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01-00
1984

Mastering Multiple Sclerosis
A Handbook For MSers & Families

by:
John K. Wolf, M.D.




Anatomy Of Neurons

ch 1
p4

We shall begin our journey with the Nerve Cell and build from there. Nerve Cells, or Neurons, are the basic unit of Nervous System Communication. Each part has special functions that Promote the Passage of Coherent Information within the Nervous System.


Dendrites are the ''Thinking'' part of the Neuron. These tiny filaments gather information from other Neurons whose Axons end on the Dendritic Tree, across the Cell Body, and eventually into the Axon.

A decrease in the Membrane Charge tends to Stimulate the Neuron to Fire, while an Increase Inhibits It.

The decision to fire or not rests with the total information that arrives on the whole Dendritic Tree and even on the Cell Body at any moment.

If the charge at the beginning of the Axon is decreased enough as a result of all that information, it fires a single shot, or a whole volley.

Neurons have as many as 80,000 receptive sites on their Dendrites. Each site recieves either Stimulating or Inhibiting information from one Nerve Cell somewhere else in the CNS.

Dendrites may be widely branched within a small region. They are usually thinner than other parts of the Neuron.

This combination of characteristics causes Impulse conduction along Dendrites to be Slow, and often results in a Prolonged Alteration Of Charge after a single incoming volley.

This long period is one of the elemental methods used by the Nervous System to handle the passage of time, and represents the simplest form of Memory for recent events.

Impulses reaching the Dendrite are ''remembered'' as an Alterated Membrane Charge for a few milliseconds, a few minutes, or even for a few hours, and affect the Firing Pattern of the Neuron while they last.


Cell Body

p6

Cell Bodies contain the mechanisms that govern most of the chemical reactions within the Cell. They Produce Energy to run cellular activities.

They manufacture needed chemicals, Cell Membranes, and other Organelles within the Neuron to keep the Cell healthy during an entire lifetime.

Because Nerve Cells do not divide and replace themselves as Cells in other tissue do, the process of Cell repair is critically important in the Nervous System.

All the chemical activity of Cells is ultimately controlled from the Nucleus, which is situated in the Cell Body.

The Nucleus contains the Genes, and these in turn control function by specifying the structure of Cellular Proteins that control Cell Chemistry.


Axon

p7

Axons are concerned only with Transmission. They are unthinking wires that slavishly obey orders. Axons branch too, but usually not as extensively as Dendrites. Each Axon Terminal connects to the Dendrites of the next Cell.

Some Axons are covered with Myelin a fatty insulation. Because of its insulating effect, Myelin Promotes Rapid Transmission of Nerve Impulses.

Most of the rapidly conducting Axons also have a large diameter that decreases resistance to the flow of electric charge along the Axon and further aids rapid transmission.

Smaller UnMyelinated Axons, and Axons with Intermediate amounts of Myelin, also occur in the CNS, each with its own normal conduction velocity.

Some are short. Others travel long distances before they connect with another Cell's Dendrites, or leave the CNS to Innervate a Muscle or a Gland.

Variability of Neuron Size, and of the Lengths of Axons provides for great variability of response.

Long, rapidly conducting fibers, allow instant and specific reaction to sudden events in the environment because of their Rapid Conduction.

Chains of smaller, more slowly conducting Neurons provide for general Posture and Body Attitude and for the languid Secetory activities of Glands (Hormones).

Consider a person whose hand was just pricked with a pin, we imagine her seated. She jerks her hand back suddenly.

Perhaps she puts her finger in her mouth for comfort and maybe does other things as well, such as crying ''Ouch! Stop that!'' or jumping up, slapping the person who pricked her, and stomping out of the room.

p9

When she jerked her hand right back, how could she move so fast and respond so quickly? Why did her hand stop only inches from the pin rather than continuing its flight backwards behind her?

Why didn't she fall off the chair? Did her feet and her other arm move?

How long did it take for her to return to normal activities, for her heartbeat to slow to normal, and her frown to disappear?

Why would a pinprick cause her to strike out in anger on one occasion and merely to respond ''sharp'' on another?

How much of her total response was Automatic and Unconscious?

The most obvious part of her response - the jerk and the slap - was actually only a tiny part of her Nervous System's Response to the pinprick.

Her entire body was actively involved, even though it was immobile.

The jerk itself was limited to the one hand, while her entire Nervous System became involved in her Anger, her Speech, and in keeping the rest of her Body in place.

Her legs moved little, but they made adjustments to prevent her from falling. Her trunk musclels surely adjusted to her new off-center of gravity.

Movements that might have pushed her finger deeper onto the pin were actively eliminated, but only for an instant.

Because they were needed almost at once to stop the hand in its flight backwards and propel it smoothly to her mouth and then move it in a slap.

How marvelously are we made!

We understand Neuronal Function only in bits and pieces. We know how Nerve Cells transmit information to other Nerve Cells.

BioChemistry is becoming an open book but we do not know how a person is built. Even so, we know enough to examine the Nervous System and determine where a Lesion is.

If It Damages Certain Well Defined Pathways That Control Specific Functions. That is an important start towards diagnosis.


Myelin

p10

Multiple Sclerosis damages the Myelin coatings of Axons, so before we move on, let's consider Myelin.

Any segment of an Axon that loses its Myelin coating (becomes DeMyelinated) conducts more slowly, because Myelin is one of the basic structures that promotes rapid conduction.

A message that must pass through a DeMyelinated Axon Segment arrives late at the other end. This results in an incoordinated response from the Affected Neuronal Chain.

A delay in conduction in large, densely packed bundles that transmit messages for Movement or Sensation produces Specific Symptoms of Paralysis or Numbness.

Lesions in many other bundles, whose location we cannot know, cause less specific symptoms, such as the Exhaustion that is almost universal among MSers, and so hard to explain.

The DeMyelinating Lesions of MS are called Plaques. They vary in size from a few millimeters to several centimeters. Their number increases gradually with the passage of years.

Their Location Determines the Character of Symptoms. The rapidity of Accumulation and the degree of Myelin destruction Determines the progress of Disability.

Only a few densely packed Axonal bundles make themselves available to direct examination.

These are especially important in the production of Specific Symptoms and in diagnosis, so we shall examine them now.


Sensory Tracts

Pain Sensation from the Body:
The Lateral Spinothalamic Tract

The perception of a pinprick is made by first traveling up the arm carried by the Nerve as it enters the Spinal Cord.

Where a second Neuron inside the Spinal Cord picks up the discharge from the first, crosses to the opposite side of the Spinal Cord, and turns upwards to the Brain.

This Ascending Nerve Fiber Bundle is the Lateral SpinoThalamic Tract. Any damage to this bundle causes Loss of Pain Sensation on the Opposite Side Of The Body Below The Lesion.

p11

The Lateral Spinothalamic Tract is actually only a very tiny part of the Pain Pathways from the Spinal Cord to the Brain.

This is the newest part of the Pain Pathways, which transmits accurate information rapidily to the Partietal Cortex of the Brain.

Here information is processed that allows the person to make a rapid and precise response to painful events.

This precise portion of the Pain Pathways dominates the clinical situation.

Damage to the ''Lateral Spinothalamic Tract'' on the left side of the Spinal Cord would cause Loss Of Pain Perception in the right hand and the entire right side of the body below the level of damage.

If there were only one lesion, pain perception on the left side of the body would be normal, even though the lesion is on the left.

Most MSers have experienced numbness ''from here on down'', during the course of their illness, and were then unable to feel a pinprick in the numb area.

The cause is damage to the region of the Lateral Spinothalamic Tract on the opposite side of the Spinal Cord, specifically at the Spinal Cord level where sensation returns to normal.

By knowing this limited piece of Anatomy, we can locate this one lesion precisely and use the information as a start to establish whether there is more than one lesion in the entire Central Nervous System - a point of great importance in the diagnosis of Multiple Sclerosis.

p12

The great majority of nerve fibers that accompany the Lateral Spinothalamic Tract are much older in evolutionary terms.

They connect with BrainStem structures and with older parts of the Brain and may account for the complex Emotional responses that accompany some painful experiences.

Because they travel as a more diffuse system, it is impossible to estimate the degree of damage to this older system in the Neurological Examination.


Sense Of Position & Movement

The Axon which carries Position and Movement Sensation from the finger joint, travels up the arm and enters the Spinal Cord accompanied by similar Axons from other joints and the skin.

Is the finger bent? How much? Is it moving? If so, in what direction, and how fast?

The thicker Axon carrying this precise information is also a newer system in evolutionary terms.

It transmits most of the precise information from limbs to Brain, and has what amounts to a private line to take the information up the fiber bundle at the Posterior part of the Spinal Cord without crossing to the other side and without connections to other Neurons.

As the column enters the Medulla, it finds a second Neuron that refines the message and sends it on to the Brain, with one intervening connection on the way.

When this highly specific message reaches the Cortex of the Parietal Lobe, it contacts columns of Cortical Neurons that have nothing to do but listen to the particular message of this Spinal Sensory Tract, refine it, and send it on to many other specific sites in adjacent pieces of Cortex.

The total Sensory message, arrives partly in the precise terms of evolutionally New Pathways and partly in the more diffuse terms of Older Pathways.

The mixture of Axons that carry a particular message varies according to ongoing activity of the Brain.

The frequency of firing in any one set of Axons helps to transmit Urgency Of Information.

In the Sensory System alone, over a million fibers go to the lower BrainStem for distribution to many parts of the Brain.

Considering the complexity available in the Sensory System, it is a small wonder that we can distinguish many degrees of sharpness, intensity, and location for sensaations all over the body.

No wonder our individual responses to a particular stimulus may be quite varied on one occasion from another!

p14

A MS Plaque in the Right Posterior Column that carries Position Information causes Loss Of Position Sensitivity in the right hand and body below that lesion.

Thus, with only a pin, and after wiggling a few joints or pieces of skin up and down, the examiner can locate not only the level of the lesion, but also can distinguish between plaques on either the left or the right side of the Anterior Spinal Cord that interrupt Pain, and Plaques on either side of the Posterior Spinal Cord that interrupt Position Sensation.

That's not bad, considering that the diameter of the Spinal Cord is much less than a dime for the greater part of its length.


Vision

p15

Like body sensation, Vision travels in tightly packed bundles that carry the most detailed information the Nervous System ever recieves from the outside world. Most MSers have experienced loss of Vision.

Those who have not usually have plaques in the Visual System any way, which may be detected by detailed examination. MS plaques often occur in the Optic Nerve, where they are easy to detect.

The great majority of nerve fibers in the Optic Nerve serve the few degrees of Central Vision where detailed discrimination occurs.

A plaque in the Optic Nerve causes loss of Visual Acuity or actual loss of Vision (a Scotoma) in that part of the Vision Field. The complaint is Blurred Vision, inability to read, or a Blind Spot in the Center of Vision in one Eye along with pain when moving the Eye.

A Central Scotoma occurs because of the predominance of central field fibers in the nerve, not because there is a special tendency for plaques to collect in one or another part of the nerve.

The diagnosis is Optic Neuritis, because MS plaques almost never destroy the entire Optic Nerve.

Visual Acuity eventually returns to normal or almost normal; remaining Optic Nerve fibers still come mostly from the Central Field and serve Visual Acuity as well as they can.

Damage to the Optic Nerves can be detected during a Neurological Examination.

The Optic Nerve ends where it can be seen inside the Eyeball with the Ophthalmoscope, and at that point it is called the Optic Nerve Head.

If the Nerve Head becomes pale through DeMyelination and loss of Blood Vessels on the surface, it is called Optic Atrophy, a very common finding during the examination of MSers.

Even without visible Optic Atrophy, electronic testing, can reveal evidence of DeMyelination by showing Slowed Conduction through the Visual Pathways.

We shall return to a discussion of Visual Evoked Potentials in the next chapter.


Hearing

p16

MSers almost never have trouble with hearing. Unlike vision, body sensation and some motor tracts, hearing travels through the BrainStem diffusely, rather than in a single, tightly packed bundle of fibers.

As they enter the BrainStem, the Axons that carry hearing from the inner ear separate immediately and travel up both sides of the BrainStem in several pathways on either side.

Eventually they reach the Temporal Lobe Cortex where hearing becomes conscious.

A single lesion in the Brain or BrainStem would have to be very large to cause deftness, and in that case, hearing loss would be the least of the person's trouble.


Motor Tracts

We have had a glimpse of the Sensory correlations that occur in the Parietal Lobe. Consider now the similar correlations that occur in the Occipital Lobe for Vision, and in the Temporal Lobe for Hearing.

    All Three Primary Sensory Areas of the Brain are further connected to the adjacent Association Cortex.
      • Body Sensation
      • Vision
      • Hearing
The Association Cortex is then interconnected among all three areas and to Frontal and other parts of the Brain.

Eventually they are connected to the Left Temporal Lobe, where associations are transferred into language by processes we only dimly understand.

All this mass of activity on both sides of the Brain occurs constantly, rapidly, and accurately before any motor response is constructed.

In addition to direct Sensory-Motor connections, the influence of language is paramount in determining the motor response.

Portions of the Brain that control Emotions also add or subtract their component, determining whether the woman in our example simply accepts the pinprick and reports it to the doctor or retaliates and leaves!

p17

Part of her unique response is determined by her previous experiences in life, part is determined by the individual situation she is in, and part by the unique ''wiring'' she has had since birth that made her slightly different from all other babies, even in the nursery.

Let us now look at some of the concentrated Motor Tracts that allow her to express herself once she has taken it all in through her Sensory Systems.


Pyramidal Tract

We imagine motor responses beginning in the Frontal Lobes because we cannot conceive of the total complexity of Brain function that finally allows the person to act.

We also know about the important motor bundle arising from Frontal regions called the CorticoSpinal Tract.

This bundle travels from Cortical Neurons directly to those Neurons in the Spinal Cord that determine details of motor function.

Actually once the CorticoSpinal Tract has reached Spinal Cord levels, it has been joined by Axons from many other parts of the Brain, which orchestrate the entire response.

The orchestra specifies background posture for all levels of the Spinal Cord, changing muscle tone to adjust to changing centers of gravity, such as holding an arm and both legs still while the other arm is active, and moving head and eyes so the Brain can observe the results of its work.

While the rest of the orchestra provides the general Brain response, the CorticoSpinal Tract acts as the Piccolo, providing the melody of the personal response: The jerk! The slap! The stomp!

Because the piccolo catches our interest, we think it is the response, but actually, without a background, the melody would fall flat.

P18

Once the CorticoSpinal Tract and the rest of the motor orchestra have reached the Spinal Cord, a large number of these Axons are gathered together in a bundle called the Pyramidal Tract.

Which leaves the Lateral part of the Spinal Cord and goes to the Motor Neuron in the Anterior part of the Spinal Cord called the Anterior Horn or Anterior Horn Cell.

This Neuron sends its Axon to a single small bundle of muscle fibers within the larger muscle in the hand. If this cell fires with many of its neighbors, together they produce a muscular contraction which moves the finger.

Like lesions in the Sensory Tracts, Pyramidal Tract lesions may be localized by the level of the disability. Weak in the leg, but normal in the arm and hand means a plaque Below the level of the neck.

Signs of Pyramidal Tract Disease include increased tendon reflexes such as the knee jerk, loss of muscle power, and the Babinski Sign that is so uncomfortable, when you put your shoe on and the toe goes up, or when the Neurologist scratches the sole of the foot and the toe goes up.

If Babinski's Sign is present there is a lesion between the Motor Cortex on the opposite side of the Brain and the lower Spinal Cord.

Symptoms of Pyramidal Tract Disease include Weakness, Slowed Movement, Ankle Clonus on the floor or foot rest.

Sometimes very painful flexor spasms, muscle pain, stiffness and exhaustion. These signs and symptoms represent Spasticity.


The Medial Longitudanal Fasciculus & Double Vision

Many MSers have Double Vision. This usually results from plaques in a tightly bound tract in the BrainStem called the Medial Longitudinal Fasciculus (MLF). It coordinates movements of the two Eyes when they look to the left and right.

Specifically, the left MLF turns the left Eye to the right during right lateral gaze, and the right MLF turns the right Eye to the left during left lateral gaze.

A plaque in the MLF interrupts that coordination so that the Eyes do not turn in precisely the same direction, and the MSer receives two visual images instead of one.

p19

The MLF is located in a region that accumulates MS plaques more often than other parts of the Brain. This location accounts for the frequent occurrence of double Vision among MSers.

When those plaques heal after an attack, Double Vision disappears. Even so, a Neurologist may discover small abnormalities of eye movement during the examination, which clearly tell of damage to the MLF and thereby aid in the process of diagnosis.


The Cerebellum

Unlike the Pyramidal Tract and the MLF or the major Sensory Systems, the Cerebellum has no major connections that directly affect individual movements.

Consequently, Cerebellar Disease is only discernible as Complex Motor Dysfunction.

Cerebellar damage causes: Imbalance, Alteration in the Speed and Cadence of Speech, Uncoordination of Willed Movements that resembles Tremor, and some Abnormalities of Eye Movements.

Each of these symptoms is disabling to a degree, but the origin is impossible to locate with the same degree of precision we can use in localizing Sensory or direct Motor Dysfunction.

During the examination, such abnormalities look Cerebellar to experienced examiners and we are often right when we state that the Cerebellum is involved.

Cerebellar activity never enters consciousness, so the MSer cannot clearly state why a hand misses or a leg walks wrong and cannot practice bypassing the defect or improving it as he can for other symptoms like weakness.

Unlike other parts of the Nervous System, the Cerebellum has no ability to learn.

It is a creature of the present only and continues to malfunction in the same old way, while other parts of the Brain accumulate experiences in physical therapy and in a lifetime of activity.


Other Sensory & Motor Systems

p20

In this discussion of major long fiber tracts of the Central Nervous System, we have ignored the local Sensory and Motor systems that inhabit each Segment of the Spinal Cord and BrainStem.

Think of the millions of nerve fibers that enter and leave the Spinal Cord in those segments, bringing Sensory information from every part of the body and returning Motor Commands.

Each Segment recieves information from a very limited area of skin (which may be examined) and many other parts of the body (which usually can NOT be detected by examination).

Each Segment sends information to specific Muscles and Glands.

Careful examination of muscle power, and examination of the details of Sensory loss can provide even more detailed information about the placement of Plaques that affect function in only one Segment.

The more you know and the more your doctor knows about the details of Segmental Anatomy, the better you both can understand the effects of the illness.

END



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