CSF protein

Acute inflammatoiy demyelinating polyneuropathy is a common cause of reversible paralysis. Acute inflammatory demyelinating polyneuropathy (AIDP), the classic form of the Guillain-Barre syndrome, often begins a week or two after recovery from cytomegalovirus, Epstein-Barr virus or Mycoplasma infection. Patients present with rapidly advancing symmetrical weakness, loss of deep tendon reflexes, often with distal numbness, and limb or back pain. Cerebrospinal fluid (CSF) protein concentration is elevated, but in most cases there is little or no increase in number of inflammatory cells in the CSF. This albumino-cytologic dissociation contrasts with the elevation of both... 

Up to 50% of patients may receive antibiotics before a diagnosis of meningitis is made, delaying presentation to the hospital. Prior antibiotic therapy may cause the Gram stain and CSF culture to be negative, but the antibiotic therapy rarely affects CSF protein or glucose. 

Analysis of CSF chemistries typically includes measurement of glucose and total protein concentrations. An elevated CSF protein of 100 mg/dL or greater... 

Examination of cerebrospinal fluid (CSF) in patients with cryptococcal meningitis generally reveals an elevated opening pressure, CSF pleocytosis (usually lymphocytes), leukocytosis, a decreased CSF glucose, an elevated CSF protein, and a positive cryptococcal antigen. 

Regulation of expression may occur at both the transcriptional and post-transcriptional levels. The mRNA for GM-CSF contains (in common with those of some other cytokines) conserved regulatory sequences in the 3 untranslated region, which may affect its rate of translation. The gene is constitutively transcribed in monocytes, endothelial cells and fibroblasts, but the mRNA is unstable and so does not accumulate to levels sufficient to allow translation into significant amounts of protein. Activation of these cells results in the increased expression of GM-CSF protein, which arises from both an enhanced rate of transcription (as detected in nuclear runoff experiments) and also an increased stability of the mRNA, perhaps by mechanisms analogous to those described above during activation of G-CSF expression ( 2.2.3.1). 

In various infectious diseases involving the central nervous system, the CSF protein may reflect gross abnormalities. 

The absolute concentration of blood-derived proteins is modulated by the CSF flow rate. In general, the actual CSF protein concentration is determined by the following variables individual serum concentration and individual diffusion pathway, age, site of puncture, and volume of extraction. 

In the case of barrier dysfunction, the serum protein proportion gradually increases and the percentage of CSF protein of local origin decreases. The serum/CSF ratio of total protein is suitable as an approximate indication when the more reliable albumin ratio is not available. In many laboratories, however, total protein is used primarily as an indicator of dilution for immunoglobulin quantification. 

The albumin quotient is the most precise, routinely used criterion for assessment of the function of the blood-CSF barrier because albumin in cerebrospinal fluid originates exclusively from serum. Its parallel determination during the monitoring of any CSF protein is necessary because this is the only way to differentiate its increased concentration in cerebrospinal fluid due to passive penetration of the respective serum protein from a more specific increase in the concentration of the monitored protein. It is based on its intrathecal synthesis or on a specific transport mechanism for the given protein across the blood-CSF barrier. Unfortunately, some clinicians disregard this recommendation, and this elementary fact is not sufficiently emphasized in publications on cerebrospinal fluid (A22). 

As yet, a phenomenon has not been observed in CSF. Orosomucoid in CSF can be considered to be a reliable tumor marker. Assessment of CSF orosomucoid levels has become a routine method in CSF laboratories and has become a mandatory parameter of the CSF protein status. 

Antithrombin HI (ATHI). There are only a few references concerning the evaluation of antithrombin III (AT III) in cerebrospinal fluid. Extension of evaluated groups of patients is not sufficient a comparison with other CSF protein fractions and with CSF cytological findings was not done. Some experimental works describe the vasorelaxant effect of AT III on brain arteries, and the inhibitory influence of AT III in subarachnoid hemorrhage on onset of vasospasms is expected (W2). AT III also plays a possible role in etiopathogenesis of ischemic stroke (A19, W2). 

In summary, complete examination of CSF, including basic biochemical analysis and qualitative cytology with the determination of specific CSF proteins and isoelectric focusing, provides very sensitive diagnostic imformation concerning serous inflammatory processes in the central nervous system, including diseases of autoimmune origin such as multiple sclerosis. 

Out of the examined CSF protein fractions, the elevation of levels occurs especially in acute-phase proteins and in immunoglobulins the destruction of nervous tissue is indicated as well as blood-CSF barrier dysfunction. 

El. Eeg-Olofsson, O., Link, H., and Wigertz, A., Concentrations of CSF proteins as a meastrre of blood-brain barrier function and synthesis of IgG within the CNS in normal subjects from the age of 6 months to 30 years. Acta Pediatr. Scand. 70, 167-170 (1981). 

F2. Felgenhauer, K., The filtration concept of the blood-CSF barrier as basis for the differentiation of CSF proteins. In New Concepts of Blood-Brain Barrier (L. Greenwood, D. J. Begley, M. B. Segal, and S. Lightman, eds.), pp. 209-217. Rlenum Rress, London, 1995. 

Mechanism of Action A benzimidazole carbamate anthelmintic that degrades parasite cytoplasmic microtubules, irreversibly blocks cholinesterase secretion, glucose uptake in helminth and larvae (depletes glycogen, decreases ATP production, depletes energy). Vermicidal. Therapeutic Effect Immobilizes and kills worms. Pharmacokinetics Poorly and variably absorbed from GI tract. Widely distributed, cyst fluid and including cerebrospinal fluid (CSF). Protein binding 70%. Extensively metabolized in liver. Primarily excreted in urine and bile. Not removed by hemodialysis. Half-life 8-12 hr. 

Mecftantsm of Action A third-generation cephalosporin that binds to bacterial cell membranes. Therapeutic Effect Inhibits synthesis of bacterial cell wall. Bactericidal. Pharmacokinetics Widely distributed, including cerebrospinal fluid (CSF). Protein binding 82%-93%. Metabolized and excreted in kidney and urine. Removed by hemodialysis. Half-life 1.6-2.4 hr (half-life is increased with impaired renal function). 

Mecfianism of Action A third-generation cephaiosporin that binds to bacteriai ceii membranes and inhibits ceii waii synthesis. Therapeutic Effect Bactericidai. Pharmacokinetics Wideiy distributed (inciuding to cerebrospinai fluid [CSF]). Protein binding 5%-17%. Primariiy excreted unchanged in urine. Removed by hemodiaiy-sis. Half-life 2 hr (increased in impaired renai function). 

Pharmacokinetics Well absorbed from gastrointestinal (GI) tract. Rate and extent reduced by food. Distributed throughout body including CSF. Protein binding 96%. Partially metabolized in liver. Primarily excreted in feces and urine. Not removed by hemodialysis. Half-life 0.7 hr. 

Pharmacokinetics Well absorbed from GI tract. Widely distributed, including to CSF. Protein binding 11%. Partially metabolized in liver. Excreted unchanged primarily in urine. Partially removed by hemodialysis. Half-lifc 20-30 hr (increased in impaired renal function). 

Mechanism of Action A carbapenem that binds to penicillin-binding proteins and inhibits bacterial cell wall synthesis. Therapeutic Effect Produces bacterial cell death. Pharmacohinetics After IV administration, widely distributed into tissues and body fluids, including CSF. Protein binding 2%. Primarily excreted unchanged in urine. Removed by hemodialysis. Half-life 1 hr. 

For example, ISOLABS, Inc. has a test used to detect IgG in cerebral spinal fluid as an indicator of infection. If no neurological disease exists the concentration of IgG is less than 10% of all CSF proteins. Should multiple sclerosis be present the [IgG] will range from 11-35%. This result plus the results of other confirmatory tests can significantly aid in diagnosis. 

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