CSF Sampling and Processing

Question 1

Diagnostic CSF

Answer 1

Measurement of CSF pressure

CSF sample for biochem, microbiology, cytology
(some blood also required as blood and CSF separated by BBB)

Question 2

Investigational Procedures

Answer 2

Radiographic investigation for structure of CSF spaces

Question 3

Treatment Interventions

Answer 3

Pressure reduction by taking some fluid out

Deliver intrathecal antibiotics or chemotherapy

Question 4

Diagnoses Supported by CSF Measurements

Answer 4

Meningitis
Sub-arachnoid haemorrhage
Inflammtory -> MS, ADEM, AHEM, Sarcoid, Vasculitis
Guillain-Barre Syndrome
Dementia -> AD, prion
Encephalitis, BIH, NPH

Question 5

Contraindications for CSF Sampling

Answer 5

1. Lesion in intracranial space
2. Non-communicating hydrocephalus
3. Generalised brain oedema
4. Above features and no CT
5. Bacterial meningitis, BUT treat first
6. Skin infection
7. Bleeding diathesis

Question 6

CSF Sampling Complications

Answer 6

1. Coning, leading to death -> hole made in dura, fluid leaks out
2. Low pressure headache
3. Infection
4. Back stiffness
5. Haemorrhage (spinal, subdural, subarachnoid)

Question 7

CSF Appearance

Answer 7

Should be clear and colourless

Infection: yellowish
Blood stained: acute haemorrhage

Question 8

Biomarkers

Answer 8

A marker that is objectively measured and evaluated as a indicator of normal or pathological processes, or pharmacological response to a therapeutic intervention

Question 9

Specific Biomarker

Answer 9

Able to differentiate between pathologies
e.g., acute vs chronic, acquired vs inherited
Should have specificity >0.9

Question 10

Sensitive Biomarker

Answer 10

Baseline should be zero.
Should mark early reversible neural damage.
Sensitivity should be >0.9

Question 11

Predictive Biomarker

Answer 11

Should be proportionate to extent of injury
e.g., biomarker increases as injury gets worse

Question 12

Robust Biomarker

Answer 12

Rapid, simple, accurate, inexpensive

Ideally non-invasive

Question 13

Ideal Biochemical Biomarker

Answer 13

Specific:
-> high target tissue/serum ratio
-> not present in non-neural tissue
-> differentiates neural pathologies

Sensitive:
-> mark early, reversible neural damage
-> kinetics so immediately detectable with injury
-> rapidly assayed

Predictive:
-> long half-life so does not need to be measured at the moment of injury
-> proportionate to the extent of injury

Question 14

CSF/Serum Ratios

Answer 14

Used to indicate BBB function

CSFAlb:
- CSF does not make albumin, so if high is must have entered through a leaky barrier
- Reflects BBB integrity
- Non-specific for disease

CSF IgG:
- Made by WBC, reflects intrathecal IgG synthesis
- Not useful in PNS diseases

QIgG/Qalb = IgG index
-> ratio of relative intrathecal to systemic IgG production

Question 15

CSF Biomarkers

Answer 15

NfH
Tau
Peripherin -> seen when there is damage to peripheral nerves

Peripheral Nerve Disease:
- NF-L
- Neuron specific enolase
- S100b
- Anti-MBP antibodies
- IL6, IL2R, TNFalpha, MCP1, IP-10

CNS Disease:
- 14-3-3 protein
- S100b
- NF-L
- Amyloid beta 1-42/1-40
- Tau/P-tau
- GFAP

Question 16

Oligoclonal Bands

Answer 16

Compare pattern of bands in sample taken from serum and CSF
Each band relates to an antibody
Can identify whether serum or CSF positive

Question 17

CSF for Xanthochromia

Answer 17

Use spectrophotometry - blood in CSF will have a higher absorbance
Test for subarachnoid haemorrhage -> severe headache
CSF must be protected from light, or bilirubin degradation can cause a false negative

Question 18

CSF Dementia Biomarkers

Answer 18

• Total Tau
• Phospho tau
• Amyloid beta (1-40 and 1-42)
• NfL
• In AD, 1-42 decreases in CSF as it sticks to plaques in the brain, 1-40 goes up
• Can use ratio to determine amyloid sink

Question 19

Biomarkers for Aiding Dementia Diagnosis

Answer 19

Amyloid:
- Low CSF 1-42

Neuronal injury:
- Elevated t-tau and p-tau

Neurodegeneration: 14-3-3
Astrogliosis: S100b -> increases with generalised brain inflammation
Axonal damage: NfL -> increases with rapid brain damage

Question 20

Pros and Cons of CSF Testing

Answer 20

Pros:
- May be positive even if serum isn’t
- Cleaner than serum (less non-specific background)
- Few other antibodies which could mask positive results

Cons:
- Harder to obtain
- Fewer validated assays
- Needs paired serum = increased cost