Lumbar puncture

Lumbar puncture (LP) is the procedure performed in order to obtain a specimen of CSF. If signs of raised intracranial 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, microbiological examination takes priority. If subarachnoid haemorrhage is suspected, it may help to collect the CSF as several separate aliquots. These will be equally blood-stained in SAH, but progressively less so if the blood in the CSF results from damage to a blood vessel during the LP procedure (a so-called ‘traumatic tap’).

Subarachnoid haemorrhage

Bleeding into the subarachnoid space most frequently results from rupture of 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 (‘thunderclap’), 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 subarachnoid 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 undergone in vivo lysis. In vitro lysis of RBCs, e.g. a traumatic LP, produces only oxyhaemoglobin, and not bilirubin. It can be detected by visual inspection, but this is unreliable, and where possible scanning spectrophotometry should be used instead. This involves measuring the absorbance of the CSF specimen across a range of wavelengths; the blood pigments have characteristic absorbance peaks (Fig 65.1).

Meningitis

Meningitis refers to inflammation of the meninges which line the central nervous system (CNS). Bacterial meningitis presents acutely and is a medical emergency. CSF biochemistry tends to reflect the nature of the infective organism (Table 65.1) but is characteristic rather than diagnostic. Microbiological analysis should take priority. It is important when interpreting the relative concentrations of, for example, glucose in the CSF to take a blood sample for comparison.

Inherited metabolic disorders

CSF analysis may be helpful in the diagnosis of several inherited metabolic disorders. For example, high CSF lactate may be seen in inborn errors of metabolism affecting the respiratory chain, even when plasma lactate is normal or only slightly increased. This may reflect tissue specificity of electron transport chain proteins, or the high-energy demand (and lactate production) of the brain. CSF pyruvate concentrations are also high in these conditions. CSF amino acid analysis may similarly be helpful in diagnosing various inherited disorders of amino acid metabolism; these are sometimes considered in children with unexplained seizures but are very rare.

Other conditions

Analysis of CSF may be helpful in the evaluation of a variety of non-acute conditions, but as with meningitis the findings are rarely diagnostic. Very high CSF protein concentrations may be seen where there is interruption to the circulation of CSF, e.g. spinal tumours; the mechanisms include increased capillary permeability (to plasma proteins) and CSF fluid reabsorption due to stasis. Increased capillary permeability is best revealed by CSF electrophoresis; the high-molecular-weight plasma proteins, which are not normally found in CSF, can readily be identified. This non-specific pattern is found in many infective/inflammatory conditions involving the CNS.

CSF electrophoresis may also reveal the presence of oligoclonal bands (Fig 65.2). If these are not seen also in the serum, they reflect local (i.e. CNS) synthesis of immunoglobulin. Ninety per cent of patients with multiple sclerosis (MS) have these bands, but they are not specific for this condition. Thus their absence in cases of suspected MS is more diagnostically useful than their presence.

Dementia

Currently, no biochemical markers meet the criteria that would allow reliable differentiation of Alzheimer’s disease from other dementias (e.g. vascular), although there are various candidates. The most promising include the ratio of a phosphorylated form of tau protein (see below) to a protein known as beta-amyloid peptide 42. Recent research claims to have identified an ‘Alzheimer’s phenotype’, based on plasma concentrations of proteins involved in intercellular communication. Though promising, these findings require to be replicated in larger studies.

Cerebrospinal fluid

Not infrequently clinicians ask the laboratory to identify specimens of fluid collected from patients with rhinorrhoea or otorrhoea. This is sometimes requested after nasal or aural surgery, where it becomes important to identify the fluid as CSF or not. The finding in the specimen of the so-called tau protein identifies it as CSF. This is an isoform of β-transferrin that is specific to the CSF.

Urine

Urine is often suspected as a contaminant of drain fluids. Contamination can usually be detected fairly easily by measuring urea and/or creatinine in serum, urine, and the fluid specimen under consideration; urinary concentrations of urea and creatinine greatly exceed serum concentrations.

Chyle

Chyle is the fluid found in the intestinal lymphatics during absorption of food postprandially. It appears milky due to the presence of fats. The intestinal lymphatics drain into the thoracic duct, and thence into the venous system. Occasionally the presence of chyle in the thoracic or abdominal cavities (known as chylothorax and chylous ascites respectively) is suspected, due for example to a leak from the thoracic duct. Although there is no unique marker of chyle, measurement of triglycerides may be helpful. Concentrations that are significantly greater in the suspected fluid than in fasting serum are suggestive.

Other fluids

Laboratory identification of other body fluids is not usually performed. In some cases, e.g. ascites and pleural fluid, there is no unique marker, and identification is rarely an issue. Other fluids, e.g. bile, are identifiable by visual inspection. Occasionally it may be helpful to distinguish amniotic fluid from maternal urine or vaginal fluid (in the context of suspected premature rupture of the fetal membranes). Although fetal fibronectin is relatively specific to amniotic fluid, it is not widely available, and diagnosis of labour can usually be made on other grounds.