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 H₂O)
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 H₂O
WBC: 400 cells/µL
Glucose level: < 40% of serum glucose concentration
Protein level: 1g/LWhat is the most likely diagnosis?
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 H₂O
WBC: 936 cells/µL (>95% PMN cells)
Glucose level: < 40% of serum glucose
Protein level: 3 g/LWhat is the most likely diagnosis?
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 H₂O
WBC: 150 cells /µL (primarily lymphocytes)
Glucose level: normal
Protein level: 90 mg/dLWhat is the most likely diagnosis?
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 H₂O
WBC: normal
Red cell count: raised
Glucose level: normal
Protein level: 80 mg/dL
Xanthochromia: positiveWhat is the most likely diagnosis?
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.