CSF Sampling and Processing Flashcards
Diagnostic CSF
Measurement of CSF pressure
CSF sample for biochem, microbiology, cytology
(some blood also required as blood and CSF separated by BBB)
Investigational Procedures
Radiographic investigation for structure of CSF spaces
Treatment Interventions
Pressure reduction by taking some fluid out
Deliver intrathecal antibiotics or chemotherapy
Diagnoses Supported by CSF Measurements
Meningitis
Sub-arachnoid haemorrhage
Inflammtory -> MS, ADEM, AHEM, Sarcoid, Vasculitis
Guillain-Barre Syndrome
Dementia -> AD, prion
Encephalitis, BIH, NPH
Contraindications for CSF Sampling
- Lesion in intracranial space
- Non-communicating hydrocephalus
- Generalised brain oedema
- Above features and no CT
- Bacterial meningitis, BUT treat first
- Skin infection
- Bleeding diathesis
CSF Sampling Complications
- Coning, leading to death -> hole made in dura, fluid leaks out
- Low pressure headache
- Infection
- Back stiffness
- Haemorrhage (spinal, subdural, subarachnoid)
CSF Appearance
Should be clear and colourless
Infection: yellowish
Blood stained: acute haemorrhage
Biomarkers
A marker that is objectively measured and evaluated as a indicator of normal or pathological processes, or pharmacological response to a therapeutic intervention
Specific Biomarker
Able to differentiate between pathologies
e.g., acute vs chronic, acquired vs inherited
Should have specificity >0.9
Sensitive Biomarker
Baseline should be zero.
Should mark early reversible neural damage.
Sensitivity should be >0.9
Predictive Biomarker
Should be proportionate to extent of injury
e.g., biomarker increases as injury gets worse
Robust Biomarker
Rapid, simple, accurate, inexpensive
Ideally non-invasive
Ideal Biochemical Biomarker
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
CSF/Serum Ratios
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
CSF Biomarkers
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
Oligoclonal Bands
Compare pattern of bands in sample taken from serum and CSF
Each band relates to an antibody
Can identify whether serum or CSF positive
CSF for Xanthochromia
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
CSF Dementia Biomarkers
- 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
Biomarkers for Aiding Dementia Diagnosis
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
Pros and Cons of CSF Testing
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
