Multiple Sclerosis: A Personal View

Multiple Sclerosis, or Disseminated Sclelrosis, as it used to be called, is one of medicine's strangest mysteries: with an unknown cause; an unexpected geographic distribution; an unpredictable course; an undiscovered cure.

While its treatment is to say the least, highly controversal. MS is associated with particular locations, rather than with any race living in these locations.

The symptoms start most often in adults from eighteen to forty years of age. In two thirds of sufferers onset is between twenty and twenty five. The age of onset in women is slightly younger than in men. It is not hereditaary, but it is familial.

MS is a disease which affects the Central Nervous System - the Brain and Spinal Cord. Through the transmission of impulses this controls such important functions as walking, talking, seeing, and eating; tying a shoe lace and opening a door.

These impulese travel along Nerve Fibers in the CNS, then to the other parts of the body. Normally the Nerve Fibers are covered by a material called Myelin, which can be compared to the insulation around a phone wire.

Composed of fatty material and proteins, Myelin permits Nerve Fibers to conduct impulses at rates up to 100 times faster than Nerve Fibers not covered with it.

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Not only is Myelination incomplete at birth, but the process of both Brain growth and Myelination proceed at different rates for different Brain centers.

The motor control area of the Cortex is the first to be Myelinated. The initial linkages are between the Visual and Motor Lobes.

Myelination of the Nervous System is not complete until the early teen years. We still do not know what factors promote optimum growth or, conversely, retard it.

Although Myelin is also present in the Peripheral Nervous System, the DeMyelination only occurs within the CNS. The reason for this is not known; but it is known that in MS changes around Veins in the CNS affect the Myelin sheath.

In effect, this is dissolved by some caustive agent, so that the Myelin is damaged; later the affected area is replaced by scar (sclerotic) tissue, from which the disease gets its name.

Early in the disease only the Myelin is involved (Primary DeMyelination), and the Nerve Fibers are not destroyed until later (Secondary DeMyelination).

If only the protective covering is diseased, the function of the fibers is impaired, but some impulses can still be transmitted, although not with full strength. Function is restored when the sheath's condition improves.

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Once the Nerve Fibers themselves are replaced by scar tissue, called plaques, nerve impulses can no longer be carried. After this scar is formed, the damage can not be reversed.

Consequently, with intense, sudden impairment or with prolonged impairment, function may be permanently lost in those parts of the body, regulated by the damaged Nerve Fibers.

There are, nevertheless, other possibilities: for one thing, if the damage occurs in one particular nerve, it is possible that other Nerve Fibers can ultimately take its place.

This may explain the waxings and the wanings, the relapses and remissions, that are characteristic of MS: the remissions marking the point at which other auxilary Nerve Fibers take over the job that the damaged one had been doing.

This alone presents two avenues of hope: to find a way to interfere with the scarring process, or to try to stimulate the formation of new Myelin.

The reason why the disease is termed multiple is that almost any portion of the CNS may be involved. The Spinal Cord is perhaps the most frequently affected; this can cause periods of partial to complete paralyses of the legs and, at times, of the trunk and arms.

With or without this weakness or paralysis, there may be lack of coordination, staggering and tremor, or poor coordination plus tremor of the extremities, and sometimes of the body and head.

Numbness, tingling and various sensory changes often occur. Eye symptoms are common, with involuntary movement of the eyeball, periods of double or Blurred Vision, even temporary to permanent blindness in one or both eyes.

In advanced cases Slurred Speech and sometimes difficulty with bladder and bowel control are not unusual.

Quite often suffers are euphoric. They seem strangly, if not unusally cheerful in spite of their incapacitating symptoms or they continue to be hopeful and optimistic despite progressive impairment.

On the other hand, many become very severely depressed. In a few, there is loss of memory for recent events and deterioration in conceptual thinking.

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Characteristically, the disease differs markedly from person to person, showing so much variation that it is difficult to forcast its course.

Typically though, symptoms come and go in the beginning, occasionally disappearing completely. As the disease goes on, however, recovery may be less and less complete, with persistence and progression of symptoms.

In a minority, less than 10 percent, MS has a relentless course without periods of remission.

In others, the symptoms occur suddenly and persist with neither improvement nor progression; most often, relapses are mild and infrequent, seperated by periods of five to fifteen years, permitting an active and full life.

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It was Jean Martin Charcot, one of France's most famous medically investigators, who in 1868 gave the world a detailed description of MS.

Charcot found that patients frequently experienced alternating exacerbation and remmission of symptoms, that the severity of the symptoms varied greatly from patient to patient and that often the illness appeared to remain stationary for many years.

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In its advanced stages he found that the disease was characterized by Paralysis and three additional symptoms now known as Charcot's Triad. One of these is Intention Tremor: the limbs, particularly the arms and hands, shake violently whenever the person tries to control his movements;

The second symptom is Slow and "Scanning Speech", where there is a pause after every syllable; The third is Ocular Abnormalities, particularly "Nystagmus", an involuntary flicking of the eye back and forth, up and down or around and around.

From the Charcot's time, many important contributions to the Multiple Sclerosis literature rapidly increased.

But although it has been known as a pathologic entity for over 150 years and as a clinical disease for more than 100 has been subjected to intensive, exhaustive and multifaceted investigation; today, most of its mysteries remain unsolved.

Breakthrough?

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Today MS is regarded as the great mystery disease, and with each new publication the mystery seems to deepen. If the veil is to be lifted on it, perhaps we should pay close heed to: The question is, what precipitates the MS plaque in those who are vulnerable?

In some respects this is comparable to that of hayfever, for in this condition a small group of people are made ill by something in the atmosphere which has little or no effect on others.

We know that in hayfever the cause is the presence of pollens in the atmosphere, and it now seems likely that in MS there must also be a factor to which vast numbers of people are exposed without haarm, and yet it is responsible for the Multiple Sclerosis plaque in those who are susceptible.

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This factor must be identified or defined as soon as possible, for it is likely that, whatever it is, it will be one from which the MS-prone can be successfully protected.

Among those now known to precipitate DeMyelination are: materials, physical injury, exposure to small domesticated animals, chemicals - it has been estimated that approximately 40,000 adults suffer PolyNeuritis, a DeMyelinating disease, as a result of Thalidomide, and inoculations.

These stressors - anything that makes the body strain that is the wear and tear induced in the body by the adaptive, day - to - day struggle of the person to retain their integrity and constancy in the face of potentially harmful agents, including physical and psychologic stressors of all kinds, from bad food and noisy neighbors to police brutality and fascist politics.

When enviromental changes were slow and naturally occurring, we responded through biologic evolution. Today, they are of such magnitude and rapidity that they seriously challenge our adaptive ability.

Thus our capacity to maintain an internal homeostasis despite changing external forces, is largely oriented to the past.

In other words, the regulatory mechanisms which govern homeostasis are Genetically linked to a period in our evolution quite unlike the present.

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Whatever adaptability we have to Ecologic upsets was shaped by past enviromental circumstances.

The catastropic strains of industrial society and the proliferation of new materials associated with our unprecedented affluence, constitute stressors which provoke unique responses from us.

These are a physiologic, morphologic, behavioral and social admix whereby we seek to adapt, maintain or regain homeostatic compatibility.

In point of fact through culture, and in particular technology, we have created an enviroment to which we no longer have an appropriate degree of fitness.

Recently we were forced to recognize that there are limits to overall growth as well as more circumscribed areas of scientific advance, such as medicine; now it seems we have reached the limit of man's capacity for enviromental change.

We do not know all the circumstances under which our ability to adapt is, or can be pushed beyond the point of no return. But we can expect to see, with growing diversity and frequency, the terrifying results when we are called upon to adapt.

Professor Hans Selye is a pioneer of modern physiologic research into stress. He has examined numerous diseases of organs and systems of organs, concluding that many are "diseases of adaptation," a statement which is, of course, a contradiction in terms.

In these instances, the person is not better adapted; rather the critical level of stability is exceeded and they are injured instead.

Paradoxically, the mechanisms implicated by Selye in disease are precisely those that Walter Cannon called homeostatic and which under appropriate circumstances tend toward a stable physiologic condition. As Cannon indicated, that these homeostatic mechanisms are clearly self preservative.

Yet, in another profound sense, Seyle has shown that these very same mechanisms are also associated with disease and death. Thus the very same mechanisms that are self-preservative on one occasion can be self-injurious on another.

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Sometimes the body's reactions are excessive and quite out of propotion to the fundamentally innocuous irritation to which it was exposed.

Here, an excessive response, say, in the shape of inflammation, may actually be the main cause of what we experience as disease. . . Could, for instance, the excessive production of a proinflammatory Hormone, in response to some mild local irritation, result in the production of a disproportionately intensive inflammation, which hurts more than it helps?

Could such an adaptive Endocrine response become so intense that the resulting Hormone excess would damage organs in distant parts of the body, far from the original site of injury in parts which could not have been affected by any direct action of the external disease - producing agent ?

The import of Selye's work is that defense is the key to understanding disease: it is the defensive reactions to an external agent, rather than the external agent itself (physical or psychologic) that is the neucleus of disease.

In short, it is the defensive response itself that is the real and dangerous disease and this response is immanent in the individual.

In 1936, Selye published a historic letter in Nature, clarifying the mechanics of general adaptation and the body's response to the threats to its stability:

"If the organism is severly damaged by acute, nonspecific noxious agents, a typical syndrome appears, the symptoms of which are independent of the nature of the damaging agent or the pharmacological type of drug employed, and represent rather a response to damage as such."

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He describes the three stages of the syndrone, he had observed:

Stage I: comes on six to forty-eight hours after the initial injury. It is characterized by a fall in body temperature, loss of muscle tone, low blood pressure, shrinking of the Adrenal Glands (as they squeeze as much Cortisone as possible into the bloodstream in an effort to set things right) and leaking of fluid from the small blood vessels into the tissues.

Selye's description of Stage I corresponds, on the whole to surgical shock.

Stage II: begins forty-eight hours after the assault on the body's stability. The Adrenals greatly enlarge, the edema or swelling of the tissues begins to subside and cell division ceases.

The Pituitary, the master gland situated at the base of the Brain, produces increased quantities of Adrenal-Cortex Stimulating Hormone (ACTH). When the noxious agent continues to be applied in sublethal doses, the body builds up a resistance, becoming adapted to the stress, and apparently returns to normal.

Stage III: the stage of exhaustion. Stage III's symptoms were similar to those seen in Stage I, but this time there was no stage of resistance or recovery to follow, only death due to exhaustion of the adaptive process.

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Explaining the significaance of these three stages, Selye wrote: "We consider the first stage to be the expression of a general alarm of the organism when suddenly confronted with a critical situation, and therefore term it the "general alarm reaction".

Since the syndrome as a whole seems to represent a generalised effort of the organism to adapt itself to new conditions, it might be termed the "General Adaptation Syndrome". It might be compared to other general defence reactions such as inflammation or the formation of immune bodies.

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The symptoms of the alarm reaction are very similar to those of Histamine Toxicosis or Surgical or Anaphylactic Shock; it is therefore not unlikely that an essential part in the initiation of the syndrome is the liberation of large quantites of Histamine or some other substance, which may be released from the tissues either mechanically in surgical injury, or by other means in other cases.

It seems to us that more or less pronouced forms of this three-stage reaction represent the usual response of the organism to stimuli such as temperature changes, drugs, muscular exercise, etc., to which habituation or inurement can occur."

Particularly in the field of Allergy - adaptation and maladaptation show themselves more as specific symptoms related to specific stressors and individuals, rather than as general to all noxious agents and all people.

That individual animals showed marked differences in their responses to the same agent, and that these responses were often specific to a particular stress, rather than general to all.

These stages are:
• Alarm;
• Adapt;
• Develop Illnesses in the Exhaustion Stage;
• And finally Die.

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The sick do not usually consult their doctors until they are entering the stage of exhaustion in their struggle to adapt to an environmental stress. Lacking a means of turning back the clock in the patient's illness, the doctor is left to speculate on causes and to treat symptoms empirically as they arise.

In MS the symptoms are attributed to the DeMyelination following the exhaustion caused by constant exposure to the stressors the patient is allergic to. The word Allergy (literally, other response) was coined in 1906 by Clemens Von Pirquet, ka Viennese pediatrician who worked on Diphtheria in children.

He defined allergy as an acquired, specific, altered capacity to react to physical substances on the part of the tissues of the body.