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Cerebrospinal Fluid (CSF) Adults produce 450 to 500 cc per day 150 cc in adult CNS at any one time Neonates have 30 to 60 cc Children have 100 cc 80 % produced by ventricular choroid plexuses Reabsorbed by arachnoid villi Drains into dural sinuses
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Lab Medicine Conference : Cerebrospinal Fluid Analysis
Cerebrospinal Fluid (CSF)
Adults produce 450 to 500 cc per day 150 cc in adult CNS at any one
time Neonates have 30 to 60 cc Children have 100 cc 80 % produced
by ventricular choroid plexuses Reabsorbed by arachnoid villi
Drains into dural sinuses Suspected Diagnoses for Which CSF Exam is
Indicated
Meningitis Encephalitis Brain abscess Neurosyphilis Subarachnoid
hemorrhage Demyelinating conditions : Multiple sclerosis
Guillian-Barre CNS malignancies Usual Recommended Tests to Run on
Sequential Tubes of CSF from an LP
First and third tubes Cell count & differential Second tube CSF
total protein, glucose, +/- other chemistries Fourth tube Gram
stain, other stains, cultures Priority Ranking of Tests to Run If
Only Small Amount of CSF Obtained
Gram stain / culture Cell count / differential Protein / glucose
Chemistries Contraindications to Lumbar Puncture
Intracranial mass lesion with impending herniation Cutaneous
infection or suspected subcutaneous abscess at LP site Systemic
coagulopathy Could result in cord compression from para-spinal
hematoma Unrestrainable patient Potential Complications of Lumbar
Puncture
Uncal or brainstem herniation 0.3 to 1.2 % mortality if papilledema
present less likely if smaller amounts of fluid removed
Arachnoiditis : can occur if needle carries in povidone-iodine
Epidermoid tumors (delayed) : from use of needle without stylet
Nerve root injury : less likely if needle bevel vertical Induced
meningitis ; paraspinal abscess Mortality from hyperflexion of head
& tracheal obstruction or from vagally induced asystole
Post-procedure headache : 12 to 39 % CSF Exam First step is measure
the opening pressure (OP) :
normal 80 to 180 mm H2O with pt. recumbent can be"falsely" elevated
by Valsalva, head-up position, or jugular compression should vary 5
to 10 mm H2O with respiration Queckenstedt & Tobey Ayer tests
(involving jugular compression & seeing the effect on OP) are
no longer recommended Causes of Elevated CSF Opening Pressure
Meningitis Intracranial mass lesions SAH CHF SVC obstruction
Thrombosis of intracranial venous sinus Acute elevation of serum
osmolarity Causes of Low CSF Opening Pressures
Severe dehydration Circulatory collapse Chronic serum
hyperosmolality Dural tears with CSF leak Neurosurgical procedures
Subdural hematomas in elderly Barbiturate intoxication Complete
spinal subarachnoid block CSF Appearance Normal is clear &
consistency similar to H2O
Causes of visual turbidity : > 200 WBC's per mm3 > 400 RBC's
per mm3 Bacteria Aspirated epidural fat Evil aliens (this was to
see if you are paying attention) Causes of CSF Clot Formation
Traumatic tap Increased protein from : subarachnoid block
neurosyphilis tuberculosis Metastatic mucinous adenocarcinoma of
the meninges Xanthochromia of the CSF
Is yellow - orange - brown coloration in supernatant of centrifuged
CSF Produced by lysis of red cells Involves 3 pigments :
oxyhemoglobin (red) : occurs in CSF within 2 hours of a SAH
bilirubin (yellow) : converted from hemoglobin in 12 hours
methemoglobin (brown) Causes of Xanthochromia Besides Red Cell
Lysis
Direct serum bilirubin levels > 10 to 15 mg % CSF protein levels
> 150 mg % Sample contamination with povidone iodine Systemic
hypercarotenemia CSF melanin from meningeal melanosarcoma CSF
Glucose Normally 60 to 70 % of serum level
Is 100 % ratio in neonates (immature CSF / blood barrier) In adults
with serum glucose > 300 mg %, no further increase in CSF
glucose occurs CSF level takes 2 hours to equilibrate with change
in serum glucose Causes of Hypoglycorrhachia
(CSF to Serum glucose ratio < 0.6) Systemic hypoglycemia
Impaired glucose transport Increased CNS use of CSF Increased use
of CSF glucose by bacteria & leucocytes Typical with bacterial,
tuberculous, or fungal meningitis Also sometimes with SAH, viral
meningitidies, sarcoidosis, neoplasms CSF Protein Normal adult
range is 17 to 55 mg %
Normal neonate level is up to 150 mg % Increased levels usually
associated with CNS inflammatory processes, especially infections
Has relation ratio with serum protein levels, so elevations of
serum protein may cause elevations in CSF protein Noninfectious
Causes of Elevated CSF Protein
Traumatic LP 1 mg % increase per 1000 RBC's per mm3 Interference
with CSF / blood barrier Cerebral hemorrhage SAH Cerebral
thrombosis Endocrine Diabetes mellitus Hyperthyroidism
Hypoparathyroidism Hyperadrenalism Other Noninfectious Causes of
Elevated CSF Protein
Guillian-Barre Syndrome Multiple sclerosis Collagen vascular
diseases Subacute sclerosing panencephalitis Mechanical obstruction
of CSF circulation tumors, abscesses, cord compression Elevated
serum protein levels (multiple myeloma, etc.) Medications / toxins
: Phenytoin, ethanol, heavy metals Causes of Low CSF Protein
Levels
Chronic leakage from CSF otorrhea or rhinorrhea Chronic increased
ICP Removal of CSF via neurosurgical procedures or repeated LP's
CSF Cell Counts Normal adult : 0 to 5 lymphs or monos
Even one poly is abnormal Normal neonates have 0 to 30 cells &
up to 60 % polys Increased neutrophils usually indicate infectious
process Comparisons of Cell Counts in Viral Versus Bacterial
Meningitis
Typically > 500 WBC's / mm3 & mainly polys 10 % of cases
have < 50 % polys Viral Typically < 100 WBC's / mm3 &
mainly monos 10 % of cases have > 50 % polys (especially if
early) 90 % convert to mononuclear pleocytosis by 12 hours
Infectious Causes of Very Low CSF Cell Counts
Meningitis from : Neisseria meningitidis Hemophilus influenzae
Overwhelming Strep. pneumoniae infection Causes of Increased
Neutrophils in the CSF
Infectious Bacterial meningitis Early tuberculous meningitis Early
viral meningitis Early mycotic meningitis Noninfectious 3 to 4 days
post - hemorrhagic infarct SAH or intracerebral hematoma Injection
of antibiotics or antimetabolites Injection of contrast media
Repeated LP's Causes of Increased Lymphocytes in the CSF
Infectious Tuberculous, fungal, or leptospiral meningitis Partially
treated bacterial meningitis Viral or syphilitic
meningoencephalitis Subacute sclerosing panencephalitis Measles
Noninfectious Multiple sclerosis, Guillian-Barre Syndrome
Polyneuritis Temporal arteritis or periarteritis Chronic ethanol
abuse Intravenous drug abuse Causes of Increased Eosinophils in the
CSF
Infectious Bacterial, fungal, or viral meningitis Cysticercosis
Noninfectious Allergic reaction to foods, meds, dyes, or
envenomation Intrathecal foreign substances or contrast dye
Synthetic intrathecal shunts Periarteritis nodosa Allergic
bronchial asthma Acute polyneuritis Rabies vaccination Causes of
Increased Macrophages in the CSF
Infectious Tuberculosis Noninfectious Presence of erythrocytes
Acute intracranial bleeding Mycotic meningitis Trauma to CNS
Contrast media Age Related Causes of Bacterial Meningitis
Intersection with line B
Intersection with line B. Join the marks on lines A & B with
the ruler, and read off the probability of acute bacterial versus
acute viral meningitis where the ruler intersects the central
probability scale. CSF Gram Stain Should be done on uncentrifuged
CSF if CSF cloudy
Should be done on centrifuged CSF if CSF clear Identifies 80 % of
bacterial CSF infections False positive only if LP tray or stain
itself is contaminated CSF gram stain showing E. coli CSF gram
stain showing Listeria monocytogenes CSF gram stain showing
Neisseria meningitidis CSF gram stain showing Streptococcus
pneumoniae CSF gram stain showing Staphylococcus aureus CSF gram
stain of Pneumococcal meningitis Use of Acrinidine Orange Stain
(AOS) for CSF
Is fluorochrome stain for bacterial nucleic acids Bacteria stain
bright orange Background of cellular debris stains yellow - pale
green Takes 2.5 minutes to prepare (versus 3.5 minutes for gram
stain) Useful if bacteria not seen on gram stain (increases pickup
rate > 75 %) Other CSF Tests for Meningitis
Lactic acid Levels > 35 mg % in 90 % of bacterial meningitis
Numerous false positives (neoplasm, injury, etc.) LDH Elevated
(especially LDH-5) with bacterial meningitis, but is nonspecific
C-reactive protein If elevated has high sensitivity &
specificity for bacterial meningitis, but is a technically
difficult assay Quelling Reaction Antisera cause swelling in
pneumococci & Hemophilus influenzae Other CSF Tests for
Meningitis (cont.)
Limulus amebocyte lysate assay Requires 60 minutes Not 100 %
sensitive CSF amino acids Elevated with bacterial meningitis May be
useful for dx if partial treatment
Countercurrentimmunoelectrophoresis CIE) Takes 30 to 60 minutes
Precipitant line forms between bacterial antigens & serum with
known antibodies Can be useful in partially treated meningitis
False positives & cross-reactions occur Causes of False
Negative CIE
Amount of antigen too small (if < 10,000 bacteria per ml.) If
infection early, not enough time for antigen to dissolve off the
bacteria Poor antibody quality for some strians (as for group B
meningococcus & pneumococci types 7 & 14) Sensitivity of
CIE in Meningitis
Meningococcal : 50 to 90 % Strep. pneumoniae : 50 to 100 %
Hemophilus influenzae : 80 % Group B strep : 60 to 90 % Latex
Agglutination Antigen Tests for Meningitis
More sensitive than CIE for pneumococci & meningococci Only
takes 15 minutes to perform Not affected by antigen excess Less
false negatives than CIE Other Tests to Consider for Suspected
Non-Bacterial, Non-Viral Meningitis
Acid fast stain Mycobacterial culture India ink prep (for
Cryptococcus) Cryptococcal antigen Fungal culture Charges at H.M.C.
for CSF Cultures & Microbial Stains
Gram stain & culture :$ 48 Sensitivity (antibiotic) :$ 45 to $
105 Agar diffusion vs. dual vs. add anerobic Fungal smear :$ 21
Fungal culture :$ 48 AFB smear & culture :$ 50 CIE :$ 37
Charges at H.M.C. for Other Standard Studies on CSF
Cell count & diff. :$ 67 (stat) Glucose (stat) :$ 35 Protein
(stat) :$ 35 Cryptococcal antigen :$ 35 Lactate :$ 26 Charges at
H.M.C. for Miscellaneous Studies on CSF
Darkfield exam :$ 54 VDRL :$ 16 India ink prep :$ 22 IgG :$ 20
Immunochemistry eval. :$ 126 ph by electrode :$ 26 Sperm count
(rule out sperm embolus) : $16 Total Charges at H.M.C. for
Different Patterns of CSF Test Ordering
CBC/diff., gm. stain / culture, glucose, protein :$ 185 All
standard, & culture / sensitivity studies : $ 322 All standard,
& culture / sensitivity, & misc. studies :$ 462 Summary of
Lab Studies on CSF for Meningitis
Measure opening pressure Send four tubes Check gram stain If gram
stain negative : Consider AOS Consider CIE +/- LA If clinical
suspicion for meningitis, start broad spectrum antibiotics prior to
initial lab results