Myasthenia: What is it? Causes, Symptoms, Diagnosis and Treatments

It is a neuromuscular autoimmune disease that affects the use of muscles. Normal communication between the nerve and the muscle is disrupted, leaving the muscle weak and fatigued.

An autoimmune disease is one in which the body’s immune system appears to attack healthy tissue and produces so many antibodies (immune blood proteins that recognize and fight infections and other foreign things in the body) that healthy tissue is damaged.

With MG, it is the voluntary (striated) muscles that are weakened. Voluntary muscles are the muscles that we can control, where the message is transmitted through our nervous system to contract the muscle.

They are the muscles of our legs, our arms and our neck; those who move the eyeball and keep the eyelids open; some of those involved in facial expression and those that involve chewing, swallowing and breathing. MG does not affect bowel and bladder function or the mental capacity of the myasthenic.

In order for a muscle to contract, the chemical acetylcholine normally transmits nerve impulses to the muscle fibers at the place where the nerve and muscle connect (the neuromuscular junction).

Physical weakness of the myasthenic muscle is caused by a defect in this neuromuscular junction. However, while the myasthenic has a problem with the transmission of nerve impulses to the muscle, the nerves and the muscles themselves can remain normal.

Research has shown that most myasthenias form abnormal antibodies against the acetylcholine receptor (sites where the chemical can be received on the surface of the muscle).

The number of acetylcholine receptors in a myasthenia is reduced due to an attack of the receptors by the body’s immune system: if receptors are missing, the muscle’s response to nerve impulses is poor, leading to weakness.

Scientists are investigating what triggers the body to develop an autoimmune response. In many myathenes, the thymus gland appears to be involved.

The onset of MG can be sudden, with severe and generalized muscle weakness, but more often the symptoms in the early stages are subtle and variable, making the correct diagnosis difficult.

Some only have ocular myasthenia that affects the muscles and lids of the eye; others mainly have difficulty swallowing or difficulty speaking; others have generalized MG that affects many muscle groups.

Muscle weakness can develop over a few days or weeks, or remain at the same level for long periods of time.

The severity varies at different times of the day and from person to person. The maximum degree of involvement in an individual patient usually manifests in the first 5 to 7 years, and then tends not to be progressive, although muscle involvement and the severity of weakness can fluctuate from hour to hour and from day to day.

Myasthenia gravis (MG) is generally not a degenerative disease, that is, with continued use, the muscle itself should not deteriorate.

A hallmark of MG, however, is fluctuating muscle weakness, worsened by the use of those muscles and enhanced by the rest of the same muscles. Consequently, a person with MG experiences phases of muscle weakness that alternate with periods of normal health.

MG is not considered an inherited disease, as there is no well-documented case of MG in a child of a mother with MG.

However, about 12% of babies born to myasthenic mothers have neonatal myasthenia, where the baby develops a weak cry, poor sucking, and shortness of breath.

These symptoms disappear during the first months of life. It is rare for babies born to non-myasthenic mothers to have myasthenic symptoms; These babies are said to have congenital myasthenia.

Currently MG is not considered fatal. It can be life threatening if muscle weakness interferes with breathing. It is treatable, but at this stage, not curable. Treatments provide patients with marked relief from symptoms and often allow them to lead full and normal lives.

What Causes Myasthenia Gravis?

Myasthenia gravis (MG) is about muscles that cannot contract. Every time your body moves, whether you’re walking, talking, or breathing, a muscle contracts.

There are three general types of muscles:

  • Smooth muscle : these are muscles that are not under conscious control, such as the muscles of the walls of the digestive tract.
  • Skeletal Muscle : Also known as striated or voluntary muscles, these are the muscles that are attached to parts of the skeleton and are under our voluntary control; we can send messages from the brain to tell the muscle what to do, for example walk and talk.
  • Cardiac muscle:   the muscles of the heart.

Muscles work by transforming chemical energy into mechanical energy, which moves the human body. In summary, for a muscle to contract, the following must occur:

An electrical impulse travels from the brain, through the spinal cord to a nerve (the nerves that control the muscle are called motor neurons).

The nerve ending then releases a neurotransmitter substance called acetylcholine (ACh).

Acetylcholine travels through a small space between the nerve and the muscle (at the neuromuscular junction) and binds to a protein (receptor) on the surface of the muscle (the muscle membrane) to which the nerve is attached
resulting in in the contraction of that muscle.

It is at the neuromuscular junction (NMJ) where MG does its damage.

In MG, receptors on the surface of the muscle are destroyed or deformed by antibodies that prevent a normal muscle reaction from occurring. Antibodies are proteins produced by the immune system to fight infection and disease.

With autoimmune diseases like MG, the body mistakenly sends antibodies to attack healthy tissue. In MG specifically, the immune system is activated to attack a healthy neuromuscular junction.

The antibodies bind to the muscle membrane and initiate a series of events that destroy the membrane and prevent ACh from binding. ACh plays a critical role in muscle contraction.

When a nerve sends a message telling a muscle to contract, a large amount of ACh is released. If ACh cannot bind to the muscle, the muscle will not contract.

No one knows exactly what triggers MG, but about 70% of all myasthenias show evidence of a particular type of abnormal immune response believed to be caused by an abnormal thymus gland (an organ in the chest that plays an essential role in the development of the body’s immune system).

About 15% of all myasthenia have tumors in the thymus, although the tumors are usually benign.

Symptoms of myasthenia gravis

Myasthenia gravis (MG) is not uniform in the way it affects people. Different people have difficulties with different muscle groups – severity can fluctuate, and reaction to treatment can also vary.

The course of the condition is variable, but in most cases progressive.

For this reason, the disease is very confusing to the undiagnosed myasthenic (and puzzling to the unsuspecting physician). At one point, the myasthenic can function normally and at another time it experiences severe loss of strength.

Others may think that myasthenics are lazy or suffering from a psychological problem. This can lead to frustration and emotional stress, which only aggravates the condition.

There are many factors that can trigger episodes of weakness in myasthenia, including other diseases (for example, viral respiratory infections), medications that affect the neuromuscular junction, hot weather, pregnancy, and emotional distress.

The undiagnosed myasthenic might not relate the various symptoms to a condition. It should be noted that pregnancy may worsen, improve, or have no effect on the condition; that is, a woman will not know how pregnancy will affect her condition until she is actually pregnant.

Symptoms of MG often consist of muscle fatigue with myasthenia complaining of a worsening of symptoms later in the day after your muscles have become fatigued or after repetitive exercise.

Eye muscle weakness is usually the first noticeable symptom. The disease can stay there, or it can progress to the rest of the body.

Symptoms can be:

  • Difficulty in eye movement resulting in double vision or droopy eyelids.
  • Soft spot.
  • Fatigue in the arms and legs.

Other symptoms can include:

  • Throat muscle fatigue – resulting in difficulty swallowing and choking.
  • Speech muscle fatigue – resulting in slurred, unintelligible speech, or shortness of breath.

Eye symptoms

Ocular myasthenia is when MG is confined to the muscles of the eye.

The impact of the condition on the eye muscles includes:

  • Drooping of one or both eyelids.
  • Double or blurred vision.
  • Weakness of the muscles that move the eyeballs.

During an episode of eye fatigue, the window of vision of a myasthenic is restricted to the narrow grooves between the upper drooping eyelids and the lower eyelid.

For this reason, several myasthenia walk with their noses in the air (when their neck muscles are strong enough to support their head). Bright lights can aggravate the symptom.

In a minority of myasthenia (about 15%), MG is limited to eye problems.

But for most of the first symptoms are ocular, MG eventually moves to other parts of the body in a couple of years.

Oral symptoms

Oral symptoms include difficulties with:

  • Swallowing ( dysphagia ).
  • Chew.
  • Talk.
  • Breathe.

Muscle weakness in the pharynx (the section of the digestive tract that extends from the mouth and nasal cavities to the larynx, where it becomes continuous with the esophagus) is another early sign of MG.

Swallowing difficulties are particularly worrisome as they can be dangerous. Myasthenias generally develop well at the beginning of a meal, but tire at the end, making swallowing difficult.

Some deteriorate to the point where there is a complete loss of the ability to chew and swallow. At this point, it is possible for food to stick in the throat, or for food and drink to start going the wrong way, for example, to the windpipe, causing coughing and choking.

Foods that can trigger MG symptoms can be:

  • Very hot.
  • Spicy
  • Dry

Foods that require a lot of chewing effort, such as tough meats or chewy sweets, can also tire myasthenium and cause difficulty swallowing.

In situations where swallowing is too difficult, the myasthenic may be advised not to eat or drink anything until symptoms improve. They will be alternately fed according to the recommendation of a dietitian or fed intravenously.

MG can affect speech in a number of ways. Fatigue is established in the muscles of:

  • The throat (does not allow to swallow saliva).
  • The tongue (does not allow one to properly move the tongue around the mouth and does not move it fast enough).
  • The mouth (not being able to manipulate the mouth to form sounds).

Speech may sound nasal or slurred. And the weakness of the facial muscles results in the inability to even smile.

In a minority of myasthenias, the voice box can be affected, resulting in an inability to speak.

MG also affects the ability to breathe. Deterioration can be abrupt and can lead to putting on a respirator. If breathing or coughing becomes insufficient, the patient is said to be in “crisis” and mechanical ventilation in a hospital may be necessary.

In a myasthenic crisis, a respirator may be necessary to breathe.

One study found that of 175 myasthenics surveyed:

  • 30% had oral, pharyngeal (throat), or laryngeal (voice) complaints. Half of that 30% had swallowing disorders.
  • 13% had dysarthria (shuffling, fatigued speech)
  • 2% had dysphonia (voice disorders).

Generalized MG (head, neck, arms and legs)

This is where many muscle groups are affected. The typical myasthenic may feel strong upon waking from a restful night or nap, but experience increased muscle fatigue as the day progresses.

Within the first year after onset, about half of ocular myasthenia will experience the involvement of other muscles, and another 30% will do so over the next two years.

Numbness, heaviness, muscle spasm, or loss of limb control may be experienced by the myasthenic. Limb weakness is often not symmetrical, with one side weaker than the other.

Shoulder weakness is demonstrated by problems holding an arm to comb or wash hair, or to shave or put on makeup.

Grip can become weak opening jars (and child-resistant medicine bottles), hips can weaken when stepping out of deep chairs or the tub, and legs can tire when climbing stairs or walking distances.

MG itself is painless, but the strain of supporting weak limbs or neck can be painful.

Another symptom, not often mentioned in literature, but complained of by some mystics, is a feeling of loss of balance.

The problem with MG, particularly in the undiagnosed myasthenic, is that an episode can occur without warning and can turn what is normally a non-threatening activity into a dangerous one.

For example, a myasthenic can really hurt themselves if there is sudden muscle weakness when they take a step and suddenly find themselves on the road.

Worse still is the sudden muscle weakness when driving a car: sudden double vision, heavy eyelids, loss of control of the right leg, weakening of the arm muscles – all are a terrifying journey for the unsuspecting undiagnosed myasthenia.

Diagnosis: how is myasthenia gravis confirmed?

The symptoms of myasthenia gravis (MG) are common complaints that can be found in a variety of medical and even psychological conditions.

Symptoms include:

  • Droopy eyelids.
  • Double vision.
  • Difficulty chewing or swallowing.
  • Weakness in almost any part of the body.
  • Simple fatigue.

One can see that the symptoms of MG are not specific to the condition. This can make the diagnosis of MG difficult, particularly in cases where the condition is mild, or when the doctor is not familiar enough with MG to suspect the condition.

In general, an individual with potential MG symptoms would be referred to a neurologist for diagnosis, but sometimes an ophthalmologist or immunologist would also make the diagnosis.

There are many different types of disorders that can cause MG-like symptoms, so a complete history and general and neurological exam are important initial steps in diagnosing MG and ruling out other disorders.

This can include a careful family history, medical history, and medication history; as disorders that can mimic MG can occur for many different reasons.

Therefore, it is important that your doctor has access to your previous medical records and any previous tests, in particular, this includes scans and X-rays. This section does not address tests that may be necessary to investigate potential diagnoses other than MG.

You often don’t realize that there is no single test that absolutely proves the diagnosis of MG. However, the combination of history, clinical examination, nerve tests, and blood tests often establishes the diagnosis beyond reasonable doubt.

If there are doubts after the tests have been completed, a MG treatment trial often helps to clarify the problem, and the diagnosis also often becomes clearer in the long term.

Treatments

Myasthenia is no longer considered a fatal disease. Most people, with the help of medications and / or surgery, lead almost normal lives.

However, there is no standard therapy for all myasthenia 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 up to the patient. What works for one person may not work at all for another. And what works for one part of the body in one patient may not work for another part of the body.

A physician 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 that doctors, family and friends can offer.

Typically, a neurologist is involved in the diagnosis and treatment of the disease.

It would be helpful if the neurologist has extensive knowledge and experience in managing MG (with the incidence of MG in only one person in at least 10,000 people, it is very likely that several neurologists have had little experience with this condition).

Current therapies for MG

  • Anticholinesterase therapy : It is an attempt to strengthen neuromuscular transmission with the use of drugs such as pyridostigmine bromide (mestinon, extended-release mestinon) and neostigmine (Prostigmin).
  • Terapia inmunosupresora : prednisona; azatioprina (Imuran); ciclofosfamida (Cytoxan); ciclosporina (Sandimmune); mycophenolate mofetil (CellCept).
  • Plasma Exchange: Plasmaféresis.
  • Intravenoso: Immune Globin.
  • Other therapies : atropine, pro-banthine, ephedrine.