130 4 SPECIALIZED INVESTIGATIONS

65 Cerebrospinal and other body fluids

Cerebrospinal fluid
Cerebrospinal fluid (CSF) is produced
by the choroid plexuses, partly by ultra-
filtration and partly by secretion, and
fills and circulates through the ventricles
and spinal cord. Compared with plasma,
it has less protein, and the concentra-
tions of protein-bound components like
bilirubin are similarly reduced. Its elec-
trolyte composition is similar to but dis-
tinct from plasma (more chloride, less
potassium and calcium). Infection or the
presence of blood in the CSF alters its
composition. This provides the basis for
biochemical analysis of CSF in the diag-
nosis of subarachnoid haemorrhage
(SAH) and meningitis.
Lumbar puncture
Lumbar puncture (LP) is the procedure
performed in order to obtain a speci-
men of CSF. If signs of raised intracra-
nial pressure such as hypertension,
bradycardia and papilloedema are
present then an LP should not be
performed.
When collecting CSF in suspected
infection, e.g. meningitis, microbiologi-
cal examination takes priority. If sub-
arachnoid haemorrhage is suspected, it
an aneurysm (swelling) in one or more
of the arteries located within the space.
The patient typically complains of a
severe headache of sudden onset (‘thun-
derclap’), often associated with vomiting
and a reduced level of consciousness.
The mainstay of diagnosis is imaging by
CT or MRI. However, in the presence of
a strong clinical suspicion, negative
imaging does not rule out a subarach-
noid haemorrhage. In these cases, LP
should be carried out, unless there are
obvious signs of raised intracranial
pressure.
Xanthochromia
Xanthochromia simply means yellow
discoloration of the CSF. It results from
the presence of bilirubin derived from
red blood cells (RBCs) that have under-
gone in vivo lysis. In vitro lysis of RBCs,
e.g. a traumatic LP, produces only oxy-
haemoglobin, and not bilirubin. It can
Oxyhaemoglobin
0.250
0.225
0.200
0.175
Absorbance
be detected by visual inspection, but this
is unreliable, and where possible scan-
ning spectrophotometry should be used
instead. This involves measuring the
absorbance of the CSF specimen across
a range of wavelengths; the blood pig-
ments have characteristic absorbance
peaks (Fig 65.1).
Meningitis
Meningitis refers to inflammation
of the meninges which line the central
nervous system (CNS). Bacterial menin-
gitis presents acutely and is a medical
emergency. CSF biochemistry tends to
reflect the nature of the infective organ-
ism (Table 65.1) but is characteristic
rather than diagnostic. Microbiological
analysis should take priority. It is impor-
tant when interpreting the relative con-
centrations of, for example, glucose in
the CSF to take a blood sample for
comparison.
Bilirubin

0.150
may help to collect the CSF as several
0.125
separate aliquots. These will be equally
blood-stained in SAH, but progressively 0.100

less so if the blood in the CSF results 0.075

from damage to a blood vessel during 0.050

the LP procedure (a so-called ‘traumatic 0.025
tap’). 0.000
350 375 400 425 450 475 500 525 550 575 583
Subarachnoid haemorrhage Wavelength (nm)
Bleeding into the subarachnoid space Fig 65.1  Absorbance spectrum of CSF in subarachnoid
most frequently results from rupture of haemorrhage.

Table 65.1  CSF parameters in health and some common disorders

Normal Subarachnoid Acute bacterial Viral meningitis Tuberculous meningitis Multiple sclerosis
haemorrhage meningitis
Pressure 50–180 mm of water Increased Normal/increased Normal Normal/increased Normal
Colour Clear Blood-stained; Cloudy Clear Clear/cloudy Clear
xanthochromic
Red cell count 0–4/mm3 Raised Normal Normal Normal Normal
White cell count 0–4/mm3 Normal/slightly raised 1000–5000 polymorphs 10–2000 lymphocytes 50–5000 lymphocytes 0–50 lymphocytes
Glucose >60% of blood level Normal Decreased Normal Decreased Normal
Protein <0.45 g/L Increased Increased Normal/increased Increased Normal/increased
Microbiology Sterile Sterile Organisms on Gram stain Sterile/virus detected Ziehl–Neelsen/auramine stain or Sterile
and/or culture tuberculosis culture positive
Oligoclonal bands Negative Negative Can be positive Can be positive Can be positive Usually positive

From Haslett C et al, Davidson’s Principles and Practice of Medicine. Churchill Livingstone, Edinburgh, 2002.
 65 Cerebrospinal and other body fluids 131

Dementia Chyle
Currently, no biochemical Chyle is the fluid found in the intestinal
markers meet the criteria lymphatics during absorption of food
that would allow reliable postprandially. It appears milky due to
differentiation of Alzhe- the presence of fats. The intestinal lym-
Oligoclonal bands imer’s disease from other phatics drain into the thoracic duct, and
Fig 65.2  Oligoclonal CSF bands. dementias (e.g. vascular), thence into the venous system. Occa-
although there are various sionally the presence of chyle in the
candidates. The most promising include thoracic or abdominal cavities (known
Inherited metabolic disorders the ratio of a phosphorylated form as chylothorax and chylous ascites
CSF analysis may be helpful in the of tau protein (see below) to a protein respectively) is suspected, due for
diagnosis of several inherited metabolic known as beta-amyloid peptide 42. example to a leak from the thoracic
disorders. For example, high CSF lactate Recent research claims to have identi- duct. Although there is no unique
may be seen in inborn errors of metabo- fied an ‘Alzheimer’s phenotype’, based marker of chyle, measurement of trig-
lism affecting the respiratory chain, even on plasma concentrations of proteins lycerides may be helpful. Concentra-
when plasma lactate is normal or only involved in intercellular communica- tions that are significantly greater in
slightly increased. This may reflect tion. Though promising, these findings the suspected fluid than in fasting
tissue specificity of electron transport require to be replicated in larger serum are suggestive.
chain proteins, or the high-energy studies.
demand (and lactate production) of the Other fluids
brain. CSF pyruvate concentrations are Laboratory identification of other body
also high in these conditions. CSF
Identification of body
fluids is not usually performed. In some
amino acid analysis may similarly be
fluids
cases, e.g. ascites and pleural fluid, there
helpful in diagnosing various inherited Cerebrospinal fluid is no unique marker, and identification
disorders of amino acid metabolism; Not infrequently clinicians ask the labo- is rarely an issue. Other fluids, e.g. bile,
these are sometimes considered in chil- ratory to identify specimens of fluid are identifiable by visual inspection.
dren with unexplained seizures but are collected from patients with rhinor- Occasionally it may be helpful to distin-
very rare. rhoea or otorrhoea. This is sometimes guish amniotic fluid from maternal
requested after nasal or aural surgery, urine or vaginal fluid (in the context of
Other conditions where it becomes important to identify suspected premature rupture of the fetal
Analysis of CSF may be helpful in the the fluid as CSF or not. The finding in membranes). Although fetal fibronectin
evaluation of a variety of non-acute con- the specimen of the so-called tau protein is relatively specific to amniotic fluid, it
ditions, but as with meningitis the find- identifies it as CSF. This is an isoform of is not widely available, and diagnosis of
ings are rarely diagnostic. Very high CSF β-transferrin that is specific to the CSF. labour can usually be made on other
protein concentrations may be seen grounds.
where there is interruption to the circu- Urine
lation of CSF, e.g. spinal tumours; Urine is often suspected as a contami-
the mechanisms include increased capil- nant of drain fluids. Contamination can
lary permeability (to plasma proteins) usually be detected fairly easily by meas- Clinical note
and CSF fluid reabsorption due to uring urea and/or creatinine in serum, The commonest side effect
stasis. Increased capillary permeability is urine, and the fluid specimen under after the removal of CSF
best revealed by CSF electrophoresis; consideration; urinary concentrations of through lumbar puncture is
the high-molecular-weight plasma pro- urea and creatinine greatly exceed headache, which occurs in up to
teins, which are not normally found serum concentrations. 30% of adults and up to 40% of
in CSF, can readily be identified. children.
This non-specific pattern is found in
many infective/inflammatory conditions
involving the CNS.
CSF electrophoresis may also reveal
Cerebrospinal and other body fluids
the presence of oligoclonal bands (Fig
65.2). If these are not seen also in the n CSF analysis may be helpful in a number of conditions but biochemical analysis alone is
serum, they reflect local (i.e. CNS) syn- rarely diagnostic.
thesis of immunoglobulin. Ninety per n When collecting CSF in suspected infection, e.g. meningitis, microbiological examination
cent of patients with multiple sclerosis takes priority over biochemical examination.
(MS) have these bands, but they are not n Xanthochromia may be due to bilirubin in the CSF from red cell lysis.
specific for this condition. Thus their n CSF electrophoresis may reveal the presence of oligoclonal bands, which are commonly
absence in cases of suspected MS is found in patients with MS.
more diagnostically useful than their n Biochemical analysis of other body fluids may be useful in identifying them.
presence.