systemic spread ⇒ viral amplification
Neutralizing Ab ⇒ resolution of infection
Subsequent infection w/ different serotype can lead to Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS)
- DSS or DHF may occur even if 1^st dengue infection asymptomatic

Question 60

Q

Dengue Virus

Secondary Infection Pathogenesis

Answer

A

1° infection w/ any serotype ⇒ virus specific Ab ⇒ life-long immunity to that serotype
Ab acts as “enhancing antibody” to other serotypes
Infection w/ a different serotype ⇒ Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS)
- Formation of immune complexes (virus-Ab) ⇒ internalized via Fc receptors into MΦ
  - More efficient infection
  - Greater replication of the virus
  - ↑ production of MΦ cytokines
- MΦ processed virus interacts with T-cells ⇒ hypersensitivity rxn @ endothelial surface
- Circulating immune complexes ⇒ ± complement activation ⇒ release of vasoactive amines
  - ↑ vascular permeability, perivascular edema, and mononuclear infiltration ⇒ effusions in the pleura and other cavities
  - ↓ Platelet production ⇒ ↓ clotting factors ⇒ ± hemorrhage from respiratory & GI tracts

Question 61

Q

Dengue Virus

Prevention & Control

Answer

A

No vaccine
- Attenuated tetravalent vaccine in clinical trials
Mosquitos feed all day w/ peak in early morning and late afternoon
Use protective clothing and insect repellant

Question 62

Q

Non-Arbo

Hemorrhagic Viruses

Overview

Answer

A

Includes:
- Arenaviruses
  - Lassa virus
  - Machupo virus
  - Junin virus
- Filovirus
  - Marburg virus
  - Ebola virus
- Hantavirus
  - Hantaan virus
  - Sin Nombre virus
All enveloped RNA viruses
Animal or insect reservoir
- Monkeys, rodents, bats
Humans are not the natural host
- Except for Dengue
Geographically restricted to where reservoir lives

Question 63

Q

Hemorrhagic Viruses

Transmission

Answer

A

Initial transmission
- Occurs when activities of reservoir, host, or vector overlap
- Transmission mech. to humans unknown
- Ex. contact w/ bush meat – Marburg
Ongoing transmission
- Once infection occurs in humans, highly transmissible by body fluids to others
- Occurs in outbreak form
- Ex. Ebola, Marburg, Lassa

Question 64

Q

Hemorrhagic Viruses

Pathogenesis and Clinical Disease

Answer

A

Initial Syndrome
- Abrupt onset of flu-like illness
- Fever, fatigue, malaise, headache, joint and muscle aches
- Progresses to either conditions below
Pulmonary shock-like syndrome
- Pulmonary edema
- Respiratory failure
- Death
Hemorrhagic syndrome
- Coagulopathy
- Petechial hemorrhage
- Bleeding from gums, eyes, ears, and GI tract
- DIC, organ failure, death

Answer 62

A

Supportive therapy only

High mortality rates

Answer 63

A

Hantaan virus
- Causes hemorrhagic fever or pulmonary shock syndrome
- Outbreaks common in US national parks
- Hikers, campers, seasonal cabin dwellers, occupational risks
- Transmission via contact w/ aerosolized mouse feces, urine
Sin Nombre Virus
- Causes pulmonary shock syndrome
- Outbreak in Four Corners region in 1993
- Endemic in Eastern Asia (China, Russia, and Korea)
- Deer mouse vector
- Transmission by breathing aerosols containing virus from contaminated urine
- Outbreaks coincide with high rainfall, increased food and rodent population

Answer 64

A

Hantavirus Pulmonary Syndrome (HPS)
- Flu-like syndrome for 2-3 days
  - Dry cough, malaise, HA, N/V, SOB
- Progresses to ARDS, kidney failure
- Mortality 35%
Hemorrhagic Fever with Renal Syndrome (HFRS)
- Eastern Asia (China, Russia, and Korea)
- Intense HA, nausea, fever, chills, back and abd pain
- Low BP, acute shock, vascular leakage
- AKI ⇒ severe fluid overload
- Mortality up to 15% depending on strain

Answer 65

A

Diagnosis:
- Serology, immunohistochemistry, PCR
Treatment:
- Largely supportive
- Intubation and oxygen therapy for HPS
- IV ribavirin for HFRS (early)

Answer 66

A

Hemorrhagic virus
Endemic in Africa and parts of South America
Enveloped, ambisense RNA
Includes Lassa, Machupo, Junin
Reservoir: persistent infection in rodents
Shedding of virus in saliva, urine, and feces

Answer 67

A

Hemorrhagic virus
Endemic in Africa and parts of South America
Enveloped ⊖-sense RNA
Includes Marburg and Ebola (50-90% mortality)
Reservoir: monkeys, bats

Answer 68

A

Severe encephalitis of midbrain and medulla

Bite of infected animal: racoons, dogs, bats
Neurotrophic transmission
Negri bodies are pathognomonic
Extraordinary CNS excitability (sensory & motor)
Pharyngeal muscle contraction ⇒ hydrophobia (do not drink water)
Flaccid paralysis, mania/stupor, coma
Pre and post-exposure vaccination is effective

Answer 69

A

Rhabdoviridae family of RNA viruses
Infect many mammals including humans
Bullet shaped w/ glycoprotein coat surrounding matrix protein
Helical ribonucleoprotein core
Unsegmented ⊖-sense ssRNA
Contains an RNA dependent RNA polymerase
Replicates entirely in the cytoplasm
Excess nucleocapsid material accumulates in cytoplasm of infected cells ⇒ forms characteristic inclusions known as Negri bodies

Answer 70

A

Incubation: 4 weeks to > 1 year
- Duration depends on bite site (shorter w/ bites of face and head), age, concentration of virus, and host immune status
- Enters muscle @ bite site & replicates
- No sx during incubation period
Virus infects the peripheral nerves ⇒ prodromal phase
- Fever, nausea, vomiting, headache, lethargy
- Retrograde axonal transport → DRG of spinal cord
Travels up the CNS to the brain ⇒ neurological phase
- Affects hippocampus, brainstem, and cerebellum
- CNS manifestations including depression, anxiety, hallucinations, hydrophobia, paralysis, delirium and seizures
  - Gross brain: may see mild congestion w/ perivascular infiltration or cuffing, no tissue necrosis
- From CNS, disseminates to the body including skin, salivary glands, cornea, adrenals, and kidneys
  - Replication takes place in the brain and probably also in salivary glands
- Stage progresses to coma and death within 1 to 3 weeks
  - Death usually occurs from pulmonary or cardiac complications

Answer 71

A

Antemortem diagnosis
- Fluorescent microscopy of skin biopsy of the nape of the neck
- Isolation of virus from saliva
- Ab in CSF or serum
Postmortem diagnosis
- Negri bodies in the brain (70-90%)

Answer 72

A

Treatment consists of three phases:

Local wound management
- Thorough flushing and disinfection of wound essential
- Assess need for tetanus prophylaxis
Passive immunization
- Given rabies immune globulin (RIG) within 24 hours
- Goal to prevent virus from entering neural tissue
- Little value once sx begin
Vaccination
- 3 commercially available inactivated virus vaccines
- 5 doses given IM within 1 month
- 1^st dose of vaccine @ the same time as passive therapy but at separate sites

Answer 73

A

Pre-exposure vaccination
- For individuals in high-risk groups
- Veterinarians, animal handlers, rabies virus lab workers and spelunkers
- Boosters may be advised for those with continuing risk
Key prevention strategies include:
- Vaccination of domestic dogs, cats and ferrets
- Avoid contact with wildlife and strays
- Seal chimneys and opening into houses to prevent den building
- Wear gloves or use a shovel to dispose of a bat once you think you’ve killed it

Answer 74

A

Some combination of:
- Headache
- Fever
- Nuchal rigidity (stiffness of the neck on passive forward flexion)
- Nausea
- Lethargy
- Reduced consciousness
- Seizures (particularly in children)
Paralysis and motor deficits more associated with encephalitis
Many of the signs and sx of encephalitis overlap with those of meningitis

Answer 75

A

Vary with patient’s age:

Neonates: E. coli and group B Streptococci
Infants: S. pneumoniae
- Immunization (1987) marked decrease in H. influenzae
Adolescents and young adults: Neisseria meningitidis
Adults: S. pneumoniae
Older Adults / Immunocompromised: Listeria monocytogenes

Answer 76

A

Group B Streptococci
Escherichia coli
Listeria monocytogenes

Answer 77

A

Streptococcus agalactiae

Causes 10% of meningitis cases overall
# 1 cause of neonatal sepsis and meningitis
~10k cases/year of GBS, ~300 deaths/year in the USA, 1-3 cases/1k births
Important in neonates but increasing in > 50 y/o
High mortality: up to 30% of cases die even w/ treatment

Answer 78

A

Gram ⊕ cocci in chains
β-hemolytic
Bacitracin resistant
CAMP test ⊕

Differentiated from Group A β-hemolytic strep ⇒ Bacitracin sensitive & CAMP ⊖

Answer 79

A

Normal intestinal flora and normal vaginal flora (10-30% of women)
- Neonates acquire during passage through birth canal
- Direct contact after birth
Entry through respiratory system, skin, GI tract
Risk factors for disseminated GBS infection:
- Lack of response to polysacc Ag
- Underdeveloped neonatal immune system

Answer 80

A

60% of infants born to colonized women become colonized
Premature delivery
Prolonged membrane rupture (>18 hrs)
Intrapartum fever of mom (38°C)
Previous neonate w/ GBS
Detection of GBS in urine

Answer 81

A

High risk groups:

African Americans
Diabetics
Sexually active
Multiple partners

Answer 82

A

Polysaccharide capsule
- 11 serotypes
- Ia, III, and V most often ass. w/ disease
  - Rich in sialic acid

Answer 83

A

Presents w/ fever, lethargy, difficulty feeding, irritability, respiratory distress, hypotension, cyanosis.

Entry through respiratory system, skin, GI tract
Normal sequence of events: Pneumonia → Bacteremia → Meningitis
- Starts w/ mucosal infection (PNA)
- Encapsulated organisms can easily move from blood into CNS
Mortality ~ 5%
- Depends on birthweight: > 1500 g = 14% mortality, < 1500 g = 65% mortality (1 kg = 2.2 lbs)
Neurologic sequalae in 15-30% of survivors

Answer 84

A

Early-onset infections
- Serotypes I, II, III
- Sx during first 5 days of life
- Infection acquired during birth
- ↑ Risk w/ premature delivery & prolonged rupture of membranes > 12 hrs
Late-onset infection
- Serotype III
- Seen in full term infants
- Presents at 7 days - 3 months old
- Direct contact transmission: nursery, mother
- ↑ survival, ↔︎ neurologic sequalae

Answer 85

A

Diagnosis:
- Cultures of blood or CSF
Treatment:
- Penicillin or Ampicillin IV
- Sometimes in combo w/ aminoglycosides
Prevention:
- Screen of pregnant women @ 35-36 weeks gestation
  - Intrapartum prophylaxis of culture ⊕ women ↓ transmission
- Colonized or high risk women
  - IV Abx during labor
- High risk newborns
  - IV Abx for 48 hrs after birth

Answer 86

A

#2 cause of neonatal sepsis (40%) and meningitis (75%)
- Enterobacter, Proteus and Klebsiella can also cause neonatal sepsis
Neonates (< 1 m/o) acquire E. coli during passage through birth canal
- Transmission from nursery personnel also seen
Virulence ⇒ anti-phagocytic K1 capsular polysaccharide
- Rich in sialic acid
- Neurotropic and assists in adherence to meninges
- Very resistant to phagocytosis

Answer 87

A

Uncommon cause meningitis & sepsis (10% overall)
Gram ⊕ rods
Elderly and pts with impaired T-cell immunity
Transmission
- Fetus via placenta
- Neonate via birth canal
- Ingestion ⇒ outbreaks
  - Young children
  - Elderly
  - Immunocompromised of all ages

Answer 88

A

Streptococcus pneumoniae
Haemophilus influenzae Type B
Neisseria meningiditis

Answer 89

A

Streptococcus pneumoniae

Causes 50% of septic meningitis cases
#1 cause of meningitis in children < 6 y/o after neonatal period and > 20 y/o
- Can cause meningitis in all age groups
Children
- Nasopharyngitis and otitis media with hematogenous spread
Elderly (very old)
- PNA with hematogenous spread
Conjugate vaccine has reduced incidence
20% mortality
Frequent cause of severe neurologic sequalae including cortical deficits and deafness (25-50%)

Answer 90

A

Transmission:
- Usually endogenous
- Exogenous via respiratory secretions
- Accompanied by pre-disposing factors
Epidemiology:
- Infects humans, no reservoir
- 20-40% are carriers in NP
- Incidence greatest < 6 y/o and > 60 y/o
- 1 mil deaths worldwide

Answer 91

A

> 80 serotypes based on capsular polysaccaride

Answer 92

A

Polysaccharide capsule ⇒ major factor
- Anti-phagocytic
- Strains w/ large capsules more virulent
- Loss ⇒ avirulent
IgA protease
- Aids establishment of infection
Pneumolysin
- Toxin w/ pore-forming action
- Injures cilia and endothelial cells ⇒ aids spread

Answer 93

A

Starts w/ mucosal infection (PNA, otitis media)
Spreads via blood to CNS
Massive inflammatory response, mostly PMNs
Edema and accumulation of pus

Answer 94

A

Smear ⇒ gram ⊕ cocci
Culture ⇒ blood agar or blood culture
Optochin sensitive
Detection of capsular Ag
- Latex agglutination test
- Quellung reaction
  - Ab to organisms in pure culture or clinical material
  - Causes capsule to swell
  - Can be used for typing

Answer 95

A

50% are PCN resistant

Fluoroquinolones or Vancomycin for serious disease.

Answer 96

A

1st gen vaccine (Pneumovax 23)
- Capsular polysacc. from 23 most common serotypes
- Rec. for high risk pts
Conjugate vaccine (Prevnar 13)
- 13 invasive serotypes polysacc. + CRM proteins
- Given to infants as part of routine vaccinations

Answer 97

A

Causes < 10% of meningitis cases overall
Formerly important pathogen in children
Nasopharyngeal infections with hematogenous spread
Less common since immunization (HIb)

Answer 98

A

Meningitis only caused by HiB
- Usually follows URT infection
Vaccine preventable
Unimmunized child < 2 y/o high risk
3-6% mortality
Sequalae frequent ⇒ 20% w/ permanent hearing loss

Answer 99

A

Small, gram ⊖ rods (cocco-bacillus)
Complex nutritional requirements
- X factor ⇒ hematin
- V factor ⇒ NAD or NADP
Grows well on chocolate agar
Small satellite colonies grow around colonies of S. aureus or other factor V excreting organisms ⇒ satellite phenomenon
Most invasive strain ⇒ causes 90% of all H. influenzae infections
Virulence due to unique polyribose-ribitol phosphate (PRP) capsule

Answer 100

A

Fastidious
Specimen from NP swab, pus, blood, or CSF for smears and culture
Grows on chocolate agar or BAP with X factor (hematin/hemin) and V factor (NAD)
PRP capsular Ag of HiB released into body fluids
- Antigen detection methods ⇒ latex agglutination

Answer 101

A

Passive protection by maternal Ab
- No episodes until after 6 m/o
Opsonizing anti-capsular Ab
- Capsule-type specific
- Enhance phagocytosis by PMNs
- Bacteriolytic in presence of complement
Active acquired Ab gradually increases up to ~ 10 y/o

Answer 102

A

Ampicillin for 5-10 days
Some are beta-lactamase producers
- ~ 25% of HiB
Newer cephalosporins are drugs of choice
- Ceftriaxone, cefotaxime

Answer 103

A

Causes 25% of meningitis cases overall
- Children < 5 y/o, adolescents and young adults
- Most common cause of epidemic meningitis
Airborne transmission
Vaccination available (military and most colleges require it)
Pyogenic gram-⊖diplococci
13 serogroups based on capsular carbohydrate composition

Answer 104

A

Respiratory droplet transmission
- Prolonged close contact ↑ risk
Humans are the only natural host
- Common in children (6 mo – 2 yrs) and adolescents
- Transient colonization of nasopharynx (1-40%)
- 5% of population chronic carriers (up to 35% of military recruits)
Epidemic outbreaks
- USA ⇒ Group B
- Rest of the world ⇒ Group C
- Usually seen in Winter and Spring
Bimodal distribution
- Maternal Ab gives protection (6-9 m/o)
- Disease peak in children (< 1 y/o)
- 2^nd peak in adolescents and young adults (15-25 y/o)

Answer 105

A

Age
Winter / dry season
Overcrowding
Certain social behaviors
- Passive exposure to cigarette smoke

Answer 106

A

Polysaccharide capsule ⇒ resists phagocytosis
- Linked to bacterial protection and invasion
- Polymers of sialic acid
Most strains have pili (outer membrane proteins)
- Attach to CD46
- Facilitates invasion into mucosal epithelial cells
- Non-piliated mutants less pathogenic
Endotoxin/LOS (lipo-oligosaccharide) ⇒ same activity as LPS
- Proinflammatory mediators
- Fever, shock, alternate complement pathway activation
IgA protease

Answer 107

A

Nasopharyngitis
- Most infections mild or inapparent
- Frequently transmitted by droplets, coughing and sneezing
Meningococcemia
- Septicemia occurs w/ or w/o meningitis
- Thrombosis of small blood vessels
- Produces metastatic lesions → skin, joints, eyes, lungs, etc.
- Skin involvement ⇒ petechial rash, may become confluent and produce purpura
- 40% mortality
Meningitis
- Inflammation and pyogenic infection of meninges
- Abrupt onset HA, fever, stiff neck, ± N/V
- ± Petechial rash and metastatic lesions in other organs
- Does not develop following every case of nasopharyngitis or meningococcemia
- 9-12% mortality w/ abx
Fulminating meningitis
- Severe meningitis w/ sudden onset of sx
- Characterized by presence of a large number of organisms in the blood stream and meninges
± DIC and gram-⊖shock
“Waterhouse-Friderichsen syndrome”
- Commonly associated w/ meningococci
- Adrenal gland bleeding and destruction

Answer 108

A

Most commonly caused by N. meningitidis
Overwhelming meningococcemia leads to massive hemorrhage in the adrenal glands
Characterized by low BP, shock, DIC, widespread purpura, and rapidly developing adrenocortical insufficiency

Answer 109

A

Need Ab response to the capsule
Carriers develop protective response (anti-capsulate Ab) over time
Complement deficiency of terminal components (C5-C8) predisposes to disseminated disease

Answer 110

A

Gram stain ⇒ presumptive dx
- Grow on chocolate agar, Thayer Martin Agar
Latex agglutination
- Direct detection of capsular polysaccharides
- Low sensitivity for serogroup B ⇒ helpful if ⊕, does not r/o if ⊖
PCR of CSF
- If abx have been used and to type strains
Biochemical tests
- All Neisseria are Oxidase ⊕
- N. gonorrhoeae is Glucose ⊕ only
- N. meningitidis is Glucose ⊕, Maltose ⊕

Answer 111

A

Treatment
- Penicillin G (no known PCN resistance)
- Ceftriaxone or chloramphenicol if febrile
  - Ceftriaxone will also cover other causes of bacterial meningitis (e.g. GBS)
Prophylaxis for close contacts (e.g. family members)
- Oral Rifampin ⇒ reaches high concentrations in oral secretions
Prevention
- Vaccines available for less prevalent serogroups
  - Serogroups A, C, Y, W-135 ⇒ ↓ carrier rate
  - Conjugate licensed for US adolescents
- New Group B vaccine
  - Poorly immunogenic capsule
  - For 16-23 y/o, high risk, or outbreak control

Answer 112

A

Organisms: Streptococci or Staphylococci
Sources:
- Direct implantation
- Local extension (mastoiditis, sinusitis)
- Hematogenous (heart, lungs, bone, teeth)
Predisposition:
- Infective endocarditis
- Right to left cardiac shunts (bypasses lungs)
- Chronic pulmonary sepsis (bronchiectasis)
Location: Frontal lobe > parietal lobe > cerebellum
Clinical:
- Progressive focal deficits
- ↑ ICP, WBCs and protein
- Normal glucose
Causes death by:
- ↑ ICP ⇒ herniation
- Abscess rupture ⇒ ventriculitis, meningitis, venous sinus thrombosis

Answer 113

A

Tuberculosis
Neurosyphilis
Neuroborreliosis

Answer 114

A

Chronic Meningoencephalitis

Part of diffuse active disease vs “isolated” seeding from undiagnosed infection (often PNA)
Most common pattern is diffuse meningoencephalitis
May spread via CSF to the choroid plexus and ependymal surface
Clinical manifestations: headache, malaise, mental confusion, and vomiting
Gross:
- Subarachnoid space w/ gelatinous or fibrinous exudate
- Characteristically involves the base of the brain, effacing the cisterns and encasing cranial nerves
Micro:
- Mixed inflammatory infiltrates
- Well-formed granulomas with caseous necrosis and giant cells
- Organisms can be seen with acid-fast stains
CSF:
- Moderately increased cellularity (lymphocytes, PMNs)
- Protein elevated, often markedly
- Glucose moderately reduced or normal
- Bacteria may be cultured from the CSF but typically not seen in cytology specimens

Answer 115

A

Arachnoid fibrosis ⇒ hydrocephalus
Obliterative endarteritis (Heubner’s Arteritis) ⇒ arterial occlusion and infarction of underlying brain
Tuberculoma
Pott Disease

Answer 116

A

Severe proliferating endarteritis (inflammation of the intima or inner lining of an artery)
Results in occlusion of artery lumen
Seen in both TB and Syphilis

Answer 117

A

Inflammation may become localized and form a mass-like lesion
Causes mass effect
Caseating granulomas
May be calcified

Answer 118

A

“Vertebral Tuberculosis”

Rare
Neurologic complications from collapse of vertebral bodies ⇒ spinal cord compression
May form soft tissue abscesses adjacent to involved vertebrae

Answer 119

A

Caused by Treponema palladium (gram ⊖ spirochete)
CNS involvement in ~10% of untreated cases
- Usually 3-10 years after primary infection
Patterns of CNS involvement:
- Meningovascular Neurosyphilis
- Paretic Neurosyphilis
- Tabes dorsalis
Transmission: sexual contact, congenital (crosses the placenta), contact with a primary lesion

Answer 120

A

Typically involves base of brain, convexities, spinal cord
Microscopic:
- Dense lymphoplasmacytic inflammation
CSF:
- WBC: variable lymphocytes and plasma cells
- ↑ Protein
- Glucose normal to low
Organisms generally not seen in cytology specimens
VDRL (Venereal Disease Research Laboratory): ⊕

Answer 121

A

Chronic meningitis due to T. palladium

Typically involves the base of the brain and more variably the cerebral convexities and spinal leptomeninges
Complications:
- Obliterative endarteritis (Heubner arteritis)
  - Accompanied by distinctive perivascular inflammatory reaction rich in plasma cells and lymphocytes
- Cerebral Gummas
  - ± Plasma cell-rich mass lesions in meninges → parenchyma
  - Typically seen in bone and skin

Answer 122

A

Invasion of the brain by T. pallidum

Clinically insidious but progressive cognitive impairment
- Mood alterations (including delusions of grandeur)
- Terminate in severe dementia (general paresis of the insane)
Parenchymal damage of the cerebral cortex most common in frontal lobe but also other areas
Micro:
- Loss of neurons
- Proliferation of microglia (rod cells)
- Gliosis
- Iron deposits
Spirochetes may be demonstrated in tissue sections

Answer 123

A

Damage to sensory axons in the dorsal roots by T. pallidum

Clinical manifestations:
- Impaired joint position sense and ataxia (locomotor ataxia)
- Loss of pain sensation ⇒ joint damage (Charcot joints)
- Characteristic “lightning pains”
- Absence of DTRs
- Other sensory disturbances
Microscopic:
- Loss of axons and myelin in dorsal roots
- Pallor and atrophy in the dorsal columns

Answer 124

A

Lyme Disease sequelae
Caused by Borrelia burgdorferi (gram ⊖ spirochete)
Transmitted by Ixodes tick
Symptoms variable:
- Facial nerve palsies
- Other polyneuropathies
- Encephalopathy

Answer 125

A

Primarily in immunocompromised individuals
CNS typically involved following widespread hematogenous dissemination
- Can be local extension (DM, Neutropenia)
Most frequent pathogens:
- Candida albicans
- Mucor species
- Aspergillus fumigatus
- Cryptococcus neoformans
In endemic areas - Histoplasma, Coccidioides, and Blastomyces
Three main forms of injury:
- Chronic meningitis
- Vasculitis – (Aspergillus & Mucor—sometimes others)
- Parenchymal invasion

Answer 126

A

Common opportunistic infection in AIDS
May be fulminant and fatal in as little as 2 weeks or indolent, evolving over months or years
Clinical: Few meningeal symptoms
CSF may contain few cells but usually has a high concentration of protein
Polysaccharide capsule (usually)
Examination of the brain shows gelatinous material within the subarachnoid space and small cysts within the parenchyma (“soap bubbles”)
Diagnosis in CSF:
- Cryptococcal antigen
- Cytology
  - India ink stain [Historical]
Treatable with antifungal drugs

Answer 127

A

Protozoal CNS Infection

Opportunistic infection ⇒ HIV
Subacute, evolving during a 1- or 2-week period
May be both focal and diffuse
Microscopic: free tachyzoites and encysted bradyzoites at the periphery of the necrotic foci
Vessels near lesions may show marked intimal proliferation or vasculitis with fibrinoid necrosis and thrombosis

Answer 128

A

Reactivation due to immune suppression
Common cause of neurological symptoms in AIDS patients
Multiple small abscesses in deep grey matter

Answer 129

A

Blood-borne from maternal infection causing necrotizing CNS lesions in the fetus that may calcify
Pregnant women shouldn’t clean the cat litter box
Multifocal, calcific, necrotizing lesions results in severe brain damage

Answer 130

A

Slow infections
Long incubation periods that can last decades
Caused by conventional viruses (JC virus and measles) or unconventional agents (prions)
Once sx manifest, death is inevitable within 1 to 2 years

Answer 131

A

Persistent, chronic measles infection
Rare (7 in 1 mil cases) ⇒ ↓ since intro of live measles vaccine
Vaccination w/ attenuated virus protects against SSPE
Children or young adults
Manifests 5-8 years after initial measles virus infection
Results in death within 2 years of onset

Answer 132

A

Variant or altered measles virus ⇒ ∆ M protein (involved in virus assembly)
- ∆ Budding ⇒ ⊗ release of progeny virus ⇒ accumulation of defective virus in neurons
Very high levels of anti-measles Ab found in CSF and serum
Lack of Ab to M protein

Answer 133

A

Slowly progressive degenerative neurological disorder
Characterized by demyelination in multiple brain regions
Spasticity, loss of motor skills, seizures, progressive dementia
Microscopic:
- Brain atrophy and gliosis
- Inclusions in oligodendrocytes and neurons
- EM: defective measles virus ⇒ nucleocapsids

Answer 134

A

JC Virus and BK Virus

Belongs to the papovavirus family
- Naked circular dsDNA genome
- Replicates and assembled in the nucleus
Most individuals acquire asymptomatic infection during childhood
- ~ 65% infected by age of 14
Latency → immunosuppression → reactivation
- Immunocompetent adults reactivate and shed virus periodically
- 40% of immunocompromised secrete JC or BK in urine

Answer 135

A

Latent polyoma virus
Causes renal disease in immunosuppressed hosts
Causes nephropathy in ~ 5% of kidney recipients
- May result in loss of a transplanted kidney
Viremia in 50% of bone marrow transplant recipients
- Ureteral stenosis, hemorrhagic cystitis

Answer 136

A

Reactivation of latent polyoma virus (JC virus)

Asymptomatic infection during childhood (65%)
Virus remains latent in the kidney
Immunosuppression ⇒ viral replication ⇒ dissemination to CNS ⇒ progressive disease
- Complication of AIDS (5-10%)
Lytic infection destroys oligodendrocytes ⇒ widespread demyelination
- Severe neurologic disability
  - Speech, vision, paralysis → death
No Ab produced
Median survival of 6 months

Answer 137

A

Transmissible Spongiform Encephalopathies

Infectious agent composed of a misfolded protein (prion)
No nucleic acid has been found ⇒ do not replicate
May be sporadic, familial or transmissible (infectious)
All known prion diseases ∆ structure of the brain or other neural tissue
All are currently untreatable and universally fatal

Answer 138

A

Proteinaceous Infectious Particle

Normal prion protein (PrP^C) encoded by a cellular gene (PRNP)
- Highest level of expression in the CNS
- Unknown function but normally found on cell surface
- Normal 3D configuration (helical) ⇒ susceptible to digestion by proteases
Abnormal prion form (PrP^SC) ⇒ identical AA sequence but 3D folding differs (β sheet) ⇒ resistant to protease digestion
- Found within vacuoles instead of cell membrane

Answer 139

A

Ingestion of infected food
Improperly sterilized surgical equipment (neurosurgery)
Infected blood products
- American Red Cross Deferral for Donors:
  - Persons who have spent long periods of time in countries where “mad cow disease” is found (UK) are not eligible to donate
  - Related to concerns about variant Creutzfeldt Jacob Disease (vCJD)

Answer 140

A

When a prion enters a healthy organism ⇒ induces existing, properly folded proteins to convert into disease-associated, prion form

PrP^SC can form dimers with PrP^C and ‘teach’ it to form the abnormal configuration
↑ formation of PrP^C ⇒ converted into PrP^SC
T_½ of days instead of hours like normal cellular form
Found inside cytoplasmic vesicles within cells and is secreted
Accumulation of non-degradable PrP proteins in the brain ⇒ neurological degeneration
No immune activation or inflammation is detected

Answer 141

A

Spongiform change

Vacuolation of neurons
Diffuse astrocytosis and cellular loss
Formation of eosinophilic amyloid plaques and fibrils comprised of aggregated PrP^SC

Answer 142

A

Caused by a specific mutation in the PRNP gene
Mutation causes asparagine → aspartate at residue 178 of PrP^C
Results in FFI when it occurs in a PRNP allele encoding methionine at codon 129
Results in CJD when present in tandem with a valine at this position
How these amino acids influence disease phenotype is not understood

Answer 143

A

Found in sheep and goats
Clinically recognized for more than 250 years
Intense itching ⇒ scrape body against fixed objects
Progressive behavioral changes, tremors, ataxia and paralysis
Spinal cord pathology

Answer 144

A

Fore tribe in New Guinea
Similar presentation to CJD (with intense itching) except for the absence of dementia
- Shaking, difficulty walking, and difficulty swallowing
Incubation period 4-20 years
Death in ~ 1 year
Transmissible agent passed during food preparation for cannibalism
- Cannibalism abolished ⇒ ↓ cases
Women and children primarily affected

Answer 145

A

Subacute dementing illness with myoclonic jerks

Sx include radial loss of muscle control and speech, tremors, shivering and dementia

Sporadic CJD (90%)
- Mutation in one neuron
- Arises in pts with no known risk factors
- Most common type
- Onset > 70 y/o
Hereditary CJD (10%)
- Mutation in germline
- ⊕ Fhx and/or ⊕ for genetic mutation associated with CJD
- Onset < 60 y/o but wide range
Acquired CJD (< 1%)
- Transmitted by contact with brain or nervous system tissue
  - Usually iatrogenic ⇒ injection, corneal transplant, transfer of pituitary material, contaminated neurological equipment
  - No evidence of transmission via casual contact with a CJD patient
- Incubation period 2-30 years

Answer 146

A

Bovine Spongiform Encephalitis (BSE)

“Mad Cow Disease”

Developed when infected feed was fed to cows that entered the human food chain
Most prevalent in the UK
American Red Cross Deferral for Donors:
- Persons who have spent long periods of time in countries where “mad cow disease” is found (UK) are not eligible to donate.
- This requirement is related to concerns about variant Creutzfeld Jacob Disease (vCJD)

Answer 147

A

Ingested prions accumulate in gut secondary lymphoid tissue
Travel lymphatogenously
Access neurons and travel up neurons to the brain/CNS
There may be genetic susceptibility to ingested/acquired prion diseases
- Polymorphisms in certain codons of the PrP protein may confer susceptibility
- Homozygosity at codon 129 is present in 95% of CJD cases and 100% of nCJV

Answer 148

A

Clinical diagnosis initially
Confirmed by immunohistochemistry of the brain on autopsy (CJ and vCJ)
vCJD can be dx by immunoblot of PrP using tonsil biopsy tissue
Elevated CSF protein 14-3-3 (marker of brain cell death) may have potential dx value

Answer 149

A

Progressive cerebellar ataxia
Autosomal dominant
Onset earlier ~ 50 y/o
Longer duration

Answer 150

A

Intractable and progressive insomnia, ataxia, autonomic disturbances, stupor, and finally coma
Caused by a specific mutation in the PRNP gene
Mid-life onset
Disease course typically less than 3 years
A non-inherited form of the disorder (fatal sporadic insomnia) has also been described

Brainscape's Knowledge GenomeTM

CNS Infections Flashcards

Brainscape's Knowledge Genome^TM