ICL 10.11: CNS Infections & Inflammation

Question 1

which types of infections are in the brain vs spinal cord?

Answer 1

BRAIN
1. acute bacterial meningitis

2. viral meningitis
3. viral encephalitis
4. brain abscess

SPINAL CORD
1. epidural abscess

2. viral myelitis

Question 2

why does a lumbar puncture help you know what’s going on around the brain?

Answer 2

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

Question 3

what are the characteristics of the BBB?

Answer 3

1. highly selective semipermeable border of endothelial cells that prevents solutes in in blood from crossing into extracellular fluid of CNS
2. these endothelial cells in capillaries have tight junctions
3. blood brain barrier does not generally allow large molecules to enter CNS by diffusion
4. 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

Question 4

what anatomical structure is effected with meningitis?

Answer 4

it’s an infection of the leptomeninges = arachnoid + pia matter

Question 5

what anatomical structure is effected with encephalitis?

Answer 5

it’s an infection of the brain parenchyma

if it’s an organized/local infection rather than diffuse then it’s an abscess

Question 6

what anatomical structure is effected with myelitis?

Answer 6

infection of the spinal cord tissue

myelitis = inflammation of the spinal cord

usually viral, not usually bacterial

Question 7

what anatomical structure is effected with neuritis?

Answer 7

infection of the peripheral nerves

HSV usually does this; more specifically zoster

Question 8

how do viruses/bacteria get into the CNS?

Answer 8

1. blood stream
2. neuronal pathways
3. direct inoculation

Question 9

what is the case fatality rate of acute bacterial meningitis?

Answer 9

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.

Question 10

which strains of bacteria did the meningitis vaccine help against?

Answer 10

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

Question 11

what bacteria is more likely to cause meningitis in kids, teens, adults vs. elderly?

Answer 11

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

Question 12

what infections predispose you to developing meningitis?

Answer 12

COMMUNITY ACQUIRED
1. sinusitis

2. otitis/mastoiditis
3. pneumonia

NOSOCOMIAL
1. bacteremia (not common)

2. postoperative
3. 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

Question 13

what conditions predispose you to develop meningitis?

Answer 13

1. asplenia**
2. complement deficiency**
3. glucocorticoid treatment (causes immune suppression)
4. diabetes mellitus
5. alcoholism
6. hypogammaglobulinemia
7. HIV infection
8. recent exposure to a case of meningitis (Neisseria)** –> pneumococcus isn’t like this
9. injection drug use
10. 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
11. recent travel, particularly to areas with endemic meningococcal disease such as sub-Saharan Africa**

Question 14

what is the pathophysiology of a meningitis infection? this goes for pneumococcus and neisseria!!

Answer 14

1. 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

2. migration and bacteremia
3. invasion and replication in subarachnoid (SAH) space
4. local inflammation and cytokine release > sepsis
5. alterations in blood brain barrier
6. edema and increase intracranial pressure
7. increase CSF outflow resistance
8. ischemia and infarction
9. Coma/Death

Question 15

what are the signs and symptoms of acute bacterial meningitis?

Answer 15

1. fever** (only immunocompromised people who are on tylenol 24/7 or someone taking immunosuppressants wouldn’t have a fever)
2. meningismus = headache + stiff neck + photophobia**

<80% have nuchal rigidity, Kernig’s or Brudzinski’s sign

3. leathery
4. confusion
5. vomiting
6. papilledema <1% = increased ICP = contraindication for lumbar puncture
7. any neurologic symptoms/cerebral dysfunction

Question 16

if a meningitis patient has papilledema, what should you NOT do?

Answer 16

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

Question 17

what is Kernig’s sign?

Answer 17

patient lies supine with thigh and knee flexed

leg is passively extended and this is resisted with meningeal inflammation

used to test for meningitis

Question 18

what is Brudzinski’s sign?

Answer 18

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

Question 19

what conditions would contraindicate a lumbar puncture?

Answer 19

1. increased intracranial pressure (ex. papilledema)
2. discrete parenchymal mass (tumor or abscess, especially if there’s edema around the mass)
3. 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
4. infected site over lumbar spine where you want to put in the needle

Question 20

what level do you do a lumbar puncture?

Answer 20

around L4/L5

you want to make sure you’re past the spinal cord and the important nerves?

Question 21

what does increased lumbar puncture opening pressure indicate?

Answer 21

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

Question 22

what will you find in a normal CSF sample when you send it to lab?

Answer 22

1. low amount of protein
2. less glucose (>50% of what’s in the serum)
3. total amount is 140-150 cc
4. opening pressure is 8-15 cm water; >20 cm water is abnormal
5. normal white cell count <5 cells/cc (so no white cells really)

sometimes people with AIDs will have some WBCs in the CSF

Question 23

how do you decide if you need to do a CT before a lumbar puncture or just a lumbar puncture?

Answer 23

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

Question 24

what are the lab results in someone who has bacterial meningitis?

Answer 24

1. high WBCs: 100 to over 1000 with predominantly neutrophils
2. low glucose
3. high protein
4. gram stain positive in >70%
5. elevated opening pressure
6. negative PCR
7. 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

Question 25

what are the lab results in someone who has viral meningitis?

Answer 25

1. normal to mildly elevated opening pressure
2. mildly elevated WBCs: 25-500 with lymphocyte predominance
3. normal to low glucose
4. normal to high protein
5. negative gram stain
6. negative bacterial culture
7. PCR positive for HSV in 25%

viral patients will be less sick than bacterial meningitis patients

Question 26

how do we treat bacterial meningitis?

Answer 26

1. empirically start with 3rd or 4th generation cephalosporin like ceftriaxone or cefandine because they have good CNS penetration AND covers strep pneumonia and neisseria
2. use vancomycin if you’re in an area with high resistance bacteria areas
3. if someone is immunocompromised, think listeria and use ampicillin

if someone has trauma or surgery, you need to cover anaerobes

Question 27

what predisposes you to N. meningitis?

Answer 27

C5-C9 terminal complement deficiency

vaccines active against serogroup A, C, W135, Y, separate vaccine for B

Question 28

what is a common skin condition of neisseria meningitis?

Answer 28

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!!

Question 29

what is the #1 cause of bacterial meningitis in 18-50 year olds?

Answer 29

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

Question 30

why do you add vancomycin to ceftriaxone when treating bacterial meningitis?

Answer 30

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!

Question 31

what are the characteristics of listeria monocytogenes meningitis?

Answer 31

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

Question 32

why do we give dexamethasone empirically?

Answer 32

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

Question 33

what are the complications associated with meningitis?

Answer 33

1. raised iCP
2. seizures
3. hearing loss
4. hydrocephalus
5. subdural empyema
6. cerebral infarction
7. cognitive impairment

Question 34

what viruses cause acute viral meningitis?

Answer 34

**enteroviruses cause 80-85% of cases of viral meningitis

1. herpes viruses**
2. mumps
3. adenovirus
4. arbovirus
5. HIV

Question 35

what are the clinical manifestations of acute viral meningitis?

Answer 35

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)

Question 36

how do you treat acute viral meningitis?

Answer 36

IV acyclovir

but usually it’s a self-limiting disease and it’s pretty mild

Question 37

what is chronic/subacute meningitis?

Answer 37

neurologic abnormalities or CSF abnormalities consistent with meningitis of > 4 weeks duration

Question 38

what organisms can cause chronic/subacute meningitis?

Answer 38

1. TB
2. nocardia
3. cryptococcus*** (especially in HIV patients)
4. Syphilis
5. Lyme Disease
6. Behçet’s
7. Meningeal Carcinomatosis
8. Sarcoidosis

Question 39

what is an intracranial abscess?

Answer 39

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%

2. from hematogenous dissemination - 25%
3. from direct inoculation - 10%
4. primary abscess - 15%

Question 40

based on the site of the abscess, where did it come from?

Answer 40

1. frontal lobe –> sinuses, teeth, direct inoculation
2. temporal lobe –> otitis, mastoiditis, sphenoid sinusitis
3. cerebellum –> otitis, mastoiditis
4. middle cerebral artery circulation –> hematogenous source like lung abscess or endocarditis
5. beneath area of a wound –> direct inoculation

Question 41

what organisms can cause a brain abscess?

Answer 41

1. otitis/mastoiditis –> strep, bactericides, GNR
2. sinusitis –> strep, bactericides, GNR, staph aureus
3. odontogenic infection –> fusobacterium, anaerobes, strep
4. wound –> staph, strep, GNR, clostridium
5. endocarditis –> staphylococcus aeros or streptococci
6. lung –> actinomycetes, anaerobes, strep, fusobacterium, nocardia
7. immunocompromised –> toxoplasmosis**, fungi, GNR, nocardia

Question 42

what are the clinical manifestations of brain abscess?

Answer 42

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….

Question 43

how do you diagnose intracranial abscess?

Answer 43

MRI or CT scan with contract

avoid lumbar puncture

Question 44

how do you treat an intracranial abscess?

Answer 44

1. surgical drainage and management of increased intracranial pressure frequently required
2. search for primary source
3. culture abscess for bacteria, fungi, mycobacteria and obtain immediate gram stain, AFB stain and fungal smears to help guide therapy
4. 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

Question 45

what is encephalitis?

Answer 45

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

Question 46

what viruses commonly cause encephalitis?

Answer 46

1. herpesviruses***: HSV1&raquo_space; HSV2

this is also the only one that’s really treatable = IV acyclovir

2. flavivirus like west nile virus**
3. togaviruses
4. HIV
5. enteroviruses

Question 47

what is the presentation of someone with viral encephalitis?

Answer 47

1. confusion, altered mental status
2. fever
3. personality changes
4. headaches, fatigue
5. focal neurologic findings and seizures
6. symptoms can evolve over several days; not acute!

MRI will show changes specifically on the temporal lobe, HSV1 loves the temporal lobe!

Question 48

how do you diagnose viral encephalitis?

Answer 48

CSF serology rather than PCR like viral meningitis