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    Preface
p. v
The primary fact about MS is all too well known: that it is potentially and often actually a disabling disease of previously healthy young adults.

Beyond this, hard facts are curiously elusive even on such basic questions as how common, how serious, and how certain is the diagnosis, let alone on the more controversial matters of cause and treatment.

Sources likely to be consulted by those with MS or their relatives are sometimes dogmatic, biased, or simply wrong, erring on the side of pessimism in describing only the effects of serious disease or, when treatment is considered, towards uncritical optimism.

There is, indeed, no lack of information but we are learning not to accept anything as factual that has not been independently confirmed.

Even allowing for this necessary but belated caution there is an air of expectancy that effective treatment and prevention cannot be long delayed.

Facts then, as accurate as we can make them and the theories that can be drawn from them will provide the answers, although not perhaps without the spice of inspiration.

p.vi
The second edition of this book contains many additions and alterations, including some suggested by MSers or their relatives.

No effective treatment for MS has been discovered but the recent increase in scientific endeavor directed towards this aim is descrbed. Further advice on coping methods have been added.


What Is MS

Ch1
p.2

The Central Nervous System (CNS) consists of the Brain within the skull, and the Spinal Cord running down the center of the backbone.

The CNS performs a great variety of functions, based essentially on the reception and analysis of information from the outside world and from internal organs, and the initiation and control of the response.

Whether this be Movement, Emotion, or some more basic activity, such as Sweating or Evacuation of the Bladder.

This crude statement should not be taken to imply that the Nervous System acts solely as an automatic machine.

There is obviously much that is controversial or unknown, particularly with regard to such functions as consciousness, memory, and reason.

p.3
All these functions, however, depend on the Neurons or Nerve Cells, of which the Nervous System contains some million million (a British billion) linked together in an orderly but literally inconceivably complex manner.

Each Neuron consists of a Cell Body and a variable number of elongated processes, of which the one that is of particular importance in MS, the Axon.

For it is along the Axon, or Nerve Fiber, that the Nervous Impulse, generated in the Cell Body, passes on its way to link with other Neurons.

The impulse, which involves both electrical and chemical changes, travels at different speeds according to the diameter of the Axon, conduction being fastest in the largest fibers.

To give an idea of the scale, the diameter of the largest fibers is of the order of one-fiftieth of a millimetre.

These large Axons, and also many of those of smaller diameter, are surrounded by a sheath of a complex chemical containing protein and lipid or fat, and is known as Myelin.

This is laid down in a spiral manner around the length of the Axon, but is not continuous, being interrupted every millimetre or so by a short bare segment of Axon known as the Node Of Ranvier.

The Myelin, although a chemical, is laid down and supported within a living cell.

These are much easier to study in the Peripheral Nervous System and most of the experimental work has been done there. However, it is known that in the CNS it is a particular form of cell that is responsible for the Myelin.

The Neuroglia or Glial Cells are the other major component of the CNS and are concerned with many supporting activities such as the nutrition of the Neurons, and with the healing process.

It is the group recognized under the rather formidable title of the Oligodendrocytes (cells with few branches) that is responsible for the Myelin sheath.

Each short segment between two nodes being formed and maintained by one Oligodendtocyte. The functions of the Myelin sheaths are not fully known.

The comparison with an insulated electric wire, with the conducting Axon in the center surrounded by insulating Myelin is certainly too simple, but it is known that Myelin has an important role in accelerating conduction along the Axon.

p.4
MS is often referred to as primarily a DeMyelinating Disease, by which is meant that the initial damage produced by the disease is to the Myelin sheaths, leaving the Axons intact.

It is in fact difficult to be certain of the exact sequence of events in the formation of a MS plaque, because the early stages are not often examined under the microscope.

From studies of what seem to be early lesions and comparison with results in experimental animals that are probably relevant, some conclusions can be reached.

As will be shown some of these facts are important when considering the cause of the disease and the means by which it produces symptoms.

Opinion is still divided on whether the Oligodendrocytes - responsible for the formation and maintenance of Myelin - disappear from the early plaque, as these cells can be difficult to identify.

It is not known whether the Myelin breaks down because the Oligodendrocytes are destroyed or whether the Myelin, from whatever cause, is destroyed first.

  • Very early in the formation of a new plaque a cluster of White Blood Cells, Lymphocytes, appear around a small Vein in the substance of the Nervous System

  • Some maintain that this change is the earliest that can be detected, while others believe that Myelin is damaged first

  • The Lymphocytes spread along the course of the Vein and are surrounded by an area in which the Myelin sheaths have been destroyed

  • The plaque appears to spread by extention from the edges

  • The plaque and surrounding tissue becomes swollen with excess fluid

  • The Axons remain intact and can be seen running apparently undisturbed through the devastated area. As time passes the broken-down Myelin is removed by scavenger cells

  • There is an increase in another form of Neuroglia, the Astrocytes, so called from their star-shaped appearance in stained sections under the microscope, and it is these cells that form the scarring or sclerosis

  • Lymphocytes disappear from the center of the plaque but may persist at the edge where the disease process may still be active

  • In the chronic plaque it is still possible to see Axons intact in the now scarred and otherwise burnt out area; but, at this stage some of the Axons finally degenerate and disappear


p.5

The factor most likely to be responsible for the symptoms of MS does therefore seem to be the loss of Myelin. There is experimental evidence to show that severe and extensive DeMyelination completely blocks Conduction through the bared Axon.

If the loss of Myelin is less severe, Conduction is slowed and in particular, the transmission of a rapid series of Impulses, of great importance to the normal functioning of the Nervous System, becomes severely defective.

That the Axons remain intact is potentially of great significance. If, within the CNS, Axons are cut or degenerate from disease, they may grow again from the end nearest the cell body; but, the original connections are never re-established.

This means that a disease that causes destruction of CNS Axons is certain to leave permanent damage and, almost certainly, permanent symptoms. Untill a late stage of MS, the Axons remain normal in appearance and do not degenerate.

This offers hope that symptoms due to Defective Conduction in the DeMyelinated but persisting Axons are at least potentally reversible in that they are not the result of irrevocable destruction.

As we shall see, spontaneous recovery from the early symptoms of MS is the rule but it is not obvious from examination of the plaque how this can come about.

In particular, it is not known whether any healing process includes ReMyelination. Such reformation of Myelin is common in diseases quite distinct from MS that can cause extensive DeMyelination in the Peripheral Nervous System.

Some Axons within the plaques can be seen to have an abnormally thin covering of Myelin, a few turns of the spiral instead of the normal thick sheath but it is not possible to distinguish between partly destoyed and perhaps partly reformed Myelin.

Another factor that is almost certainly important both in the production of symptoms and in the initial rapid recovery is the swelling in the plaque.

The excess fluid could exert pressure on the bared Axons and block conduction, which would be restored when the swelling subsided even in the absence of Myelin sheaths.

p.6
These then are the plaques. They are multiple in the sense that certainly by the time the Nervous System can be examined, there are virtually always many plaques in different stages of development scattered throughout the CNS.

It is not known whether the plaques are multiple from the onset of the disease and in many patients the initial symptoms suggest that there is a single lesion.

Even in advanced cases plaques do not seem to be scattered entirely at random.

They are never completely symmetrical, but do show a strong tendency to develop on both sides at certain apparently vulnerable sites, including the Optic Nerves and the Spinal Cord in the neck.

The plaques are not only scattered in their Anatomical Positions but are also scattered in Time, so that both the appearance of the CNS and the history of the illness indicate either successive outbreaks or, less commonly, continuous spread, often over 20 years or more.

p.7
This pattern of disease is not totally unfamiliar as there are obvious parallels with many diseases of the skin. Here too there is often no sign of general ill health and the colloquial word "spot" indicates that the disease is patchy, with most of the skin free from blemish.

Certain forms of Urticaria, or Nettle Rash, and some rashes due to sensitivity to drugs bear a close resemblance to some of the features of MS.

Particular areas of skin are involved, seemingly at random, while the rest is spared although the noxious agent must be present throughout the body. The rash goes and comes, often with long intervals of freedom, and returns, often without a recognizable reason.

Even in skin disease where the course can so easily be followed, the cause may be difficult to uncover but, once found, prevention is completely successful.

There are certainly many enigmas in the disease process of MS but these are not the main obstacle to fruitful research as, in many diseases effective treatment or prevention has been achieved without reaching the probably unattainable goal of total comprehension.


Early Symptoms

Ch3
p.16

MS can affect any part of the CNS the initial symptoms can be extremely varied. The distribution of plaques is not completely haphazard and there are certain sites that are particularly vulnerable. In consequence the majority of the initial symptoms fall into well-defined groups.

As will be recalled the Optic Nerves are part of the CNS and as such are susceptible to involvement in MS. In approximately 15% of patients, the initial symptom is what is known as RetroBulbar or Optic Neuritis.

These terms simply mean inflammation of the Optic Nerve and Retrobulbar indicates that this has affected the nerve some way behind the Bulb of the Eye - the Eyeball.

The original significance of these two labels was that in Optic Neuritis it is possible for the doctor, using an Ophthalmoscope, actually to see the inflammed Optic Nerve.

Whereas in RetroBulbar Neuritis the inflammation does not reach the Retina and the diagnosis can be made only from the symptoms.

In a typical attack the Vision is noticed to be blurred in one Eye, particularly on looking up or to one side and Vision continues to deteriorate for several days.

The effect on eyesight varies from slight dimming of the normal vividness of color appreciation to complete blindness in the affected eye, but the usual result is severe loss of Central Vision.

This is most disturbing as the act of looking at anything involves turning the Eyes so that light from the object looked at falls on the area of the Retina in which the light receptor cells are most densely packed.

It is the Axons carrying Impulses from this that most often lose their Myelin sheaths, in an attack of Retrobulbar Neuritis.

These fibers do, in fact, make up a large part of the Optic Nerve. They lie centrally and are therefore involved in any sizeable plaque within the Nerve. Fortunately both Eyes are rarely affected simultaneously.

p.17
Vision usually continues to decline for about a week, seldom for longer. At about this stage the pain subsides and a week or two later, Vision begins to improve.

The expected result is complete recovery over the succeeding weeks with normal Visual Acuity as is measured on the familiar wall charts.

Sometimes, even when the lowest line can be read with ease, there may be a persistent awareness that Vision is not perfect; Colors may remain a little dull or contrasts of light and shade may be less sharp.

Occasionally Central Vision remains more severely affected but even here there will have been great improvement over the initial loss of Acuity.

This recovery is a characteristic example of that remarkable phenomenon in MS, the remission; a term that means substantial or complete recovery from the effects of an attack or relapse.

It would be difficult to exaggerate the importance to the eventual understanding of MS of the potentiality for complete reversal of often severe disabilty. The implications will be discussed in a later chapter.

p.18
The commonest site from which symptoms are produced during an initial attack is the Spinal Cord. Within it run tracts or bundles of Myelinated Axons conveying Nerve Impulses to and from the Brain and any of these may be involved in a plaque.

Most frequently it is the tracts conveying Impulses concerned with the Brain's Initiation and Control Of Movement that are first affected.

This bundle of Axons is called the Pyramidal Tract. It travels from the Cerebral Cortex Hemispheres to the lower end of the Spinal Cord.

Many of the Axons form connections with other Neurons within the Spinal Cord, whose Axons in turn enter the Peripheral Nervous System and eventually supply the muscles. The effect of DeMyelination involving the Pyramidal Tract is Weakness, nearly always of one or both Legs.

#1 - The Onset may be relatively rapid, particularly when influenced by Fatigue. For example, the first few miles of a country walk may be accomplished normally, but weakness may make the return journey impossible.

More usually, Weakness increases over a few days or a week or two, remains unchanged for a further few weeks and then recovers.

The degree of weakness in a first attack is seldom severe and often amounts to the dragging of a leg, inability to run and some difficulity on stairs.

The Sensory Tracts within the Spinal Cord carry Nerve Impulses derived directly or indirectly from a variety of Sensory Receptor Organs.

Sensations of Touch, Pain, and Difference in Temperature derived from the Skin, and of Pain from both the Skin and Internal Organs are familiar enough.

But there are other highly important Sensory Impulses that do not give rise to anything that we are normally aware of as sensation at all.

We are aware of the Positions of our Limbs, Trunk, and Head in Space in a most precise manner without having to think about the matter.

Information of which we are completely Unconscious is fed into the CNS from minute structures in the Muscles, Ligaments, and the Joints sensitive to Stretch.

This Sensory Input is essential for the efficient control of movement and for many of the Automatic or Reflex reactions of the body to Change Of Posture.

The symptoms arising from DeMyelination in the Sensory Tracts ascending to the Brain vary according to which of the different forms of Sensation are affected.

A common mode of Onset of MS is with a sensation of Numbness in the Feet, ascending in the course of a few days to the Waist.

Numbness implies loss of feeling, although it is often difficult to distinguish from loss of use, but it is seldom severe. A pinprick may still be felt as sharp but somehow distant.

The loss of feeling may involve the bladder and bowels so that, although there is no loss of control, the normal sensation of passing water or the desire to do so is absent.

Vaginal sensation may also be absent or unpleasantly distored. There is no difficulty in walking as neither Strength nor the Sensory inflow from the muscles and joints is affected. Remission normally occurs after several weeks.

#2 - Rather more disabling is an attack in which the Sense Of Position, the Knowledge of where the Limb is in space, is lost. When this occurs it usually affects the upper limbs, resulting in a useless arm.

The arm is not weak in the least, but Loss Of Sense Of Position and of all the essential information from the Muscles and Joints makes any coordinated movement impossible.

The Spinal Cord is also involved in the Reflexes that control the function of the Bladder, Bowel and of Sexual Function in men.

These are often disturbed late in the course of the disease, but also occasionally at the Onset, even without any other obvious symptoms.

This may present with the sudden complete inability to pass Urine - acute Retention of Urine - for some reason virtually always in young women.

There are other causes for this uncomfortable event and MS is certainly not the most common. Impotence is a common symptom in the late stage of MS and may rarely be present in the initial attack.

p.20
#3 - The other two common modes of onset are due to plaques in what is known as the BrainStem.

This is a part of the Brain immediately above the Spinal Cord through which pass all the Motor and Sensory Tracts already mentioned, but which is also crowded with Nuclei, or groups of Neurons, controlling, among other important functions: the Movement of the Eyes and the Reception of Sensory Information from the Ears.

Weakness of one of the six muscles that control the movement of the Eyeball causes Double Vision and the two Eyes are no longer always correctly coordinated.

Double vision as a first symptom of MS is transitory, but always persists for at least several days, and therefore does not resemble the Momentary Double Vision of fatigue acting on imperfectly balanced eye muscles that many otherwise normal people experience.

For unknown reasons MS plaques only rarely cause Deafness, although the BrainStem contains Nuclei concerned with Hearing.

The delicate mechanisms of the Ear, are not solely concerned with Hearing but also with Balance, and here again the BrainStem is an important relay station for Nerve Impulses serving this function.

p.21
#4 - Plaques often form in the Cerebellum or in the Tracts of Nerve Fibers leading to or from it and to other centers in the Nervous System, but more commonly later in the disease than at the onset.

The Cerebellum is a complex organ of the Brain situated at the back of the head, to which information from all the Sensory Systems is carried, analyzed, and used to regulate movement.

The effect of interruption of its functions is not to produce loss of any form of sensation, but Loss of Control Of Movement. Strength is retained but smooth action of the Limbs becomes impossible and movements are said to be incoordinated in Walking or Clumsiness in the use of one or both Hands, Without Weakness or Loss Of Sensation on testing.

p.22
These then are the common modes of Onset of the more usual forms of MS, that with remissions and relapses. I have described the onset as affecting a single part of the CNS; Optic Nerve, Clonus or BrainStem, and this is often so.

The disease is however, Multiple Sclerosis, and even at the Onset there may be symptoms and signs of damage to several areas that could not possibly be due to any form of disease confined to a single circumscribed site.

Thus a combination of Double Vision and Vertigo with Loss Of Feeling below the Waist would clearly indicate disease in both the BrainStem and the Spinal Cord, and thus provide evidence of multiple plaques.

#5 - In approximately 10% of patients the mode of Onset differs from that described above in that It Is Progressive from the beginning.

In many of these patients symptoms begin at a relatively late age, beyond the peak age of those in the early 30's. In this group the first symptom is nearly always gradually Progressive Weakness of one or Both Legs.

There is nothing resembling an acute attack and unfortunately no remission either. In technical terms these patients have Progressive Spastic Paraparesis.

Progressive is self evident. Spastic refers to the type of Weakness that results from interruption of the Pyramidal Tracts.

In addition to Weakness of the Legs there is Loss Of Control over certain Essential Automatic Reflex Actions that are normally carried out through the Nerve connections in the Spinal Cord.

These can be tested by the doctor's rubber hammer, which is used to tap the Tendons at the Knee or Ankle to stretch the Muscles and induce a Reflex Contraction

A knee jerk is, as everyone knows, a normal finding, but when the Pyramidal Tracts are not functioning normally, the Knee Jerk is much increased.

In itself this is of little consequence, but is an indication of abnormally increased Reflex activity, so that stretching the muscles in ordinary movement also causes Exaggerated Reflex Contraction.

Sometimes a Repetitive Reflex may set up, particularly in the Calf Muscles. This may first show itself when the Foot is firmly pressed on the brake pedal of a car.

The Calf Muscles are stretched and contracted reflexly, causing a jerk, and this is repeated for as long as pressure is maintained.

The technical term for this is Clonus. The result of these increased reflexes is a stiff leg and the patient scrapes the toe on walking and drags the limb.

p.23
The abnormality also shows itself in an abnormal reaction to firm stroking of the Sole of the Foot when the Toes normally curl under, but in a Spastic Leg they stretch out in the opposite direction. Many people find this test unpleasant but it is of considerable value in diagnosis.

It is virtually impossible to elicit this Reflex on oneself and self-examination is to be depreciated.

The word Paraparesis means Weakness of Both Legs and is a milder form of the more familiar Paraplegia used when there is Complete Paralysis such as may follow injury to the Spinal Cord.

The symptoms and signs as described above are present alone or in combination at the Onset of MS in perhaps 85% of cases, the remainder having other symptoms more commonly encountered later in the course of the disease.

______________
Cont'd_In_19-02



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