Index

MUSCLE FATIGUE
MENTAL FATIGUE
CHEMICAL FATIGUE
METABOLIC
PATHWAYS – CARBOHYDRATE METABOLISM
REVERSIBLE and
IRREVERSIBLE REACTIONS
PROTEIN and LIPID METABOLISM

COMPARISON BETWEEN MULTIPLE SCLEROSIS and MYASTHENIA GRAVIS

IMPORTANCE of THIAMIN HYDROCHLORIDE in NEUROLOGICAL DISEASES

EARLY USE of THIAMIN HYDROCHLORIDE in NEUROLOGICAL DISEASES
RECOMMENDED TREATMENT SCHEDULE
ETIOLOGY of
MULTIPLE SCLEROSIS – HISTORICAL
OTHER
HYPOTHESES on ETIOLOGY of MULTIPLE SCLEROSIS
CONCEPTS CONCERNING
MYASTHENIA GRAVIS
CASE HISTORIES
CONCLUSION
APPENDIX
BIBLIOGRAPHY – PAPERS
BIBLIOGRAPHY – TEXT BOOKS
BIOGRAPHY
of FREDERICH R. KLENNER B.S., M.S., M.D.

Two devastating pathological syndromes affecting nerves are Multiple
Sclerosis and Myasthenia Gravis. To adequately understand the
significance of these diseases, one must have a working knowledge of
fatigue, normal and abnormal. The phenomena of fatigue according to
Starling’s Principles of Human Physiology has been recognized for years
to depend on two factors: l)The consumption of the substances available
for the supply of potential energy to the contractile material; 2)The
accumulation of products of the contractile process. We must consider a
third: The inability to use available energy-producing substances
because of distribution roadblocks.

Two general locations for normal fatigue are: 1) At the synapsis, the
delicate junction between neuron and neuron recognized as highly
susceptible to fatigue; 2) The junction between motor nerves and the
fibers of skeletal muscle, made possible by motor end plates. Synaptic
fatigue and endplate fatigue occur in such minute structures that quick
recovery seems always possible. We must recognize, however, that
although the feeling of fatigue may apparently be quickly dissipated,
actual restoration of the fatigued structure will require much time.

When a plant is fatigued it wilts; unless relieved of the fatigue, it
dies. Proper atmospheric conditions, proper soil, or these equivalents
conferred by man will restore, to some degree, the faltering plant. Even
prayer has been advanced as an active agent to not only relieve the
failing plant of its fatigue, but also to encourage its growth. Plants
do indeed have a soul – the soul of growth. This predicates a potential
capable of responding to kindness of various types. In this light, then,
people with “green thumbs” are nothing more than accepted plant
missionaries. When an animal is fatigued, it usually follows an innate
faculty supplied by Nature and rest. When sick, like the dog, it will
eat grass to relieve the gastric complaint. The dog’s master can go
further and supply various drugs or vaccines to either cure the malady
or to prevent several types of illness from ever coming into existence.
Animals have not only a soul for growth like the plant, but also a soul
of sensation. Proper rest, proper drugs and proper food, along with
understanding, will secure for the dog mental and physical relaxation,
thus assuring the animal a more serene and longer life as compared to a
dog running loose on the streets or in the wild, and required by
circumstances to scavenge for itself. Man has been endowed by his
Creator with a soul for growth, like the plant; a soul for recording
sensations, like the animal and what is truly a heavenly gift, a soul
for reasoning intellect. Shakespeare, through Hamlet, had this to say of
man: “What a piece of work is man! How noble in reason! How infinite in
faculty! In form, in moving, how expressed and admirable! In action, how
like an angel! In apprehension, how like a god! But Hamlet concluded
with this question:  “What is this quintessence of Dust?”

It is a common experience to obtain marked relief from physiological
fatigue by taking a short nap, often called “Edison cat nap”.  An
ordinary night’s rest is none too long for recovery from fatigue created
by a day’s labor. The almost universal habit of abstaining from ordinary
duties one day out of seven has real significance. It is the
acknowledged necessity of allowing at intervals longer period for
restoration than the usual nightly ones in order that accumulative
fatigue will not be experienced. Work is labor and so is play. There is
a real and significant difference between being pleasantly tired and
being fatigued. The sharecropper working in the field, where fresh air
abounds can easily expend far more energy than one who works in a poorly
ventilated factory, yet the farm worker will register relative fatigue
compared to the factory worker who often will be physiologically
exhausted. This suggests that oxygen plays an important role in the
production of fatigue.

MUSCLE FATIGUE

In the laboratory, one can demonstrate that repeated stimulation of
striated muscle diminished the force of the contraction and that
indefinite repetition of such stimulation will so exhaust the muscle
that eventually it will fail to response. The fatigue which is here
observed can be due either to the exhaustion of the glycogen and the
hexose phosphates or to the accumulation of lactic acid within the
muscle. Contraction is essentially anaerobic process.  Lactic acid
production, the fundamental chemical reaction producing energy for
muscle contraction, does not require oxygen. Such energy-yielding
reactions of partial decomposition, not requiring oxygen, are called
fermentations. Muscle then, obtains energy incidentally of its immediate
oxygen supply by the rapid fermentation of glycogen to lactic acid, in
the same way a brewer’s  yeast derives one energy by the fermentation of
sugars to alcohol. This anaerobic explosion of energy is akin to jet
propulsion, and similarly, its potential is limited. Ultimately, muscle
requires oxygen for the maintenance of normal irritability, for
oxidative energy production, and for the restoration of its anaerobic
energy-yielding system. Muscle action and muscle fatigue is indeed a
very complex chemical system. Such units as phosphocreatine, adenosine
triphosphate and calcium and magnesium ions deserve limited explanation.
Eagleston and others, independently, discovered that most of the
creatinine in muscle is in labile combination with phosphoric acid. The
free creatine which occurs in muscle fatigue in proportional to the
amount of phosphocreatine which is decomposed. Creatine is derived in
the body from the amino acids Arginine and Glycine, plus a labile methyl
group. According to Cameron and Gilmour creatine, in acid solution,
readily loses water to give a ring compound, an internal anhydride,
creatinine. Creatinine is a constant constituent of urine, and its
amount is sometimes increased in the later stages of nephritis and
always in Myasthenia Gravis. The simplest conception of
creatine-creatinine metabolism is that creatinine is formed from
creatine during periods of muscular activity when creatinine is
transiently free in muscle and then passes by way of the blood, without
change, into the urine. Creatine phosphate breaks down in the presence
of adenosine diphosphate (ADP) to form adenosine triphosphate (ATP).
Creatine phosphate acts as the immediate energy source for the synthesis
of adenosine triphosphate for relatively short periods during bursts of
contractile activity. The usable life of creatine phosphate is limited.
Once it is used up by muscle action, the muscle must then rely on the
adenosine triphosphate (ATP) which is synthesized during the chemical
activity of the Krebs cycle in glycolysis. Adenosine triphosphate is the
essential high-energy package, and it is responsible for delivery of
necessary power for the activation of all cells; it is the basic energy
unit for life. During muscle relaxation phase, some of the adenosine
triphosphate reacts with creatine to form creatine phosphate at the
expense of adenosine triphosphate which is reduced to adenosine
diphosphate (ADP): a low-energy package. This change of reactions
continues until such a situation exists when muscle cells can no longer
synthesize ATP due to lack of oxygen and essential substrates. When this
happens, a state of muscle rigor mortis exists. Frequently, Myasthenia
Gravis patients experience minimal rigor mortis; sometimes no adenosine
triphosphate is available and so actual death.

We must briefly discuss still other phases of muscle activity. The
filaments in skeletal muscle are composed primarily of the proteins
actin and myosin. Small amounts of other proteins play important roles
in the contractile cycle. Part of the energy for movement comes from the
splitting of adenosine triphosphate by the myosin molecule. Actin
increases the ability of myosin to split adenosine triphosphate.
Magnesium ions and calcium ions are also necessary in muscle action.
Besides actin, tropomyosin and troponin are responsible for the effects
of calcium on the contractile apparatus. One must also consider the part
played by acetylcholine and its esterase in muscle activity. Too much or
too little of these substances prevents or slows down muscle action even
when all other factors are within normal limits. The neuromuscular
junction potential can be modified by drugs and disease. One such drug
is curare. Curare merely occupies a reactive site so that acetylcholine
is prevented from interaction with motor end-plates. Myasthenia Gravis
is a disease whereby too much pyruvic acid (pyruvates), due to faulty
metabolism, affects the interaction of acetylcholine at the site of the
motor end-plates at the neuro-muscular junction. In Multiple Sclerosis,
the sluggish and sometimes bizarre muscle activity is due to absence or
inability to utilize essential factors because of mechanical and
chemical roadblocks.

Like nerve action potential, muscle action potential is an
all-or-none event, the overall effects of motor unit recruitment depends
upon the anatomical relationship between the contracting units.
Specifically whether the fibers are in series or parallel. When linked
in parallel by connective tissue, the force generated by each fiber is
additive, producing a total force proportional to the number of fibers
contracting. When the fibers are in series, the total force is equal to
that generated by a single fiber no matter how many fibers fire
simultaneously. These relationships exert quite a different effect on
the degree and velocity of shortening. No matter how many fibers in
parallel contract together, the amount of shortening and velocity are
the same as when a single fiber contracts but both the degree and the
velocity of shortening are proportional to the number of contracting
fibers in series. Long muscles shorten more and faster than short
muscles. Thick muscles exert more tension than thin muscles. These
differences, however, disappear when the values are expressed per unit
length and cross-section area. The total range of length changes a
muscle can undergo while attached to the bone is much less than the
changes that would cause the active tension to fall to zero. Muscle
exerts a force on the bones to which they are attached through tendons.
As muscle shortens, it exerts only a pulling force called flexion.
Opposing muscles straighten the unit flexed which is known as extension.
This review on muscle action and fatigue is, apologetically, very
elementary, but sufficient to establish a basic understanding of what is
happening in the pathological conditions entertained in this treatise.

These physiological processes battling fatigue, as enumerated, are
such that the sudden expenditure of a large part of the potential energy
of the muscle, by the conversion of glycogen to lactic acid, does not
mean a permanent loss of glycogen capital. This is so because one-fifth
of the lactic acid produced is subsequently completely combusted.
Paradoxically, this re-yields energy which is sufficient to convert
four-fifths of the lactic acid produced back to glycogen. The grade of
muscle effort, which an individual can endure before reaching his
fatigue point, is governed by his capacity for absorbing oxygen and
discharging carbon dioxide during respiration. Each of us is absorbing
some 200cc to 300cc of oxygen per minute. If we should suddenly start to
run for a bus, or climb several flights of stairs, the amount of oxygen
required might rise to 2,000cc to 3,000cc and even 4,000cc. One liter of
oxygen will remove seven grams of lactic acid. The individual who can
absorb four liters of oxygen per minute can endure the production of
twenty-eight grams of lactic acid per minute by his muscular effort.
This tells us that our ventilating system must be in grade A condition.
Anything such as smoking, or even chronic sinusitis will have a
detrimental effect on neurological diseases, and supportive treatment
along these lines must also be entertained if success is the desired end
point.

MENTAL FATIGUE

There are other types of fatigue besetting man. Mental fatigue can
best be considered in the light of active and passive. Passive mental
fatigue represents that type of medical syndrome which includes such
symptoms and signs as “brain lag”, sensations of pressure in the head,
poor memory, loss of power of concentration, irritability of temper,
increased reflexes, insomnia, anorexia and a general variety of aches
and pains – the classical syndrome of neurasthenia. Active mental
fatigue is elicited by continuous work and is proportional to the
duration and difficulty of the task performed. The effects are
manifested by lessening in feeling, in tone, in output and in organic
change. The organic change is small compared to that from equivalent
periods of heavy muscular work. Most of this change can be attributed to
the sensory-motor rather than to the neural element of the mental work.
Mental performance is never perfectly continuous, but is alternated with
pauses, which become longer and more frequent in proportion to the
length and difficulty of the task performed. The effects are
accumulative in that they are transferable from one task to another in
proportion to the tasks similarity. Total sleep during a day off is not
necessary, since the primary area of this phase of fatigue is the
synapses which beg only diversion of interest and activity – something
foreign to one’s usual occupation. In this manner, the fatigued synapses
can rest while others are busy.

CHEMICAL FATIGUE

Chemical fatigue represents one of the major groups of internal
medicine. Passive chemical fatigue represents that group which makes
itself known through body lassitude following the administration of a
chemical compound. This group of compounds is represented by the
soporific drugs, the analgesics, the many tranquilizers, and those which
lower blood pressure. One must guard against seemingly harmless
chemicals. Sodium bicarbonate, for example, is capable of rendering
hemoglobin less capable of normal oxygen surrender to tissues. Sodium
bicarbonate can take up as much as 70% of the available oxygen. The
immediate result of this anoxia is weakness, even collapse; the remote
effect is tissue breakdown. Sodium bicarbonate can mimic the action of
carbon monoxide. This gas, as you know, combines with reduced hemoglobin,
displacing oxygen from oxyhemoglobulin to form the specific compound
carboxyhemoglobin. Proper doses of ascorbic acid will prevent or relieve
this syndrome. It is good to remember that monoxide poisoning can exist
from many sources other than auto exhausts. Smoke poisoning from fires
is nothing other than monoxide poisoning, and carboxyhemoglobin blood
levels up to seven percent have been reported in cigarette smokers. This
can be serious, especially in a patient with a neurological pathology.
Patients with Myasthenia Gravis and Multiple Sclerosis will not make
progress if they use tobacco. There are other reasons against the use of
tobacco. The hypnotic effect of carbon monoxide may act in a synergistic
manner with other factors operative in ischemic heart disease,
outstripping the limited coronary reserve and augmenting the production
of stress-induced myocardial ischemia. (I need not remind you that
adequate ascorbic acid intake will also “handle” this situation.)

Active chemical fatigue represents that type of exhaustion which
results from the breakdown or inability to handle the normal
physiological processes in the body. A classical example of this is
Myasthenia Gravis. Before the advent of Prostigmin, Mestinon and
Mytelase, all those who have had this disease have died unless favored
with spontaneous remission and one special type of treatment which will
be outlined later. The physostigmine class of drugs inhibit the action
of cholinesterase. They also have a direct effect on muscle fibers, on
neurons and on ganglion cells of the central nervous system, much like
jumper cables on an automobile, or like a cardiac pacemaker. Their
action is limited. Although the etiology differs markedly, Multiple
Sclerosis is also the end result of an active chemical problem.

METABOLIC
PATHWAYS – CARBOHYDRATE METABOLISM

From any textbook of physiology, one might read concerning the
metabolic pathways. The sequence of enzyme-mediated reactions leading to
formation of a particular product is known as a metabolic pathway. When
dealing with glucose it is termed glycolysis. The primary function of
carbohydrates in the body is to provide a source of chemical energy. The
metabolic pathway for glucose degradation to carbon dioxide and water is
divided into two parts: l) Involves the breakdown of glucose to pyruvic
acid or lactic acid; 2) Conversion of pyruvic acid to carbon dioxide and
water in the presence of oxygen. Whether the end product of glycolysis
is pyruvic acid or lactic acid depends upon the supply of oxygen in the
cell. When the oxygen supply is adequate, pyruvic acid is formed;
conversely an inadequate oxygen supply will lead to lactic acid
formation. These are generally referred to as aerobic and anaerobic
glycolysis. Adequate oxygen can be made available not only through a
high rate of gas exchange in the lungs, assuming that the pulmonary
function tests are within normal limits, but also by taking 10 to 30
grams ascorbic acid by mouth every 24 hours. Oxygen from vitamin C
becomes available through the loss and eventual breakup of water in the
reaction of ascorbic acid to dehydroascorbic acid. We reported this
chemistry in several papers dealing with the use of massive doses of
vitamin C in Monoxide poisoning. Enzymes are also necessary in making
the glucose reactions possible. Many pathological conditions in man can
be traced to faulty enzyme production. This is usually due to genetic
fault.

Food, regardless the kind, must be reduced to glucose if it is to be
used to produce energy. We have already implied that only glucose can
undergo glycolysis, which produces as one type end point, pyruvic acid.
Pyruvic acid is a critical agent in Multiple Sclerosis, because it is
the starting component of the Krebs Cycle. Each step in glycolysis, that
is, the change in chemical structure occurring along the pathway to
pyruvic acid from one molecule to the next is relatively small, but the
total sequence of reactions alters the structure of glucose
dramatically. Biochemists record that in the first glucose reaction, one
of nineteen, the phosphate from adenosine-5-triphosphate (ATP) is
transferred to glucose to form glucose-6-phosphate. In the third
reaction a second molecule of adenosine5-triphosphate (ATP) is used in
the transfer of phosphate to fructose-phosphate. Two molecules of ATP,
the key power source for life, being utilized in getting to fructose 1,
6-diphosphate, but eventually four molecules of ATP are formed resulting
in a net gain for the cell of two Adenosine-5-triphosphate molecules.
During glycolysis reaction number six, additional ATP molecules are
synthesized from or by way of the coenzyme nicotinamide adenine
dinucleotide plus 2 hydrogen atoms (NADH2) by the process of oxidative
phosphorylation. This, however, cannot occur without oxygen since in the
reaction NADH2 is reduced to NAD by transfer of the hydrogen atoms and
electrons to the cytochrome system. Fortunately,
adenosine-5-triphosphate (ATP) can be synthesized by direct substrate
phosphorylation occurring during anaerobic glycolysis.
Adenosine-5-triphosphate (ATP) provides the ionized phosphate groups
that trap the intermediates within the cell and forms the intermediate
structures required for the later stages of glycolysis. It is important
to recognize that all the intermediates between glucose and pyruvic acid
contain an ionized phosphate group and that ionized molecules are
generally unable to cross the lipid barrier of a cell membrane. Once
glucose has been phosphorylated, the intermediates of glycolysis are
trapped within a given cell. Glucose enters the cell through a
carrier-mediated facilitated-diffusion system. The amount of energy
transferred to ATP is roughly five percent of the total potential of
glucose. Thus, 95 percent of the ATP synthesized from the energy
released from glucose depends upon oxygen and the oxidative
phosphorylation occurring in the mitochondria. This gives us notice
concerning the importance of good ventilation practices to maintain a
high degree of vital capacity. It also argues for high daily intake of
vitamin C.

REVERSIBLE and IRREVERSIBLE REACTIONS

Most of the reactions of the tricarboxylic acid cycle (Krebs Cycle)
are reversible, but the reaction in which pyruvic acid is converted to
acetyl co-enzyme A and carbon dioxide is irreversible.  It is true that
all chemical reactions are theoretically reversible, but some are
limited to the plant kingdom. For example: Carbon dioxide and water can
react to form glucose and oxygen, reversing the reaction which led to
the breakdown of glucose, but to make it work in this reverse direction,
the same amount of energy (685kcal) released during glucose glycolysis
must be returned to the molecules of carbon dioxide and water. This
actually happens, as you know, in plant cells through a process called
photosynthesis, where the energy is obtained from sunlight.  Pyruvic
acid, which comes from phosphoenolpyruvate, the last step in glycolysis,
and which cannot be reversed once acted upon by coenzyme A to form
acetyl coenzyme A, can be produced by direct decarboxylation of
oxalacetic acid. Pyruvic acid from this source can be phosphorylated in
the presence of ATP to form phosphopyruvate, and this can then serve as
a direct precursor of the hexoses and glycogen by the reversal of the
glycolytic system. Pyruvic acid (plus CO2), according to Ochoa, can be
“shuttled” into the Krebs cycle through malic acid when this compound is
reversibly oxidized and decarboxylated using triphosphopyridine
nucleotide (TPN) as hydrogen acceptor, and catalyzed by malic enzyme. We
mention these chemical routes for pyruvic acid since it plays a very
important part in Myasthenia Gravis. The reversibility of the
decarboxylation reactions in the Krebs cycle enhances the importance of
the mechanism of CO2 fixation by animal tissues. CO2 fixation implies
the utilization of carbon dioxide for metabolic purposes. As noted in
any text of physiological chemistry, the assimilation of CO2 by green
plants during photosynthesis leads to the formation of phosphoglyceric
and phosphopyruvic acids, and that malic acid is a subsequent product of
the reaction. One can speculate that the fundamental processes of CO2
assimilation known for plants can also be assigned for man.

There is evidence sufficient to believe that coenzyme A, which is the
physiologically active form of pantothenic acid in animals, is in
limited supply in Myasthenia Gravis. This special enzyme is chemically
situated at the gateway to the Tricarboxylic Acid Cycle where it
“intercepts” pyruvic acid at the end point of glycolysis The absence or
reduced supply of this coenzyme is actually due to the absence or
reduced supply of cocarboxylase. When it is present, it not only splits
the carboxyl group (COOH) away from pyruvic acid to form CO2 and “free”
H; with the “H” being positively ionized, but it also bonds or joins the
remaining two carbon fragments of pyruvic acid, known as active acetate,
to form acetyl coenzyme A. This leaves the low-energy package
niacin-adenosine-dinucleotide (NAD) free to pick up two molecules of
hydrogen. (At one time it was thought that the low-energy package was
diphosphopyridine nucleotide (DPN), but through the employment of
radioactive isotopes and the electron microscope, this was proved to be
in error.) One molecule from the carboxyl group of pyruvic acid, and the
second molecule from the sulfur group of coenzyme A, makes a high-energy
package with the “call letters” NADH2. One method in getting coenzyme A
from pyruvic acid, which has been established for heart tissue by Koroes
et al, is the reaction between pyruvic acid, coenzyme A, and
diphosphopyridine nucleotide (DPN or coenzyme I), in the presence of
diphosphothiamine which is cocarboxylase. There are other important
low-energy packages operative in this system and necessary for good
health. Flavinadenosine-dinuclectide (FAD) picks up two molecules of
hydrogen to form the high-energy package FADH2 and adenosine diphosphate
(ADP). Adenosine diphosphate picks up available P04 radicals to form
adenosine-5-triphosphate (ATP).

PROTEIN and
LIPID METABOLISM

In dealing with muscle and nerve pathology, the metabolism of lipids
and protein must also be considered, although in a lesser degree. There
is a close relationship between neutral fats and glucose metabolism. The
neutral fats, consisting of three fatty acids attached to the
three-carbon molecule glycerol, constitutes the majority of the lipid in
the body. The breakdown and synthesis of neutral fats is closely
associated with the metabolism of glucose because of the formation of
intermediates common to both pathways. The breakdown of fatty acids
requires coenzyme A and hydrogen carriers such as niacin-adenosine-dinucleotide
(NAD). ascorbic acid can operate as a hydrogen transport in cellular
oxidation, thus facilitating these reactions. The starting point for
fatty acid synthesis is acetyl coenzyme A. In the diseases in which we
are concerned, myelin is very important. Myelin is a fat-like substance
forming the principle component of the myelin sheath of nerve fibers. It
is composed of cholesterol, certain cerobrosides, phospholipids and
fatty acids.

Protein metabolism is far more complicated than lipid or carbohydrate
metabolism. Proteins are formed from twenty different amino acids, all
of which have different chemical structures and require different
pathways for their synthesis and degradation Synthesis of a protein
molecule from amino acids involves more than the formation of chemical
bonds between amino acids. The amino acids must be placed in a precise
sequential order. Unlike fats and sugars, amino acids contain nitrogen
in addition to carbon, hydrogen and oxygen. It is more than of academic
interest to know that thiamin hydrochloride is a pyrimidine compound:
thus containing nitrogen, like amino acids. Because of this amine
factor, Funk originally spelled vitamin with an “e” – vitamine. “Vit”
comes from the Greek “vita”, meaning life, and E amine for the nitrogen
factor. Since only thiamin hydrochloride of all vitamins had this
factor, the “e” was dropped, and the name vitamin retained for symbolic
reasons. Although all amino acids are important, some more than others,
and still others necessary for the continuance of life, the one we are
interested in is the amino acid glycine. Glycine is noted for its
specific dynamic action. Bodansky states that not only does the body use
any preformed glycine that may be present either in the diet or in the
tissues, but it is forced, at times, to synthesize this amino acid in
large amounts. The conversion of glycine into sugar in the animal body
has been well documented. Rapport and Kats have shown that when glycine
is added to perfused muscle, the oxygen absorption is 40 percent higher
than otherwise, indicating that the presence of the amino acid glycine
stimulates the combustion of other tissue constituents. Glycine with the
amidine group from Arginine through a process of transamidination and
transmethylation yields creatine.

COMPARISON BETWEEN MULTIPLE SCLEROSIS and MYASTHENIA GRAVIS

Myasthenia Gravis and Multiple Sclerosis differ only in that the
former will not require as intensive treatment as will Multiple
Sclerosis. The answer for this difference is obvious. One is a
peripheral nerve pathology, the other being central nerve pathology. In
the diagnosis, one will find the eyelids in Myasthenia Gravis drooping.
In Multiple Sclerosis there will be nystagmus – constant involuntary,
more or less cyclical movement of the eyeballs. Movement may be in any
direction, but usually lateral as the patient follows the examiner’s
finger. (It is definitely more pronounced than that found in Meniere’s
disease.) There may be heaviness of the legs in Myasthenia Gravis, but
it will always be present in at least one leg in Multiple Sclerosis.
Myasthenia Gravis patients will have difficulty in chewing and
swallowing, the jaws might sag, and some will present a sad, masked-like
expression, but never like Parkinson’s disease. Scanning speech will be
in evidence in advanced cases in Multiple Sclerosis, and words will come
slow and syllabic. General weakness increases as the day goes on in
Myasthenia Gravis; some increase in fatigue only with activity in
Multiple Sclerosis. Remissions and exacerbations are common in both
diseases in the early stages, but more so in Myasthenia Gravis. In
Multiple Sclerosis, the patient will experience numbness of the hands
and legs as the disease progresses, or a tremor in the hand will
develop, making signing of one’s name a problem. The tremor is
intentional. Well along in the disease of Multiple Sclerosis, the gait
will be awkward and stiff. Ataxia is due mainly to the inability to
coordinate and control movements. The knee-jerks will be exaggerated,
with positive Babinski and ankle clonus. The Babinski can be normal and
no clonus, but there are other signs equally as important. Oppenheim’s
tibia test; Gordon’s calf muscle test; Chaddock’s external malleolus
test, and the Hoffman reflex – a finger reflex. Anyone of these, along
with temporal whiteness of the optic nerve can be considered early or
minimal Multiple Sclerosis. Abdominal reflexes are variable. Pain,
bilateral, of the sartorius muscles with any positive reflex is always
very suspicious of Multiple Sclerosis. In Myasthenia Gravis, the old
neostigmine test is conclusive. More detailed symptoms and signs on
these two pathological conditions can be found in such common reference
as Merck’s Manual. The important factor is early diagnosis. Do not
hesitate to commence treatment in either disease even though the
impression might be guarded. Response to treatment is sufficient
evidence that your judgment is sound.

There are three forms of Multiple Sclerosis: 1) Pseudo-Multiple
Sclerosis or Cerebral, which is the syndrome characterized by mental
symptoms, emotional lability, convulsive seizures, hemiplegia and
aphasia. This type is caused by an Adenovirus which gains entry into the
brain through damage to the choroid plexus much like the encephalitis
that follows pneumonias. Actually, the resulting pathology is an
encephalitis.  Many who have experienced this syndrome have died; many
who have lived might just as well have died, for the return trip is
costly, long, and requires a great amount of tender, loving care. 2)
cerebellar-brain-stem-spinal: This is true Multiple Sclerosis and is
manifested by nystagmus, scanning speech, intention tremor, ataxia,
transient parenthesis, weakness in one or more extremity, and visual
disturbances. 3) Spinal or minimal Multiple Sclerosis: These cases are
never given a diagnosis. These patients come with other complaints, but
singular upper motor neuron pathology will be evident. This might be, as
we have seen them, positive Hoffman, positive Gordon, positive Oppenheim,
and occasionally, a patient with a footdrop limb.

IMPORTANCE of THIAMIN HYDROCHLORIDE in NEUROLOGICAL DISEASES

The importance of thiamine in treating Myasthenia Gravis and Multiple
Sclerosis cannot be over-emphasized. Two molecules of thiamin
hydrochloride in combination with two molecules of phosphoric acid is
cocarboxylase. For the reaction of acetyl coenzyme A plus oxaloacetic
acid to continue through to citric acid with the release of coenzyme A,
cocarboxylase must be present. If this reaction does not take place, due
to one of many factors, there will be no coenzyme A present to react
with another molecule of pyruvic acid to set in motion the elements
necessary for the continuance of the metabolic cycle. In thiamin
deficiency, both pyruvates and lactate accumulate in the blood.
Pyruvates also accumulate at the neuromuscular junction causing cloudy
swelling of the distal portion of the nerves. Cocarboxylase, also known
as diphosphothiamine, is necessary in the synthesis of acetylcholine and
in the control of its hydrolysis. The activity of choline esterase of
serum is also strongly inhibited by cocarboxylase.

The chief chemical factor in both diseases is thiamine hydrochloride.
Other fractions of the B complex are also essential but in lesser
amounts. Myasthenia Gravis is due to genetic fault, most likely
involving an intermediate lethal gene or group of genes. Multiple
Sclerosis is more complex. The initial pathology is sickness caused by
the Coxsackie virus. This virus mimics poliomyelitis, and for many years
accounted for thousands of so-called polio cases. This virus, like the
polio viruses, can cause paralysis but never permanently. The nerve
damage is the result of microscopic hemorrhages in the central nervous
system. With the contraction of the scar at the site of bleeding, the
vessels carrying nutrients to the nerve cells are virtually clamped off.
This leaves nerve tissue, in many instances, alive but not capable of
work. As time goes on, this wasting of nerve tissue results in loss of
its myelin protection. This is similar to electrical wires that have
lost their insulation when exposed to the wear of daily use, or exposure
to the elements. Myelin is a lamellated structure composed of neurilemma
cell membranes. Neurilemma cells have marked affinity for axis
cylinders, apply themselves closely and seemingly engulf them. At the
same time, their cytoplasm flows around the axis cylinder. The myelin
sheath is actually part of the neurilemma plasma membrane with its lipid
and protein layers. Myelin in the central nervous system is likewise
lamellated. It is laid down by neuroglia cells. The sheath of the nerve
fiber is known to have a relationship to speed of conduction – the speed
of propagation being in direct proportion to the fiber diameter.
Impulses are thought to travel along the surface of a nerve fiber and
its speed over the large myelinated fibers is approximately 337 miles
per hour, 150 meters per second. We can reconstruct the nerve pathways
and re-myelinate the damaged nerve channels. There is nothing new about
this physiology. Each one of us has demonstrated or experienced positive
Babinski reflexes. A child is born without completed laminated sheath.
This is the reason for the spastic movements of the child. The nerve
channels are minute in comparison tc the adult person, thus we can
expect a longer interval of tine necessary for repair. If the baby can
complete the myelination of its nerve channels with only mother’s milk,
surely we can duplicate this performance – – and we can. There will,
however, be situations where the pathology has existed for so long a
time that recovery seems impossible. This is true because it requires
approximately two years of treatment, with massive doses of vitamins and
a high protein diet, to repair one year of the disease. Physicians are
too afraid to make an early diagnosis, and some patients now under my
care experienced as much as ten years in that process. In Myasthenia
Gravis, the chief concern is with the build-up of pyruvic acid at the
neuromuscular junction. We also find decreased amounts of acetylcholine
along with limited amounts of cocarboxylase. As we noted in the
discussion of glycolysis, cocarboxylase plays a very important role in
various reactions involving principally the decarboxylation of pyruvic
acid and other keto acids. In the brain, cocarboxylase participates in
the anaerobic dismutation of pyruvate to lactate and acetate, and their
subsequent oxidation to carbon dioxide and water. Cocarboxylase is also
involved in the synthesis of acetylcholine which is definitely in short
supply in Myasthenia Gravis. The activity of choline esterase is
strongly inhibited by this same double thiamin unit. The conversion of
thiamin hydrochloride to cocarboxylase takes place in the liver, the
kidneys, and to a small degree, in brain and muscle. One can have
nephritis, yet the small amount manufactured in the kidneys continues to
be produced. The liver is the main source for this conversion. An
individual with liver pathology would have a decreased capacity for
phosphorylation of thiamin. The storage capacity of the body for thiamin
is limited. It does accumulate rapidly in the liver in its original form
and also as the pyrophosphoric ester. Thiamin deficiency inhibits lactic
acid metabolism at the stage of pyruvic acid. When we refer to thiamin
deficiency, we actually mean a lack of cocarboxylase. Pyruvic acidemia
is an index of this type of thiamin deficiency. We might mention here
that niacin deficiency can induce hepatic insufficiency. The amount of
nicotinic acid required to elevate blood coenzyme, the active
physiological form of nicotinic acid, increases dramatically in liver
stress. Cocarboxylase (thiamin pyrophosphate) operates as a coenzyme in
the oxidative decarboxylation of ketoglutarate to succinate and of
pyruvate to acetoacetate. Succinic acid in turn is acted upon by the
enzyme succinic dehydrogenase, yielding fumaric acid by oxidative
dehydrogenation. Fumaric acid readily undergoes hydration in the
presence of the enzyme fumarase to form malic acid, which on oxidation
in the presence of the enzyme malic dehydrogenase, yields oxalacetic
acid. At this point of cell metabolism, the entrance of another molecule
of pyruvic acid follows the Krebs cycle to be repeated. We are never
concerned with the amount of pyruvic acid formed by the various routes,
provided we can maintain normal cell metabolism.

EARLY USE of THIAMIN HYDROCHLORIDE in NEUROLOGICAL DISEASES

In the late thirties, Stern from Columbia University was employing
thiamin hydrochloride intraspinally with astonishing results in Multiple
Sclerosis. He reported taking patients to the operating room on a
stretcher, and following 30 mg. thiamin given intraspinally, they would
walk back to their room. The response was relatively transient, but it
led Stern to believe that Multiple Sclerosis was nothing more than
vitamin B1 avitaminosis, the “modus operandi” being damage to the filter
bed of the choroid plexus. Stern also found that the effective dose of
vitamin B1, when given into the lumbar subarachnoid space, was too close
to the lethal dose as was demonstrated in dogs. Stern’s hypothesis was
backed by the knowledge that degeneration of the myelin sheaths of
peripheral nerves as well as of the ganglion cells of the brain arid
spinal cord can be produced in experimental polyneuritis. Similar
findings are observed in starvation, even when the supply of thiamin
appears to be adequate. One school of thought regards the neurological
syndrome of polyneuritis as a functional defect concerned with the
neurons. From thirty years of observation, I am certain that in
Myasthenia Gravis and Multiple Sclerosis, it is not a functional defect,
nor is it due to impaired diffusion which would deny to the total
metabolism sufficient quantities of the vitamin to satisfy the
requirements of the neuromuscular systems The problem is supply and
demand. In this light, Dr. Leon Rosenberg of Yale University Medical
School, in working with B vitamins, distinguishes between
vitamin-deficiency diseases and vitamin-dependent diseases. He states
that the successful treatment of vitamin-dependent diseases requires
dosages up to 1000 times the calculated minimal daily requirement. 1.3
mg. has been established for thiamin hydrochloride which would indicate
that in the pathological conditions being considered, the daily
requirement would be at lease 1300 me. Moore in 1940 published a
monograph on the use of high intravenous doses of nicotinic acid for the
cure of Multiple Sclerosis. Moore employed a drug combination called “Nicobee”.
This preparation contained 100 mg. nicotinic acid and 60 mg. of thiamin
in each 10 cc solution.

Many of the components of the B complex must also be administered in
varying amounts, along with thiamin hydrochloride, since they too exert
a dynamic influence in general metabolism. Many believe that the B
vitamins are actually metabolic reagents. Hoagland has referred to them
as “protective catalysts”.

RECOMMENDED TREATMENT SCHEDULE

Our treatment schedule follows.

1) Thiamin hydrochloride: 300mg. to 500 mg., 30 minutes before meals
and bed hour, and during the night if awake. (The higher amounts in
long-standing cases.) This requirement is high, since much is lost
through action of gastric juices and loss due to perspiration. 400-mg.
daily by needle, given intramuscularly. During summer months this can be
given every 12 hours to good advantage. Two to three times each week,
and where office access is convenient, 20 mg. per kg. body weight, or at
least 1000-mg. is administered intravenously. This is given with 100 mg.
to 200 mg. Niacine (nicotinic acid) which is available 100 mg. in 10 cc
ampules (The concentrated Niacin available in 30 cc vials, must be
diluted if employed intravenously.) The intravenous dose is given with
the patient in a recumbent position. A 20 cc to 30 cc syringe, carrying
a one-inch 22-gauge needle should be employed. The injection is given
slowly (5 to 7 minutes) holding the syringe with one hand. The
usually-employed three fingers of the other hand must be on the
patient’s pulse. An increased pulse rate indicates too fast a flow of
the medicine. This indicates the rate of phosphorylization. Thiamin
hydrochloride is, indeed, a toxic substance, and anaphylactic reactions
have been reported, but I have never seen a case in treating thousands
of patients (not necessarily Myasthenia Gravis or Multiple Sclerosis),
in 30 years of clinical observation. I have observed one case of extreme
sensitivity in which itching was present within one minute after an
intramuscular injection of 100 ing. This was immediately controlled with
5 cc Benadryl (diphenhydramine) IM It must be remembered that once
thiamin hydrochloride is phosphorylated it is no longer a critical
allergic substance, but is cocarboxylase, a necessary but absolutely
harmless agent. (My problem has been the PRESERVATIVES now required by
FDA regulations, and they should be removed.) Higher doses of thiamin
can be used, but then the dilution factor must be greater.

2) Niacin nicotinic acid: We recommend 100mg. to 3 grams, thirty
minutes before meals and at bed hour, and also during the night if awake
whichever dose will produce a strong body flush. Niacin dilates the
blood vessels, even those that have been compressed by scar tissue,
allowing a greater amount of nutrient material to reach the cell
laboratory or factory comprising muscles and nerves. This constant,
repeated dilatation of the blood vessels acts in the same manner as the
dilating urethral catheter to correct constriction. One is chemical, the
other is mechanical. Hot fluids taken at the same time as the niacin
will enhance the flush. Pyridoxine. has been a suggested stimulant The
lack of constant flushing in Multiple Sclerosis is disappointing but not
hopeless. It will require a longer time to achieve results. Many times
patients will flush with intramuscular niacin when they fail to flush by
the oral route. An occasional patient will experience the sensation of a
chill following nicotinic acid flush. This is transient and of no
consequence. Food, even jelly beans or a glass of milk, will reverse or
minimize the experience. Some patients will flush sometimes and not at
other times, even during a single day.  If no flush develops within 45
minutes, the dose should be repeatedly delayed reaction of several hours
can occur, and should this be superimpose upon a previous medication,
the result could be severe. Do not scratch when itching from niacin.
Just press the area with your fingers, or better still, with a cube of
ice. Antihistamines will stop the itching and limit the flush, should
this he necessary. Niacin should be given very slowly by the intravenous
route in the geriatric patient, with or without cardiac pathology, since
it can produce dilatation great enough to effect right-side heart
failure. Myasthenia Cravis patients sometimes attain geriatric status.
Vasomotor collapse of peripheral vessels, although rare, can occur.
Eight mg Decadron given I.M. will reverse this condition.

3) Pyridoxine (Vitamin B6): Lack of this vitamin has been shown to
induce microcytic hypochromic anemia and neurologic lesions in dogs and
pigs. The term includes not only pyridoxine but also pyridoxal and
pyridoxamine, all three compounds being found in nature. These
derivatives have biological activity equal to that of pyridoxine, as
demonstrated in rats. Pyridoxine plays a part in the metabolism of
unsaturated fatty acids. It is also important in the metabolism of amino
acids. Pyridoxal phosphate functions as a coenzyme, and in
transamination reactions. 100mg. to 200 mg. is given before meals and
bed hour. At least 100 mg. daily is given intramuscularly.

4) Cobalamin (Vitamin B12 ): It is thought that vitamin B12 acts as a
catalyst in the formation of the purine and pyrimidine deoxyribosides
which are present in deoxyribonucleic acid. Technically, B12 is
cyanocobalamin. Vitamin B12 with pterylglutamie reduces the requirement
for choline essential in the treatment of neurological diseases.
l000mcg. is given three times each week by needle (repository type). The
incident of dermatitis from continued use of vitamin B12by needle is
roughly 15 percent. I have never seen this develop in a patient with
Myasthenia Gravis or Multiple Sclerosis. B12 is recognized as a factor
in the synthesis of Myelin

5) Ascorbic Acid (vitamin C): The use of high daily doses of vitamin
C will prevent a superimposed illness and will lend itself in
metabolism. Ten to twenty grams should be taken daily by mouth in
divided doses.

6) Riboflavin (Vitamin B2): A deficiency of vitamin B2 in young
animals results in inhibition of growth terminated by death. The yellow
enzyme can, as demonstrated by Warburg and Christian, participate in a
series of enzyme reactions involved in the metabolism of carbohydrates.
It is capable of transporting hydrogen from reduced coenzyme II, a
niacin coenzyme which attacks hexosemonophosphate, regenerating the
riboflavin phosphate-protein complex. Riboflavin also takes part in
enzymic reactions as a dinucleotide prosthetic group, consisting of
riboflavin, two phosphoric acids, ribose and adenine. Riboflavin is very
important in the regulatory function of the hormones involved in
carbohydrate metabolism It is classified as a low-energy package. 40mg.
to 80 mg. given daily by needle IM 25 mg. before meals and bed hour.

7) Vitamin E as d-alpha Tocopherol acetate or d-alpha Tocopherol acid
succinate. The latter is more practical since it is a pure form. Complex
biochemical changes in the. muscle tissue in chrome vitamin E deficiency
are followed by histological lesions characteristic of muscular
dystrophy. Deficiency has also been shown to produce dernyelinization
and distortion of the axon pattern in the spinal cord, giving rise to
hypalgesia and progressive paresis. Fatal massive liver necrosis occurs
in animals maintained on diets low in vitamin E and sulfur-containing
amino acids. 800 international units before meals and bed hour must be
adhered to in this treatment.

8) Crude liver: This substance contains factors still unknown but
essential in metabolism. Patients with pernicious anemia often show
neurological involvement, and are tremendously benefited by liver
injections which, of course, contain vitamin B12 .  Degenerative changes
brought on by other factors, therefore, can also be benefited by daily
injections of crude liver.

9) Adenosine-5-Monophosphoric acid: One of the purine bases occurring
in muscle is adenine It, along with other purines, exists in various
forms. Adenosine polyphosphate is of primary interest in this
discussion. The basic structure is adenosine, adenine-9-riboside This is
esterified with phosphoric acid at the 5-position of the ribofuranose to
form adenosine-5-phosphoric acid, also known as adenosinemonophosphate
(AMP). Inosinic acid is a commonly-occurring breakdown product of AMP,
formed by deamination in muscle extract. Myosin displays enzymic
activity similar to adenylic deaminase. By attaching further phosphoric
acid residues in pyrophosphate linkage adenosinediphosphate (ADP) and
adenosinetriphosphate (ATP) are obtained.  ATP, as previously noted, is
the energy package essential for life. By adding this to our treatment,
we enhance all chemistry dealing with cell metabolism.

10) Choline: Choline is a structural component of fat and nerve
tissue, thus has a strong relationship to the phospholipids and to its
acetyl ester. Acetylcholine plays an important role in the humoral
transmission of parasympathetic and other nerve impulses to effector
organs. It also plays a part in transmethylation. Choline serves as a
methylating agent in the physiological process – guanidoacetic acid to
creatine. We give 700mg. to 1400mg. after each meal and at bed hour.

11) Lecithin:  Lecithin is the glyceryl ester of a pair of fatty
acids and a substituted phosphoric acid group attached to a choline
radical. “Choline” is one of the products of lecithin, representing
about 15 percent of the molecule. Lecithin placed in water and observed
under the microscope, will diffuse out, forming long, curving strands
(myelin forms). The hydrophilic nature of the lecithin molecule plays an
important part in the structure and properties of cell membranes. It is
the lipid used in nerve tissue. We give 1200 mg. Soybean Lecithin after
each meal.

12) Magnesium: 100 mg. after each meal to supply additional ions for
muscle activity. It is an enzyme activator.

13) Calcium Gluconate (10-grain tablets): We give two tablets after
each meal and at bed hour to supplement dietary intake for muscle
activity. At times this is given intravenously, one gram twice weekly.

14) Calcium pantothenate:  The physiologically active form of
panthothenic acid is coenzyme A.  Its acetyl derivative (acetyl CoA) is
synonymous with active acetate. Metabolic transformations are very
complex and involve numerous enzymes and coenzymes. Coenzyme A
participates in the acetylation of amines. The panthothenic acid
coenzyme plays a vital role in carbohydrate metabolism and acetyl
transfer also occurs in the metabolism of fatty acids. We give 200 mg.
after each meal and at bed hour.

15) Aminoacetic acid (glycine): Glycine enters into a variety of
metabolic functions. It is directly concerned in the synthesis of
glutathione, the tripeptide which plays an important part in
intracellular oxidation and reduction. Rapport and Katz have shown that
when glycine is added to perfused muscle, the oxygen absorption is 40
percent higher than otherwise, indicating that the presence of this
amino acid stimulates the combustion of other tissue constituents. To
the body in general, glycine is no doubt most important because of its
wide adaptability in the detoxicating process of the body. More than one
hundred substances, when fed, are joined in the body with glycine. In
the deamination of glycine, three products will be formed: ammonia,
carbon dioxide and water. The ammonia from this reaction is then
quantitatively converted to urea. One heaping tablespoon of the powder
in a glass of milk four times each day. Much of the oral medication can
be taken with this drink.

16) Make certain that the hemoglobin is at least 13 grams.

17) High protein diet with two to three eggs for breakfast.

18) One Theragram-M cap. daily for trace minerals.

19) Dantrium has value for relieving intentional tremor and Symmetrel
for relieving stiffness in Multiple Sclerosis. Dose must be
individualized.

20) Zinc gluconate: 10 mg. three times each day has some value in
Myasthenia Gravis. Take several hours after vitamin B2

This treatment works so dramatically in Myasthenia Gravis, that
should a given patient’s physician refuse to administer this schedule, I
have this recommendation: One gram thiamin hydrochloride one hour before
meals and at bed hour, and during the night if awake. Niacin taken at
the same time, and in amounts sufficient to produce a good body flush.
Two hundred mg. calcium pantothenate and one hundred milligrams
pyridoxine before meals and at bed hour. Ten grams ascorbic acid, taken
in divided doses. Amino acetic acid: one heaping tablespoon in a glass
of milk, four times each day. Naturally, the full schedule will afford
more dramatic response.

For a long time, it has seemed to me that virus bodies might have the
potential tc alter their protein coat, and therefore their dimension,
and become another virus for another disease. In our long practice, we
would see, as I an certain many of you have, chicken pox just before
Thanksgiving, mumps by Christmas, red measles in the Spring, and polio
or a virus mimicking polio in the Sumner, German measles, virus colds,
and virus pneumonitis just about any time.

ETIOLOGY of
MULTIPLE SCLEROSIS – HISTORICAL

As for etiology of Multiple Sclerosis, a good history will tell the
story. I have one patient who was diagnosed Polio in 1950. He
experienced total paralysis, but made a complete recovery. Five years
ago, he began to demonstrate the signs and symptoms of Multiple
Sclerosis, he was given a “strong” course of ACTH with relief of
symptoms. Three months later, this had to be repeated, but the results
were not as good. Some three months later, a third series of injections
of ACTH was worthless. (This has been the pattern with the use of ACTH,
and represents nothing more than whipping a tired horse. In my book, it
borders on malpractice.) His myelin sheath has just about been
destroyed. He has so many areas of “no insulation” that his movements
are like that of a newborn baby. – Had he received our treatment at the
onset of his illness, he would be in good health today without any
physical handicap. This individual never had Poliomyelitis.  The virus
that brought him down was the COXSACKIE virus, and this explains his
initial recovery. Another case seen was a 31 year-old female. This young
lady was diagnosed Poliomyelitis when she was 19 years of age. Three
years ago, she began developing signs and symptoms of Multiple
Sclerosis, and that is her present diagnosis. Her neurologist, who made
the diagnosis of Polio, now tells her that there is no doubt in his mind
that what she has now, actually started when she was 19. He is
absolutely correct, because she had a COXSACKIE virus infection. In 80
percent of the cases that have come under my supervision, an illness
compatible with a Summer virus has been entertained. Unless an illness
is associated with paralysis, it is understandable when a patient or the
family have difficulty in establishing a workable timetable.

OTHER
HYPOTHESES on ETIOLOGY of MULTIPLE SCLEROSIS

Dr. Henry Kempe, from the University of Colorado School of Medicine,
as reported by Medical World News believes that Multiple Sclerosis is
caused by vaccinia virus. He found a correlation between severity of the
clinical disease and antibody titer. He also observed that only in
demyelinating disease were antibodies to vaccinia virus in the cerebral
spinal fluid. This brings to mind the work of Horsefall and his
co-workers at the Rockefeller Institute. They were able to culture an
organism, which they designated Streptococcus MG, from a large
percentage of their patients with primary atypical pneumonia. This
proved later to have no value, and the viral nature of the disease was
recognized.

The sleeping virus theory of Dr. Milton Alter and others, as reported
in Medical Tribune, along with the environmental aspect for Multiple
Sclerosis is another “ripe apple” for public consumption and public
press exaggeration. Most of this theory rests with the circumstantial
evidence that filterable transmissible agents having slow virus
properties are present in other diseases.

Another theory, that of Dr. Dmil K. Schandi, a Nova University
biochemist, in Fort Lauderdale, Florida, and published in “The Charlotte
Observer”, relates it to an environmental agent: specifically carbon
monoxide and the lack of the vitamin pyridoxine (vitamin B6). Pyridoxine
is concerned with the enzymatic decarboxylation of amino acids and the
incidence of Multiple Sclerosis is too low in terms of the availability
of carbon monoxide.

Still another theory has been advanced by Doris Dahl and Amico
Eignami8 of Stanford University, Palo Alto, California. They report the
discovery of a substance that “may” prevent the self-renewing of myelin
Scar tissue is indeed the problem, but it is the end result of
microscopic hemorrhages following virus invasion.

CONCEPTS CONCERNING MYASTHENIA GRAVIS

In Myasthenia Gravis the accepted reasoning is initiated by Thymomas
in 20 percent of patients over forty, and hyperplasia of the thymus in
others. Antibodies to muscle have been reported in roughly 33 percent.
Excessive pyruvates at the neuro-muscular junction has been recognized
but not appreciated.

CASE HISTORIES

CASE HISTORY: MULTIPLE SCLEROSIS Male, white, was in a wheel chair at
a Veterans’ hospital for two years. Patient seen while home on 30-day
vacation. Treatment given every day with marked improvement. Upon
returning to Veterans’ hospital, the physician in charge recognized the
improvement and advised the young man to return home and continue the
treatment. After three years, he was given a clean bill of health by
three neurologists in three different places and was given a responsible
position. This was in 1950. The individual remains in excellent health,
but continues with modified therapy.

CASE HISTORY: MYASTHENIA GRAVIS  Male, white, receiving treatment
from nearby medical centre for one year. He was receiving guanidine
(amount unknown) and 90 mg. prostigmine bromide each day. He was first
seen in a Myasthenia Gravis crisis. The emergency treatment consisted of
two ampules of prostigmine methylsulfate of a strength of 1:2000, and
5cc of coramine. Within a period of eight or ten minutes, the patient
experienced a generalized convulsive seizure which lasted some five
minutes and required 4 men to hold him on the bed. Prostigmine, by
needle, was continued for three weeks, and then 15mg. tablets every six
hours, Thiamin hydrochloride was given three times each day,
intramuscularly, as well as other fractions of the B complex. In one
year’s time, he had been “weaned off’ prostigmine Although given only
two weeks to live by the physicians at the medical centre the day prior
to our first visit, this individual lived a normal life for 18 years his
death was due to a cerebral accident.

CASE HISTORY:  Female, white, with diagnosis, (August 1967), Poly
Neuritis.  Began with pain and burning of legs associated with jerking.
Ran high fever 10 days. Paralysis started on left side along with
weakness of hands, soon followed with complete paralysis lower
extremities. Seen first time 7/5/69. Paralysis and weakness as
described. Started on medication by mouth and intramuscular injections.
Several months later, began intravenous schedule. In approximately 16
months, was able to move right leg. Upper extremities returned to
normal. On 6/10/72, began to move left foot. Patient now able to walk
approximately fifty yards with knee braces and walker. Does all the
cooking for family of four, as well as sewing clothes for herself and
two daughters. (I can personally vouch for her ability as a cook.) April
1973, she was able to go without a back brace that was previously
necessary for her to use to even get out of bed. One marvels at her
ability to pedal a stationary bicycle “contraption” made for her by her
husband so that she might exercise her legs. Our diagnosis in this case
is Transverse Myelitis (200 grams ascorbic acid given IV in divided
doses would have saved this patient from paralysis.) She has also
received 300mg. ribonucleic acid four times each week.

CASE HISTORY:  Female, white, who developed weakness in extremities
around June 25, 1961. Sensory examination revealed hypalgesia over
medial aspect of right foot and calf. Motor examination revealed a
partial foot drop on the right, with rather marked weakness and
inversion, eversion, and dorsiflexion of right foot. Reflexes upper
extremities 3 – 4 plus. Abdominal reflexes absent. Knee jerks were 3 – 4
plus with patellar clonus. Right ankle jerk was 4 plus and the left, 3
plus. Bilateral, sustained, ankle clonus. Babinski’s “brisk”.

Later examined and hospitalized at a nearby medical centre where
Medrol was tried. She was sent home with a diagnosis of Multiple
Sclerosis, superimposed by a viral meningoencephalic. Blurring of vision
was established as due to a left six-nerve paralysis She came home to
ride a wheel chair provided she lived. Seen in our office one month
later, we concurred with the impression of Multiple Sclerosis. Our
treatment schedule became operative. It has been a long journey since
June 1961, but the results have been phenomenal. This individual has
been returned to full activities, and as a gesture of gratitude, comes
to my office to serve in the capacity of an office assistant several
days each week. She does, however, still maintain her treatment
schedule. Whether this is necessary or not, I follow the advice of
another patient who has been continuing modified treatment for 22 years;
“Why stop when you feel so good?”

CASE HISTORY:  Male, white, 28 years. Seen first time 2/26/72.
History of numbness in lower extremities with loss of muscle control
from waist down. This started approximately 2 years before this visit.
Difficulty with bladder control at times. Seen by several neurologists
at a nearby medical centre who failed to make a diagnosis other than to
say he had a Central Nervous System Pathology. Babinski’s, Cordon and
Oppenheim signs were all positive, and ankle jerks were 4-plus. Ankle
clonus was bilateral and sustained on right. be demonstrated a right
foot drop. We entertained a diagnosis of Multiple Sclerosis. Treatment
was not started since he had an appointment to be examined at a nearby
Veterans hospital clinic. We advised him not to accept ACTH therapy. The
following week we did start treatment. After 5 weeks, we did not see the
patient again for three weeks, at which time he confessed that he
thought that he was well and had stopped treatment. The weakness and
other symptoms were again returning. He has been back to gainful
employment for the past 12 months.  Incidentally, he has been a “crack”
pistol shooter, and he still can hold a steady hand on the gun.

CASE HISTORY:  Female, white, 57 years. Seen first time 5/19/72.
Chief complaint was fatigue. This started approximately seven years
before coming to our office. The onset of illness was gradual.
Generalized weakness as the day went on, but was always feeling
refreshed in the morning. Drooping of the eyelids became a problem so
that she automatically would tilt her head backward so that the ptosed
eyelids would be partially corrected. Fatigue of the muscles of
mastication on chewing became so embarrassing that for the past several
months, she avoided all social events, even dinner with friends.
Swallowing also became a serious problem forcing her to a bland and
sometimes liquid diet. Even a few minutes talking, while taking the
history, would so fatigue her that she found it necessary to recline on
the examining table so as to regain her strength. She visited many
clinics and medical centres in the United States and Europe, but always
was given the same-diagnosis – her review of conditions labeled her as
PSYCHOSOMATIC. To us it was obvious that she suffered from advanced
Myasthenia Gravis.   1000mg. Thiamin Hydrochloride and 300mg. pyridoxine
given by needle had her demonstrating jaw and face-movements to her
husband in less than 10 minutes. She remarked that she had not been able
to do that in three years. She was given our schedule for treatment, but
had great difficulty getting her local physician or any physician to
give her the needed injections. In desperation, she returned to one of
the medical centres and confronted them with the diagnosis, which they
did not believe. She, however, demanded that they employ their test for
this disease, which they did. From the patient’s description, given at a
later visit, I surmised that Tensilon was used. Her response was the
greatest ever seen at that University. She is also receiving RNA 300mg.
tablets three times each week, which we believe have stimulated or
furthered her progress. She no longer hesitates to eat in public, and
her stamina is approaching normal. During a visit to our office in April
of this year (1973), she laughed and joked about her experiences in
getting the diagnosis confirmed so that she could receive the vitamin
injections under supervision. She also favored us with a platter of
delicious cakes that she had baked prior to coming to the office.

Although we could write a book on cases treated and cured (or
established a permanent remission), time is a prohibiting factor.

CONCLUSION

The treatment of Multiple Sclerosis has been empiric since it was
first described by Sir Robert Carswell in 1838. Brickner, in 1336, gave
a review on treatment which included preparations of Antimony and
Arsenic, fever induced by various methods such as diathermy, malaria
typhoid vaccine, and fever brought on with the use of drugs. Surgical
procedures such as cervical sympathectomy and root section were also
employed. Serums, hypnotism and intraspinal injections of lecithin had
their day. Moore administered nicotinic acid and thiamin following the
dissertation by Zimmerman and Burack on diseases of the nervous system
resulting from a deficiency of the vitamin D Complex, and the paper by
Spies and others on the use of nicotinic acid in the treatment of
Pellagra associated with mental pathology. Spies and Aring in 1938
published a paper on the effects of Vitamin B1 on peripheral neuritis as
associated with Pellegra. Moore also had the benefit of the work of
Stern, who published an article on the intraspinal use of Vitamin B1 for
the relief of intractable pain, and for inflammatory and degenerative
diseases of the Central Nervous System. We learned early in our approach
to this disease that small and infrequent doses of thiamin hydrochloride
would not accomplish our purpose, and we also realized that more than
one unit of the B Complex would be required, even though the
physiological chemistry relative to this phase of metabolism had not
been completely established. Although Moore used nicotinic acid for
vasodilation purposes, we rationalized that the degenerative process
taking place in nerves, and thus also in muscle, was of a greater
magnitude. Inasmuch as the only sickness remembered by the patient,
family or relatives took place during the summer months we immediately
suspected a virus to be the offending agent. This idea gained momentum
with the greater incidence of Multiple Sclerosis following the epidemic
of encephalitis lethargia of 1920 to 1926, and the epidemic of
encephalitis B in St. Louis and Toledo in1934. However, the incidence of
Polio was also up. Mixed, abortive or unrecognized cases of
Poliomyelitis became a tantalizing factor. After the isolation of the
Coxsackie virus with its mimicking of Polio, and the knowledge that the
paralysis with this type virus infection was never permanent, the real
devastating factor, in time and place, at least to me, became apparent.
Flexner and Lewis were able to demonstrate that in Polio, vascular and
lymphatic lesions constituted the primary causes of the lesions of the
nervous system. Multiple hemorrhagic accidents take place in Multiple
Sclerosis with ensuing scar tissue .  As these microscopic scars
contract, they impinge on the vessels carrying nutrients to the Central
Nervous System cells. In muscle, the “devastation” is brought about
through lack of function, there being no “electrical charge” present to
keep muscle active. For this reason, the Sister Kenney treatment for
Polio had merit, since it helps to maintain muscle and muscle-nerve
integrity. Our employment of nicotinic acid is to effect adequate
dilatation of existing vascular structures, producing over a time,
chemically, what the Urologist accomplished with his catheters in
mechanical fashion. Once these channels are sufficiently operative, the
metabolic factors that we supply will go about revamping the myelin
sheaths. Due to lack of full energy components, cells can temporarily
lose the ability of normal physiological activity. We can restore the
normal function of cells which depends upon their ability to extract and
use the chemical potential energy locked within the structure of organic
molecules. We accomplish this by placing massive amounts of the
essential material at the disposal of cells. We categorically make this
statement: Any victim of Multiple Sclerosis who will dramatically flush
with the use of nicotinic acid, and who has not yet progressed to the
stage of myelin degeneration, as witnessed by sustained ankle clonus
elicited in the orthodox manner, can be CURED with the adequate
employment of Thiamin Hydrochloride and other factors of the Vitamin B
Complex in conjunction with essential proteins, lipids, carbohydrates
and injectable crude liver. If sustained ankle clonus is not bilateral,
then it is not a deterrent. I have had patients who did demonstrate
bilateral sustained ankle clonus, and who were in wheel chairs, and who
returned to normal activities after 5 to 8 years of treatment. These
patients, fortunately, had not received ACTH. One patient was given a
single course of Medrol 4 mg. Q.I.D. This had little effect on her
pathology, and apparently no “blocking action” on our treatment. The
general use of ACTH in Multiple Sclerosis will extend the recovery
period by a time directly proportional to the amount of the drug
employed. It is hoped that this paper will bring an end to this
senseless practice of medicine, since ACTH never works the third time.

The theories recognized as playing a part in Myasthenia Gravis still
rest in the main with Thymus enlargement or tumor, Endocrine
dysfunction, metabolic fault, and the build-up of pyruvic acid in the
vicinity of the motor end-plates. In reality, it is a genetic fault
involving a lethal intermediate gene or group of genes. There is
definitely an over-supply of pyruvates, and an under-supply of
acetylcholine. The cue in this drama is cocarboxylase. Coenzyme A is
also in limited supply. Two molecules of thiamin hydrochloride, and two
molecules of phosphoric acid yields cocarboxylase. One way in obtaining
acetyl coenzyme A, a by-product of coenzyme and pyruvic Acid, is in the
reaction between pyruvic acid, coenzyme A and diphosphopyridine
nucleotide in the presence of diphosphothiamine (cocarboxylase).
Cocarboxylase is also involved in the synthesis of acetylcholine and in
the control of its hydrolysis. The activity of choline esterase of serum
is strongly inhibited by this same agent. Thiamine occupies a key
position in at least the terminal stages of carbohydrate metabolism.
Cocarboxylase plays an active role in the decarboxylation of pyruvic and
other keto acids. In the brain, cocarboxylase participates in the
anaerobic dismutation of pyruvates to lactate and acetate, and their
subsequent oxidation to carbon dioxide and water. In liver and other
tissue cells, cocarboxylase is involved in the conversion of pyruvates
to oxalacetate which combines oxidatively and irreversibly with another
molecule of pyruvate to enter the tricarboxylic acid cycle. In thiamin
deficiency, a form of peripheral neuritis markedly demonstrated in some
cases of chronic alcoholism exists, affecting both sensory and motor
nerves.

The treatment of Myasthenia Gravis is that of any pathology dealing
with the interruption of the normal physiology of nerve cells.  In years
past, when we were treating Poliomyelitis successfully with massive
doses of ascorbic acid, we would always follow with an indefinite
time-table giving the 3 vitamins for nerve repair.  We see the same
results when treating damage to the spinal cord, whether this is due to
mechanical trauma, or to the inflammation caused by a virus – any virus.
As pointed out by Lipschitz et al., the replenishing of vitamin restores
the ability of the nervous system to handle properly pyruvic acid and
dextrose. This action of thiamin makes its function in Myasthenia Gravis
seem elementary. A German scientist once speculated that cocarboxylase
was actually the “food” required for nerve life. In treating Myasthenia
Gravis with the schedule outlined, the intensity to which it is applied
in Multiple Sclerosis will never be necessary. We are not confronted
with the loss of myelin sheaths in extra vital areas. The chemistry,
however, is more complex than in Multiple Sclerosis, since it involves
muscle cells to a greater degree. Enzymes and their balance is a
necessary approach. When we realize that over 900 different enzymes have
been identified, it makes more knowledge knowledgeable the need for
extensive vitamin therapy. This suggests that normal liver function is
necessary for good results. A simple liver function test can be used to
good advantage. One that I “worked out” many years ago to demonstrate
“liver stress” is performed as follows. Have patient bring 90 cc from
first voiding upon arising. Fill ordinary test tube to within one cm of
top. Allow to set for 24 hours and read. One will find in most specimens
a gelatinous fluid resting at the bottom of the test tube. The amount
present, which can measure 2.5 cm, indicates the degree of liver stress
present. Choline by needle or by mouth will remove this finding from the
urine. Some urine specimens will show a heavy, white sediment
obstructing proper reading of liver stress. Glacial Acetic Acid alone,
and/or heat will temporarily remove these phosphates. Should the deposit
of phosphates be exceedingly heavy, then it is advisable to secure a
bed-hour specimen, or one 2 hours after breakfast. The night specimen
should be placed in a cool area until delivery. Occasionally, the urine
specimen will grossly look like skim milk. This is clue to earthy
phosphates and can be cleared by adding Glacial Acetic Acid to the tube.
(After ascertaining liver stress; one can then add 20 drops Glacial
Acetic Acid to the specimen if none was previously added – and allow to
remain an additional 48 hours to check for Uric Acid Crystals. A red
shower indicating an abnormal level for uric acid.) This test must be
run every week when administering ribonucleic acid (RNA).

APPENDIX

Since presenting this paper, we have observed that improvement in all
categories is enhanced when the intravenous injection contains 800 mg.
to 1000 mg. thiamin hydrochloride, 200 mg., pyridoxine, 400 mg
niacinamide, 100 mg. nicotinic acid. The thiamin hydrochloride solution
MUST be clear. The amount of niacin employed must be calculated from the
“flush factor” of a given patient. The injection is made with a 20 cc or
30 cc syringe, using a 23Ga. x ¾ inch or 22G x 1-inch needle.
Intravenous medication can be given daily; it should be administered at
least twice weekly. Due to sensitivity possibilities, we always have the
patient take the intramuscular injections for three weeks before
starting intravenous therapy.

BIBLIOGRAPHY –
PAPERS

• 1. Stern, L.L.: The Intraspinal
  Injection of Vitamin B1 for the Relief of Intractable Pain, and for
  Inflammatory and Degenerative Diseases of the Central Nervous
  System. Am,.J. Surg. 34:495,,1938.
• 2. Rosenberg, L.L., Vitamin
  Deficiency Diseases and the Vitamin Dependent Diseases With
  Reference to arid D. Nat’l. Health Ped’n. Bulletin Vol. XVIII, No.
  10, November 172.
• 3. Moore, M.T.: Treatment of
  Multiple Sclerosis Pith Nicotinic Acid and Vitamin B1 Archives In
  .Med Vol. 65, pp. 18, Jan. 1940.
• 4. Bijou, S.W., Baer, M: Child
  Development II Universal Stage of Infancy. Appleton- Century-
  Crofts, 1965.
• 5. Kempe, C.H.: Key to the Secret of
  M.S. Medical World News, July 7,1972.
• 6. Alter, M. et al: Dissertation on
  Environmental and Sleeping Virus Theory. Medical Tribune.
• 7. Schandi, D.K.: Dissertation on
  Environmental and Pyridoxine Cause of M.S. The Charlotte Observer,
  Charlotte, N.C. April 23, 1973.
• 8. Dahl, Doris; Bignami, Amico:
  Report of Substance Preventing Renewal Myelin. Reidsville Review,
  April 23, 1973.
• 9. Brickner, R.M.: A Critique of
  Therapy in Multiple Sclerosis. Bulletin Maur. Inst., New York, Vol.
  6:665, April 1936.
• 10. Zimmerman, H.H., Burack, F
  Lesions of the Nervous System Resulting from a Deficiency of the
  Vitamin B. Complex Arch. Pathology, Vol. 13:207, February 1932.
• 11. Spies, T.D;’ Cooper, C,
  Blankenhorn, M.A. The Use of Nicotinic Acid in the Treatment of
  Pellagra. J2\MI\, Vol. 110:622, February; 1936.
• 12. Spies, T.D.; Aring, C.D. The
  Effect of Vitamin on the Peripheral Neuritis of Pellegra. Vol.
  110:1031, April 1938.
• 13. Klenner, F.P. Fatigue-Normal
  arid Pathological with Special Consideration of Myasthenia Gravis
  and Multiple Sclerosis. Southern Medicine and Surgery, Vol. III, No.
  9; September 1949.
• 14. Flexner, S.; Lewis, P.A.
  Experimental Epidemic Poliomyelitis In Monkeys. Journal Experimental
  Medicine, Vol.12:227, 1910.
• 
  BIBLIOGRAPHY – TEXT BOOKS
  
  • a. Alpers, E.J.: Clinical Urology,
    2nd Ed., F.L. Davis Co., 1950
  • b. Bodansky, M.: Intro. to
    Physiological Chemistry, 2nd Ed. John Wiley & Sons, Inc., 1930.
  • c. Cameron, A.T., Gilmour, C.R.: The
    Biochemistry of Medicine William Wood & Co., 1933.
  • d. Evans, A.L., Hartridge, L.:
    Starling’s Principles of Human Physiology 5th Ed., J.& A. Churchill,
    London, 1930.
  • e. Fieser, L.F.; Fieser, Mary:
    Organic Chemistry. 3rd Ed, D.C. Heath and Company, 1956.
  • f. Harrow, B.: Casimir Funk, Pioneer
    In Vitamins & Hormones. Dodd, Mead & Co., New York, 1955.
  • g. Hawk, P.B.; User, B.L.;
    Suramerson, W.H.: Practical Physiological Chemistry. 13th Ed.,
    McGraw-Hill Book Co. Inc., 1954.
  • h. Lichtman, S.S.: Diseases of the
    Liver, Gallbladder and Bile Ducts, Vol. 1, Lea & Febiger,
    Philadelphia, 1953.
  • i. Lowenberg, S.A.: Medical and
    Physical Diagnosis.7th Ed. F.A. Davis Co., 1946
  • j. Martin, H.N.; Martin, E.G.; The
    Human Body. 11th Ed. Revised. Henry Holt and Cc., 1932
  • k. Srb, A.M.; Owen, H.J.; Edgar, R.S.:
    General Genetics, 2nd Ed., W.E. Freeman and Co., 1965.
  • l. The Merck Manual, 12th Ed. Merck
    Co. Inc., Rahway, N.J. 1972.
  • m. The Vitamins: A Symposium, 1939,
    A.M.A.
  • n. Vander, A.J.; Sherman, J.H.;
    Luciano, D.S.: Human Physiology McGraw-Hill Inc., 1970.
  • o. Wells, H. C.: Chemical Pathology,
    5th Ed. revised. R.B. Saunders Co., 1925.