CNS Infections Flashcards
what are some general key differences in CSF between CNS bacterial and viral infections?
Glucose is low and neutrophils and protein are high in bacterial infections
lymphocytes and monocytes will be high in viral infections, protein in CSF is slightly elevated
what are the most common enteroviruses that cause encephalitis?
Coxsackie A and B viruses
Echo virus
describe the infectious course of enteroviruses - pathogenesis
Virus replication begins in the intestinal
mucosa and lymphoid tissue of the tonsils
and pharynx
spreads by viremia to
cells of the lymph nodes, spleen and liver -> replicates some more
cytolysis - burst out of cells they infect
immune response is IgA and IgG antibodies
what are the syndromes associated with coxsackie viruses?
Hand, foot and mouth disease
herpangina
pleurodynia
myocardinal and pericardial infections
aseptic meningitis
what are the ways the viruses get into the CNS?
Transported over in infected white blood cells - hematogenous dissemination?
invading peripheral nerves and traveling into the CNS - neuronal retrograde dissemination
infecting cells that form anatomical barriers
what’s the most common cause of encephalitis?
encephalitis - infection of the brain parenchyma
viral is more common than bacterial and fungal
often accompanied by viral meningitis
how does viral meningitis present?
inflammation of the subarachnoid membrane
fever, headache, nuchal rigidity and photophobia
CSF - lymphocytic pleocytosis
viral meningitis is typically a milder disease than bacterial or fungal meningitis
what classes of viruses are the most common causes of non-sporadic aseptic meningitis?
enteroviruses
arboviruses - responsible for epidemics
acid fast stain
TB
India Ink stain
cryptococcus neoformans
how is viral meningitis diagnosed?
evaluation of the CSF profile - lymphocytic pleocytosis, with normal protein, glucose
negative acid fast and india ink stains
negative cultures
what’s the primary diagnostic test for viral CNS infections?
PCR of the CSF
this is how you can tell the exact virus that’s infecting
describe the pathogenesis of enteroviruses
they spread by the oral-fecal route and divide in the GI tract.
They get out of the GI tract through peyer’s patches
viremia - virus travels in blood to lymph nodes. spleen and liver to replicate some more (symptoms)
viral replication damages the cell -> signs and symptoms of disease
IgA is the primary immune defense
hand, foot, and mouth disease
coxsackievirus virus syndrome - serotype A16
painful red blisters in the mouth, palms of hands and soles of feet.
self limited infection
herpangina
infection of the throat - rid ringed blisters and ulcers on tonsils and soft palate
fever, sore throat, pain on swallowing and vomiting
self-limited, coxsackie A
pleurodynia
bornholm disease - coxsackie B virus
acute illness with painful spasms in the muscles of the chest and upper abdomen, fever and pain ^
myocardinal and pericardinal infection
coxsackie B virus
sporadic occurance in all ages, life threatening in newborns
in newborns -> febrile illness and sudden heart failure
aseptic meningitis - coxsackieviruses
rarely encephalitis also occurs
can occur with petechiae/rash, full recovery in absence of encephalitis
can also be caused by echoviruses
arboviruses - how do they spread? In what ways can they present?
arthropod borne viral illness - spread by mosquitos and ticks, ofter get the infection themselves from a bird
often presents with few flu-like symptoms but can lead to dangerous encephalitis
can also present with hemorrhagic fevers which are life threatening
complications of encephalitis - coma, permanent brain damage and death
compare and contrast eastern and western equine encephalitis?
Both are spread by mosquito, with a bird intermediate, and infect horses as well as humans
eastern is rare and in the eastern US, 1/3 of people with clinical encephalitis die from this virus infection
western is in the west of the US and canada, patient presents with flu-like symptoms, anorexia, altered mental status and sign of meningeal irritation
st. louis encephalitis
SLE - leading cause of epidemic flavivirus encephalitis - most common mosquito transmitted disease in continental US
illness severilty ranges from febrile headache to meningoencephalitis
case fatality ratio of 5-15%
west nile virus
started in queens, 1999
infection can be asymptomatic or mild febrile disease but can also be severe and fatal
migratory birds play a role in disease spread
most common is desert-y areas of the US (SoCal., Az) and the midwest.
La Crosse Encephalitis
most cases are reported in children, 75 cases/yr
life cycle includes bird and small mammals (chipmunks and squirrels) Lives over winter in mosquito eggs - vector borne
Colorado tick fever
.
Colorado tick fever
most common tick borne viral disease in the US
animal reservoirs - small mammals
symptoms - headache, retro-orbital pain and muscle/joint aches
dog tick - prevalent in the Rocky Mountains
Japanese encephalitis
widespread in Asia, most important cause of arbovirus encephalitis worldwide
life cycle involves aquatic birds and mosquitos
there is a formalin-inactivated vaccine available
diagnosis of an arbovirus infection
using symptoms - headache, drowsiness and fever (less common are vomiting and stiff neck)
CSF lymphocytic pleocytosis, normal Glucose, normal or mildly elevated protein
definite diagnosis is based on IgM presence in CSF (this means the BBB has been broken)
also, PCR testing.
powassan encephalitis and deer tick virus
Ixodid ticks
powassan is rare but mostly found in the north east.
Deer tick virus is a relative of powassan - also rare cause of encephalitis but is becoming more common in Hudson Valley region of NY
serum/CSF detection using virus-specific monoclonal antibodies
HSV 1
Cowdry type A intranuclear inclusion bodies - from viral replication
infects epithelial cells at site of entry - mouth is most common - cold sores
visualized by Tzanck Smear using Giemsa stain
lives in the trigeminal ganglion where it stays latent, gets reactivated and replicated and reinfects.
HSV2
Cowdry type A intranuclear inclusion bodies - from viral replication
genital herpes - latency in sacral ganglia
also forms painful fluid filled cysts - result of viral replication
identified with a Tzanck smear via the giemsa stain
HSV Encephalitis
typically caused by HSV 1
upon reactivation the virus can spread to the lips (cold sores) but also to the brain or the meninges
most common cause of sporadic viral encephalitis
adults and pediatric
diagnosis of HSV Encephalitis
postive Tzanch smear - reveals the syncytia forming cells wit the cowdry type A intranuclear inclusions
CSF - lymphocytic pleocytosis, elevated protein but normal glucose, erythrocytes in CSF - disrupted/damaged brain tissue.
Varicella-Zoster Virus
chicken pox in primary infection
subsequent infections causes shingles/herpes zoster
requires cell-mediated immunity for control of infection
herpes zoster infects dermatomes - forms a painful rash (postherpatic neuralgia)
more common in elderly, also causes viremia
diagnosis of VZV infection
veiwing of syncytia and Cowdry type A intranuclear inclusions microscopically or Tzanck smear
JC virus - infection in immunocompetent vs immunocompromised individuals? How is it diagnosed?
human polyoma virus
viral replication in host nucleus
virus enters vis the respiratory tract, spreads to kidneys, B cells and monocytes.
Latent infection people with competent immune systems.
reactivation in immunosuppresed - most commonly AIDS patients and organ transplantation
causes PML - progressive multifocal leukoencephalopathy: subacute demyelinating disease
diagnosed by symptoms, MRI/CT, PCR amplification of CSF
Rabies virus
acute encephalitis in all warm-blooded hosts
reservoirs historically were dogs but now seen in raccoons, bats and rats - transmitted by salvia (bite) or through mucous membranes - eyes, nose, mouth
travels to CNS by way of sensory or motor neurons and forms cyoplasmic inclusion bodies known as Negri Bodies
Lymphocytic choriomeningitis
arenavirus
flu-like disorder followed by meningitis
found in rodents: gray house mouse and hamster - they excrete the virus in urine, feces, semen and nasal secretions. Spread by contamination
Prion Diseases -Transmissible Spongiform Encephalopathies
isoform of a normal protein that causes the protein to change shape and aggregate.
the altered protein is insoluble - amyloid-like plaques
neuronal degeneration
Creutzfeldt-Jakob disease is most common
rare are kuru, gerstmann-straussler syndrome and fatal familial insomnia
CJD is diagnosed by immunoassay
treatment of HSV
acyclovir, valacyclovir,
penciclovir and famciclovir
pathogenesis of the primary infection of VZV?
primary infection starts in the mucosa of the respiratory tract, replication happens in the lungs, disseminates through the bloodstream and causes the fluid-filled chicken pox vesicles. Travels on sensory nerves of the skin to lye latent in the DRG.
Zostavax
vaccine for shingles
can only be given to those over 60 who had not had shingles before
similar to chicken pox vaccine
Variant CJD
Variant creutzfeild jakob disease is thought to be caused by consumption of BSE infected meat/
prion protein can be detected in lymphoid tissue
occurs in young patients - psychiatric manifestations and ataxia
CJD is diagnosed by immunoassay
whats the most common cause of bacterial meningitis in newborns?
s. agalactiae
l. monocytogenes
e. coli
whats the most common cause of bacterial meningitis in the elderly?
L. monocytogenes
whats the most common cause of bacterial meningitis in infants and toddlers? (up to 60mo)
S. pneumoniae
presentation of acute bacterial meningitis
isolated clinical event.
fever, stiff neck, headache, global/focal CNS dysfunction, petechia on trunk and lower extremities.
causes elevated intracranial pressure because of blocked CSF flow due to pus accumulation
fatal without treatment - immediate Ab followed by CSF gram stain
what antibiotics are good treatments for bacterial meningitis?
beta-lactams despite being polar
cefotaxime/ceftriaxone
dexamethasone - h. influenzae
chemoprophlyaxis for immediate contact
which antibiotics are NOT for treating bacterial meningitis? WHY?
erthromycin
tetracycline
cefoxitin
1st generation cephalosporins
why? because these polar compounds cannot cross the BBB
streptococcus pneumoniae - treatment, transmission and virulence factors
lives in throat and nasopharynx
spread by aerosol droplets
infection is purulent and associated with severe neurologic deficits and 21% mortality
often resistant to beta-lactams - treat with vancomycin
2 vaccines are available, the 13 valent is typically given to children and the 23 valent to elderly.
bacteria is encapsulated, contains IgA protease and pneumolysin
neisseria meningitidis - treatment, transmission and virulence factors
colonizes healthy people, spread by aerosol droplets
grows on blood agar
encapsulated, IgA protease, B-lactamase
host immunity complement systems is very important
treatment with 3rd generation cephalosporins
vaccines available for A, C, Y and W135 serotypes but none for B
listeria monocytogenes - treatment, transmission and virulence factors
most prevalent in immunocompromised patients with high mortality in elderly and neonates.
can be transmitted maternally through the placenta
treatment with ampicillin
salt and nitrite tolerant, can grow at low temperatures (4C)
vireulence factor - listerolysin O and actin polymerization
streptococcus agalactiase - group B
group B strept
colonizes URT and GU tract
acquired by neonates during pregnancy or birth
no vaccine, treat with penicillin G
Gram stain of CSF and PCR for organism identification
increases risk for premature rupture of membranes. prolonged labor, preterm birth, disseminated maternal group B streptococcal disease and decreases maternal complement.
chronic meningitis - bacterial causes
caused by latent TB activation
bacilli gets into CSF, settles in subarachnoid space where it causes an intense type 4 hypersensitivity reaction causing inflammation around CN’s leading to coma.
Acid fast stain for identification - only positive a small percentage of the time –> PCR
treated with several Abs
Bacteria - brain abscess - what is it?
infection of the brain parenchyma can comes directly from paranasal sinuses, middle ear or mastoids.
can happen from dental surgery, trauma (penetration/surgery) or spread from blood during acute bacterial endocarditis
Bacteria - brain abscess - what causes it?
staph aureus
anerobic and arobic microflora
group A or B strept
chronic - mycobacteria - TB
bacteria - brain abscess - diagnosis and treatment
diagnosed by CT, MRI, aspiration of abscess
treated with antibiotics - Methicillin/vancomycin, ceftriaxone/cefotaxime &
metronidazole
not always effective, still 10-20% mortality with treatment, fatal without.
chronic meningitis - clinical presentation
meningeal infection with pleocytosis lasting more than 4 weeks
Initial symptoms are headaches and fever.
Progression - seizures, change in mental status, confusion, hallucinations, development of focal neurologic deficits, hydrocephalus and increased ICP
Nuchal rigidity is either subtle or absent
What type of microbial agents cause chronic meningitis?
fungal and parasitic microbes
infection and progression into meningitis in opportunistic - immunodeficit or suppressed peoples
cryptococcus neoformans
fungi - india ink stain
(only fungus with capsule)
presents as subacute meningoencephalitis with progression to fever and hydrocephalus
Lab tech - Cryptococcal antigen latex agglutination
What is the treatment for crypococcus neoformans caused chronic meningitis?
amphotericin B
flucytosine - nucleoside analogue that inhibits replication by inserting itself into the growing strand.
histoplasma capsulatum
rare - endemic in Ohio River Valley
chronic meningitis
presents with fever, oral lesions, hepatosplenomegaly and hydrocephalus
lab diagnosis - seeing yeast cells inside macrophages, sometimes cultures, histoplasma polysaccharide antigen in urine/CSF/Blood
Treatment of histoplasma capsulatem - chronic meningitis
amphotericin B
Pseudallescheria - p. boydii
most common fungal agent of mycetoma
in immunocompromised - meningitis, meningoencephalitis and brain abscesses
organism acquired from polluted water, sewage and swamps
near drowning victim
resistant to amphotericin B
taenia solium
parasitic
pork tapeworm - neurocysticercosis
chronic meningitis
presents with seizures, obstructive cysts, and space-occupying lesions
endemic in Mexico. South America and Asia
Lab Diag - CT and lymphocytic pleocytosis with eiosinophils (CNS?)
treatment of chronic meningitis causes by taenia solium
albendazole
steroids
analgesics
anti-epileptic drugs
surgical resection of lesions and placement of ventricular shunts
angiostrongylus cantonensus
parasitic chronic meningitis
rat lung worm - round worm
endemic in Asia and Pacific Islands
from ingestion of undercooked or raw shellfish or snails
can incubate for up to a year
presents with nausea, vomiting, neck stiffness and headaches that are global and severe. Rash with pruritus is also common (itchy)
diag - history and CSF - peripheral eosinophilia
no treatment
Naegleria fowleri
Parasitic encephalitis
Protozoan - thermophile
Amebic meningoencephalitis - brain-eating disease
fatal
enters nose while swimming - freshwater in southern states, summer months, children and young adults are at highest risk
altered level of consciousness and lost sense of smell
lab diag - neutrophilic pleocytosis, motile trophozoites on wet mound of CSF, brain histopathology
Balamuthia mandrillaris
parasitic encephalitis
protozoan in soil of Central America
entry - Cuts and wounds on skin or inhalation
Granulomatous Amebic Encephalitis - often misdiagnosed as TB
a) Subacute progressive disease with Space-
occupying lesions
b) Cranial nerve palsies
c) Hydrocephalus
lab DX - Serology and brain histopathology, Lymphocyte pleocytosis and depressed glucose, Real-time PCR of brain
poor prognosis, high mortality and slow progression (2yrs)
Baylisascaris procyonis
Raccoon roundworm (helminthes)
caught by ingestion of eggs (contanmation) - eating dirt
Lab Dx - eosinophillic pleocytosis, peripheral eosinophillia and deep matter abnormalities, serology on CSF/Serum
mid-Atlantic, northeastern &
Midwestern states &
California
Gnathostoma spp
round worm
Eating undercooked or raw freshwater
fish, eels, frogs, birds, & reptiles
tropical and subtropical areas - Thailand and Japan
Moves from skin to brain
DX - microscopic ID or larvae in tissue and ELISA
Entamoeba histolytica
Predominantly a GI
disease
Diagnosis: serology &
PCR of brain abscess
aspirate or CSF
Treatment
Metronidazole or
tinidazole
Followed by
paromomycin or
iodoquinol
Schistosoma japonicum aka Bilharzia
blood fluke - not found in the US
second highest impact worldwide after malaria - most devastating parasitic disease
lives in fresh water snails
Lab DX - Microscopic,, ELISA for anti-schistosomal Abs, granuloma formation in brain
Paragonimus spp.
Lung fluke (flat worm)
Ingestion of raw or undercooked
crab or crayfish - rare in US but in Midwest (river raft in Missouri)
P. kellicotti - Symptoms similar to TB
Dx - microscopic examination of eggs and peipheral eosinophilia
Parasites that can causes brain abscesses
Taenia solium
Entamoeba histolytica
Schistosoma japonicum
Paragonimus spp
fungi that can cause brain abscesses
aspergilliuss spp - bone marrow and transplants
cryptococcus neoformans - T-cell immunity defects
Neutropenia pts - Aspergillis, Mucor and Candida
symptoms of brain abscesses
headache altered mental status focal neurologic findings fever nausea and vomiting seizure
Labs of brain abscesses
peripheral leukocytosis Low serum Na+ platelet counts may be high or low elevated erythrocyto sedimentation rate elecated CRP
Schistosoma japonicum - brain abscess treatment
praziquantel
Paragonimus spp. - brain abscess – Treatment
praziquantel
