11/13/24, 7\:31 PM Guide | CSF interpretation

CSF interpretation

Table of contents

Introduction

This guide provides a structured approach to cerebrospinal
processes. Reference ranges vary between labs, so always follow local guidelines.
A lumbar puncture is usually required to obtain a sample of CSF for analysis. The most common indication for a diagnostic
lumbar puncture is to investigate cases of suspected CNS infection (e.g. meningitis). CSF interpretation is also used to
diagnose important non-infective pathologies, including subarachnoid haemorrhage.

Normal CSF

To understand CSF abnormalities in certain disease states, it is important to understand normal CSF composition.
Normal CSF is acellular. However, up to 5 white blood cells (WBCs) and 5 red blood cells (RBCs) per microlitre (µL) are
considered normal after lumbar puncture.
White blood cell analysis in CSF usually separates WBCs into lymphocytes and polymorphonuclear leukocytes (PMNs).
PMNs include neutrophils, eosinophils, basophils and mast cells. In ‘normal’ CSF, WBCs should be predominantly lymphocytes.
The presence of PMNs in the CSF, particularly neutrophils, suggests bacterial meningitis.
The blood-brain barrier is e
glucose). As such, CSF is generally a low-protein

Normal CSF ranges (adults)

Appearance\: clear and colourless
White blood cells (WBC)\: 0 – 5 cells/µL, predominantly lymphocytes.
Red blood cells (RBC)\: 0 – 5/µL
Protein\: 0.15 – 0.45 g/L (or \<1% of the serum protein concentration)
Glucose\: 2.8 – 4.2 mmol/L (or ≥ 60% serum glucose concentration)
Opening pressure\: 10 – 20 cm H O
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Meningitis

Meningitis is caused by in
Viral infection is the most common cause. However, bacterial meningitis carries a much higher morbidity and mortality burden.
CSF analysis is a vital investigation to separate bacterial from viral aetiology.
Table 1. CSF
Normal CSF Bacterial meningitis Viral meningitis
Appearance Clear/colourless Cloudy/turbid Usually clear
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White blood
cells (WBCs)
0-5/µL
P r i m a r i l y l y m p h o c y t e s
Elevated, >100/µL
P r i m a r i l y P M N s
Elevated, >100/µL
P r i m a r i l y
l y m p h o c y t e s
Protein 0.15-0.45g/L Elevated, >0.5g/L Elevated, >0.5g/L
Glucose
2.8 - 4.2mmol/L
> 6 0 % s e r u m g l u c o s e
Low
\< 4 0 % s e r u m g l u c o s e
Normal g l u c o s e
> 6 0 % s e r u m
Opening
pressure
10-20cm H O 2 2
Elevated (>25cm H O) Normal or elevated
Relevant further investigations in suspected meningitis include\:
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CSF microscopy, gram stain & culture
CSF polymerase chain reaction (PCR)
Blood cultures
Imaging to rule out other intracranial pathology (e.g. CT / MRI head)

Bacterial meningitis

Bacterial meningitis typically presents with headache, fever, neck stinon-blanching
(petechial) rash is often present in meningococcal disease. Patients are often systemically unwell and require urgent
treatment with IM/IV antibiotics following local antibiotic guidelines.
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Treatment should not be delayed to obtain CSF analysis. The presence of turbid CSF with high opening pressure, elevated
polymorphonuclear leukocytes and low serum glucose is highly suggestive of bacterial infection. Gram stain and CSF culture /
bacterial PCR con
Gram staining
The appearance of causative bacterial organisms on Gram stain\:
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Gram-positive diplococci\: pneumococcal infection (S t r e p t o c o c c u s p n e u m o n i a e )
Gram-negative diplococci\: meningococcal infection (N e i s s e r i a m e n i n g i t i d i s )
Gram-positive rods / coccobacilli\: listerial infection ( L i s t e r i a m e n i n g i t i d i s )

Viral meningitis

Viral meningitis is typically more insidious in onset than bacterial infection but causes similar symptoms (headache, fever, neck
sti
causative agents are herpes viruses (HSV / VSV) and enteroviruses. 5
Treatment is with an intravenous antiviral agent, most
commonly aciclovir.
CSF with a markedly raised lymphocyte count and elevated protein but normal glucose is highly suggestive of viral infection.
Diagnosis can be con

Other causes of meningitis

Rarely, meningitis can be caused by mycobacterial (TB) infection in those with speci
infection in the severely immunosuppressed. Meningitis can also be non-infective (e.g. in paraneoplastic syndromes).
Tuberculosis meningitis
Tuberculous meningitis should be suspected in those exposed to a patient with pulmonary tuberculosis, or those with known
risk factors for TB (e.g. people from areas of high disease prevalence, homelessness, immunosuppression etc).
CSF typically shows high protein, low glucose levels, and elevated WCC with lymphocyte predominance. In early TB meningitis,
there may be PMN predominance, and thus CSF analysis can appear very similar to bacterial meningitis. To con
diagnosis, CSF is sent for acid-fast-bacilli smear and culture alongside TB polymerase chain reaction (PCR).
Appearance\: opaque, if left to settle it forms a
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Opening pressure\: elevated
WBC\: elevated (typically lymphocyte predominance)
Glucose level\: low
Protein level\: elevated (1-5 g/L)
Fungal meningitis
Fungal meningitis is rare, most commonly seen in cases of profound immunosuppression, such as untreated HIV. CSF analysis
can vary depending on the pathogen involved, and diagnosis can be con
(e.g. cryptococcal antigen).
Appearance\: clear or cloudy
Opening pressure\: elevated
WBC\: elevated (typically more modest elevations seen)
Glucose level\: low
Protein level\: elevated

Non-infective CNS pathology

CSF interpretation also plays a key role in many non-infective neurological disorders.

Subarachnoid haemorrhage (SAH)

Appearance\: blood-stained initially, with xanthochromia (yellowish) >12 hours later
Opening pressure\: elevated
WBC\: elevated (WBC to RBC ratio of approximately 1\:1000)
RBC\: elevated
Glucose level\: normal
Protein level\: elevated
The classical presentation of subarachnoid haemorrhage is thunderclap headache. Modern CT scans have a sensitivity of over
99% when performed within 6 hours of symptom onset. Sensitivity decreases progressively after this time.
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It is vital not to miss a diagnosis of subarachnoid haemorrhage, as ‘re-bleeds’ can be devastating. In most cases, they occur
secondary to potentially treatable cerebral aneurysms. In cases where clinical suspicion of SAH is high, but CT is not
diagnostic, CSF analysis is performed to assess for xanthochromia.
Xanthochromia
Xanthochromia is the yellow discolouration of CSF caused by the presence of bilirubin. A lumbar puncture must be
performed >12 hours after symptom onset to assess for xanthochromia. During this time, the red blood cells in the CSF
will have been broken down, releasing their oxygen-carrying molecule heme, which is further metabolised by enzymes
in the CSF to form bilirubin. The presence of bilirubin and other RBC breakdown products in the CSF is con
laboratory by spectrophotometry. The presence of xanthochromia is diagnostic of SAH.
Occasionally, a traumatic lumbar puncture (‘traumatic tap’) will lead to a high number of RBCs in the CSF. In these cases,
the absolute number of RBCs will generally decrease in each bottle of CSF collected (as the RBCs are due to local
trauma rather than being present throughout the CSF), and xanthochromia will not be present as the RBCs are yet to be
broken down.

Multiple sclerosis (MS)

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Appearance\: clear
Opening pressure\: normal
WBC\: 0 – 20 cells/µL (primarily lymphocytes)
Glucose level\: normal
Protein level\: mildly elevated (0.45 – 0.75 g/L)
CSF electrophoresis\: oligoclonal bands present
Multiple sclerosis can present with various neurological de
immunoglobulin on CSF electrophoresis can be key to diagnosing MS alongside classical MRI

Guillain-Barré syndrome (GBS)

Appearance\: clear
Opening pressure\: normal or elevated
WBC\: normal
Glucose level\: normal
Protein level\: markedly elevated (>5.5 g/L)
Guillain-Barré syndrome is characterised by rapidly progressive ascending weakness. CSF interpretation is usually performed
to aid diagnosis and exclude alternate pathologies.
CSF generally shows a normal cell count and raised protein in cases of GBS. However, this may not be seen in the
the illness.

CSF interpretation examples

Case 1

A 28-year-old man presents with a 12-hour history of high fever, severe headache, confusion, photophobia and neck sti
He has no signi
CSF results
Appearance\: cloudy
Opening pressure\: 30 cm H O
₂
WBC\: 936 cells/µL (>95% PMN cells)
Glucose level\: \< 40% of serum glucose
Protein level\: 3 g/L
The most likely diagnosis is bacterial meningitis. This patient has presented with meningeal symptoms, fever and confusion,
which have progressed rapidly over the last 12 hours. The CSF is cloudy on inspection, the white cell count is signi
raised, and glucose levels are low.
The history and CSF results strongly suggest bacterial meningitis, and he should be treated empirically whilst culture results
are awaited.

Case 2

A 38-year-old woman presents with 24 hours of headache, photophobia, mild neck sti
orientated, and her observations are stable.
CSF results
Appearance\: clear
Opening pressure\: 23 cm H O
₂
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WBC\: 150 cells /µL (primarily lymphocytes)
Glucose level\: normal
Protein level\: 90 mg/dL
The most likely diagnosis is viral meningitis. This patient has presented with a history of meningitic symptoms alongside
coryzal symptoms, suggesting a viral illness. The CSF
appearance of the CSF, the mildly raised WCC (consisting mainly of lymphocytes), raised protein level and normal glucose.
Further investigations, including CSF PCR, would be useful in identifying the speci

Case 3

A 52-year-old man presents with a sudden onset severe headache. The headache started 14 hours ago. Since the headache, he
has felt nauseated. He is otherwise well and fully orientated. Clinical examination is largely unremarkable, but he does appear
to have some mild neck sti
CSF results
Appearance\: yellowish
Opening pressure\: 23 cm H O
₂
WBC\: normal
Red cell count\: raised
Glucose level\: normal
Protein level\: 80 mg/dL
Xanthochromia\: positive
The most likely diagnosis is subarachnoid haemorrhage (SAH). The typical history of a sudden severe headache and
meningitic symptoms (neck sti
decreases after six hours from symptom onset. As a result, lumbar puncture is used to rule out SAH.
The CSF typically shows a persistently raised red cell count (due to blood in the CSF from the initial bleed). Within several
hours, the red blood cells in the cerebrospinal
metabolised by enzymes to bilirubin, a yellow pigment. This yellow pigment can be detected, and its presence is called
xanthochromia.

References

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UpToDate. C l i n i c a l f e a t u r e s a n d d i a g n o s i s o f a c u t e b a c t e r i a l m e n i n gi t i s i n a d u l t s . October 2022. Available at [LINK].
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UpToDate. T u b e r c u l o u s m e n i n g i t i s \: C l i n i c a l m a n i f e s t a t i o n s a n d d i a g n o s i s . April 2023. Available at [LINK].
UpToDate. A n e u r y s m a l s u b a r a c h n o i d h e m o r r h a g e \: C l i n i c a l m a n i f e s t a t i o n s a n d d i a gn o s i s . September 2022. Available at [LINK].
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