CSF

How much circulating CSF is there typically at any time?

120-150cc

Up to ________ WBC and ____________ RBC are considered normal if CSF is obtained by a LP. Normally, the majority of WBCs in CSF should be ______________

5WBCS 5RBCs Lymphocytes

What does CSF normally look like?

Clear, colorless

What does cytology of CSF help to evaluate for?

•Examine cells in the CSF to determine if they are malignant •Tumors in CNS can shed cells into the CSF •Can assess for primary tumors or metastases

What is glutamine? What is the importance of glutamine in regards to the CNS?

•Glutamine = amino acid produced when ammonia combines with α-ketoglutarate •Provides a mechanism for removing ammonia from CNS •Most prominent amino acid in CSF •Should be tested in patients with coma of unknown origin

List the reasons to obtain a lumbar puncture.

1. Diagnostic -Determine CSF pressure and allow for documentation of impaired CSF flow -Evaluate for various medical conditions (meningitis, subarachnoid hemorrhage, CNS malignancy and demyelinating diseases) 2. Therapeutic -Remove extra CSF fluid (pseudotumor cerebrii, hydrocephalus, normal pressure hydrocephalus) -Introduce anesthetics, medications, blood patch, or contrast media

What is the normal range of pressure of CSF (opening pressure)?

6-20 cm H2O

How are lumbar punctures performed? Where?

A needle is inserted into the subarachnoid space Typically done at L3-L4 or L4-L5 (because the spinal cord ends at L1-L2 and pooling occurs in the lumbar sac around L4-L5)

Explain what causes a traumatic tap and how to differentiate a traumatic tap from evidence of a subarachnoid bleed.

A traumatic tap is caused by accidental trauma to a blood vessel during LP. See picture for differentiation.

What can cause the CSF to look turbid?

As few as 200 WBCs or 400 RBCs will cause the CSF to appear turbid 1+ (slightly cloudy) to 4+ (very cloudy) Rule of thumb: should be able to read a newspaper through the tube

Why should cell counts be done immediately after LP?

Because the cell count may be falsely LOW if the specimen is evaluated more than 60 mins after collection (thought to be due to cells sticking to the sides of the plastic tubes)

Describe the importance of the blood brain barrier and the blood CSF barrier.

Both are responsible for managing the transport of molecules/solutes The blood brain barrier has tight junctions that help to stop various molecules and solutes in the blood from diffusing into brain tissue. The BBB controls the contents of the brain and interstitial fluid. The Blood CSF barrier is found in the choroid plexus and helps to control what substances from the blood can enter the actual CSF itself. This has transporter proteins as well.

Explain the significance of oligoclonal bands, particularly IgG.

Causes of oligoclonal bands: •Multiple sclerosis (An elevation of IgG is a diagnostic criterion) •Autoimmune diseases •Meningitis, encephalitis •Brain tumors •Multiple myeloma

What are the tight junctions and where are they found?

Component of the BBB that is found in between endothelial cells. The tight junctions help to stop various molecules and solutes in the blood from diffusing into the brain tissue

Describe the differential diagnoses associated with pleocytosis from neutrophils, lymphocytes, macrophages and eosinophils.

Correlate clinically!!!

What is the blood CSF barrier?

Found in the choroid plexus and is formed by ependymal cells with tight junctions. It helps to control what substances from the blood can enter the CSF

What can cause CSF to look bloody?

Grossly bloody if >6000 RBCs are present

What are causes of elevated glutamine in the CSF?

Hepatic encephalopathy Reye's syndrome (swelling in liver and brain) Encephalopathy secondary to sepsis or hypercapnea

What are causes of decreased opening pressure on LP?

Hypovolemia Chronic leakage of CSF through an LP site or nasal fracture with dural tear

What is pleocytosis? What does this indicate?

Increased WBCs in the CSF •An elevation of WBCs in CSF DOES NOT diagnose infection •Can be elevated from infectious and noninfectious causes •May also be elevated during traumatic tap (ratio of WBC:RBC should be the same in serum and CSF) •Need to look at amount of types of WBC's and correlate with clinical picture

What special tests can be ordered to evaluate for different things in CSF?

Infectious workup: •Gram stain •Culture (bacterial, fungal) •PCR studies (Viral, tuberculosis) •India Ink •VDRL Protein electrophoresis Cytology

What happens to LDH when CNS tissue is damaged?

It increases

What does the BBB allow to pass through?

Lipid soluble small molecules can pass the BBB Transporter proteins help to control the movement of glucose, amino acids, and various ions across the BBB

Describe how much protein you would typically expect to find in CSF and reasons for elevated protein levels.

Normal: 23-38mg/dL •Subarachnoid hemorrhage (SAH) or traumatic tap (Protein raises 1g/dL per 1000 RBCs/microL) •CNS infections (Meningitis, encephalitis, brain abscess, neurosyphillis) •Guillain-Barre •Peripheral neuropathy •CNS Tumors (Froin's syndrome) •Multiple sclerosis

What is the function of astrocytes?

Part of the BBB that overlaps capillary walls and produces growth factors to maintain the tight junctions. The astrocytes also act as antigen-presenting cells to modulate the immunologic response of the CNS.

Describe patient education that should be offered to a patient to prevent a spinal headache following lumbar puncture.

Patient needs to stay flat for 4-8 hrs after procedure Fluids are encouraged in order to rehydrate the pressure

Where is the CSF produced?

Produced in the lateral, third, and fourth ventricles by the choroid plexus

What is the purpose of CSF?

Protection Regulates ICP Transports nutrients/removes waste products

How can you differentiate if the cause of xanthochromia is a subarachnoid hemorrhage vs a traumatic tap?

SAH: •Discoloration and RBC count will remain constant through all tubes •After centrifugation, will still note discoloration Traumatic tap: •RBC count will decline with successive collection tubes •After centrifugation, fluid will be clear

What are causes of xanthochromia?

Subarachnoid Hemorrhage (SAH) Traumatic tap Elevated CSF protein Significant systemic hyperbilirubinemia

List the different uses for the four tubes of CSF collected from a lumbar puncture.

Tube 1: Cell counts and differential (WBC, RBC) Tube 2: Protein and glucose Tube 3: microbiology studies (gram stain, culture) Tube 4: special studies based on your differential (protein electrophoresis, cytology, etc)

What is in the CSF?

Very similar to the composition of the plasma (electrolytes, glucose, etc)

Explain ways to rule out increased intracranial pressure prior to performing a lumbar puncture and the importance of doing this step.

You do not want to lower the high pressure because it can cause brainstem herniation -Get a CT first

How can CSF LDH levels be helpful clinically?

•90% of bacterial meningitis cases have increased LDH •Occurs in only 10% viral meningitis •When elevated in viral meningitis = poor prognosis •Can also be elevated in patients with SAH, but not traumatic tap (can help differentiate the two)

What can PCR of CSF be used to look for?

•Assess for multiple causes of meningitis and encephalitis (Viral and others): •Herpes Simplex •Varicella Zoster •Enterovirus •Epstein-Barr Virus •Cytomegalovirus •Tuberculosis •Lyme disease •West nile virus

How do spinal headaches present?

•Can occur 15 minutes to 4 days after procedure •Symptoms can last up to one week •Headache worsens when sitting up, better when lying down

What is the treatment for spinal headaches?

•Conservative care generally •If headache persists --> blood patch by inserting some of the patients own blood into the same puncture site as the original LP site (to close off the mechanism of the CSF leak)

What is the usefulness of lactic acid levels in CSF?

•Differentiate between various types of meningitis •Bacterial meningitis have highest levels (>35 mg/dL) •Fungal and TB meningitis have intermediate levels (25-35mg/dL) •Viral meningitis have low levels (<25 mg/dL) •Monitor severe head trauma •Persistently elevated levels have poorer prognosis •Will be high in a sample with elevated RBC (RBC have high concentration of lactate)

What are options for tests you can run on CSF for an infectious workup?

•Gram stain •Culture and sensitivity •Polymerase Chain Reaction (PCR) •Acid-fast bacillus (Tuberculosis) •India Ink (fungal) •VDRL (syphilis)

What is CSF immunoglobulins looking for?

•Immunoglobulins are hardly ever seen in CSF •Oligoclonal band --> Elevations of one type of immunoglobulin •Can test via CSF protein electrophoresis

What are contraindications of lumbar puncture?

•Increased intracranial pressure (exception: pseudotumor cerebrii) •Suspected epidural infection •Infection or severe dermatologic disease in lumbar area •Anatomic malformation, previous spinal surgery at same level •Anticoagulation (INR > 1.4, taking other Factor Xa inhibitors) •Coagulopathy •Platelet count <50K •Pt unable or unwilling to cooperate •Chronic back pain (relative contraindication)

What are causes of increased opening pressure?

•Intracranial tumor, abscess or lesion •Pseudotumor cerebrii •Meningitis (bacterial and cryptococcal) •Hydrocephalus •Subarachnoid hemorrhage •Obstructed SVC

What are the risks of lumbar puncture?

•Mild back pain •Bleeding (at LP site, traumatic tap, epidural hematoma) •Spinal headache •Brainstem herniation (if done with elevated ICP)

What CSF findings would you expect to find with SAH?

•Opening Pressure: Elevated •Color: Xanthochromia (Continues throughout all 4 tubes) •RBC: Elevated •Protein: Elevated

What are routine values tested in CSF?

•Opening pressure •Color •Cells (WBC's) •Protein •Glucose •Glutamine •Lactate •Lactate Dehydrogenase (LDH)

What are reasons someone needs a CT scan before performing an LP?

•Papilledema (ALWAYS LOOK FOR THIS!!!) •Immunocompromised state •Abnormal level of consciousness •Focal neurological deficits on exam •Seizure within one week of presentation

What is the opening pressure? What do you do if it is high?

•This is the first pressure noted as soon as the LP needle enters the subarachnoid space •Should be measured while patient in lateral decubitus position with legs straight •Will have slight fluctuations with pulse and respirations •If opening pressure is elevated, limit volume of CSF removed to prevent risk of cerebellar herniation

How does CSF glucose compare to blood glucose normally? What would cause abnormally low glucose?

•Typically 60% of serum glucose •Need to obtain serum glucose 1 hour before LP for accurate comparison •Causes of abnormally low glucose: •Meningitis (bacterial, fungal, tuberculosis) •Occasionally lowered in subarachnoid hemorrhage •Will be normal during viral CNS infections with a few exceptions •Herpes Zoster or simplex, mumps, enteroviruses

When do you order a gram stain on CSF? How long does it take to get the results?

•Typically order gram stain with culture and sensitivity to assess for bacterial meningitis •Assess physical and chemical component of bacteria (gram positive, gram negative, cocci, rods, etc) •Does not assess antibiotic sensitivities •Can take 1-5 days to result (quicker than culture results)

When would you order a culture on CSF? How long does it take for results?

•Used to evaluate specific organism that is causing meningitis •Can assess bacteria, fungi, viruses •Can determine which antibiotics will treat the bacteria •May take 3-7 days for results to finalize •If high clinical suspicion for meningitis, ok to give antibiotics before obtaining culture = Results should still be accurate

What CSF findings would you expect with Guillain-Barre?

•WBC Count: Usually normal •Protein: Elevated

What would you expect CSF studies to look like with MS?

•WBC: Usually normal •Protein: Usually normal •Protein electrophoresis: elevated oligoclonal IgG bands

Explain the expected CSF findings for the following types of meningitis: bacterial, viral, TB, and fungal.

•Will also want to obtain infectious workup •Gram stain, culture and sensitivity •Viral PCR •Consider India Ink, AFB, and/or VDRL depending on clinical situation •DO NOT WAIT TO ADMINISTER ANTIBIOTICS - OK TO GIVE PRIOR TO LUMBAR PUNCTURE

Describe the cause of the color variation that creates xanthochromia.

•Xanthrochromia = yellow or pink discoloration •Often secondary to red blood cells in CSF •RBCs rapidly lyse after entry into CSF •The Hb is first broken down into oxyhemoglobin (pink) and then to bilirubin (yellow) •Will appear pink (oxyhemoglobin) within first 2-4 hours, then yellow (bilirubin) 10-12 hours after RBCs enter the CSF