Multiple Sclerosis or disseminated sclerosis is the most common demyelinating disorder. It is usually pleomorphic and difficult to define completely in the absence of specific diagnostic tests.
There are a number of well recognized and readily diagnosed syndromes, but borderline cases may be difficult to categorize clinically and pathologically. Generally it is chronic and relapsing, but fulminating attacks occur and as many as 30 per cent of patients tend to progress steadily from the onset. The symptoms and signs reflect involvement of central myelitis, but occasionally symptoms are typical of neuronal or gray-matter involvement. Multiple sclerosis (MS) is a disease of the central white matter with “lesions separated in time and space.”
Multiple Sclerosis Incidence.
The prevalence of multiple sclerosis- in the United States varies from about 10 per 100,000 in the South to 60 per 100,000 in the North, with similar prevalence and distribution in Europe. The disease affects males and females about equally. About 67 per cent of cases begin between the ages of 20 and 40 years and 95 per cent between 10 and 25 years.
Populations residing between latitudes 40° N. and 40° S. (tropical and subtropical zones) have a low risk of multiple sclerosis. With a few notable exceptions, all populations residing north of this latitude in North America and Europe are at higher risk. Other exceptions to these generalizations are found in other parts of the world; e.g., a low incidence is reported in the Union of South Africa and in Japan. Efforts have been made to correlate these geographic variations with dietary intake, temperature, solar radiation, and geomagnetic latitude, without success. Racial factors seem to play little part in the United States since the incidence in Negroes is almost the same as in Caucasians.
Genetic studies have not elucidated the cause of multiple sclerosis. There are occasional reports of a greater family incidence than could be expected by chance, but these fail to exclude the common effects or environmental/ factors.
The external surface of the brain and cord generally shows no abnormality. Occasionally there is atrophy of the optic nerves and rarely focal or generalized atrophy of the cerebral hemispheres. Acute large lesions may cause swelling of the cord. Rarely there may be sufficient focal swelling of the cerebrum to give the appearance of a neoplasm in gerontological contrast studies!
Cut sections of the brain or spinal cord reveal numerous scattered, grayish, predefined lesions that are slightly depressed and vary in diameter from a few millimeters to a few centimeters. These are found throughout the white matter of the ordain, optic nerves, and spinal cord and occasionally extend into gray matter. The number of lesions is usually greater than would be expected from the clinical picture.
An ineffective process (upper respiratory infection, “influenza,’’ urinary tract infection, gastroenteritis, etc.) is said to precede the initial attack or a relapse of multiple sclerosis in 10 to 40 per cent. Immunizations are without apparent effect on the course of the disease, and any exacerbation’s seen following these are probably coincidental.
Many workers have stated that pregnancy aggravates the disease, but this is open to question. The disease and pregnancy occur in the same age group, and although some studies show a higher incidence in married child-bearing women, more attacks occur during the puerperal than during pregnancy itself. The physician must consider many non-medical factors when advising on this problem. Pregnancy is generally considered non- deleterious to the course of multiple sclerosis in any patient who has not had an attack in two years.
There seems to be no clear-cut association of attack Or relapse with surgical procedures, and indications for surgery in patients with multiple sclerosis should be judged solely on their own merit.
Trauma has likewise been incriminated in an almost anecdotal manner, but there is no statistical evidence to support a relationship between peripheral trauma and the onset or relapses of multiple sclerosis. There is a tendency for patients to associate trauma with the onset of an attack or re)ajxge, but in many cases it is more likely that the trauma resulted from the disability of mu/Ci’p/e sclerosis. Similarly, emotional stress has been incriminated as a precipitant of attacks or relapses of multiple sclerosis. This is difficult to substantiate, but it is reasonable to assume that the cerebral changes in multiple sclerosis make it more difficult for the patient to cope with emotional stress.
Certain diagnostic procedures such as lumbar puncture, electroencephalography, cerebral angiography, and holography have been implicated in the worsening of symptoms in multiple sclerosis. However, these procedures are performed usually in patients whose disease is progressing or soon after an attack or relapse. They should be performed in cases in which there are serious questions whether a neoplasm exists in the nervous system, and not simply in frustration because “there’s nothing else that can be done.”
Multiple Sclerosis Clinical Manifestations.
The clinical picture of multiple sclerosis is isomorphic, but there are usually sufficient typical features to enable one to diagnose the disorder in the absence of a specific diagnostic test or without extensive “excluding diagnostic procedures. The disease is chronic, often characterized by exacerbations and remissions, with evidence of multiple lesions in central white matter occurring in young adults without other systemic disorders. The symptoms of central white matter involvement are usually those of antinuclear weakness, in-coordination, parenthesizes, and visual complaints. Other symptoms and signs that are more characteristic of lesions in gray matter, e.g., aphasia, seizures, fascia dilation, and neurotic atrophy, are rare. Mental changes have an intermediate incidence and affect perhaps 30 per cent of patients.
The onset may be acute, with symptoms appearing within minutes to hours, or it may be insidious, with gradual, slow progression of symptoms over a period of months.
Multiple Sclerosis Laboratory Data.
Abnormal findings in multiple sclerosis are usually confined to the cerebrovascular fluid. In the acute disease, there may be a mild mono-nuclear Pleistocene of as much as 200 to 300 cells per cubic millimeter, but usually less than 40. The protein content is usually normal or slightly elevated (50 to 100 mg. per 100 ml.); values higher than this are rare. The gamma globulin content is elevated in about two thirds of the cases and, correspondingly, there is often an abnormal colloidal gold curve (first or second zone) accompanied by a negative seismologic test for syphilis.The electroencephalogram may be mildly abnormal in about two thirds of cases revealing either focal or generalized abnormalities.
Because of the pleomorphic nature of the disease, it is often necessary to exclude many other neurologic disorders. Most often one must consider spinal cord, brainstem or cerebellar tumors, degenerative diseases such as the spinocerebellar degenerations, and combined system disease.
The fact that multiple sclerosis has a remitting nature in many instances and the dissemination of symptoms and signs should indicate that one is not dealing with an expanding lesion involving the nervous system. If all the symptoms and signs can be explained by a single lesion, then one should assume that the condition is not multiple sclerosis.
If the patient complains of headache, seizures, or progressive focal neurological signs, which are uncommon in multiple sclerosis, and if these are accompanied by abnormalities such as increased cerebro spinal fluid pressure, roentgenographic changes in the skull or spine, marked elevation of cerebrovascular fluid protein, etc., then one must proceed further to exclude a neoplasm. This can be done in most cases by a neurological procedure such as myelography, electroencephalography, or cerebral angiography. Vascular disease, particularly that involving the brain-stem, can be confused with multiple sclerosis in middle-aged patients. In some of these cases only prolonged follow-up reveals the true diagnosis.
Treatment of Multiple Sclerosis Every Doctor Must Know.
There are several aspects to the management of multiple sclerosis. The first is the possible benefit to be gained from ACTH or corticosteroids during acute exacerbations. Many authorities advise a course of three to four weeks of therapy with suitable precautions against complications, and some recent controlled studies have shown that this treatment has some benefit in the acute symptom complex. There are no indications for long-term maintenance therapy on ACTH or corticosteroids, and the risks out weigh- any possible benefit. Preliminary studies with other immunosuppressive agents indicate that the course of the disease may be stabilized with fewer exacerbations. From a consideration of the pathology, it is unreasonable to expect alleviation of symptoms that have been static for many months.
The second aspect is the general management of the patient. During acute exacerbations, especially severe ones, there may be some benefit from bed rest, though the demoralizing effects of prolonged immobilization must be avoided. The prevention of complications, especially genitourinary infections, bedsores, contractures, and flexor spasms, requires adequate nursing care, physiotherapy, and occasionally more specific measures such as rhizotomy, tenotomy, antimicrobials, and other indicated measures. Exhausting physiotherapy with active exercises offers no benefit and may even be harmful. Certain other measures such as unnecessary catheterization have serious consequences and should be avoided.
The third aspect of patient care is the management of long-term disabling illness with an. unpredictable course. Initially there arises the question of informing the patient, and this must be dealt with on an individual basis after considering the emotional makeup of the patient and his family, the patient’s responsibilities, and
other factors. This is particularly important in relation to pregnancy. The route of delivery is an obstetrical decision.
One must encourage and support the patient to remain active and yet protect him from constantly seeking untried and potentially harmful therapies or unnecessary diagnostic tests and operations.
In the early stages of the disease it is not possible accurately to predict the course, although certain symptoms seem to indicate a better prognosis.Within the first five years after onset, about 70 per cent of patients are able to be employed, although with occasional interruptions in some cases. By the end of ten years this drops off to 50 per cent. At the end of 20 years 35 per cent are still employed, with minor interruptions, and about 20 per cent of patients succumb to complications of the disease by this time. The major disabilities are spastic, disturbances of coordination, and disturbance in bladder and bowel function.
Life expectancy varies considerably, ranging from a few weeks to over 50 years regardless of whether one considers hospitalized, severe cases or the more benign forms. The average life expectancy is from 13 to more than 25 years after onset. The cause of death is often an inter current infection, usually respiratory or genitourinary.