ABSTRACT
Early electrophoretic studies 259 Cerebrospinal fluid protein composition 259 Electrophoretic methods to study CSF 264 Multiple sclerosis and oligoclonal bands 268
Other conditions with CSF oligoclonal bands 272 Detection of CSF leakage in nasal and aural fluid
following head trauma 273 References 277
Early studies by Kabat et al.1,2 reported that cerebrospinal fluid (CSF) from control individuals contained relatively little g-globulin compared with serum, whereas CSF from patients with a variety of neurological conditions had an elevation of the total CSF protein with a decreased ratio of albumin/globulin. They pointed out that in patients with either multiple sclerosis or neurosyphilis, there was a consistent increase in both the g and the transthyretin (prealbumin) fractions.1,2
Currently (as discussed below), the most specific laboratory test for multiple sclerosis is the demonstration of oligoclonal bands in the CSF that are not present in a corresponding serum.3,4
Cerebrospinal fluid is an ultrafiltrate of plasma that is continuously produced at the rate of about 500 ml/day in the choroid plexus.5 Since the total volume of CSF is only 135 ml, it must turn over every 6 h.6 Reabsorption occurs into
the bloodstream at the superior sagittal sinus by the arachnoid granulations.7 The vast majority of CSF proteins are serum proteins that pass through the blood-CSF barrier at the choroid plexus. Only about 20 per cent of CSF proteins are synthesized locally.8 Proteins passing through the choroid plexus are limited by molecular size, charge, their concentration in plasma and the integrity of the blood-CSF barrier.6,9 Whereas, their plasma concentration and the integrity of the blood-CSF barrier may change dramatically in some disease processes, the size and the charge of the proteins are relatively constant factors (with some exceptions in charge and genetic structural variants). The sieve effect of the blood-CSF barrier is not as clear-cut as that of the glomerular basement membrane in the kidney; however, small molecules such as transthyretin (prealbumin) preferentially pass into the CSF, and the larger a2-macroglobulin and haptoglobin are greatly restricted.10,11
While most proteins are passively transferred into the CSF, some, such as transferrin, have an active mechanism. Transferrin binds to specific receptors on the endothelium of cerebral capillaries and neurons.12,13 Once within the cytoplasm, transferrin releases its attached iron and some of the transferrin molecules also lose their terminal sialic acid residues from its carbohydrate side-chain. This forms the desialated transferrin (t protein also
called ‘CSF-specific slow transferrin’) that exists in CSF along with the usual sialated form of transferrin.6 As discussed below, the presence of this desialated transferrin can be used as a marker of CSF leakage into nasal and aural fluids as a result of damage to the cranial vault.14 Although some of the desialated transferrin finds its way into the blood, most of it is quickly taken up by receptors on reticulo-endothelial cells that do not bind transferrin containing the terminal sialic acid residues.6
