Multiple sclerosis is a slowly progressive disease of the central nervous system ("CNS"), characterized pathologically by disseminated patches of demyelinization in the brain and spinal cord, and clinically by multiple symptoms and signs with remissions and exacerbations. Demyelinization is the removal of the myelin, a protective, lipid substance that surrounds the axon of nerve fibers. Multiple sclerosis related diseases are those conditions which exhibit demyelinization of nerves.
Onset of multiple sclerosis is usually insidious. Commonly, minor visual disturbances, a fleeting ocular palsy, transient weakness, slight stiffness or unusual fatigability of a limb, minor interference with walking, difficulties with bladder control, occasional dizziness, or mild emotional disturbances--all evidence of scattered involvement of the CNS--occur months or years before the disease is recognized.
Among the varied symptoms of multiple sclerosis are the following: paresthesias involving one or more extremities or one side of the face, weakness or heaviness of the limbs; visual disturbances such as partial blindness in one eye, double vision, dimness of vision, or visual scotomas; bladder dysfunction; and mood disorders. (Paresthesias is an abnormal sensation, such as burning, prickling, and formication.)
Spontaneous remissions make any treatment difficult to evaluate. Though the average duration of life is 10 to 20 years following onset, many patients live longer. Some patients have frequent attacks and are rapidly incapacitated, while others have remissions that last as long as 25 years.
Diagnosis of the disease state is difficult owing to the overlap of the above-noted symptoms of multiple sclerosis and similar symptoms of other CNS diseases. Diagnosis of multiple sclerosis is most frequently premised upon a history of remissions and exacerbations of the various symptoms over a period of years in combination with systematic elimination of other possible diseases which display similar symptoms. Extensive testing, at substantial cost and often physical discomfort to the patient, is performed to eliminate the following diseases as the source of the symptoms: intracranial lesions, cerebrovascular accidents, acoustic neuroma, cerebellar tumors, gliomas of the brain stem, spinal cord tumors, syphilis, pernicious anemia, arthritis of the cervical spine, ruptured intervertebral disk, platybasia, and hereditary ataxia.
Substantial efforts have been directed toward development of diagnostic methods and materials useful in the early diagnosis of multiple sclerosis. Positive results in colloidal gold tests on cerebrospinal fluids are considered supportive, but not dispositive of a positive diagnosis. Also, the same is true of testing for elevated gamma globulin in cerebrospinal fluids--the test tends to verify diagnosis in advanced stages but is not helpful in diagnosis of early stages. Similarly, active demyelinization associated with the disease frequently is signified by elevation of analytical results in basic protein assay testing of spinal fluid, but test levels drop rapidly once acute exacerbation is over. Non-dispositive correlations have been made between the presence of the disease state and elevated levels of measles antibodies in serum and cerebrospinal fluids. Finally, certain researchers have proposed that electron microscopic examination of lymphocytes for certain distinct morphological changes may provide a fruitful basis for diagnosis of multiple sclerosis.
U.S. Pat. No. 4,294,818, describes a potential immunological marker for multiple sclerosis. This marker was not purified or characterized. In addition, there was no indication in the prior art that all or most animals responded with production of the proper isotype and amount of antibodies, and no demonstration was made that all or most animals from different species would respond in a consistent manner. Some or all of these requirements are necessary for commercial applications as, for example, with the use of antisera in a diagnostic test.
There remains a substantial need for diagnostic methods and materials for rapidly, simply, and accurately determining the presence of multiple sclerosis. Such methods should be highly specific for multiple sclerosis and closely related diseases to avoid the generation of false positive results due to other central nervous system diseases, other immune disorders or ingested drugs. Further, such methods should be capable of diagnosing multiple sclerosis in its early stages, should not involve painful or hazardous withdrawals of patient tissue samples, and should preferably involve standardized laboratory techniques which do not require expensive or complex apparatus.