MYASTHENIA GRAVIS

What is myasthenia gravis?

Myasthenia gravis is a chronic autoimmune neuromuscular disease

characterized by varying degrees of weakness of the skeletal (voluntary)
muscles of the body. The name myasthenia gravis, which is Latin and Greek
in origin, literally means "grave muscle weakness." With current therapies,
however, most cases of myasthenia gravis are not as "grave" as the name
implies. In fact, most individuals with myasthenia gravis have a normal life
expectancy.
The hallmark of myasthenia gravis is muscle weakness that increases during
periods of activity and improves after periods of rest. Certain muscles such
as those that control eye and eyelid movement, facial expression, chewing,
talking, and swallowing are often, but not always, involved in the disorder.
The muscles that control breathing and neck and limb movements may also
be affected.

What causes myasthenia gravis?

Myasthenia gravis is caused by a defect in the transmission of nerve

impulses to muscles. It occurs when normal communication between the
nerve and muscle is interrupted at the neuromuscular junctionthe place
where nerve cells connect with the muscles they control. Normally when
impulses travel down the nerve, the nerve endings release a
neurotransmitter substance called acetylcholine. Acetylcholine travels from
the neuromuscular junction and binds to acetylcholine receptors which are
activated and generate a muscle contraction.
In myasthenia gravis, antibodies block, alter, or destroy the receptors for
acetylcholine at the neuromuscular junction, which prevents the muscle
contraction from occurring. These antibodies are produced by the body's own

immune system. Myasthenia gravis is an autoimmune disease because the

immune systemwhich normally protects the body from foreign organisms
mistakenly attacks itself.

What is the role of the thymus gland in myasthenia gravis?

The thymus gland, which lies in the chest area beneath the breastbone,
plays an important role in the development of the immune system in early
life. Its cells form a part of the body's normal immune system. The gland is
somewhat large in infants, grows gradually until puberty, and then gets
smaller and is replaced by fat with age. In adults with myasthenia gravis, the
thymus gland remains large and is abnormal. It contains certain clusters of
immune cells indicative of lymphoid hyperplasiaa condition usually found
only in the spleen and lymph nodes during an active immune response.
Some individuals with myasthenia gravis develop thymomas (tumors of the
thymus gland). Thymomas are generally benign, but they can become
malignant.
The relationship between the thymus gland and myasthenia gravis is not yet
fully understood. Scientists believe the thymus gland may give incorrect
instructions to developing immune cells, ultimately resulting in autoimmunity
and the production of the acetylcholine receptor antibodies, thereby setting
the stage for the attack on neuromuscular transmission.

What are the symptoms of myasthenia gravis?

Although myasthenia gravis may affect any voluntary muscle, muscles that
control eye and eyelid movement, facial expression, and swallowing are most
frequently affected. The onset of the disorder may be sudden and symptoms
often are not immediately recognized as myasthenia gravis.
In most cases, the first noticeable symptom is weakness of the eye muscles.
In others, difficulty in swallowing and slurred speech may be the first signs.
The degree of muscle weakness involved in myasthenia gravis varies greatly
among individuals, ranging from a localized form limited to eye muscles
(ocular myasthenia), to a severe or generalized form in which many muscles
sometimes including those that control breathingare affected.
Symptoms, which vary in type and severity, may include a drooping of one or
both eyelids (ptosis), blurred or double vision (diplopia) due to weakness of
the muscles that control eye movements, unstable or waddling gait, a

change in facial expression, difficulty in swallowing, shortness of breath,

impaired speech (dysarthria), and weakness in the arms, hands, fingers,
legs, and neck.

Who gets myasthenia gravis?

Myasthenia gravis occurs in all ethnic groups and both genders. It most
commonly affects young adult women (under 40) and older men (over 60),
but it can occur at any age.
In neonatal myasthenia, the fetus may acquire immune proteins (antibodies)
from a mother affected with myasthenia gravis. Generally, cases of neonatal
myasthenia gravis are temporary and the child's symptoms usually
disappear within 2-3 months after birth. Other children develop myasthenia
gravis indistinguishable from adults. Myasthenia gravis in juveniles is
uncommon.
Myasthenia gravis is not directly inherited nor is it contagious. Occasionally,
the disease may occur in more than one member of the same family.
Rarely, children may show signs of congenital myasthenia or congenital
myasthenic syndrome. These are not autoimmune disorders, but are caused
by defective genes that produce abnormal proteins instead of those which
normally would produce acetylcholine, acetylcholinesterase (the enzyme that
breaks down acetylcholine), or the acetylcholine receptor and other proteins
present along the muscle membrane.

How is myasthenia gravis diagnosed?

Because weakness is a common symptom of many other disorders, the

diagnosis of myasthenia gravis is often missed or delayed (sometimes up to
two years) in people who experience mild weakness or in those individuals
whose weakness is restricted to only a few muscles.
The first steps of diagnosing myasthenia gravis include a review of the
individual's medical history, and physical and neurological examinations. The
physician looks for impairment of eye movements or muscle weakness
without any changes in the individual's ability to feel things. If the doctor
suspects myasthenia gravis, several tests are available to confirm the
diagnosis.

A special blood test can detect the presence of immune molecules or

acetylcholine receptor antibodies. Most patients with myasthenia gravis have
abnormally elevated levels of these antibodies. Recently, a second antibody
called the anti-MuSK antibodyhas been found in about 30 to 40 percent
of individuals with myasthenia gravis who do not have acetylcholine receptor
antibodies. This antibody can also be tested for in the blood. However,
neither of these antibodies is present in some individuals with myasthenia
gravis, most often in those with ocular myasthenia gravis.
The edrophonium test uses intravenous administration of edrophonium
chloride to very briefly relieve weakness in people with myasthenia gravis.
The drug blocks the degradation (breakdown) of acetylcholine and
temporarily increases the levels of acetylcholine at the neuromuscular
junction. Other methods to confirm the diagnosis include a version of nerve
conduction study which tests for specific muscle "fatigue" by repetitive nerve
stimulation. This test records weakening muscle responses when the nerves
are repetitively stimulated by small pulses of electricity. Repetitive
stimulation of a nerve during a nerve conduction study may demonstrate
gradual decreases of the muscle action potential due to impaired nerve-tomuscle transmission.
Single fiber electromyography (EMG) can also detect impaired nerve-tomuscle transmission. EMG measures the electrical potential of muscle cells
when single muscle fibers are stimulated by electrical impulses. Muscle
fibers in myasthenia gravis, as well as other neuromuscular disorders, do not
respond as well to repeated electrical stimulation compared to muscles from
normal individuals.
Diagnostic imaging of the chest, using computed tomography (CT) or
magnetic resonance imaging (MRI), may be used to identify the presence of
a thymoma.
Pulmonary function testing, which measures breathing strength, helps to
predict whether respiration may fail and lead to a myasthenic crisis.

How is myasthenia gravis treated?

Today, myasthenia gravis can generally be controlled. There are several

therapies available to help reduce and improve muscle weakness.
Medications used to treat the disorder include anticholinesterase agents such
as neostigmine and pyridostigmine, which help improve neuromuscular
transmission and increase muscle strength. Immunosuppressive drugs such
as prednisone, azathioprine, cyclosporin, mycophenolate mofetil, and

tacrolimus may also be used. These medications improve muscle strength by

suppressing the production of abnormal antibodies. Their use must be
carefully monitored by a physician because they may cause major side
effects.
Thymectomy, the surgical removal of the thymus gland (which often is
abnormal in individuals with myasthenia gravis), reduces symptoms in some
individuals without thymoma and may cure some people, possibly by rebalancing the immune system. Thymectomy is recommended for individuals
with thymoma. Other therapies used to treat myasthenia gravis include
plasmapheresis, a procedure in which serum containing the abnormal
antibodies is removed from the blood while cells are replaced, and high-dose
intravenous immune globulin, which temporarily modifies the immune
system by infusing antibodies from donated blood. These therapies may be
used to help individuals during especially difficult periods of weakness. A
neurologist will determine which treatment option is best for each individual
depending on the severity of the weakness, which muscles are affected, and
the individual's age and other associated medical problems.

What are myasthenic crises?

A myasthenic crisis occurs when the muscles that control breathing weaken
to the point that ventilation is inadequate, creating a medical emergency and
requiring a respirator for assisted ventilation. In individuals whose respiratory
muscles are weak, criseswhich generally call for immediate medical
attentionmay be triggered by infection, fever, or an adverse reaction to
medication.

What is the prognosis?

With treatment, most individuals with myasthenia can significantly improve

their muscle weakness and lead normal or nearly normal lives. Some cases
of myasthenia gravis may go into remissioneither temporarily or
permanentlyand muscle weakness may disappear completely so that
medications can be discontinued. Stable, long-lasting complete remissions
are the goal of thymectomy and may occur in about 50 percent of individuals
who undergo this procedure. In a few cases, the severe weakness of
myasthenia gravis may cause respiratory failure, which requires immediate
emergency medical care.

What research is being done?

Within the Federal government, the National Institute of Neurological

Disorders and Stroke (NINDS), one of the National Institutes of Health (NIH),
has primary responsibility for conducting and supporting research on brain
and nervous system disorders, including myasthenia gravis.
Much has been learned about myasthenia gravis in recent years.
Technological advances have led to more timely and accurate diagnosis, and
new and enhanced therapies have improved management of the disorder.
There is a greater understanding about the structure and function of the
neuromuscular junction, the fundamental aspects of the thymus gland and of
autoimmunity, and the disorder itself. Despite these advances, however,
there is still much to learn. Researchers are seeking to learn what causes the
autoimmune response in myasthenia gravis, and to better define the
relationship between the thymus gland and myasthenia gravis.
Different drugs are being tested, either alone or in combination with existing
drug therapies, to see if they are effective in treating myasthenia gravis. One
study is examining the use of methotrexate therapy in individuals who
develop symptoms and signs of the disease while on prednisone therapy. The
drug suppresses blood cell activity that causes inflammation. Another study
is investigating the use of rituximab, a monoclonal antibody against B cells
which make antibodies, to see if it decreases certain antibodies that cause
the immune system to attack the nervous system. Investigators are also
determining if eculizumab is safe and effective in treating individuals with
generalized myasthenia gravis who also receive various immunosuppressant
drugs.
Another study seeks further understanding of the molecular basis of synaptic
transmission in the nervous system. The objective of this study is to expand
current knowledge of the function of receptors and to apply this knowledge
to the treatment of myasthenia gravis.
Thymectomy is also being studied in myasthenia gravis patients who do not
have thymoma to assess long-term benefit the surgical procedure may have
over medical therapy alone.
One study involves blood sampling to see if the immune system is making
antibodies against components of the nerves and muscle. Researchers also
hope to learn if these antibodies contribute to the development or worsening
of myasthenia gravis and other illnesses of the nervous system.

Investigators are also examining the safety and efficacy of autologous

hematopoietic stem cell transplantation to treat refractory and severe
myasthenia gravis. Participants in this study will receive several days of
treatment using the immumosuppressant drugs cyclophosphamide and
antithymocyte globulin before having some of their peripheral blood cells
harvested and frozen. The blood cells will later be thawed and infused
intravenously into the respective individuals, whose symptoms will be
monitored for five years.

Ptosis - Ptosis is the medical term for a drooping eyelid. It refers only to the
upper eyelid; it does not refer to lower eyelid sagging.
Prednisone - a corticosteroid which suppress your immune system, and can
help control conditions in which your immune system mistakenly attacks its own
tissues.
1. What are the clinical features of osteoporosis?

There typically are no symptoms in the early stages of bone loss. But once
bones have been weakened by osteoporosis, you may have signs and symptoms
that include:
Back pain, caused by a fractured or collapsed vertebra
Loss of height over time
A stooped posture
A bone fracture that occurs much more easily than expected

2. Who are at risk for osteoporosis?

A thorough history should be obtained to screen for and identify the presence
of known risk factors for osteoporosis and osteoporotic fracture. Specifically, the
history should focus on the following:
Age (>50 years), sex (female), and race (white or Asian)
Family history of osteoporosis, particularly maternal history of fractures
Reproductive factors, especially regarding early menopause and estrogen
replacement therapy: postmenopausal women are at high risk, as are women who
have undergone hysterectomy and oophorectomy
Hypogonadal states: men with hypogonadism secondary to any genetic or
other conditions are at higher risk ; the USPSTF notes that there is insufficient
current evidence to assess the risk versus benefit of screening for osteoporosis in
men
Smoking: smokers are at higher risk
Alcohol consumption
Low levels of physical activity: immobility increases the risk; spinal cord
injury and stroke cause physical impairment and are common causes of immobility
Strenuous exercise that results in amenorrhea (such as that which occurs
in marathon runners)
Calcium and vitamin D intake
History of low-trauma "fragility" fracture in patients aged 40 years or older:
a fragility fracture is defined as a fracture due to trauma that would not normally
cause fracture (a force equal to or less than that resulting from a fall from standing
height)
Signs of vertebral fracture (see below)
Coexisting medical conditions associated with bone loss
Medications associated with bone loss
Risk factors for falls in older patients: these include poor balance,
orthostatic hypotension, weakness of the lower extremity muscles and
deconditioning, use of medications with sedative effects, poor vision or hearing, and
cognitive impairment

3. What are the classifications of osteoporosis?

Primary osteoporosis
Primary osteoporosis is the most common type of osteoporosis. It is more
common in women than men. A person reaches peak bone mass (density) at about
age 30; after that, the rate of bone loss slowly increases, while the rate of bone
building decreases. Whether a person develops osteoporosis depends on the
thickness of the bones in early life, as well as health, diet, and physical activity at all
ages.
In women, accelerated bone loss usually begins after monthly menstrual
periods stop, when a woman's production of estrogen slows down (usually between
the ages of 45 and 55). In men, gradual bone thinning typically starts at about 45 to
50 years of age, when a man's production of testosterone slows down. Osteoporosis
usually does not have an effect on people until they are 60 or older. Women are
usually affected at an earlier age than men because they start out with lower bone
mass.
Secondary osteoporosis
Secondary osteoporosis has the same symptoms as primary osteoporosis. But
it occurs as a result of having certain medical conditions, such as
hyperparathyroidism, hyperthyroidism, or leukemia. It may also occur as a result of
taking medicines known to cause bone breakdown, such as oral or high-dose
inhaled corticosteroids (if used for more than 6 months), too high a dose of thyroid
replacement, or aromatase inhibitors (used to treat breast cancer). Secondary
osteoporosis can occur at any age.
Osteogenesis imperfecta
Osteogenesis imperfecta is a rare form of osteoporosis that is present at
birth. Osteogenesis imperfecta causes bones to break for no apparent reason.
Idiopathic juvenile osteoporosis
Idiopathic juvenile osteoporosis is rare. It occurs in children between the ages
of 8 and 14 or during times of rapid growth. There is no known cause for this type of
osteoporosis, in which there is too little bone formation or excessive bone loss. This
condition increases the risk of fractures.
4. How do you diagnose osteoporosis?

A DEXA scan can be used to help diagnose osteoporosis. It's a quick, safe and
painless procedure that usually takes about five minutes, depending on the part of
the body being scanned. The scan measures your bone mineral density and
compares it to the bone mineral density of a healthy young adult and someone
who's the same age and sex as you.
5. What is the treatment for osteoporosis?

Bisphosphonates are the most common medications prescribed for

osteoporosis treatment. These include:
Alendronate (Fosamax)
Risedronate (Actonel)
Ibandronate (Boniva)
Zoledronic acid (Reclast)

Hormones, such as estrogen, and some hormone-like medications approved

for preventing and treating osteoporosis, such as raloxifene (Evista), also play a role
in osteoporosis treatment. However, fewer women use estrogen replacement
therapy now because it may increase the risk of heart attacks and some types of
cancer.
Still, women who have reasons such as menopausal symptoms to
consider using hormones or who are considering using Evista for breast cancer
prevention, can weigh the benefit of improved bone health into their decision.
6. What is the recommended daily intake of calcium for all ages? For
the patient?

For calcium, the daily recommendations vary by age and gender:

Newborns to 6 months: 200 milligrams
Babies 7-12 months: 260 milligrams
Kids 1-3: 700 milligrams
Kids 4-8: 1,000 milligrams

 Kids and teens 9-18: 1,300 milligrams

Adults 19-50: 1,000 milligrams
Adult men 51-70: 1,000 milligrams
Adult women 51-70: 1,200 milligrams
All adults 71 and older: 1,200 milligrams
Pregnant/breastfeeding women: 1,000 milligrams
Pregnant teens: 1,300 milligrams

7. How can you prevent osteoporosis?

Three factors essential for keeping your bones healthy throughout your life
are:
Adequate amounts of calcium
Adequate amounts of vitamin D
Regular exercise

8. Can men suffer from osteoporosis?

Yes, men do get osteoporosis, but women are at greater risk.

9. What is myotonia congenita?

Congenital myotonia (also myotonia congenita) (Myo- from Greek; muscle,

and Tonus from Latin; tension), is a genetic, neuromuscular channelopathy that
affects skeletal muscles (muscles used for movement)
10. What are the manifestations of myotonia congenita?

Early symptoms in a child may include:

Difficulty swallowing
Gagging
Stiff movements that improve when they are repeated
Frequent falling
Difficulties opening eyelids after strenuous contraction or crying (von
Graefe's sign)

Possible complications may include:

Aspiration pneumonia (caused by swallowing difficulties)
Frequent choking or gagging in infants (also caused by swallowing
difficulties)
Abdominal muscle weakness
Chronic joint problems
Injury due to falls

11. What is Amyotrophic Lateral Sclerosis (ALS)?

Amyotrophic lateral sclerosis (ALS) Lou Gehrig's disease, and rarely Charcot
diseaseis a neurodegenerative disorder with various causes. The term motor
neuron disease (MND) is sometimes used interchangeably with ALS, while others
use it to refer to a group of similar conditions that include ALS.[3] ALS is
characterized by muscle spasticity, rapidly progressive weakness due to muscle
wasting. This results in difficulty speaking, swallowing, and breathing. The disease
usually starts around the age of 60, except in cases that are directly inherited when
the usual age of onset is around 50.
12. Is there any treatment for ALS? What is the prognosis?

Because there's no reversing the course of amyotrophic lateral sclerosis,

treatments focus on slowing the progression of symptoms, preventing unnecessary
complications and making you more comfortable and independent.
Fifty percent of patients with Lou Gehrig's disease (ALS) live at least three or
more years after diagnosis; 20 percent live five years or more; and up to 10 percent
will survive more than ten years. Many ALS patients can live longer and more
productive lives because of current research into the cause, prevention and cure for
the disease.
Improvements in medical management, including nutrition and breathing,
regularly increase patient survival. Estimates suggest that ALS is responsible for as
many as five of every 100,000 deaths in people aged 20 or older.
13. What is the role of the neuromuscular junction in myasthenia
gravis?

In myasthenia gravis, antibodies block, alter, or destroy the receptors for

acetylcholine at the neuromuscular junction, which prevents the muscle contraction
from occurring. These antibodies are produced by the body's own immune system.
Myasthenia gravis is an autoimmune disease because the immune systemwhich
normally protects the body from foreign organisms mistakenly attacks itself.
14. Why is M.G. experiencing difficulty in chewing and double vision?

The hallmark of myasthenia gravis is muscle weakness that increases during

periods of activity and improves after periods of rest. Certain muscles such as those
that control eye and eyelid movement, facial expression, chewing, talking, and
swallowing are often, but not always, involved in the disorder. The muscles that
control breathing and neck and limb movements may also be affected.
15. What is thymectomy and how is it useful in treating some MG
patients?

A thymectomy is the surgical removal of the thymus gland. The thymus has
been demonstrated to play a role in the development of MG. It is removed in an
effort to improve the weakness caused by MG, and to remove a thymoma if present.
About 10% of MG patients have a tumor of the thymus called a thymoma. Most of
these tumors are benign and tend to grow very slowly; on occasion they are
malignant (cancerous).

16. Why must she undergo plasmapheresis when her symptoms

become severe?

Plasmapheresis is a form of apheresis that involves selective removal of the

patients plasma which is then replaced by special intravenous fluids. Myasthenia
gravis (MG) is the best example of a condition which can be successfully treated
using plasmapheresis in addition to oral medications. The exact cause of MG is not
known, but it is known that certain antibodies present in the patients plasma cause
interference at the nerve-muscle junction. In other words, the nerve
and the muscle are not communicating properly and this leads to muscle
weakness. By removing plasma and replacing it with a plasma substitute, it is
possible to relieve some of the symptoms of muscle weakness. The best way to
understand plasmapheresis is to think of it in terms of a continuous withdrawal of a
small amount of blood, and then having that blood continuously returned without
the antibodies that were causing the symptoms.
17. Which muscles, when weakened, place the patient at risk of
respiratory failure? Explain.

Weakness of the muscles of ventilation can cause acute respiratory failure.

This is an acute neurological emergency that requires ventilation. Weak pharyngeal
muscles can also lead to compromise of the airway. Muscles of ventilation include
the diaphragm.