ICL 10.11: CNS Infections & Inflammation Flashcards
which types of infections are in the brain vs spinal cord?
BRAIN
1. acute bacterial meningitis
- viral meningitis
- viral encephalitis
- brain abscess
SPINAL CORD
1. epidural abscess
- viral myelitis
why does a lumbar puncture help you know what’s going on around the brain?
CSF circulates, is made and is reabsorbed continuously so whatever is around the spinal cord reflect the quality of the CSF around the brain too
this is why when you do a lumbar puncture you know what’s going on around the brain too
what are the characteristics of the BBB?
- highly selective semipermeable border of endothelial cells that prevents solutes in in blood from crossing into extracellular fluid of CNS
- these endothelial cells in capillaries have tight junctions
- blood brain barrier does not generally allow large molecules to enter CNS by diffusion
- prevents organisms from penetrating into brain which is good but it also makes it difficult for desirable molecules like complement, antibodies and antibiotics as well
what anatomical structure is effected with meningitis?
it’s an infection of the leptomeninges = arachnoid + pia matter
what anatomical structure is effected with encephalitis?
it’s an infection of the brain parenchyma
if it’s an organized/local infection rather than diffuse then it’s an abscess
what anatomical structure is effected with myelitis?
infection of the spinal cord tissue
myelitis = inflammation of the spinal cord
usually viral, not usually bacterial
what anatomical structure is effected with neuritis?
infection of the peripheral nerves
HSV usually does this; more specifically zoster
how do viruses/bacteria get into the CNS?
- blood stream
- neuronal pathways
- direct inoculation
what is the case fatality rate of acute bacterial meningitis?
17-25% WITH treatment so this is insanely high!!
without treatment it’s basically fatal
and even if they survive, 21-28% of survivors have permanent neurologic sequelae like loss of hearing, cognitive problems etc.
which strains of bacteria did the meningitis vaccine help against?
haemophilus b influenza was basically eliminated by the vaccine
it may be associated with sinusitis, otitis, epiglottis, pneumonia etc. but you don’t see it much
predisposing conditions include DM2, alcoholism, asplenia, CSF leak, hypogammaglobulinemia
however, streptococcus pneumoniea and group B strep still cause significant amount of meningitis even with vaccine
what bacteria is more likely to cause meningitis in kids, teens, adults vs. elderly?
in the elderly there’s higher rates of listeria induced meningitis
streptococcus pneumoniae in adults
neisseria meningitidis was more prominent in teens and young adults or in the military
in kids it’s kind of a mix but mostly streptococcus pneumoniae, neisseria meningitidis and then GBS
in neonates, it’s GBS
what infections predispose you to developing meningitis?
COMMUNITY ACQUIRED
1. sinusitis
- otitis/mastoiditis
- pneumonia
NOSOCOMIAL
1. bacteremia (not common)
- postoperative
- device related
neisseria is usually something you get from someone else
with streptococcus pneumonea, you can have sinusitis, otitis mastoiditis, or pneumonia that could develop into meningitis
what conditions predispose you to develop meningitis?
- asplenia**
- complement deficiency**
- glucocorticoid treatment (causes immune suppression)
- diabetes mellitus
- alcoholism
- hypogammaglobulinemia
- HIV infection
- recent exposure to a case of meningitis (Neisseria)** –> pneumococcus isn’t like this
- injection drug use
- recent head trauma (CSF Leak)** –> at risk for pneumococcus infection: if there’s colonization of upper airways, there’s a direct communication between their sinus and their CNS then the bacteria will invade
- recent travel, particularly to areas with endemic meningococcal disease such as sub-Saharan Africa**
what is the pathophysiology of a meningitis infection? this goes for pneumococcus and neisseria!!
- mucosal colonization
pneumonia patient grows gram negative e. coli and they grew neisseria meningitidis – strains without a capsule won’t cause a disease though; you can be colonized and not progress to the rest of these steps
- migration and bacteremia
- invasion and replication in subarachnoid (SAH) space
- local inflammation and cytokine release > sepsis
- alterations in blood brain barrier
- edema and increase intracranial pressure
- increase CSF outflow resistance
- ischemia and infarction
- Coma/Death
what are the signs and symptoms of acute bacterial meningitis?
- fever** (only immunocompromised people who are on tylenol 24/7 or someone taking immunosuppressants wouldn’t have a fever)
- meningismus = headache + stiff neck + photophobia**
<80% have nuchal rigidity, Kernig’s or Brudzinski’s sign
- leathery
- confusion
- vomiting
- papilledema <1% = increased ICP = contraindication for lumbar puncture
- any neurologic symptoms/cerebral dysfunction
if a meningitis patient has papilledema, what should you NOT do?
lumbar puncture
this is because papilledema signifies increased intracranial pressure so if you do a lumbar puncture you can decrease the pressure and cause the brain to herniate town into the spinal column and you’ll kill them
what is Kernig’s sign?
patient lies supine with thigh and knee flexed
leg is passively extended and this is resisted with meningeal inflammation
used to test for meningitis
what is Brudzinski’s sign?
passive flexion of the neck causes flexion of pelvis/hips
so they’ll lift their knees when you flex their neck
used to test for meningitis
what conditions would contraindicate a lumbar puncture?
- increased intracranial pressure (ex. papilledema)
- discrete parenchymal mass (tumor or abscess, especially if there’s edema around the mass)
- platelet count <40,000 or prolonged PT –> if you have low platelets and you put in a needle, you can cause a lot of problems
- infected site over lumbar spine where you want to put in the needle
what level do you do a lumbar puncture?
around L4/L5
you want to make sure you’re past the spinal cord and the important nerves?
what does increased lumbar puncture opening pressure indicate?
if the pressure is increased it suggests fungal or bacterial meningitis but it’s not 100%
cryptococcal meningitis with people who are immunocompromised, we use lumbar puncture
what will you find in a normal CSF sample when you send it to lab?
- low amount of protein
- less glucose (>50% of what’s in the serum)
- total amount is 140-150 cc
- opening pressure is 8-15 cm water; >20 cm water is abnormal
- normal white cell count <5 cells/cc (so no white cells really)
sometimes people with AIDs will have some WBCs in the CSF
how do you decide if you need to do a CT before a lumbar puncture or just a lumbar puncture?
if they’re immunocompromised, have CNS disease, seizures, papilledema, focal neurological deficit, or delay in the doing the lumbar puncture, do blood cultures STAT –> dexamethasone + empirical antimicrobial therapy –> negative CT scan of the head with no sign of ICP –> perform lumbar puncture
if they don’t have any of those above conditions, then do blood cultures and a lumbar puncture STAT –> dexamethasone + empirical antimicrobial therapy –> CSF findings confirm bacterial meningitis –> positive CSF gram stain –> dexamethasone + targeted antimicrobial therapy
so if you see pneumococcus vs neisseria on the gram stain then you give a targeted treatment
specific for each bacteria
dexamethasone is a steroid that helps curb the inflammation from bacterial lysis following administration of antibiotics
what are the lab results in someone who has bacterial meningitis?
- high WBCs: 100 to over 1000 with predominantly neutrophils
- low glucose
- high protein
- gram stain positive in >70%
- elevated opening pressure
- negative PCR
- bacterial culture positive in >70%
however, pneumococcus and nisseria are strongly effected by antibiotics so if you give ceftriaxone and then do the LP 12 hours later, there will almost never be anything that grows on the culture
what are the lab results in someone who has viral meningitis?
- normal to mildly elevated opening pressure
- mildly elevated WBCs: 25-500 with lymphocyte predominance
- normal to low glucose
- normal to high protein
- negative gram stain
- negative bacterial culture
- PCR positive for HSV in 25%
viral patients will be less sick than bacterial meningitis patients
how do we treat bacterial meningitis?
- empirically start with 3rd or 4th generation cephalosporin like ceftriaxone or cefandine because they have good CNS penetration AND covers strep pneumonia and neisseria
- use vancomycin if you’re in an area with high resistance bacteria areas
- if someone is immunocompromised, think listeria and use ampicillin
if someone has trauma or surgery, you need to cover anaerobes
what predisposes you to N. meningitis?
C5-C9 terminal complement deficiency
vaccines active against serogroup A, C, W135, Y, separate vaccine for B
what is a common skin condition of neisseria meningitis?
violacious patches
neisseria is infecting the CSF and causing a lot of inflammation with a strong cytokine release and coagulopathy
so they will have DIC!!
what is the #1 cause of bacterial meningitis in 18-50 year olds?
streptococcus pneumoniae
it’s often associated with respiratory infections
people who are asplenic, have CSF leak, DM2, alcoholism, HIV, or hypogammaglobulinemia are predisposed too S. pneumoniae
vaccines cover most common serotypes associated with meningitis so that’s good
why do you add vancomycin to ceftriaxone when treating bacterial meningitis?
ceftraixone treats neiseria meningitidis and streptococcus pneumoniae just fine but the B-lactam resistant pneumococcus is the reason we add vancomycin
vancomycin doesn’t have as much CNS penetration and it’s not as good of a killer as the B-lactams so we give vancomycin on top of ceftriaxone, we don’t stop the ceftriaxone!
what are the characteristics of listeria monocytogenes meningitis?
it only causes 2-3% of meningitis
highest risk is in neonates, pregnant women, elderly and immunocompromised
cephalosporins are not active against Listeria and vancomycin is not reliably effective
ampicillin or trimethoprim-sulfamethoxazole (TMP/SMX) are treatments of choice –> use bactram if allergic to ampicillin or otherwise contraindicated
why do we give dexamethasone empirically?
give dexamethasone then give targeted antibiotics you decrease the mortality and disability of your patients when given for 5 days!
giving antibiotics causes bacterial lysis which initiates a big inflammatory response from the immune system which can lead to increased ICP so dexamethasone is a steroid that helps curb the inflammation caused by the antibiotic
also in kids, it’s shown to decrease hearing loss
however with AIDs patients that didn’t have pneumococcus in 3rd world countries, dexamethasone didn’t play a role in treatment
what are the complications associated with meningitis?
- raised iCP
- seizures
- hearing loss
- hydrocephalus
- subdural empyema
- cerebral infarction
- cognitive impairment
what viruses cause acute viral meningitis?
**enteroviruses cause 80-85% of cases of viral meningitis
- herpes viruses**
- mumps
- adenovirus
- arbovirus
- HIV
what are the clinical manifestations of acute viral meningitis?
sudden onset of fever, severe frontal headache, photophobia, nuchal rigidity and myalgias, vomiting, diarrhea, anorexia, cough, sore throat
usually occurs in the summer months
may also be associated with recognizable enteroviral syndromes (eg - classic rash of hand-foot-and-mouth disease, the painful mouth vesicles of herpangina)
how do you treat acute viral meningitis?
IV acyclovir
but usually it’s a self-limiting disease and it’s pretty mild
what is chronic/subacute meningitis?
neurologic abnormalities or CSF abnormalities consistent with meningitis of > 4 weeks duration
what organisms can cause chronic/subacute meningitis?
- TB
- nocardia
- cryptococcus*** (especially in HIV patients)
- Syphilis
- Lyme Disease
- Behçet’s
- Meningeal Carcinomatosis
- Sarcoidosis
what is an intracranial abscess?
collection of purulent fluid surrounded by inflammation in brain parenchyma
may or may not be associated with meningeal involvement
can be:
1. from contiguous foci - 50%
- from hematogenous dissemination - 25%
- from direct inoculation - 10%
- primary abscess - 15%
based on the site of the abscess, where did it come from?
- frontal lobe –> sinuses, teeth, direct inoculation
- temporal lobe –> otitis, mastoiditis, sphenoid sinusitis
- cerebellum –> otitis, mastoiditis
- middle cerebral artery circulation –> hematogenous source like lung abscess or endocarditis
- beneath area of a wound –> direct inoculation
what organisms can cause a brain abscess?
- otitis/mastoiditis –> strep, bactericides, GNR
- sinusitis –> strep, bactericides, GNR, staph aureus
- odontogenic infection –> fusobacterium, anaerobes, strep
- wound –> staph, strep, GNR, clostridium
- endocarditis –> staphylococcus aeros or streptococci
- lung –> actinomycetes, anaerobes, strep, fusobacterium, nocardia
- immunocompromised –> toxoplasmosis**, fungi, GNR, nocardia
what are the clinical manifestations of brain abscess?
headache, N/V, seizures, mental status change, focal neurologic deficit depending on location of abscess
deficit depends on location – cerebellar abscess may have ataxia, temporal lobe may have visual field defect, etc
generally < 50% have fever with presentation so half won’t have a fever….
how do you diagnose intracranial abscess?
MRI or CT scan with contract
avoid lumbar puncture
how do you treat an intracranial abscess?
- surgical drainage and management of increased intracranial pressure frequently required
- search for primary source
- culture abscess for bacteria, fungi, mycobacteria and obtain immediate gram stain, AFB stain and fungal smears to help guide therapy
- empiric regimen depends on source of infection (odontogenic vs trauma vs postsurgical vs hematogenous)metronidazole + 3rd/4th gen cephalosporin + vancomycin
don’t give steroids unless lots of edema
what is encephalitis?
inflammation of the brain that is characterized by alteration in consciousness
many non-infectious diseases can be associated with encephalitis (eg- drug reactions, vasculitis)
in general, infectious encephalitis is due to viral infection, less commonly bacterial, fungal, or tubercular infection
what viruses commonly cause encephalitis?
- herpesviruses***: HSV1»_space; HSV2
this is also the only one that’s really treatable = IV acyclovir
- flavivirus like west nile virus**
- togaviruses
- HIV
- enteroviruses
what is the presentation of someone with viral encephalitis?
- confusion, altered mental status
- fever
- personality changes
- headaches, fatigue
- focal neurologic findings and seizures
- symptoms can evolve over several days; not acute!
MRI will show changes specifically on the temporal lobe, HSV1 loves the temporal lobe!
how do you diagnose viral encephalitis?
CSF serology rather than PCR like viral meningitis
