Cerebrospinal Fluid (CSF) Interpretation

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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 H2O


CSF findings in specific diseases

Bacterial meningitis

Appearance: cloudy and turbid

Opening pressure: elevated (>25 cm HO)

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

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

Protein level: elevated (>50 mg/dL)

Aetiology

Causes of bacterial meningitis include:

  • 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

Clinical features

Typical clinical features of bacterial meningitis include:

  • Headache
  • Fever
  • Neck stiffness
  • Photophobia
  • Meningococcal sepsis presents with a characteristic petechial rash

Further investigations

Further investigations to assist in the diagnosis of bacterial meningitis include:

  • CSF gram stain and cultures
  • CSF bacterial antigens
  • CSF PCR
  • Blood cultures
  • Imaging to rule out other intracranial pathology (e.g. 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)

Aetiology

Causes of viral meningitis include:

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

Clinical features

Typical clinical features of viral meningitis include:

  • Headache
  • Fever
  • Neck stiffness
  • Photophobia

Further investigations

Further investigations to assist in the diagnosis of viral meningitis include:

  • CSF PCR for viruses (e.g. herpes simplex virus, varicella-zoster virus)
  • Blood cultures
  • Imaging to rule out other intracranial pathology (e.g. CT/MRI head)

Fungal meningitis

Appearance: clear or cloudy

Opening pressure: elevated

WBC: elevated (10 – 500 cells/µL)

Glucose level: low

Protein level: elevated

Aetiology

Causes of fungal meningitis include:

  • Cryptococcus neoformans
  • Candida

Clinical features

Typical clinical features of fungal meningitis include:

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

Further investigations

Further investigations to assist in the diagnosis of fungal meningitis include:

  • CSF cultures
  • CSF PCR
  • CSF staining
  • HIV test (with consent)
  • Blood cultures
  • Imaging to rule out other intracranial pathology (e.g. 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 mononuclear)

Glucose level: low

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

Clinical features

Typical clinical features of tuberculosis meningitis include:

  • Headache
  • Fever
  • Neck stiffness
  • Photophobia
  • Delirium
  • Cranial nerve palsies

Further investigations

Further investigations to assist in the diagnosis of tuberculosis meningitis include:

  • CSF cultures
  • CSF bacterial antigens
  • CSF PCR
  • HIV test (with consent)
  • Blood cultures
  • Imaging to rule out other intracranial pathology (e.g. CT/MRI head)
  • Chest X-ray to look for pulmonary tuberculosis

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

Aetiology

Causes of subarachnoid haemorrhage include:

  • Trauma
  • Ruptured vascular malformations (e.g. aneurysms, arteriovenous malformations)

Clinical features

Typical clinical features of subarachnoid haemorrhage include:

  • 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

Further investigations to assist in the diagnosis of subarachnoid haemorrhage include:

  • 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)

Aetiology

Causes of Guillain Barre syndrome include:

  • Campylobacter jejuni
  • CMV
  • EBV
  • Mycoplasma pneumonia
  • VZV

Clinical features

Typical clinical features of Guillain Barre syndrome include:

  • Symmetrical ascending muscle weakness primarily affecting proximal musculature (trunk/respiratory muscles)

Further investigations

Further investigations to assist in the diagnosis of Guillain Barre syndrome include:

  • Serologic studies
  • Nerve conduction studies
  • EMG
  • Imaging to rule out other intracranial pathology (e.g. 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)

Clinical features

Typical clinical features of multiple sclerosis include:

  • Optic neuritis
  • Limb weakness
  • Sensory disturbances
  • Diplopia
  • Ataxia

Further investigations

Further investigations to assist in the diagnosis of multiple sclerosis include:

  • MRI head
  • Oligoclonal bands of IgG on electrophoresis (CSF and serum)
  • Evoked potential tests (visual and somatosensory)

Worked examples

Case 1

A 55-year-old woman has become increasingly 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 HO

WBC: 400 cells/µL

Glucose level: < 40% of serum glucose concentration

Protein level: 1g/L

The most likely diagnosis 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 HO

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 young gentleman 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 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 and 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 HO

WBC: 150 cells /µL (primarily lymphocytes)

Glucose level: normal

Protein level: 90 mg/dL

The most likely diagnosis 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 would be useful in identifying the specific causative 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 HO

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 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 presence of blood 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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