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MSC: Disease of major orgns > Subarachnoid haemorrhage and CSF xanthochromia analysis > Flashcards

Subarachnoid haemorrhage and CSF xanthochromia analysis Flashcards

1
Q

What is the Subarachnoid space?

A
  • Sits between the pia mater (inner) and the arachnoid (outer) mater
  • Contains CSF as a protective layer around the brain
  • Arteries and veins reside in the subarachnoid space before penetrating the surface of the brain
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2
Q

What is a Subarachnoid Haemorrhage?

A

Escape of blood from a cerebral artery into the subarachnoid space

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3
Q

What are causes of Subarachnoid Haemorrhage?

A
  • Most SAH are due to rupture of a cerebral aneurysm
  • Protruding lesion caused by haemodynamic stress at a weak spot in a blood vessel, often at bifurcation points/bends
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4
Q

What are causes of SAH?

A
  • Congenital defects
  • Injury or infection of the vessel
  • Medical conditions such as arteriovenous malformations and connective tissue disorders

An aneurysm may be unsuspected until rupture occurs. Physical exertion may trigger a rupture but most aneurysmal SAH occur without an identifiable trigger

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5
Q

What are symptoms of Subarachnoid haemorrhage?

A
  • Severe headache of acute onset (“thunderclap headache”), classically occipital
  • Vomiting
  • Altered level of consciousness, coma unusual
  • Blurred vision (retinal haemorrhage)
  • Neck pain
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6
Q

What are causes of the symptoms in subarachnoid haemorrhages?

A
  • Meningeal irritation
  • Hydrocephalus: blood in the subarachnoid space affects the flow and absorption of CSF, may lead to increased intracranial pressure
  • Vasospasm of cerebral blood vessels leads to: release of substances during lysis of blood clots causes endothelial damage and smooth muscle contractionrestricts blood supply to parts of the brain, may cause cerebral ischaemia.
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7
Q

What are other differential diagnosis when consider Subarachnoid Haemorhage?

A
  • Spontaneous intracranial hypotension
  • Pituitary apoplexy
  • Ischaemic stroke
  • Acute hypertensive crisis
  • Infections (eg acute complicated sinusitis)
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8
Q

What are epidemiological statistics surround SAH?

A

Incidence of SAH from ruptured aneurysms is approximately 12 cases per 100,000 people per year in North America and Europe

Mean age for SAH is 50 years

Hypertension, cigarette smoking and family history are the most consistently observed risk factors

Of patients with aneurysmal SAH:

  • ~25% die within 24hrs
  • ~45% die within 30 days
  • ~50% re-bleed within 6 months
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9
Q

What are survivors of SAH afflicted with?

A

Survivors commonly experience deficits in:

  • •Memory
  • •Cognition
  • •Language

These may be further compounded by depression, anxiety, fatigue and sleep disturbance

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10
Q

How is SAH acutely managed?

A
  • Discontinue antithrombotic/anticoagulant therapy
  • Manage increased intracranial pressure: physically (drain or shunt) and medically (diuresis)
  • Consider antiepileptic drugs to prevent seizures (evidence of benefit is unclear)
  • Prevention of vasospasm (Nimodipine (calcium channel blocker))
  • Maintain euvolaemia (IV fluids): hypovolaemia is a risk factor for ischaemic complications
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11
Q

What are forms of aneurysm repair?

A

Clipping

  • A clip is placed across the neck of the aneurysm, preventing blood flow
  • Surgical intervention
  • Requires craniotomy

Coiling

  • A platinum wire is fed through a catheter into the aneurysm
  • A small thrombosis forms around the coil, preventing blood flow
  • Can be done as an extension of angiography
  • Generally better outcomes than clipping
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12
Q

How is SAH diagnosed and the advanatges of using CT scans?

A

High resolution CT scan without contrast within 48 h of initial bleed will detect ~95% of SAH. Highest sensitivity within 6-12 h

Advantages

  • Location of ruptured aneurysm
  • Condition of ventricles
  • Overall blood load
  • Presence of cerebral infarction
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13
Q

Late presenting cases

  • Within 48hrs of bleed, 5% patients with SAH show no evidence on CT
  • After 1 week, 50% patients with SAH show no evidence on CT
  • After 2 weeks, 70% patients with SAH show no evidence on CT

May fail to detect small SAH

  • Especially if imaging is performed several days post-bleed
  • CT scans are affected by patient motion; sedation may be necessary to obtain satisfactory diagnostic images
A
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14
Q

What is angiography for SAH?

A

Positive CT scan – proceed to angiogram

  • Catheter inserted into major artery & threaded through circulatory system
  • Contrast agent injected to visualise blood vessels
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15
Q

What are benefits and disadvantages of Angiography?

A
  • Determine location of aneurysm & relationship with surrounding blood vessels
  • Resource intensive
  • Invasive procedure with (small) risk of morbidity and mortality
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16
Q

What is the role of biochemistry in the diagnosis of Subarachnoid Haemorrhage?

A

Biochemical analysis of the CSF is a second line test in SAH. Lumbar puncture is useful in the following:

  • Patients who are CT negative but where there is a strong clinical suspicion of SAH
  • Patients who present at late time points following the onset of symptoms
17
Q

How is Haemoglobin broken down in CSF?

A
  • Erythrocytes lyse within 2-4hrs of SAH and liberate oxyhaemoglobin
  • Heme oxygenase and Bilverdin Reductase in macrophages
  • Enzymes present in macrophages and other cells of the leptomeninges
  • Conversion can only occur in vivo
18
Q

What is xanthochromia and traumatic tap?

A
  • Xanthochromia = yellow discolouration of CSF due to bilirubin
  • Traumatic tap = bleeding into the subarachnoid space at the puncture site
19
Q

What are specimen requirements of CSF for analysis?

A
  • Collected >12hrs and <2 weeks after the onset of symptoms (exact timing should be noted)
  • Least bloodstained fraction (usually the last, ideally at least the 4th) used for spectrophotometry
  • Specimen must be protected from light (conformational change of bilirubin on exposure to light affects results)
  • Use of pneumatic tube systems is best avoided – if the CSF sample contains red blood cells the pneumatic tube will encourage in vitro haemolysis and release of oxyhaemoglobin

CSF is a precious sample, so should always be analysed, regardless of transportation method.

20
Q

What are CSF collection packs?

A

Laboratories may provide acute wards with “Lumbar puncture packs” to assist with the collection of the appropriate samples and information

Example contents:

  • Clear instructions for sampling and transport
  • At least 4 sterile bottles for CSF collection
  • Blood collection tubes (?dark coloured)
  • Envelope: protect CSF sample for xanthochromia analysis from light during transit
  • Guide to completing request forms: ensure correct tests are requested and ensure correct samples are sent to the appropriate laboratory
  • Data-gathering questionnaire: e.g. time post-onset of symptoms, results
21
Q

What are things to take into account for pre-analytical and analysis of CSF?

A
  • Centrifuge specimen at >2000 rpm for 5 min as soon as possible after receipt. Preferably within 1 hour of collection
  • If analysis is delayed, store the supernatant in the dark at 4°C until sample can be analysed
  • Using a quartz cuvette with a 1 cm path length, perform a zero order scan between 350 and 600nm on the undiluted specimen. Appropriate cuvette volume is an important factor when procuring a spectrophotometer
  • Adjust the scale of the y-axis so that it has a maximum of at least 0.1 AU. If any peaks exceed 0.1 AU a larger maximum may be used
22
Q

What is Chalmers correction?

A
  • Draw a predicted baseline which forms a tangent to the scan between 350 and 400nm and again between 430 and 530nm
  • The baseline should never cut the scan
  • Measure the absorbance of the scan above the baseline at:
    • 410-418 nm (absorbance maximum for oxyhaemoglobin) to gives the net oxyhaemoglobin absorbance (NOA)
    • 476nm (not the absorbance maximum for bilirubin) to gives the net bilirubin absorbance (NBA) and If the baseline cuts the scan before 476nm, then the measured NBA is by definition zero
23
Q

Why does 476 nm for measurement of bilirubin?

A
  • Bilirubin absorbance maximum is 453 nm, but there is significant overlap from oxyhaemoglobin
  • In many CSF samples, oxyHb absorbance is greater than that of bilirubin
  • The absorbance due to oxyHb could therefore influence results if bilirubin was measured at 453 nm
  • The broad peak of bilirubin means it is possible to measure significant absorbance at a longer wavelength and reduce interference
24
Q

What are advantages and disadvantages of automated software packages?

A

Advantages:

  • Reduce operator error & subjectivity

Disadvantages:

  • Unable to “interpret in a clinical context”
  • Loss of staff skills and expertise?
25
Q

What are difficulties and interferences of Spectrophotometry?

A

Non-specific interferences

  • Centrifugation should remove most interfering substances. However any particles still present in solution can lead to a high background absorbance in the region of interest making it difficult to see any significant increase in absorbance at a specific wavelength eg high CSF protein. Still important to look at and think about scans even if software packages and logic engines are in use.

Abortive LP attempts

  • Can cause false positive results in subsequent CSF samples if blood has entered the subarachnoid space traumatically during the aborted procedure
26
Q

What are techniques for SAH?

A
  • Haem products are typically coloured due to the highly conjugated double bond structure of the tetrapyrrole ring – bilirubin is a yellow pigment
  • Unreliable, subjective, insensitive, physiologically proven that human colour vision can not reliably detect CSF xanthochromia
  • Was still prevalent in ER of hospitals in USA until early 2000’s
27
Q

What is Clearing of Blood?

A
  • Declining CSF red blood cell count with successive collection tubes thought to be consistent with a traumatic LP
  • Steady number of CSF red blood cells in successive collection tubes thought to be consistent with SAH
  • Unreliable
28
Q

What is the quantitative measure of CSF bilirubin for SAH?

A
  • Adapt automated method for serum bilirubin to measure low concentrations of bilirubin in CSF
  • Increased CSF bilirubin is key finding in SAH
  • A specific method could measure bilirubin without interference from oxyhaemoglobin
  • Interpreting spectrophotometric scans requires expertise and experience, can mean that analysis is limited to working hours
  • Potential for a 24/7 service with easy interpretation if a quantitative method could be used
  • Not well established, published reference range does not agree with the 0.007 AU cutoff used for spectrophotometry
  • Serum methods not validated for this purpose, no CE mark
  • UKAS accreditation issues ?could be used as an initial screening test if sensitivity a
29
Q

How is CSF Ferritin used for SAH?

A
  • Ferritin is synthesised in the CNS in response to the iron released from haem following an intracranial bleed
  • Not affected by traumatic tap
  • May remain elevated for longer than bilirubin after SAH so may have role in late presenting cases
  • A cut-off that delivers required test sensitivity and specificity not yet been established

MSC: Disease of major orgns (23 decks)

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