Discuss the importance of CSF proteins including any significant recent developments.
CSF total protein is a biochemical test that is used to determine the amount of protein in cerebrospinal fluid or CSF. CSF is a clear fluid and circulates within the space around the spinal cord (Einstein, 1982). Whenever there is an abnormal protein level recorded in the CSF, it is an indication that there is an abnormal process occurring in the central nervous system as well. Usually the presence of CSF proteins is determined by a test and in the test, CSF is obtained by a lumbar puncture or spinal tap and the cerebrospinal fluid obtained is analysed in the lab (Thompson, 1988). Patients might feel a numbness or irritation in the limbs when the fluid is collected for testing purposes. Certain specific biochemical techniques are used for diagnosis of CSF proteins and there has been considerable research to suggest that new and more specific techniques should be used. Several important research studies in this area have been on the the specificity and non-specificity of the humoral immune reactions; the role of barriers between the central nervous system and the CSF, and between blood and CSF. The importance of both qualitative and quantitative study of CSF has been discussed.
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In this discussion, we describe the role of CSF proteins and its importance as a diagnostic tool for several abnormal brain conditions. Several recent research studies have been analysed for the purposes of the paper.
The Role of CSF Proteins
CSF proteins are used to determine the total protein content in the cerebrospinal fluid using the method of electrophoresis. Quantitative measures of CSF protein fractions aid in the diagnosis of inflammatory and demyelinating disease of CNS, although routine CSF protein electrophoresis is highly insensitive and non-specific and may not be able to diagnose complicated conditions such as the presence of multiple sclerosis (MS). Routine CSF protein electrophoresis plays no role in screening for demyelinating diseases (eg, MS) and for such complicated conditions, high-resolution electrophoresis is required. The presence of proteins in the CSF may indicate severe conditions as severe cranio-cerebral trauma is characterized by a three to fourfold increase in globulins over the 1st week following trauma. In several other conditions such as diabetes, brain tumour, spinal cord tumour, meningitis, syphilis, uremia and brain haemorrhage, CSF proteins may be detected in high quantities. Thus when the protein level in the cerebrospinal fluid increases considerably and drastically, it may indicate the presence of tumours, haemorrhage, polyneuritis, trauma, or blood in the CSF (Thompson, 1988). When the protein level decreases, it can indicate rapid CSF production.
Many biochemical testing agencies analyse lumbar cerebrospinal fluid (CSF) samples provided by clients and use biochemical techniques of nucleotide photo affinity labelling, two dimensional (IEF x SDS-PAGE) and autoradiography to determine if there are aberrant protein-nucleotide interactions and whether this is indicative of particular diseased conditions within the body or central nervous system (Thompson, 1988; Einstein 1982). This provides a diagnostic tool for the physicians although may not confirm any specific diseased condition. CSF examination and presence of proteins give several distinct results and findings for specific disease conditions although for all abnormal brain conditions CSF protein content reaches above 45 mg/dl. The normal protein range within the CSF is 15 to 45 mg/dl (Marshall, 1995). The level of proteins in the cerebro spinal fluid can thus be a very important determinant of abnormal brain conditions and paralysing diseases. The biochemical specifications of CSF proteins can be supported or characterised by recent research findings.
Dohi et al (2005) examine the role of hypothalamic hypocretin / orexin system in complications of delayed ischemic neuronal deficit (DIND) resulting from symptomatic vasospasm in patients with aneurysmal subarachnoid haemorrhage (SAH). For the study, the CSF protein levels, hypocretin-1/orexin-A levels were measured in 15 patients with SAH haemorrhage conditions. The study found that DIND complications occurred in seven patients with symptomatic vasospasm. Hypocretin-1/orexin-A levels were low in SAH patients during the first 10 days following the SAH event. CSF hypocretin-1/orexin-A levels were lower in patients with DIND complications than in those who did not develop neuronal deficits. Some levels of decline in CSF protein hypocretin-1/orexin-A levels was also observed in patients with delayed ischemic neuronal deficit showing symptomatic vasospasm. The authors claimed that reduced levels of hypocretin / orexin production observed in SAH patients may reflect reduced brain function due to the decrease in cerebral blood flow (Dohi et al, 2005). These experimental findings indicate hypocretin receptor 1 (orexin 1 receptor) mRNA and protein levels are elevated following middle cerebral artery occlusion, although a reduction in hypocretin/orexin production in SAH and DIND patients is associated with alterations in brain hypocretin/orexin or general protein level signalling response to ischemia and neuronal deficits.
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In another interesting study, Stefani et al (2005) investigated whether CSF biomarkers beta-amyloid 1-42 and protein levels phosphorylated at threonine 181 could discriminate between patients with Alzheimer's disease (AD) from vascular dementia (VD) patients. Samples of cerebro spinal fluid were collected for measures on Aß1-42, t-tau, and p-tau181 from 35 patients with probable AD with white matter changes (WMC) and also indicative of concomitant cerebro vascular disorder and this sample was matched with patients with showing neurological disorders (OND) without cognitive impairment (n = 24). Both subgroups showed similar amounts of CSF biomarkers. the aalysis showed that Aß1-42 could discriminate patients with AD from patients with VD. T-tau increased aspecifically in all cognitively impaired patients although the discrimination between patients with AD vs patients with VD seems to be more pronounced (Stefani et al, 2005). The authors concluded that, Aß1-42 proved to be a valuable tool to discriminate AD vs. VD patients and this can be especially helpful to improve diagnostic accuracy in clinical forms, improperly classified as "mixed dementia" based on radiological vascular lesions. Thus with CSF protein level diagnoses, it is possible to be more specific and improve differentiation of brain disorders to specify a more precise form of treatment.
In this discussion we suggested the uses, clinical methods and indications of CSF protein levels. The ways in which CSF levels can be measured, the uses of such measures, the clinical implications and associated disorders and brain conditions for high levels of CSF have been discussed along with critical evaluation of the importance of CSF considering recent research findings. The importance of CSF protein measures lies in the fact that CSF protein levels are not just indicators of specific diseases but also showing much differentiation in brain disease conditions help to identify, diagnose and provide treatment for any specific condition taking medical practice to new levels of precision.
K. Dohi, B. Ripley, N. Fujiki, H. Ohtaki, S. Shioda, T. Aruga and S. Nishino
CSF hypocretin-1/orexin-A concentrations in patients with subarachnoid hemorrhage (SAH)
Peptides, Volume 26, Issue 11, November 2005, Pages 2339-2343
Alessandro Stefani, Sergio Bernardini, Marta Panella, Mariangela Pierantozzi, Marzia Nuccetelli, Giacomo Koch, Andrea Urbani, Angela Giordano, Alessandro Martorana, Antonio Orlacchio et al.
AD with subcortical white matter lesions and vascular dementia: CSF markers for differential diagnosis
Journal of the Neurological Sciences, Volume 237, Issues 1-2, 15 October 2005, Pages 83-88
Thompson, E. J. (Edward John)
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Einstein, E R.
Proteins of the brain and CSF in Health and Disease.
Springfield, IL : C C Thomas, 1982.
Marshall, William J.
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London : Mosby, 1995.
Protein Electrophoresis, Cerebrospinal Fluid