During the first month of life, the CSF contains a larger number of mononuclear cells than in adults. Beyond this period, the CSF is normally nearly acellular (i.e., fewer than 5 lymphocytes or other mononuclear cells per cubic millimeter). An elevation of WBCs in the CSF always signifies a reactive process, either to infectious agents, blood, chemical substances, an immunologic inflammation, a neoplasm, or vasculitis. The WBCs can be counted in an ordinary counting chamber, but their identification requires centrifugation of the fluid, preferably with a Wright stain of the sediment. Identification of malignant cells by the cytology laboratory is usually done by cytocentrifugation or other semiautomated liquid-based method, followed by cell fixation and staining (Bigner and Den Hartog-Jage). One can recognize and differentially count neutrophilic and eosinophilic leukocytes (the latter being prominent in some parasitic infections, neurosyphilis, and cholesterol emboli), lymphocytes, plasma cells, mononuclear cells, macrophages, and tumor cells (see Bigner and also Den Hartog-Jaeger). Bacteria and fungi can be seen in routinely stained preparations. An India ink preparation helps to distinguish between lymphocytes and Cryptococcus organisms. Acid-fast bacilli will be found in appropriately stained samples. The monograph by Ali and Cibas is an excellent reference on CSF cytology. Flow cytometry permits the distinction between polyclonal and monoclonal proliferations, thus aiding in the detection of leukemia and lymphoma, and immunostaining techniques help identify metastatic solid tumors. These and other methods for the examination of cells in the CSF are discussed in the appropriate chapters.
In contrast to the high-protein content of blood (5,500 to 8,000 mg/dL), that of the lumbar spinal fluid is 45 to 50 mg/dL or less in the adult. The protein content of CSF from the basal cisterns is 10 to 25 mg/dL and that from the ventricles is 5 to 15 mg/dL. Based on work by Fishman and colleagues, this gradient may reflect the fact that CSF proteins leak to a greater degree at the lumbar roots than at higher levels of the neuraxis. An alternative explanation derives from the manner in which the spinal fluid is an ultrafiltrate of blood made by the choroid plexus in the lateral and the fourth ventricles, analogous to the formation of urine by the glomerulus. The amount of protein in the CSF would then be proportional to the length of time the fluid is in contact with the blood–CSF barrier. Thus shortly after it is formed in the ventricles, the protein is low. More caudally in the basal cisterns, the protein is higher and in the lumbar subarachnoid space it is highest of all. In children, the protein concentration is somewhat lower at each level (<20 mg/dL in the lumbar subarachnoid space). Levels higher than normal indicate a pathologic process in or near the ependyma or meninges—in either the brain, spinal cord, or nerve roots—although the cause of modest elevations of the CSF protein, in the range of 75 mg/dL, frequently remains obscure.
As one would expect, bleeding into the ventricles or subarachnoid space results in spillage not only of RBCs but of serum proteins. If the serum protein concentrations are normal, the CSF protein should increase by about 1 mg/1,000 RBCs. The same holds for a traumatic puncture that allows seepage of venous blood into the CSF at the puncture site. However, in the case of subarachnoid hemorrhage, caused by the irritating effect of hemolyzed RBC upon the leptomeninges, the CSF protein may be increased by many times this ratio.