CNS Flashcards

(57 cards)

1
Q

What is the CNS made up of

A

brain, spinal cord & cranial nerves (but not peripheral nerves).
-protected by skull, vertebrae & layers of meninges.

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2
Q

What is CSF
where is it found
function

A

-found in subarachnoid space & ventricles.
-Produced by fluid filtered out of blood by brain capillaries called choroid plexus
-circulates around the spine , around the brain and returns to blood

Protect brain/spinal cord.
Regulates pressure.
Supplies nutrients & removes wastes.
Provides some immune cells

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3
Q

CHARACTERISTICS OF CSF

A

-Clear colorless, sterile fluid.
-has normal amount of WBC
-newborns have higher protein, glucose & WBC (monocytes & neutrophils).
Infection of CSF associated with increased WBC count & change in amount of protein & glucose

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4
Q

BLOOD BRAIN BARRIER (BBB)

A

Semi-permeable membrane -separates brain tissue from blood.
Protects brain from toxins, & pathogens while letting nutrients in.
If microorganisms get past = encephalitis

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5
Q

BLOOD CSF BARRIER (BCB)

A

Functional barrier found in choroid plexus of brain ventricles.
Separates blood from CSF & CSF from brain.
Also protects brain from toxins, & pathogens while letting nutrients in.
If microorganisms get past = meningitis or encephalitis

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6
Q

MENINGITIS

A

Inflammation/infection of CSF & meninges due to virus or bacteria getting past the blood-csf barrier
-serious and can be fatal
-can cause death quickly
-can cause brain damage, hearing loss and learning disabilities
-medical emergency

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7
Q

PATHOGENISIS OF BACTERIAL MENINGITIS

types of spread

A

Hematogenous spread: Organism enters bloodstream & from blood spreads to CSF & meninges

Contiguous spread:
Organism causing infection in sinus or OM passes through mucosa & gets directly into CSF.

Direct spread via cranial trauma or surgery
Once in CSF, replicate, & cause massive inflammatory reaction – increased fluid in brain& <O2.

Symptoms: Fever, headache/neck pain, altered mental status, death

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8
Q

chart

A
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9
Q

OTHER BACTERIAL CAUSES OF MENINGITIS

Anaerobic bacteria

A

Rarely cause meningitis.
When they do, is usually because person had/has brain abscess & organism spreads to CSF

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10
Q

LISTERIA MENINGITIS IN FETUS OR NEWBORN

A

-if occurs in pregnancy – organism ingested in contaminated food (dairy, lunchmeat, poorly washed raw veg).
-Invades cells & survives intracellularly –moves from cell-cell using actin filaments.
-Enters mom’s blood & cross placental barrier.
Mild flu like illness & diarrhea in mom but can cause premature labor & septic/spontaneous abortion or stillbirth.
-listeria can survive at cold temps
-have actin filments to be able to enter cells and can penetrate intestinal lymph nodes allowing them to spread

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11
Q

if baby has listeria
newborn under or over 7 days

A

Early onset Listeria in Newborn <7 days:
From intra uterine infection or during birth, causes sepsis & more rarely meningitis - high mortality rate (50%)

Late onset Listeria in Newborn >7 days:
Infection from mom after birth or from environmental source-manifest more as meningitis – has < fatality rate

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12
Q

GBS MENINGITIS IN FETUS OR NEWBORN

A

-colonize adult intestine & genital tract in women
-can cause endocarditis
-If pregnant can cause serious infection to baby.
-Can infect amniotic fluid & baby - premature rupture of membranes & still birth.
-Screening of GBS on all pregnant women - vaginal /rectal swab at 35-37 wks. gestation.

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13
Q

early vs late onset of GBS

A

Early onset GBS in Newborn (prenatal & <7 days old)
Baby aspirates amniotic fluid with GBS during birth. Causes pneumoniae or sepsis & sometimes meningitis- > mortality

Late onset GBS in Newborn (at least 7 days old)
Baby infected by mom or from other source after birth.
Causes mostly meningitis, sometimes septicemia or pneumonia-mortality rate is lower than early onset.

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14
Q

GBS
GRAM
CAT
BE
MOT

A

Col morph: grey, sm/med BH
Gram: GPC in pairs & chains
Catalase: neg
Bile esculin: neg - BIG DIFFERENCE
Motility at 250C: neg
Hippurate hydrolysis: pos
Camp: pos (arrowhead)
PDX: groups with B

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15
Q

Listeria
GRAM
CAT
BE
MOT

A

Col morph: grey, sm/med BH
Gram: small GPB
Catalase: pos - BIG DIFFERENCE
Bile esculin: pos
Motility at 250C: pos (umbrella)
Hippurate hydrolysis: pos
Camp: pos (rectangle)
PDX: may cross react with group B antisera

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16
Q

VACCINES TO PREVENT MENINGITS

A

-. influenzae type B conjugate vaccine
a
strep pneua

neiseeira meninigtis

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17
Q

CSF SHUNTS

A

-Shunts placed in patients with hydrocephalus (excess CSF) drain fluid to relieve pressure
-size of ventricles are increased and puts pressure on the brain
-one goes into CSF and other in the abdomen

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18
Q

BACTERIAL CSF SHUNT INFECTIONS

A

Early Shunt Infections:
Occur in 4wks of shunt insertion.
Mostly due to normal skin flora like CONs & S. aureus
Happens when proximal end of shunt touches skin. surgical implation . S epi, S aurus, cutibac, corynebac

Late Shunt Infections:
Occur later, > 4wks after shunt insertion.
Usually due to intestinal flora like Enterococcus & GNB.
Happens when fluid from shunt causes perforation or peritonitis.
Strep, entrococcus GNB

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19
Q

ENCEPHALITIS

A

Inflammation/infection of brain
-small children or elderly
-Caused by invasion of organism (most often due to virus but can also be bacteria, fungus or parasite).
Non-infectious encephalitis due to autoimmune response from tumor or triggered by infection

Brain swelling, headache, stiff neck, sensitivity to light, mental confusion, seizures & death.
medical emergency.

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20
Q

SPECIMEN COLLECTION

A

-of CSF & blood cultures (blood draw into special BC vials).
-CSF obtained by inserting sterile hollow needle into subarachnoid space of lower lumbar-
-If patient has brain abscess tissue biopsy or aspirates taken because CSF may be normal – also placed in sterile empty container

All CNS specimens are sterile & STAT
All specimens must be transported to the lab as soon as possible – must be plated to media within 1 hour
If CSF delay <24hrs- keep at RT – not refrigerated affects integrity

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20
Q

BRAIN ABSCESS

A

Pus-filled pocket of infected material in brain
-direct contiguous spread of a cranial infection (skull osteomyelitis, sinus, ear infection).
-hematogenous spread (bacterial endocarditis, IV drug abuse, pneumonia).
-penetrating head wound & neurosurgery.
Is often a polymicrobial infection that includes anaerobes.
-can stop blood from flowing to the brain

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21
Q

INSUFFICIENT QUANTITY OF CSF RECEIVED

A

only one tube collected, it MUST go to microbiology lab first to ensure sterility of culture

consult with physician to determine testing priorities.

DONT REJECT

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22
Q

CSF SPECIMEN tubes for what

A

Microbiology gets tube that is least likely to have contamination (tube 2 or 3) for culture & AST -(if possible, never tube 1 in case there wasnt aseptic technique)
Tube 1 sent to Chemistry for glucose & protein testing. least affected by traumatic tap
Tube 3 or 4 sent to Hematology for cell counts (< cell debris)

chem 1, micro 2 , hem 3

23
Q

consult with physician to determine testing priorities.

A

-Clear/colorless: normal CSF
-Cloudiness: indicates bacterial or fungal meningitis, a high WBC count, presence of protein or lysed RBC.
-Color, xanthochromia (yellow discoloration): indicates presence of bilirubin & sometimes only sign of acute subarachnoid hemorrhage. check in 30 mins
-Bloody & Cloudy: subarachnoid bleed or traumatic tap

24
DIRECT SPECIMEN TESTS PERFORMED IN MICROBIOLOGY
<1ml of CSF: use directly – do not spin ≥ 1 mL of CSF: spin & use sediment to inoculate a drop to each media & to glass slide for Gram staining. Direct specimen gram India Ink for Cryptococcus Direct Cryptococcal, H. influenzae type B, N. meningitidis, S. pneumoniae, GBS, E. coli (K1) antigen tests Other special diagnostic stains – DFA, acid fast stain (for TB) Calcofluor white (for fungus). Serology PCR Culture of specimen
25
CNS SPECIMENS YOU MIGHT GET AT THE MICHENER
CSF sterile - pipette drop and streak pasteur pipette for slide and plate Brain biopsy or brain abscess aspirate sterile- roll the swab Quantify & report pus Quantify & report any organisms seen Do not quantitate either the pus or organisms if the gram was made from a cytospin. gram needs to be read, phoned and reported in ≤ 1 hour. Direct specimen India Ink is performed if yeast seen in direct specimen gram to rule out Cryptococcus
26
ANTIBIOTIC CONSIDERATIONS FOR CNS INFECTIONS
Only antibiotics that cross blood-brain barrier & are effective therapeutically for organism isolated are reported for CSF, brain abscess/tissue specimens. Should not use oral antibiotics.
27
PATIENT WITH ASEPTIC MENINGITIS ***** FOR CSMLS
CSF is not infected with bacteria Or is infected with an organism that can’t be gram stained -due to a virus or tb because you cant stain tb with gram -lymphocytes & no organisms seen microscopically.
28
What is Syphilis
-Sexually transmitted disease, caused by Treponema organism but, *Not all Treponema spp. are pathogenic* -humans are only reservoir and are able to carry some as NF -caused by Treponema pallidum subspecies pallidum -*Anaerobic, motile, GN spirochete bacillus -obligate intracellular pathogen cant make its own metabolic products -cant be gram stained -very invasive and enter through epithelial cells and uses the host cell energy to replicate - slowly -CANT BE GROWN ON ROUTINE MEDIA
29
NEUROSYPHILIS What are its 4 stages
Primary, secondary, latent & tertiary -can last 10 years or more in primary -person gets fluid filled chancres on genitals, rashes on palms and feet -motile 2ndary & tertiary stages (where CNS is most affected) 2ndary Stage, Syphilitic meningitis at 4-8 weeks -org goes into lymph, bloodstream and organs -when it crosses the BCB =syphilitic meningitis (can change personality) Tertiary Stage, Meningoencephalitis at 10-20yrs: - infects CNS & form gummas on brain tissue. - neuron destruction, atrophy of brain tissue, decline in motor & cognitive abilities
30
SPECIMENS TO TEST FOR SYPHILIS
*Fluid from chancres/lesions in primary, secondary stages, best for direct tests like darkfield or direct fluorescence. *Tissue biopsy/CSF for direct tests like fluorescence or histological staining *Blood serum or CSF specimens for serological tests.–Latent Syphilis can only be diagnosed via serological testing *Fluid from lesion, body fluids can be used for PCR – (not done in every lab yet)
31
SYPHILIS DIRECT SPECIMEN SCREENING TEST Darkfield or Direct Fluorescence
-on chancre/lesion fluid in early stages. -can be done on tissue biopsy anytime -must be confirmed with serology if positive because darkfield positive for any spirochete, & fluorescence positive for any Treponema pallidum -can’t differentiate subspecies - cant tell if its pathogenic or not -both are prelim and need to follow up with serology
32
2 types of SYPHILIS Serological test
Screening or Confirmatory
33
SYPHILIS SEROLOGICAL TESTS screening not treponemal tests
*Venereal Disease Research Laboratory test (VDRL) *Rapid Plasma Reagin test (RPR) *Detect non-specific reagent Abs, to lipid antigens like cardiolipin, released from damaged host cells, or any treponeme -you have to confirm treponemal test because these can be pos for TB or leprosy
34
SYPHILIS SEROLOGICAL TESTS Confirmatory Treponemal Ab Tests
*EIA:Enzyme Immunoassay *FTA-ABS: Fluorescent Treponemal Antibody Absorption *TPHA: Treponema Pallidum Hemagglutination *TP-PA: Treponema pallidum passive particle agglutination *Detect specific Abs to T. pallidum
35
LYME DISEASE ( BSL 2)CNS MANIFESTATIONS what specimen should be used for testing and how should the testing be done
-Borrelia burgdorferi -Transmitted by infected deer tick *Slow growing, motile spirochete , HARD TO GRAM *3 stages of disease – starts with a bullseye rash Serum, body fluid including CSF, tissue Serology by EIA, or immunofluorescent assay for total Ab + 2ndary EIA or Western blot for specific IgG or IgM antibodies to confirm. *PCR but only sensitive for synovial fluid, CSF or tissue
36
Stages of Lyme disease that affect the CNS:
2nd or Early disseminated stage: Gets into joints & nervous system, causes bells palsy, & memory loss (weeks and months later) 3rd Late disseminated stage: Gets into brain & spinal cord, causes meningitis/encephalitis.
37
CLOSTRIDIAL TOXINS THAT AFFECT THE CNS Tetanus: Clostridium tetani toxin
Anaerobic, large, GPB with spores (BSL2 -spores in soil, dust, & manure - transmitted thru breaks in skin or puncture wound -spores will germinate and make neurotoxin- causes spastic ridged paralysis, lock jaw, back arches -diagnosed by symptoms and pt history no direct tests
38
CLOSTRIDIAL TOXINS THAT AFFECT THE CNS Botulism: Clostridium botulinum toxin
-spores in environment -spores in improperly home-canned, or fermented foods, or gets in a wound, spores germinate, organism grows & makes neurotoxin -very heat resistant' -can happen to babies if they eat natural honey - causes flaccid paralysis. -Diagnosed by symptoms & evidence of toxin in serum or stool -give person the antitoxin but there is not vaccine **Both types of paralysis can affect breathing and are fatal
39
MYCOBACTERIA (BSL3) CNS INFECTIONS
-start in the lungs and travels thru lymphatics or blood to get to organs -able to cross BCB and BBB into meninges or brain -children and sick people at risk -considered chronic form on CNS -in the brain small abscesses or granulomas form which burst to cause meningitis/encephalitis -if arteries are involved then infarctions and tissue death can occur sympts: Headache, fever, behavior & cognitive changes - death
40
DIAGNOSIS OF MYCOBACTERIAL CNS INFECTIONS
1.CT scan or MRI of brain 2.Specimens: CSF or brain aspirate/ tissue biopsy 3.Direct specimen visualization or detection via Ziehl Neelsen, Kinyoun , Auramine O fluorescent stain, PCR from positive broth or specimen 4.Culture (solid media + broth media): *On solid egg-based media Lowenstein-Jensen(LJ) *on agar-based media Middlebrook *And a broth media Middlebrook liquid media *Or just automated system broth 5. ID Testing: *Biochemical tests, MALDI BSL3 organism so must be worked up in CL3 lab
41
PARASITIC CNS INFECTIONS
-parasites can invade anywhere -if cns is infected the increased d morbidity & mortality -most at risks are poor people living where the parasite is endemic or those with HIV -only in North America because of travel and immigration -survivors of this type of infection can have lifelong disabilities and chronic seizures
42
Naegleria fowleri (BSL3) PRIMARY AMOEBIC MENINGOENCEPHILITIS (PAM) what forms does it exist in
1.Free living amebic trophozoite (infective) gets in through the nose when you inhale contaminated water in water sports, gets into the olfactory nerves - eats them and into CNS = lethal infection PAM 2.Transient flagellate form- when nutrients are scarce -known as a shapeshifter 3.Environment resistant cyst can get from nette pots
43
DIAGNOSIS of N. fowler diagnostic form and diagnosed by
Diagnostic forms: *Trophozoite in CSF or brain tissue *flagellate in CSF Diagnosed by: *Direct wet prep of CSF *CSF/brain tissue smears stained with special histological stains. *PCR on CSF or immunohistochemical tests on brain tissue.
44
Acanthamoeba spp. (BSL2)
*Free-living amebae *Found in soil & water *Trophozoite & cyst are infective stage. *Enter nose or skin, *Can invade CNS by hematogenous route. *Causes granulomatous amebic encephalitis *Or hemorrhagic encephalitis *Both are fatal Diagnosis: *CT or MRI *Stained biopsy of brain lesion to look for cysts or trophozoites *PCR of CS
45
Taenia solium (BSL2)NEUROCYSTICERCOSIS and diagnosis
-when you swallows embryonated eggs of pork tapeworm parasite Taenia solium - eggs hatch larvae in intestine, go into the tissues to form tissue cysts - cysticerci .*If cysts form in brain, called neurocysticercosis. *Seizures, headaches, confusion &hydrocephalous – fatal Diagnosis: *CT or MRI *Serology *Finding larval cysts in brain biopsy by performing special stains (hematoxylin and eosin) *PCR on CSF?
46
Toxoplasma gondii (BSL2) IN BRAIN which forms does it exist in
*Cat is definitive (where parasites replicates and sexually mature form ) host. Mammals are Intermediate (non sexual form is found) hosts & humans are accidental host (not the preferred host and it wont be able to go from accidental to definitive). Exist in 3 forms: *Tissue forms, tachyzoites or bradyzoites transmitted when you eat contaminated meat, food or water. *Oocysts transmitted by contact with cat feces *In body Oocysts become tachyzoites, move to muscle, eyes, heart and brain- transform into bradyzoites in tissue cysts. *Mother can infect fetus in utero *Healthy people -asymptomatic or flu-like symptoms .*Immune system keeps parasite in cysts- in tissue forever. *If immunosuppressed, cysts rupture & causes tissue damage. *Symptoms in CNS: headache, confusion, seizures & death
47
DIAGNOSIS OF TOXOPLASMOSIS
*CT or MRI of brain – look for lesions *Serology for IgG or IgM Toxoplasma antibodies *Histological stains for parasite tissue form in brain biopsy *Direct fluorescent antibody stain to find antigen in CSF or tissue *PCR
48
African Trypanosomiasis SLEEPING SICKNESS what is it, what forms does it exist in and the diagnosis
-endemic to Africa -Spread by tsetse fly infected with Trypanosoma spp. (BSL2) blood parasite. Not often spread by transfusion, mom to baby Two stages: 1.Haemolymphatic- parasite in blood & lymphatic system 2.Meningoencephalitic - parasite invades CNS.–Once in CNS, causes sleep/wake cycle reversal, & neurological problems, seizures, coma Diagnosis: * Wet prep or special stains to detect parasite in blood, lymph, bone marrow or CSF.
49
CEREBRAL MALARIA how infection is caused and diagnosis
* Anopheles mosquito infected with Plasmodium falciparum (BSL2) blood parasite. *Parasite enters RBC. *Infected RBC cling to blood vessel wall. *Avoid removal by spleen & pass thru BBB into brain. *Blocks vessels in brain = decrease in nutrients & O2 *Inflammation = brain swelling .*Causes neurological disorders, seizures, coma. Diagnosis: *CT or MRI and symptoms *seeing asexual form of parasite in RBC by thick & thin blood smears, stained by Giemsa. *PCR available but must be correlated with symptom
50
FUNGAL CNS INFECTIONS
-rare and starts with yeast or mold lung, skin or CSF shunt infection -in sick ppl the fungus crosses the BCB and BBB spreading to the csf or brain -can happen in healthy people who have had brain surgery or come in contact with contaminated medical equipment/drugs -CNS fungal infections cause meningitis/encephalitis, cerebral abscess/granulomas, or stroke *Cryptococcus neoformans most common (BSL2) *C. albicans or Candida spp. (BSL2) *Dimorphic fungi (BSL3**) or Aspergillus spp (BSL2)
51
DIAGNOSIS OF FUNGAL CNS INFECTIONS
*Direct microscopic exam of CSF stained by gram or India ink (for Candida or Cryptococcus). *Histological stains or calcofluor white on tissue biopsy. *Culture of CSF or CNS tissue on fungal media- must be kept for 4-6 weeks. *Dimorph culture must have a plate at 350C and one at RT – (remember are BSL3 organisms) .*LPCB stain once fungus grows to look for characteristic microscopic fungal elements. *Direct specimen Latex aggl or lateral flow for antigen to C. neoformans. *Serological tests likecomplement fixation or immunodiffusion tests to detect Ab in blood
52
TYPICAL TEST RESULTS FOR YEAST \Candida albicans
*Wet prep or gram shows budding yeast *Germ tube: pos *Urea: neg *Chlamydospore: pos * MALDI for ID
53
TYPICAL TEST RESULTS FOR YEAST Cryptococcus neoformans
can be mucoid *Wet prep or gram shows budding yeast *India ink: pos for capsule *Germ tube: neg *Urea: pos *Chlamydospore: neg * MALDI for ID
54
VIRAL CNS INFECTIONS and symp
*Most common cause of CNS infection *starts as respiratory, intestinal or skin infection. *Enters lymphatic system & blood - can cross BCB or BBB causing meningitis or encephalitis. *Called ‘Aseptic Meningitis’ because no organisms seen microscopically, & none grow in routine culture. *Milder than bacterial meningitis (unless person is immunocompromised). *Symptoms: headache, fever, photophobia, & less neck stiffness – usually person completely recovers
55
DIAGNOSIS OF VIRAL CNS INFECTIONS
*PCRon CSF (qPCR, & also multiplex available to detect several virus from CSF at same time) *Fluorescent Ab to detect antigen directly from brain tissue biopsy *EIA *Serology to detect Ab in blood *Cell culture – but not all viruses grow in cell culture
56
PRIONS
*protein that causes normal brain proteins to fold abnormally into amyloid plaques - toxic to neurons *neurodegeneration – dementia like symptoms that progress quickly & always fatal. *Creutzfeldt-Jakob disease (CJD) – is inherited or sporadic *Variant CJD is variant form of Bovine Spongiform Encephalopathy (mad cow) transmitted when humans eat infected cow meat. *Human form is different than BSE form – not “mad cow” *Another example in humans is Kuru –transmitted via cannibalism. Diagnosis: MRI & immunochemical detection of prion proteins from brain tissue or CSF