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Myasthenia Gravis (MG) is no longer
considered a fatal disease. Most myasthenics, with the help of
either drugs and/or surgery, lead near-normal lives.
However, there is no standard therapy
for all myasthenics and there is still much to learn about MG
- how it is diagnosed and how it is treated. As is usual with
all things myasthenic, the success of one treatment over another
is really dependant on the patient. What works for one person,
may not work at all for another. And what works for one body part
in a patient, may not work for another body part. A doctor may
experiment with various therapies and prescription levels to achieve
relief from myasthenic symptoms for the patient.
There is no one recipe for all situations, so the choice of treatment
for an individual patient requires judgment and experience. Patients
and their doctors are often required to make decisions even when
the evidence is inconclusive. Patients need all the support which
doctors, family and friends can offer.
Normally a neurologist is engaged
for diagnosis and management of the disease. It would be helpful
if the neurologist has extensive knowledge and experience in the
management of MG (with the incidence of MG in only 1 person for
at least every 10,000 people, it is highly likely that a number
of neurologists have had little experience with this condition).
Current therapies
for MG include:
1. Anticholinesterase
Therapy - an attempt to strengthen neuromuscular transmission
with the use of drugs such as pyridostigmine bromide (Mestinon,
Mestinon extended-release) and neostigmine (Prostigmin).
2. Immunosuppressant
Therapy - Prednisone; azathioprine (Imuran); cyclophosphamide
(Cytoxan); cyclosporine (Sandimmune); mycophenolate mofetil
(CellCept).
3. Plasma Exchange
- Plasmapheresis
4. Intravenous Immune
Globin
5. Thymus & Thymectomy
6. Other Therapies
- atropine; pro-banthine; ephedrine
Hopefully, the neurologist will
explain the various forms of treatment to the patient, and suggest
the best way forward. There are advantages and disadvantages to
each type of therapy, and the impact of the therapy could affect
one's ability to cope with the condition and such things as self
image. Some factors to consider are:
- the patient's current condition
- for example, therapy for somebody in a myasthenic crisis such
as breathing difficulties would be different to that for droopy
eye lids.
- the patient's reaction to the
therapy - some medications may cause undesirable side effects
such as nausea, dizziness and stomach pains and so could not
be tolerated over long periods.
- the effect of the therapy on
the patient's ability to carry on with daily activities eg plasmapheresis
requires hospital visits; thymectomy requires several weeks
rest after surgery which could have an impact on income and
ability to work.
- cosmetic implications - some
therapies not only deal with the myasthenia, they will have
other physical impacts - a thymectomy will leave the body scarred,
some medications may cause bloating, or affect appetite.
Normally, the first treatment step
is medication. There is no cure for MG, and so the drugs used
to combat MG merely provide temporary assistance to help the body
function normally. Additionally, the danger of using any drug
is that the body may become tolerant of it over time, and so the
drug becomes less effective. The choice is then to move to a stronger
drug or to a different form of therapy, such as a thymectomy,
which offers long term management of the condition.
In under 20% of myasthenics, MG
goes into spontaneous remission which lasts longer than a year.
No one knows why MG fluctuates or why natural remissions occur.
Anticholinesterase Therapy
(Mestinon, Prostigmin, Mytelase)
Anticholinesterase drugs include:
- pyridostigmine (brand-name "Mestinon")
- neostigmine (brand-name "Prostigmin")
- ambenonium chloride (brand-name "Mytelase")
We described the functioning of
the muscle in the section What Causes Myasthenia
Gravis. You might recall that for a muscle to contract, the
nerve sends a message to the muscle through a neurotransmitter
substance called acetylcholine (ACh). The nerve end releases a
large amount of ACh, which travels through the neuromuscular junction
(NMJ) (the gap between the nerve and the muscle) and binds to
a receptor on the muscle membrane. In MG, the attacking antibodies
bind to the muscle's membrane and initiate a series of events
that destroy the membrane and prevent ACh from binding. If ACh
cannot bind to the muscle, the muscle does not receive the message
from the nerve and will not contract.
Anticholinesterase drugs boost the
body's ACh by blocking the enzyme which usually breaks down ACh.
This allows the build up of ACh to concentrate at the at the muscle
receptor, which is where it is needed to transmit messages from
the nerves to the muscles, and its effect is prolonged.
The most commonly used anticholinesterase
is "Mestinon". This comes in 60 milligram (mg) or 10
mg tablets and is released immediately. “Mestinon TimeSpan"
is a 180 mg tablet in which 60 milligrams is released immediately
and the remaining 120 milligrams are released over several hours.
TimeSpan is usually prescribed for patients who require medication
throughout the night (this allows for comfortable, uninterrupted
sleep and reasonable strength in the morning). Timespan's uneven
release provides less predictable results than with ordinary Mestinon
and is usually not recommended for day time use, but some myasthenics
prefer taking it. Liquid "Mestinon" syrup is for children
and for adults who have trouble swallowing pills.
There are no fixed dose or time
schedules for anticholinesterases as muscle involvement and severity
vary so much among myasthenics. An increase in muscle strength
is usually noticeable within 20 to 40 minutes after taking the
medication, and they produce their maximal effects about one to
two hours after ingestion (although muscle strength rarely returns
to normal). The effects start wearing off after three or four
hours. The medication must be taken at regular intervals so that
muscle strength is maintained throughout the day. For those myasthenics
who have trouble chewing or swallowing, it is best to take medication
at a time that will produce optimal strength during meals.
The need for anticholinesterases
varies from day-to-day, and during the same day in response to
infection, menstruation, emotional stress, and hot weather. Different
muscles respond differently; with any dose, certain muscles get
stronger, others do not change, and still others become weaker.
A "brittle myasthenic" may be adequately medicated during
one 3 to 4 hour period and over-dosed with the same dose in the
next 3 to 4 hour period. Medication dosage may require frequent
adjustment according to one's response to the drug and to hourly/daily
activity level.
Anticholinesterases are the gentlest
of the drugs available to treat MG. However, some people do experience
side effects, including:
- stomach cramps
- queasiness and nausea
- gut hyperactivity and diarrhea
- vomiting
- increased perspiration
- increased salivation
- muscle twitching and muscle cramps
- palpitations
- increased urinary frequency
- the muscle controlling the pupil of the eye is also affected,
and there may be difficulty in focusing
- there are Acetylcholine receptors in the heart and so Mestinon
may cause a very slow heart beat, which can, in turn, cause
dizziness.
The presence of these symptoms may
be a sign of taking too much medication, in which case the medication
should be taken at longer intervals or in lesser amount. Other
symptoms of overdose could include the worsening of generalized
weakness, swallowing difficulties and respiratory failure (in
which case a doctor should be contacted immediately). The myasthenic
who is prescribed large daily dosage of anticholinesterase and
suffering severe side effects or a worsening of their condition
should question their doctor about their therapy.
To lessen the side effects, the
drug can be taken with bland foods such as crackers and milk.
If the unwanted side effects are particularly intense, they can
be prevented or reduced by simultaneously taking other drugs -
either anticholinergics (atropine) and hydrozyzine (Vistaril).
It is also important to emphasise that all the unwanted effects
of Pyridostigmine are short-lasting, and that it does not cause
any permanent or long-term problems.
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Immunosuppressant
Therapy
As the name suggests, immunosuppressant
drug therapy attempts to suppress the body's immune system, although
no one really knows how they work in MG. They are commonly called
steroids (those used for MG are properly known as corticosteriods,
not the anabolic steroids used by sports people). Steroids and
other immunosuppressive drugs are often very effective in producing
remission of symptoms.
The immune system produces antibodies
to fights against foreign bacteria and viruses. In illnesses such
as MG, the antibodies become overactive and start attacking the
body's tissues. Immunosuppressive drugs suppresses the production
of antibodies to stabilize an overactive immune system. In MG,
it is the ACh receptor antibodies that are suppressed, therefore
allowing the receptors to regenerate and function in neuromuscular
transmission. Hence, there is a return of muscle strength.
In the use of immunosuppressants,
the best responses occur in patients with recent onset of symptoms,
but patients with chronic disease may also respond. The severity
of disease does not predict the ultimate improvement.
In decreasing order of their frequency
of use in MG, they are:
- prednisone
- azathioprine ("Imuran")
- cyclophosphamide ("Cytoxan") and
- cyclosporine ("Sandimmune").
Except for prednisone, none of these drugs is endorsed by its
manufacturer specifically for treatment of MG.
Unfortunately these drugs can make
it harder for the body to fight infection, and can also have serious
effects, especially after prolonged use.
Prednisone
Prednisone is a synthetic drug
which resembles natural hormones produced by the cortex of human
adrenal glands, and is used to treat many illnesses. The body
depends upon these hormones, called corticosteroids or "steroids,"
during stress.
Unique to MG is the possibility
of increasing weakness during the first two weeks of prednisone
therapy, which requires close medical supervision when first
administered. Some doctors try to avoid this initial weakening
by starting with a low dose of prednisone and gradually working
up to a recommended amount of 50 to 60 milligrams every day
for several months. Onset of improvement in muscle strength
usually occurs within 2 weeks but may take as long as 2 months.
Marked improvement or complete relief of symptoms occurs in
more than 75% of patients treated with prednisone.
When prednisone is taken in doses
higher than 20 milligrams daily for longer than a week, the
body's natural production of adrenal hormones begins to decrease.
This is called "adrenal suppression," and is an undesirable
but inevitable effect of taking high doses of a synthetic steroid.
Once this occurs, prednisone cannot be stopped all at once but
must be slowly tapered down over several months to give the
adrenal glands a chance to "wake up" and begin producing
natural adrenal hormones again.
Prednisone has a great many potential
undesirable effects, usually related to dose and duration of
drug use. In order to lessen the chance of undesirable effects,
a gradual transition to alternate-day therapy is made after
about two months of daily therapy, so that eventually twice
the usual dose is given every other day for several more months.
As soon as is feasible (3 to 12 months), the drug is very slowly
tapered over many months to a long-term maintenance dosage (around
5 to 10 milligrams every other day) sufficient enough to keep
myasthenic symptoms at bay. The choice of prednisone therapy
is thus a long-term commitment lasting several years.
30% of myasthenics on high-dose
prednisone therapy experience a drug-dependent symptom-free
remission, and another 50% obtain marked improvement. However,
25% of patients also experience serious complications from this
drug.
The side effects of using Prednisone
(and any other steroid) are:
- Risk of developing osteoporosis
- this is probably the most serious long-term effect. It results
in thinning and consequently in weakening of bones and particularly
those of the spine and the pelvis. The effect is worse in
those who are already at risk of thinning of their bones such
as the elderly or women past the age of childbearing. Exercise,
particularly weight-bearing exercise such as walking and aerobics,
is highly recommended (although some myasthenics may find
this difficult). Diet should be high in calcium, protein and
Vitamin D. There are now also available drugs (such as etidronate)
which are being used successfully to treat bone thinning.
- Increased susceptibility to
diabetes - steroids make the body less capable of dealing
with glucose and other sugars, which affects diabetic patients.
It may also induce mild diabetes in patients who didn't previously
have it. Strict dietary control may be necessary to counter
this side effect.
- Thinning of skin and wasting
of muscles - steroids tend to break down body tissues, and
deplete them of protein. This can be counteracted by strenuous
exercises, which again may be difficult for people with MG.
Thinning of the skin leads to it being easily cut or broken,
delayed healing of wounds, and also to increased susceptibility
to the affects of sunlight.
- Increased risk in developing
glaucoma and lens.
- Irritation of stomach lining
and gullet causing indigestion, increased acid in the stomach
and possibly ulcers.
- Sodium and water retention, causing
some puffiness or swelling
Other side effects include:
- mood changes and insomnia
- increased appetite and weight gain
- decreased resistance to infection
- high blood pressure
- increased sweating, especially at night
- increased hair growth
- acne on the face, back, and chest
- thrush (Candida) growth in the mouth
Patients on prednisone should:
- watch their weight
- keep as active as possible
- eat a balanced diet (high in protein, calcium and potassium
but low in salt, free sugar and fat)
- stay out of crowds in enclosed areas (to avoid people with
infections)
- see their doctors regularly.
Azathioprine
(brand-name Imuran)
Imuran also suppresses the production
of ACh receptor antibodies. It is used an alternative to prednisone
where the patient either cannot tolerate prednisone or does
not respond to it. Others respond better to treatment with both
drugs than to either alone. In some patients, imuran is used
as an aid to decreasing the dosage of prednisone.
The beneficial effects of Imuran
seem to take months to occur, and often emerge so slowly and
subtly that they are apparent only in retrospect. Because the
response to Imuran is delayed, both prednisone and imuran may
be started simultaneously with the intent of rapidly tapering
prednisone when Imuran becomes effective. If Imuran is working,
after about 3 to 12 months (or even longer in some patients),
the myasthenic should notice a gradual improvement in how they
feel. This improvement can be measured clinically by:
- Decrease in the number or
severity of symptoms
- Need for less prednisone or Mestinon
- Need for less frequent plasmapheresis treatments
- Lower AChR antibody titer
Remissions which occur on Imuran
are drug-dependent. Imuran is a long term treatment and a patient
may have to stay on this medication indefinitely. Once improvement
begins, it is maintained for as long as the drug is given, but
MG symptoms recur 2 to 3 months after the drug is discontinued
or the dose is reduced below therapeutic levels.
As with any immunosuppressive
drug, it is important that the patient take Imuran exactly as
prescribed by their doctor.
The undesirable effects of Imuran
are less varied than those of prednisone but they can be very
serious:
- Some people have a hypersensitivity
or allergy to Imuran and develop fever, chills, joint and
muscle pains, vomiting and dizziness. This usually occurs
soon after commencement of treatment. When this unwanted reaction
occurs, treatment must be stopped and cannot usually be restarted.
- Women who may want to have
children should avoid this drug, because it has a known potential
for producing fetal deformities.
- Imuran depresses the formation
of new blood cells, just as it depresses antibody forming
cells. It is therefore necessary to have complete blood counts
of red and white cells frequently at the start of treatment,
and three to four times a year once treatment is established.
If the count drops significantly, it may be necessary to stop
treatment temporarily.
- Liver function may be upset
by Imuran. This can be monitored by blood tests. The effects
are reversible on stopping treatment or reducing the dose.
- Susceptibility to infection
- as Imuran depresses immunity, it increases susceptibility
to infections. Special care must be taken to avoid contact
with shingles and chicken pox which are much more severe in
patients with lowered immunity.
- There is still much to learn
about Imuran, including answers to such worrisome questions
as whether it may increase the risk for cancer many years
later. This is the most controversial, unwanted effect of
Imuran. There are reports of an increased frequency of tumours
mainly of the lymph glands in patients with rheumatoid arthritis
taking Imuran. The sort of tumours that occurred in these
patients were those that respond well to treatment once Imuran
is stopped. However, a more recent report in 755 patients
taking Imuran for bowel disease and who were followed for
up to 29 years found no increase in the number of tumours
of any sort. There are no comparable figures for MG Patients,
but, on the basis of current knowledge, there is little cause
for alarm.
Approximately one-third of patients
have mild dose-dependent side effects that may require dose
reductions but do not require stopping treatment.
Imuran is generally tolerated
without serious adverse effects. The patient should check with
the doctor immediately if any of the following occur:
- Nausea and vomiting
- Fever or chills
- Loss of appetite
- Upset stomach
- Skin rash
- Diarrhea
- Cough or shortness of breath
- Cold sores in the mouth or on the lips
- Blood in the urine or stool
- Unusual bruising
- Fatigue
- Missed menstrual period
- Yellowing of the eyes and skin
- Hair loss
- Muscle or joint pain
- Darkening of the skin and fingernails
More information about Imuran can
be found at: www.gsk.com.au/gskinternet/publishing.nsf/Content/Imuran
Cyclophosphamide (brand-name Cytoxan)
Cytoxan is considered only for
the most severe cases of MG when other therapies have failed.
It is used either intravenously and orally for the treatment
of MG.
Whilst experience from the Philippines
reports good results with complete drug-free remission for a
year and a half in three out of four MG patients who were treated
with Cytoxan, the side effects are common and can be quite serious.
They include:
- hair loss (almost universal
occurrence on the drug)
- risk of bladder hemorrhage and bladder cancer.
These effects may be reduced by
having the drug taken intravenously or orally once a week instead
of daily. This drug usually requires the assistance of a rheumatologist
or oncologist who is more familiar with it than are most neurologists.
Cyclosporine (brand-name Sandimmune)
Sandimmue is an immunosuppresion
used during organ transplantation, and could be of benefit to
myasthenics in reducing the dose of prednisone. A preliminary
study without prednisone suggested that such a dose of cyclosporine
could produce significant improvement in some MG patients if
they could tolerate the side effects of this medication, the
most prominent of which are elevated blood pressure, headaches,
and increased body hair.
Most patients with MG improve
1 to 2 months after starting cyclosporine and improvement is
maintained as long as therapeutic doses are given. Maximum improvement
is achieved 6 months or longer after starting treatment. After
achieving the maximal response, the dose is gradually reduced
to the minimum that maintains improvement.
Adverse effects of this medication
include:
- renal toxicity
- hypertension
- many drugs interfere with Sandimmune metabolism and should
be avoided or used with caution.
Mycophenolate Mofetil (CellCept)
CellCept is a relatively new
immunosuppressive drug that was originally developed to prevent
immune rejection of transplanted organs. Whilst its treatment
of MG is still being investigated, it appears that it may be
of assistance to myasthenics who have found prednisone and other
immunosuppressive drugs ineffective.
In a pilot trial conducted by
Dr Donald Sanders (director of the MDA clinic at Duke University
in Durham, N.C.), 8 out of 12 patients on CellCept for several
months gained strength or were able to reduce their need for
prednisone. In another study, 92 patients in Chicago were prescribed
the drug for 3 to 45 months. Improvement was seen in 67 of these
patients, including 5 who went into complete remission (http://www.mdausa.org/news/030404mg.html).
The advantage of CellCept over
other immunosuppressant drugs is reported to have more rapid
onset and fewer side effects. The drug has been reported to
cause birth defects in animals, and so women of child bearing
age should avoid getting pregnant whilst on the drug as the
effect on unborn babies is unknown).
A pamphlet on CellCept can be
found on the websdite of The Myasthenia Gravis Foundation of
America (MGFA) at http://www.myasthenia.org/information/CellCept.pdf
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Plasma Exchange (plasmapheresis)
Plasmapheresis is a blood purification
procedure used to treat several autoimmune diseases. It involves
the exchange of the blood plasma which contains antibodies and
other substances that interfere with the transmission of nerve
impulses and replacement with fresh or artificial plasma.
The need for plasma exchange, and
its frequency of use is determined by the response in the individual
patient. The procedure is expensive, time consuming and not totally
risk free, and is not meant for long-term treatment. So why is
it used?
1. To stabilise the condition
of patients in myasthenic crisis where the condition is life
threatening.
2. To reduce moderate to severe
muscle weakness before thymectomy.
3. Some myasthenics do not respond
sufficiently to more traditional forms of treatments, and so
plasmapheresis offers their only relief from near paralysis
and life-threatening respiratory problems.
The course of the exchange normally
involves six to ten exchange treatments over two to ten weeks.
To access blood, one tube is inserted into a large vein (possibly
in the crook of the arm), and another placed in the opposite arm
or foot. Around 3 to 4 litres of blood (depending on one's body
weight) is removed from the first tube. The blood passes through
a blood separator, which works in one of two ways - either by
spinning the blood at high speed to separate the cells from the
fluid; or by passing the blood through a membrane with pores so
small that only the fluid part of the blood can pass through.
The plasma, which contains the antibodies, is discarded. The red
blood cells are returned in artificial plasma (albumin and saline
solution) via the second tube. Anticoagulant is added to the blood
to keep it from clotting, but most of the anti-clotting agent
is removed prior to returning the blood to the patient. Treatment,
which can be uncomfortable, but is not painful, can take 2 to
5 hours. The patient lies down only during treatment but is able
to walk around before and after treatment.
Maximum improvement may be reached
as early as after the first exchange or as late as the fourteenth,
but exchanges do not have a cumulative benefit.
The following difficulties may arise
during the procedure:
1. Sometimes it is not possible
to achieve adequate blood flow from veins in the arms. Therefore,
alternative blood access, which might involve some minor surgery,
will be necessary.
2. Although the latest technology
blood cell separators remove only a small portion of blood from
the patient at any one time, the changes in blood volume or
the type of replacement fluid utilized my make some patients
feel dizzy or lightheaded. Patients should immediately tell
the medical staff if they begin to feel uncomfortable or if
they suffer numbness, tingling associated with the mouth, eyes,
fingers or toes and leg cramps, dizziness and mental confusion
(all of which may indicate a low blood calcium or potassium
level). Tiredness usually occurs after treatment.
3. The anticoagulant used to keep
the blood from clotting and certain types of replacement fluids
might cause a patient to notice a sour taste in the mouth, tingling
around the lips, or sharp pains, like pins being stuck in the
fingers or toes. Patients should immediately tell the medical
staff if they have any of these symptoms.
4. The procedure isn't selective
about which antibodies it removes, and so it may result in excessive
suppression of the immune system. The body can replenish anti
bodies in time, but day patients may have to take special precautions
against infection.
5. Patients with clotting disorders
may not be suitable for this sort of procedure.
Plasmapheresis does not cure MG
- it only temporarily reduces the level of circuiting antibodies
that attack the neuromuscular junction. It does not prevent the
production of more antibodies, and usually the patient is given
medication to help combat the condition.
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Intravenous Immune Globin
Intravenous immune globin (IVIG)
is the opposite of plasmapheresis - instead of drawing off the
offending antibodies, IVIG swamps the body with pooled gamma globulin
antibodies from many donors.
The process does not require special
equipment, and the usual dose is small (eg 400 mg per kilogram
per day infused for five successive days). Whilst the mechanism
of action remains unknown, IVIG is thought to have a nonspecific
suppressive effect upon the production of antibody by the immune
system. It produces rapid improvement to help patient through
a difficult period of myasthenic weakness. In patients who respond,
improvement begins within four or five days, and may be sustained
for weeks to months.
The process is quite expensive,
and like plasmapheresis, the treatment is short term. As with
plasmapheresis, its use is really limited to critical patients
or those who are not responding to traditional treatments. It
should be noted that there is a theoretical risk of transmission
of blood born infections, although this has not happened now for
some years.
Adverse reaction occur in fewer
than 10 percent of patients. Symptoms include headache, fluid
overload, and in rare cases, renal failure. Plenty of fluids should
accompany the treatments to minimize the severe headache which
can occur.
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Thymus & Thymectomy
It is accepted that there is a connection
between the thymus and Myasthenia Gravis (MG) but the reason for
the connection is not fully understood.
The thymus gland is an organ involved
in the development of the immune system. It is located in the
upper chest under the breastbone and is composed of many small
lobes. During the formation of the fetus, the thymus migrates
from the neck into the chest, and in adults it lies beneath the
breastbone (sternum). Like tonsils and adenoids, the thymus is
large in infants and gets smaller, to be replaced by fat, as we
get older, making it hardly functional.
The myasthenic adult has thymic
abnormalities. The thymus could be enlarged (as seen by CT scan)
or it can contain more cells than normal (as seen under the microscope)
- this is called hyperplasia and is often seen in myasthenics
of many years standing.
Around 10% to 15% of myasthenics
have tumours, called thymomas, which are usually relatively benign,
but may become malignant. Thymomas are normally removed as soon
as possible to prevent local spread (although, only around 30
to 50% of people with thymomas also have MG - and in some, MG
develops after they have their thymectomy!). The risk of development
of thymoma has led to thymectomy as well for MG patients without
thymoma. (For more information on THYMOMAS, go to the Myasthenia
Gravis Association UK website [http://www.mgauk.org/]. There are
two excellent papers by Dr Nick Willcox of the Institute of Molecular
Medicine , University of Oxford on The Mysteries of Thymoma and
MG.)
If most of the thymus gland is removed
at surgery, myasthenic symptoms usually lessen and in some individuals
go away completely. Although the relation of the thymus glad to
myasthenia gravis is not totally understood, it appears that the
thymus gland is linked to the production of acetylcholine receptor
antibodies or other substances that interfere with neuromuscular
transmission.
A thymectomy is the removal of the
thymus gland by surgery. The goal of thymectomy as a treatment
for MG is to induce remission, or at least improvement, permitting
a reduction in immunosuppressive medication. Remission is the
complete elimination of symptoms without medication.
Drug therapy, plasmapheresis and
IVIG are short term treatments and do not completely relieve the
symptoms of MG. They are beneficial, but in some patients may
not be sufficient to allow the patient to return to full activity.
Eventually the myasthenic with more than just mild disease, must
decide on what to do next to attempt long term remission. This
is especially true for patients with serious trouble swallowing
or breathing, for whom long-term treatments may protect against
rapid deterioration of these functions.
Most neurologists will therefore
advocate thymectomy as the next step for the management of the
condition - particularly for patients with generalised MG. Factors
influencing the decision may include:
- age
- duration of the disease
- severity of the disease
- response to medication
- allergies
- cosmetic considerations.
In 1937, Dr. Alfred Blalock removed
the thymus of a myasthenic patient when the thymus was found to
have a tumour. He discovered that the symptoms of MG in the patient
showed improvement. Since that time, thymectomy has been used
as a normal course of treatment for myasthenics around the world,
although the precise reason why it is beneficial is still not
known.
In the past, it was thought that
thymectomy would not benefit older patients (over 45 years old),
or people who have had the disease for over 5 years. Yet some
older patients and some long-standing MG patients have benefited
from thymectomy, so now the recommendation for this procedure
has to be considered on an individual basis. Although, there is
uncertainty about the persistence of thymic tissue in such patients
after the age of 60.
After a thymectomy, remission or
marked improvement occurs in more than half of cases. Those who
had thymomas do not usually improve as much as in young myasthenics
without a thymoma.
Access to the thymus can be gained
either by:
1. transsternal thymectomy - the
incision is made length-wise on the chest and the breastbone
(sternum) is split open; or
2. transcervical thymectomy where access is gained through the
neck.
There are advantages and disadvantages
to each approach. The splitting of the sternum is more traumatic
than surgery through the neck, and the recovery time is longer,
but it is more common because it more thorough allowing easier
identification and removal of all thymic tissue (some doctors
believe that leaving any remnant of thymic tissue in the body
will increase the likelihood of the procedure failing).
About 30% of MG patients without
a thymoma who undergo thymectomy eventually go into complete drug-free
remission, and another 50% experience marked improvement. This
improvement usually does not occur immediately after surgery,
but may take up to several months or years to reach its peak effect.
You cannot predict beforehand who will benefit from thymectomy,
and even after benefit occurs there is still a small possibility
of subsequent relapse. However, thymectomy itself rarely worsens
the long-term course of MG.
Even invasive thymomas are not always
detected with imaging tests and have been discovered during thymectomy
surgery. Such experiences would argue in favor of eventual thymectomy
over immunosuppressive drug therapy in otherwise healthy young
or middle-aged MG patients, once the patient is up to the surgery.
The possibility of an eventually complete symptom-free remission
after thymectomy without the need to take any drugs, compared
to a remission dependent upon the continued treatment with immunosuppressive
drugs, is another significant advantage of thymectomy.
It is normally preferred that children
wait until puberty before undertaking thymectomy because of the
established role of the thymus in development of the immune system.
The process for a thymectomy is
as follows:
1. An x-ray is taken of the patient's
chest to determine the location of the thymus and to determine
the existence of a thymoma.
2. An anesthetist will consult
the patient about the anesthesia plan - how the patient will
be put to sleep, the use of any special drugs that will be needed
to help the patient relax before surgery, and how the patient
will generally feel after surgery. It is important that the
patient tell the anesthetist about any allergies or reactions
to any foods or medicines.
3. Food and fluids will be withheld
after midnight, or on the day of surgery. Routine medication
for Myasthenia may or may not be given.
4. On the morning of surgery,
a pre-operative medicine may be given by injection. This medication
can cause relaxation, drowsiness, and dryness of the mouth.
5. After surgery, a one to three
hour stay in the recovery room is required. The patient will
then be transferred to Intensive Care Unit for 12 to 24 hours
to ensure that everything is proceeding normally. In this phase
of the recovery, fluids and medication will be given by means
of a needle in the vein called an intravenous, or I.V. They
will then be transferred back to their ward. Very occasionally
if the patient has some breathing difficulties he or she may
temporarily be connected to a ventilator so as to ease this
problem.
6. Once fluids are tolerated by
the mouth, the intravenous fluids will be stopped. Solid foods
will be started slowly, and the patient's medication will once
more be given by mouth. If progress is maintained, the patient
will probably be allowed home in 7 days (although length of
stay in the hospital varies for each patient).
7. Most patients complain of some
chest soreness and pain after surgery. This can be lessened
with pain medication. At intervals, the patient will be asked
to do coughing and deep breathing exercises to clear the lungs
of mucus. This does cause discomfort which can be lessened by
hugging a pillow and supporting the chest while coughing. Pain
medication can be taken prior to any activity or exercise to
alleviate after-surgery discomfort.
8. The recovery period away from
work varies. Most patients take 4 - 6 weeks off work for convalescence.
Those with jobs which require heavy lifting or any strain on
the chest may need a longer recovery time so that the chest
is more fully healed before starting work. The patient should
discuss this with the surgeon prior to the surgery in order
to plan the recovery time.
After surgery there may be an increase
in muscle weakness in some patients. However, treatment will be
adjusted to meet individual needs.
Thymectomy may lessen the severity
of the myasthenic symptoms; however, the degree to which the symptoms
are lessened differs in each patient. The mechanism by which thymectomy
produces benefits in MG is still uncertain. In general, ACh antibody
levels fall after thymectomy, although there are conflicting reports.
A study published in 1983 study findings found as high as 85%
of patients who underwent thymectomy showed clinical improvement,
and the maximal favorable response generally occurs 2 to 5 years
after surgery (but some people may experience better health 7
to 10 years after surgery). The best responses to thymectomy are
in young people early in the course of their disease, but improvement
can occur even after 30 years of symptoms. Patients with thymomas
do not respond as well to thymectomy as do patients without thymoma.
The worst response rate to the surgery was from those who had
surgery when they were over 60 years of age.
When considering surgery, it is
important for the myasthenic to tell their neurologist and their
surgeon of any concerns - the length of time of surgery, the effects
of the anesthetic, the resultant scar, after surgery care, pain
management.
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