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Cerebrospinal Fluid (CSF) Interpretation

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Ohiowele Ojo February 16,


2017

This guide provides a structured approach to cerebrospinal fluid interpretation (CSF


interpretation), including typical CSF results for specific disease processes. Reference
ranges vary between labs, so always consult your local medical school or hospital
guidelines.

Normal CSF ranges (adults)


Appearance: Clear and colourless

White blood cells (WBC): 0 – 5 cells/µL

No neutrophils present, primarily lymphocytes


Normal cell counts do not rule out meningitis or any other pathology

Red blood cells (RBC): 0 – 10/mm³

Protein: 0.15 – 0.45 g/L (or <1% of the serum protein concentration)

Glucose: 2.8 – 4.2 mmol/L (or ≥ 60% plasma glucose concentration)

Opening pressure: 10 – 20 cm H 2O

CSF findings in specific diseases

Bacterial meningitis
Appearance: Cloudy and turbid

Opening pressure: Elevated (>25 cm H₂O)


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WBC: Elevated >100 cell/µL (primarily polymorphonuclear leukocytes (>90%))

Glucose level: Low (<40% of serum glucose)

Protein level: Elevated (>50 mg/dL)

Causes
Newborns: Listeria monocytogenes, E. Coli, Group B Streptococci
Older children: Neisseria meningitidis, Haemophilus influenzae Type B,
Streptococcus pneumoniae
Adults: Neisseria meningitidis, Streptococcus pneumoniae, Listeria
monocytogenes

Symptoms
Headache
Fever
Neck stiffness
Photophobia
Meningococcal meningitis presents with a characteristic petechial rash

Further investigations
CSF gram stain and cultures
CSF bacterial antigens
CSF PCR
Blood cultures
Imaging to rule out other intracranial pathology – CT / MRI head

Viral (aseptic) meningitis


Appearance: Clear

Opening pressure: Normal or elevated

WBC: Elevated (50 – 1000 cells/µL, primarily lymphocytes, can be PMN early on)

Glucose level: Normal (>60% serum glucose however may be low in HSV infection)

Protein level: Elevated (>50 mg/dL)

Causes
Herpes simplex virus (HSV 2 is more common than HSV 1)
Enteroviruses
Varicella zoster virus (VZV)
Mumps
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HIV
Adenovirus

Symptoms
Headache
Fever
Neck stiffness
Photophobia

Further investigations
CSF PCR for viruses (e.g. Herpes simplex virus (HSV) / Varicella-zoster virus (VZV))
Blood cultures
Imaging to rule out other intracranial pathology – CT / MRI head

Fungal meningitis
Appearance: Clear or cloudy

Opening pressure: Elevated

WBC: Elevated (10 – 500 cells/µL)

Glucose level: Low

Protein level: Elevated

Causes
Cryptococcus neoformans
Candida

Symptoms
Patients are often immunocompromised
Headache
Confusion
Nausea
Vomiting
Fever and neck stiffness are less common

Further investigations
CSF cultures
CSF PCR
CSF staining
HIV test (with consent)
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Blood cultures
Imaging to rule out other intracranial pathology – CT / MRI head

Tuberculosis meningitis
Appearance: Opaque, if left to settle it forms a fibrin web

Opening pressure: Elevated

WBC: Elevated (10 – 1000 cells/µL, Early PMNs then mononuclears)

Glucose level: Low

Protein level: Elevated (1-5 g/L)

Symptoms
Headache
Fever
Neck stiffness
Photophobia
Delirium
Cranial nerve palsies

Further investigations
CSF cultures
CSF bacterial antigens
CSF PCR
HIV test (with consent)
Blood cultures
Imaging to rule out other intracranial pathology – CT / MRI head
Chest X-ray

Subarachnoid haemorrhage
Appearance: Blood stained initially, then xanthochromia (yellowish) >12 hours later

Opening pressure: Elevated

WBC: Elevated (WBC to RBC ratio of approx 1:1000)

RBC: Elevated

Glucose level: Normal

Protein level: Elevated

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Causes
Trauma
Vascular malformations (e.g. aneurysms, arteriovenous malformations)

Symptoms
Sudden onset “thunderclap” headache (patients may describe it as the “worst
headache ever”)
Stiff neck
Vomiting
Seizures
Confusion
Neurological deficits (e.g. weakness / sensory disturbance)

Further investigations
Cerebral angiogram
CT angiography

Guillain Barre syndrome


Appearance: Clear or xanthochromia

Opening pressure: Normal or elevated

WBC: Normal

Glucose level: Normal

Protein level: Elevated (>5.5 g/L)

Causes
Campylobacter jejuni
CMV
EBV
Mycoplasma pneumonia
VZV

Symptoms
Often occurs after a recent bacterial / viral illness
Symmetrical ascending muscle weakness primarily affecting proximal musculature
(trunk/respiratory muscles)

Further investigations

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Serologic studies
Nerve conduction studies
EMG
Imaging to rule out other intracranial pathology – CT / MRI head

Multiple sclerosis
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)

Symptoms
Optic neuritis
Limb weakness
Sensory disturbances
Diplopia
Ataxia

Further investigations
MRI head
Oligoclonal bands of IgG on electrophoresis (CSF and Serum)
Evoked potential tests (visual/somatosensory)

Worked examples

Case 1
A 55-year-old woman has been getting more confused over the last 2 months. Over the
last 3 days, she has been vomiting and suffering from lack of energy. She has no neck
stiffness and a CD4 count of 100/mm³

CSF results
Appearance: Cloudy

Opening pressure: 25 cm H₂O

WBC: 400 cells/µL

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Glucose level: < 40% of serum glucose concentration

Protein level: 1g/L

This is fungal meningitis, in this particular case this lady is found to have cryptococcal
meningitis on CSF culture. The patient is also found to have HIV, likely the cause of her
impaired immune function (CD4 count 100/mm³), leaving her vulnerable to cryptococcal
infection.

Case 2
A 28-year-old male presents with a 12-hour history of high fever, severe headache,
confusion, photophobia and neck stiffness. He has no significant past medical history
and takes no regular medication.

CSF results
Appearance: Cloudy

Opening pressure: 30 cm H₂O

WBC: 936 cells/µL (>95% PMN cells)

Glucose level: < 40% of serum glucose

Protein level: 3 g/L

This is bacterial meningitis. This young gentleman has presented with meningeal
symptoms, fever, confusion which have progressed rapidly over the last 12 hours. The
CSF is cloudy on inspection, the white cell count is significantly raised and glucose levels
are low. The history and CSF results are strongly suggestive of bacterial meningitis and
therefore he should be treated empirically whilst culture results are awaited.

Case 3
A 38-year-old female presents with 24 hours of headache, photophobia, mild neck
stiffness, in addition to coryzal symptoms. She is fully orientated and her observations
are stable.

CSF results
Appearance: Clear

Opening pressure: 23 cm H₂O

WBC: 150 cells /µL (primarily lymphocytes)

Glucose level: Normal

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Protein level: 90 mg/dL

This is viral meningitis. This lady has presented with a history of meningitic symptoms
alongside coryzal symptoms which suggests the presence of a viral type illness. The CSF
findings are more suggestive of viral meningitis given the clear appearance of the CSF,
the mildly raised WCC (consisting mainly of lymphocytes), raised protein level and
normal glucose. Further investigations including CSF PCR can be useful in identifying the
specific virus.

Case 4
A 52 year old male presents to A&E with history of a sudden onset severe headache
which occurred whilst he was at his desk yesterday. Since the headache he has been
feeling nauseated, but he is otherwise well and fully orientated. Examination is largely
unremarkable, but he does appear to have some mild neck stiffness.

CSF results
Appearance: Yellowish

Opening pressure: 23 cm H₂O

WBC: Normal

Red cell count: Raised

Glucose level: Normal

Protein level: 80 mg/dL

Xanthochromia: positive

This is subarachnoid haemorrhage (SAH). The typical history of a sudden severe


headache (often described as thunderclap) and meningitic symptoms (neck stiffness) is
strongly suggestive of SAH. CT head is often the first line investigation, but it has a
sensitivity of 98% in the first 12 hours and becomes less sensitive after that. As a result
lumbar puncture is used to rule out SAH. The CSF typically shows a persistently raised
red cell count (due to blood present in the CSF from the initial bleed). Within several hours,
the red blood cells in the cerebrospinal fluid are destroyed, releasing their oxygen-
carrying molecule heme, which is metabolized by enzymes to bilirubin, a yellow pigment.
This yellow pigment can be detected and its presence is referred to as xanthochromia

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