Biochemical analysis of cerebrospinal fluid

For the diagnosis, the ratio between the number of cellular elements and the protein is essential. 

Determination of the amount of protein in liquor

Normally, cerebrospinal fluid contains 0.1-0.3 g / l protein, mainly albumin. With neuroinfections and other pathological processes, the amount of protein increases with the penetration of the hematopoietic barrier by getting it from the blood plasma. With viral neuroinfections, the protein content can reach 0.6-1.5 g / l, with bacterial - 3.0-6.0 g / l, and in later terms - up to 16-20 g / l. The composition of proteins changes. With bacterial meningitis in the cerebrospinal fluid, globulins and even fibrinogen appear. In case of tuberculous meningitis, after settling the cerebrospinal fluid in the refrigerator for a day, a mesh of fine fibrin filaments appears in it, and in fensiform pneumococcal meningitis a dense fibrin clot forms.

In viral meningitis, in the early stages of bacterial meningitis observed a sharp increase in the number of cells at a normal protein content - cell-protein dissociation. With viral encephalitis, tumors, and subarachnoid hemorrhage  , a significant increase in protein concentration can occur with normal cytosis or insignificant pleocytosis-protein-cell dissociation. 

The concentration of protein in the cerebrospinal fluid increases with a violation of BBB, delayed reabsorption or increased local synthesis of immunoglobulins (lg). - Violation of BBB can occur due to inflammation, ischemia, trauma or neovascularization. The normal concentration of protein in the lumbar cistern does not exceed 0.45 g / l and is the highest in comparison with that in other parts of the subarachnoid space. The protein content in the cerebrospinal fluid increases proportionally to the distance from the site of its synthesis and is up to 0.1 g / l in the brain ventricles, up to 0.3 g / l in the brain basal cistern, and up to 0.45 g / l in the lumbar cistern.

A significant increase in protein content is characteristic of Guillain-Barre syndrome (from the 3rd week of the disease) and CVD. A particularly high concentration of protein is typical for tumors of the spinal cord. Tumors of the lower parts of the vertebral canal are often accompanied by a fluvial syndrome of Nonlinear Frelllich: the cerebrospinal fluid is xanthrome, drained in a test tube, and the protein content in it is increased 10-20 times.

For qualitative and quantitative analysis of proteins of the cerebrospinal fluid, electrophoresis and immunoelectrophoresis are used. Normally about 70% is albumin and about 12% - y - globulin. Proteins in the cerebrospinal fluid come from the blood plasma by selective transport or are synthesized in the subarachnoid space itself. Therefore, an increase in the concentration of protein in the fluid can occur as a result of a general violation of the immunological status in the body, and as a result of enhanced local synthesis. An increase in the concentration of y-globulins (hypergammaglobulinurahia) with normal content of the total protein is characteristic primarily of multiple sclerosis. If there is an increase in immunoglobulins in the cerebrospinal fluid, then surely their level should be checked in the blood serum. An increase in Ig can be observed even with a normal content of total protein in the liquid. Thus, the increase in IgG is detected with multiple sclerosis and acute polyradiculoneuropathy, and sometimes with intracranial tumors and various inflammatory diseases of the central nervous system, including encephalitis, meningitis, subacute sclerosing panencephalitis, and others.

Polyclonal Ig at electrophoresis form a single diffuse band. Monoclonal Ig form separate distinct bands in the region of precipitation of y-globulins. Since it is believed that each clone of B-lymphocytes produces a specific Ig, a group of clear strips (oligoclonal bands) arising from electrophoresis reflects the presence in the cerebrospinal fluid of oligoclonal Ig synthesized by specific clones of lymphocytes. The fact of Ig synthesis within the CNS is confirmed by the absence of oligoclonal bands in the serum electrophoresis. Detection of oligoclonal bands is very important for the diagnosis of multiple sclerosis, since in 70% of patients with clinically reliable diagnosis of multiple sclerosis, oligoclonal bands are revealed during electrophoresis of cerebrospinal fluid.

[1], [2], [3], [4], [5], [6]

Determination of the amount of glucose in the liquor

The hematopoietic barrier is semipermeable for glucose, therefore its content in the cerebrospinal fluid is on average 50% of the blood content and is within the range of 2.2-3.3 mmol / l. Due to increased permeability of the hematopoietic barrier in aseptic inflammatory processes, the amount of glucose increases to 3.5-5.0 mmol / l, while in viral serous meningitis and encephalitis it remains within 2.5-4.5 mmol / l. In bacterial meningitis in the first day, the glucose level is within normal limits or increased. Subsequently, due to the consumption of glucose by microbial flora and neutrophils, the glucose level is steadily decreasing up to complete absence, which indicates the age of the pathological process. The study of glucose level is important for evaluating the effectiveness of treatment of bacterial meningitis. With effective antibacterial therapy 2-3 days later, the glucose level is normalized, in the absence of effect - remains reduced or decreases even more.

Of the additional research methods that are currently being introduced into practice as differential diagnostic rapid tests, it is recommended to determine the level of lactate and the pH of the cerebrospinal fluid. Normally the lactate content is 1.2-2.2 mmol / l, with bacterial meningitis its level is increased 3-10 times or more. Normally, the cerebrospinal fluid has a slightly alkaline reaction, pH 7.35-7.40, with bacterial meningitis, the pH level drops to 7.0-7.1.

The concentration of glucose decreases as the cerebrospinal fluid circulates from the ventricles of the brain to the lumbar cistern. Normally the ratio between the glucose concentration in the lumbar cistern fluid and in the blood plasma is at least 0.6. It should be remembered, however, that the ratio of the concentration of glucose in the cerebrospinal fluid to the plasma concentration may decrease for some time (about 2 hours) after eating. At a very high level of glucose in the blood (more than 25 mmol / l) there is a complete saturation of the membrane glucose transporters, and therefore its relative concentration in the liquid may be lower than the theoretically expected. The normal level of glucose in the cerebrospinal fluid at an elevated level in the blood can indicate an increased utilization of glucose in the subarachnoid space. Low glucose in the cerebrospinal fluid can be observed with hypoglycemia, but the coefficient of cerebrospinal fluid / plasma remains unchanged. Significantly more often, hypoglycorhychy, ie, a low glucose content in the subshell, arises from a violation of active membrane transport, which is accompanied by a decrease in the cerebrospinal fluid / plasma ratio. This is observed with many inflammatory processes in the membranes of the brain. Thus, acute bacterial, tuberculosis, fungal and carcinomatous meningitis lead to a low level of glucose. A less pronounced decrease in glucose concentration is often noted in sarcoidosis of the meninges, parasitic infections (cysticercosis and trichinosis), and meningitis caused by chemical factors. In viral meningitis (parotitic, herpetic, lymphocytic choriomeningitis), the glucose level decreases slightly and often remains normal. Subarachnoid hemorrhage also causes hypoglycemia, the mechanism of which remains insufficiently clear. Reducing the concentration of glucose in the cerebrospinal fluid may persist for 2-3 weeks after the normalization of cytosis in acute meningitis.

[7], [8], [9]