Saviola: Bacterial and Viral infections of the CNS Flashcards
What are normal protein and glucose concentrations plasma? CSF?
Plasma:
protein: 6000
glucose: 100
CSF:
protein: <45
glucose: 2/3 blood glucose (about 60)
What is meningitis?
inflammation of the meninges of the brain or spinal cord, infection located within the subarachnoid space; CSF
What is encephalitis?
inflammation of the brain tissue
what is myelitis?
inflammation of the spinal cord
How can antibiotic therapy potentially exacerbate symptoms of meningitis?
may exacerbate symptoms by lysing cells and releasing immunogenic cell wall components and allowing more vigorous immune response. The worsening symptoms are likely from an increased immune response and inflammation
corticosteroids can be given with antibiotics to decrease the immune response
When is it likely that antibiotics will cross the BBB and kill bacteria?
early in therapy when the BBB is breached due to inflammation
What is a normal immune response of the CNS? How is this different from an infected CNS?
normal: low [Ab], small numbers of lymphocytes, no plasma or polymorphonuclear leukocytes and no complement components found in the CNS
infected:
w/inflammation, BBB is breached at microvascular endothelium. secretion of cytokines from local macrophages into the subarachnoid space–> breack in NNN. serum proteins into CSF, polymorphonuclear leukocytes present. Ab production by plasma cells may occur at site and CMI cells present. Antibiotics can also cross this BBB
What are some routes of infection of the CNS? (8)
- Hemtogenous (blood borne) spread with most infectious agents. From extracranial foci or by retrograde propagation of infected thrombi within emissary veins.
- Neurotropic spread in the case of some viruses
- Spread of organisms through bone
- Injury- traumatic inoculation of extradural bacteria.
- Surgery- shunts etc.
- Congenital problems
- Otitis- by extension.
- Sinusitis- by extension.
What are some symptoms of acute bacterial meningitis? What will the CSF gram stain and bacterial culture show?
fever, headache irritability, stiff neck, convulsions, drowsiness, coma
CSF gram stain and/or bacterial culture usually positive, unless the patient has been treated with antibiotics prior to evaluation.
What is the most common way that organisms enter the subarachnoid space?
blood borne –> crossing the vascular endothelium or the choroid plexus
usually after nasopharyngeal colonization
What is the pathogenesis of acute bacterial meningitis?
organism enters subarachnoid space
organisms multiply
cell wall components accumulate in the CSF and are inflammatory
Migration of neutrophils
Loosening of the BBB results in inflow of fluids and proteins and antibiotics
Cerebral edema as a result of release of toxic factors
Obstruction of flow of CSF back to blood.
Increased ICP.
What are some characteristics of H. influenzae?
gram negative, pleomorphic bacilli.
polysaccharide capsule (type B)=more invasive (we have vaccine for most common invasive/encapsulated types)–>antiphagocytic
requires X and V factors if grown on blood agar, chocolate agar releases X and V factor
respiratory transmission
Nasopharyngeal carriers common of non type b, but not associated with a high incidence of meningitis
What is the most common cause of meningitis in adults and children under the age of 5?
S. pneumoniae (smokers over 65 yo are predisposed)
What are some characteristics of S. pneumoniae?
Gram + lancet shaped diplococcus, a- hemolytic, optichin positive (optichin inhibits its growth)
antiphagocytic capsule
transported across microvasular endothelial cells in a receptor dependent manner.
Meningitis may be a complication of bacteremia, pneumonia, mastoiditis, endocarditis, and sinusitis.
Associated w/ meningitis after a head wound.
pili help adhere to the oropharynx
What are some characteristics of Neisseria meningitidis?
Gram- diplococcus, oxidase positive (cytochrome C), ferments maltose and dextrose (glucose).
Respiratory transmission.
Virulence associated with antiphagocytic capsule, invasive disease- 13 serotypes. Vaccine against A, C, Y, and W-135.
Causes disease mainly in children and young adults.
LOS (Lipooligosaccharide) = important pathogenic factor.
Some strains coat themselves in HOST sialic acid that are attached to galactose residues on LOS and prevents complement induced killing and survive in the blood.
grown on blood agar or chocolate agar plates
Thayer-martin selective agar to isolate from throat
What are some characteristic of Listeria monocytogenes? Who is most likely affected by this?
gram + rod
Motile (tumble at 22C) (actin rockets)
catalase +
food-borne (lunch meat)
**can cause fetal death and and maternal death in pregnant women. also can affect immunocompromised pts
What are some characteristics of S. agalactiae? (where found? who is normally infected and how to prevent it?)
Group B Streptococcus (GBS).
Found in vagina of some women.
Common cause of meningitis, pneumonia, sepsis in newborns
Untreated carriers have 1 in 200 chance of delivering an infected baby.
Preventable- screen for bacteria; intrapartum antibiotics (to the mother).
When are aerobic gram - bacilli likely to cause acute bacterial meningitis?
predisposing conditions= head trauma, neurosurgical procedures, neonates, elderly, immunocompromised
What are some predisposing factors of staphylococci infections in the brain (S. aureus and S. epidermis)?
postneurosurgical, CSF shunts, head trauma, sinusitis, pneumonia.
What is chronic meningitis? What can cause it?
Neurological symptoms and signs persist or progress clinically, and the CSF remains abnormal for at least 4 weeks (replicates slowly)
More rare than acute meningitis.
M. tuberculosis, Brucellosis, Syphilis, Lyme disease.
What is a brain abscess?
focal intrcranial infection in the brain;
Develops into a collection of pus surrounded by capsule
likely Spread from contiguous source- otitis media, mastoiditis, sinusitis, dental trauma, penetrating trauma.
what is an epidural abscess?
lesion has created space between dura mater and the skull. Infection must peel the dura mater from the skull in order to spead in this plane.
What is subdural empyema?
What often causes this and how?
There is a potential space between the dura mater and the arachnoid. The membranes are held together by outward pressure of the brain, but infection can create space and move easily within it.
S. aureus and other gram - rods and anaerobes
paranasal sinuses are often the source. then the middle ear and mastoid.
may follow skull trauma, surgical procedure, infection of a preexisting subdural hematoma
What is a spinal epidural abscess or subdural empyema and what is it normally an extension of? What organism often causes this?
Fills actual space within the spine.
The dura mater adheres to the skull in the cranium, whereas in the spine there is an actual space (the epidural space)–> The infection can spread unimpeded in this space.
Extension of osteomylitis or paravertebral infection or via hematogenous spread.
S. aureus or gram - bacilli or streptococci
How do viruses invade the CNS?
Most invade directly across cerebral capillary endothelial cells
Some directly infect cerebral microvasculature endothelial cells before infection of adjacent glia and neurons.
May transverse the Chroid plexus epithelium- dispersion of virus in CSF with resultant contact of meningeal and ependymal cells.
May be carried between cerebral endothelial cells in infected immune cells (T-cells, macrophages) after BBB disruption
How do most viruses infect the CNS? What are the exceptions and how do they infect the CNS (2)?
hematogenous spread
exceptions:
1. herpes: HSV encephalitis may result from reactivation of virus from trigeminal ganglia
- rabies: enters CNS via retrograde movement within neurons
What is the most common cause of viral meningitis?
enterovirus
mumps used to be before the vaccine
What type of infection do viruses typically cause?
aseptic meningitis (inflammation of meninges and choroid plexus without an identifiable etiological agent from a gram stain or culture of CSF)
or encephalitis
(DO NOT cause abscesses)
What is fatal viral encephalitis?
an inflammatory reaction is usually prominent in the meninges and in a perivascular distribution within the brain (monocytes and some polymorphonuclear cells).
Neural cells may show degenerative changes and there may be phagocytosis of neurons by macrophages.
There may be multinucleated giant cells with viral antigens present in the brain.
What is important for clearance of a virus from the CNS?
in tat host immune response (cell-mediated immunity!!)
What are some treatments of viral CNS infections? (3)
chemotherapy for HIV and herpes
supportive care and immunoglobin
vaccination
What are some characteristics of enteroviruses? (how spread? when infect? virulence?)
the leading cause of aseptic meningitis
summer/fall seasonality
fecal-oral
lytic viruses
resistant to stomach acid and disinfection
infants and young children most commonly affected (<2 weeks=severe disease and poor outcome)
What are some characteristics of poliomyelitis? (what causes it? when and how?)
poliovirus (enterovirus) causes an acute illness involving meninges and replicates in the motor neurons of the anterior horn of the spinal cord and brain stem.
May produce permanent paralysis (flaccid paralysis)
virus multiplies in neurons and kills them
can be caused by the live oral vaccine (OPV) –>VAPP-vaccine associated paralytic polio (give IPV instead of OPV but IPV doesn’t provide good mucosal immunity in the GI tract)
what is post-polio syndrome?
25-35 years after recovery there is a gradual progression of muscle weakness.
possibly due to motor neurons which survived polio eventually losing axon terminals
What is the virus that has been recently found in California children causing polio-like illnesses?
enterovirus-68
–> new strands of enterovirus
What are some characteristics of mumps virus?
paramyxovirus (large –SSRNA).
Spread by respiratory route, most common in late winter and spring.
Incubation period 16-18 days.
Neurological complications are 3x more frequent in males.
Symptomatic meningitis in as many as 4-6% of mumps patients, and asymptomatic CSF presence in 50%.
Encephalitis 1 in 6000 mumps cases.
In an unimmunized population, mumps is the most common cause of aseptic meningitis and encephalitis.
How is mumps virus spread within the body?
respiratory inoculation–> local replication–> viremia–> systemic infection–> parotid gland, tested, ovaries, peripheral nerves, inner ear, CNS, or pancreas
What are some characteristics of arboviruses?
obligatory cycle of multiplication in the arthropod before transmission to the next vertebrate host (extrinsic incubation period)
virus multiplies without damaging its arthropod vector and sometimes its reservoir
highest incidence in late summer and fall when vector is active
What viruses have increased incidence in the summer?
enteroviruses, tick-borne and mosquito-borne viruses
What are some arboviruses?
- togavirus: small enveloped +ssRNA
2. EEE, WEE and VEE can cause serious encephalitis and high fatality in children
What are some characteristics of EEE?
arbovirus
uncommon but found in costal areas where mosquitoes breed.
transmission cycle: between mosquitoes and birds with horses and humans occasionally infected
cause serious encephalitis and can leave grave neurological sequelae in survivors
What is the principal cause of epidemic encephalitis in the US? how is
St. Louis Encephalitis (SLE)
less severe than EEE but more likely to attack elderly
What is a risk factor for a severe case of West Nile virus?
advanced age
severe case: neurological disease and fever. 1/150 get this
What are some characteristics of bunyaviruses?
enveloped, -ss RNA, segmented
part of the California Encephalitis Group
it is the most commonly reported cause of arbovirus encephalitis in non-epidemic years.
mosquito affects mainly people in the woods
causes benign aseptic meningitis to severe encephalitis
What are some characteristics of Colorado Tick Fever Virus?
Reovirus. Double stranded RNA virus w/ 12 genomic segments.
Has an outer capsid of undefined shaped and inner capsid of icosahedral shape.
Causes disease in the western and northwestern United States, w/ hundreds of cases occurring annually.
The virus infects erythroid precursor cells.
Neuronal infection can lead to meningitis and encephalitis.
Usually a benign disease, but occasional nuchal rigidity and pleocytosis.
How can arboviruses be controlled?
surveillance
eliminate standing water
screens
avoid outdoor activity in the evening
wear insect repellent and protective clothing
What are some characteristics of herpesviruses? What is the most common herpesvirus in encephalitis?
Large double-stranded DNA viruses, with envelopes acquired at modified nuclear membrane
latency
HSV-1 (causes 95% of herpes related encephalitis)
What are some characteristics of HSV-1?
Very common virus.
The most common cause of nonepidemic fatal encephalitis in the U.S.
Spread-direct contact with infected secretions, usually oral.
Primary infection asymptomatic or gingivostomatitis, or pharyngitis
can remain latent in the trigeminal ganglia in the face
encephalitis may be primary infection or activation of a latent infection
**causes cowdry type A inclusion bodies
What is HSV-2 normally associated with?
meningitis, not encephalitits
What is rabies? How do you get it and what causes it?
almost invariably fatal encephalomyelitis
Caused by a rhabdovirus-bullet shaped negative strand ssRNA virus with lipoprotein membrane. Easily inactivated by heat and drying.
Usually transmitted through bite of infected animal
get vaccine if get bit==> 10-14 days for immunity
What is post infectious encephalomyelitis? What can cause this? Do sequelae normally occur?
an unusual neurological outcome of viral infection
Short lag occurs between encounter with viral antigen and onset of disease.
Pathologic hallmarks are inflammation and demyelination. A reaction to CNS myelin in brain, spinal cord and optic nerve
varicella, mumps, measles
50% of survivors will have sequelae such as blindness, paraplegia, and ataxia. 10% have residual seizure disorders.
*most frequently seen after nonspecific upper respiratory infections where the etiologic agent is unknown
What is subacute sclerosing pan encephalitis (SSPE)?
- caused by variant measles virus (reduced matrix protein, fusion protein and hemmaglutinin)
- mature viruses are not produced
- large numbers of nucleocapsids in many cells
- no treatment
1 case/1X106 per year before vaccine was widely used.
Most common in children who had measles before age 2.
Average onset 7 to 8 years old.
Males 3X more often than females.
Occurs 6 years or so after measles infection
symptoms:
- Insidious onset with behavior problems, and early dementia.
- Later disturbed motor function, seizures.
- Stuporous rigid state.
- Death in 1 to 3 years
What is guillain-barre syndrome?
Acute inflammatory demyelinating polyradiculonueropathy.
Significant association with antecedent virus-like respiratory or gastrointestinal illness.
Occurs 1-4 weeks after infection.
May be due to sensitization to peripheral nerve myelin.
There is ascending motor weakness.
85% recover, but it may take 4-6 months
*most frequent cause of acute severe generalized human paralytic disease (with the decline in poliomyelitis)
