Rare patients with MS have a coexisting polyneuropathy or mononeuropathy multiplex, a relationship that always invites speculation and controversy, especially as several autopsy cases have shown demyelinating lesions in both the central white matter and scattered in peripheral nerves. The infrequency of the combination, however, suggests a purely coincidental occurrence, perhaps with another underlying disease as an explanation (e.g., Lyme disease, AIDS). Another view, expressed by Thomas and colleagues and by Mendell et al, is that an autoimmune demyelination has been incited in both spinal cord and peripheral nerve, the latter taking the form of a chronic inflammatory polyradiculoneuropathy. Of course, myelination is provided by oligodendrocytes in the CNS and schwann cells in the peripheral nervous system, implying that there are differences in antigens that typically separate MS and CIDP. More commonly in MS, radicular and neuropathic symptoms are the result of involvement of myelinated fibers in the root entry zone of the cord or fibers exiting from the ventral white matter.
In about one-third of all MS patients, particularly those with an acute onset or an exacerbation, there may be a slight to moderate mononuclear pleocytosis (usually in the range of 6 to 20 and virtually always, less than 50 cells/mm3). In rapidly progressive cases of NMO (see further on) and in certain instances of severe demyelinating disease of the brainstem, the total cell count may reach or exceed 100, and rarely in the hyper-acute cases, 1,000 cells/mm3.
It has been shown that the gamma globulin proteins in the CSF of patients with MS are synthesized in the CNS (Tourtellotte and Booe) and that they migrate in agarose electrophoresis as abnormal discrete populations. These oligoclonal bands in the CSF (after comparing to monoclonal proteins that may be present in the serum) are detected in more than 90 percent of cases of MS in some populations, but in a lower proportion of patients in Asian countries. Furthermore, oligoclonal bands are not specific for MS; such bands also appear in the CSF of patients with disorders such as syphilis, Lyme, and subacute sclerosing panencephalitis. The presence of bands in a first attack of MS is predictive of a chronic relapsing course, according to Moulin and coworkers and others. Oligoclonal bands are usually reported as being present if there is more than 1 band; the meaning of a single band is not clear, and we have treated this result as a negative test. As will be pointed out, the conditions of necrotic myelopathy and Devic disease generally lack oligoclonal bands.
Also, in approximately 40 percent of patients, the total protein content of the CSF is increased. The increase is slight, however, and a concentration of more than 100 mg/dL is so unusual that the possibility of another diagnosis should be entertained. Another diagnostic test sometimes used is measurement of IgG and the IgG index in the CSF. The latter refers to proportion of gamma globulin (mainly IgG) in reference to the total protein in CSF; a positive test is considered to be greater than 12 percent of the total protein. The same diseases mentioned above as being associated with oligoclonal bands can also increase the IgG index.
It has also been shown, by the use of a sensitive radio-immunoassay, that the CSF of many patients contains high concentrations of MBP during acute exacerbations of MS and that these levels are lower or normal in slowly progressive MS and normal during remissions of the disease. Other lesions that destroy myelin (e.g., infarction) can also increase the level of MBP in the spinal fluid. Thus the assay is not particularly useful as a diagnostic test and probably simply reflects the destruction of central myelin.