Myasthenia gravis

Myasthenia gravis is a chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles, which are responsible for breathing and moving parts of the body, including the arms and legs. The name myasthenia gravis, which is Latin and Greek in origin, means “grave, or serious, muscle weakness.”

• Myasthenia gravis (MG) is an autoimmune disorder affecting nicotinic acetylcholine receptors (ACHR) of the post synaptic neuromuscular junction (NM).
• It is clinically characterized by fluctuating weakness without sensory or autonomic dysfunction, fatigability and a predilection for oculobulbar musculature.

INCIDENCE 

• Myasthenia gravis is rare, with a prevalence of 5 per 100000
• Female to male ratio about-2:1
• The increase of autoimmune disorders in patient and first degree relatives and association of the disease with certain histocompatibility antigen (HLA) –B7, B8 , and DR2-suggests an immunological basis.

AETIOLOGY

• Antibodies bind to the receptor sites resulting in their destruction.

• These antibodies are referred to as acetylcholine receptor antibodies (ACHR antibodies)
• In human myasthenia gravis a reduction of acetylcholine receptor sites has been demonstrated in the postsynaptic folds.
• Reduced receptor synthesis and increase receptor destruction, as well as the blocking of receptor response to acetylcholine, all seem responsible for the disorder.

The role of the thymus:-

• Thymic abnormalities occur in 80% of patient.
• The main function of thymus is to affect the production of T lymphocytes, which participate in immune response.
• Thymus dysfunction is noted in a large number of disorders which may be associated with myasthenia gravis.e.g. – systemic lupus erythematosus.

Muscle biopsy- may show abnormalities:

• Lymphocytic infiltration associated with small necrotic foci of muscle fiber damage.
• Muscle fiber atrophy (type I and II or type III alone)
• Diffuse muscle necrosis with inflammatory infiltration, when associated with thyoma.

Motor point biopsy:- may show abnormal motor end-plates.

• Supravital methylene blue staining reveals abnormally long and irregular terminal nerve branching.
• Light and electron microscopy show destruction of ACH receptors with simplification of the secondary folds of the postsynaptic surface.

CLINICAL FEATURES

• Up to 90% of patient in early adult life (<40 years of age)
• Several clinical subdivisions are recognized:-
  • Class 1- ocular muscles only-20%
  • Class 2- mild generalized weakness
  • Class 3- moderate generalized and mild to moderate ocular-bulbar weakness
  • Class 4- severe generalized and ocular-bulbar weakness.
  • Class 5- myasthenic crises
• Respiratory muscle involvement accompanies severe illness.
• Cranial nerve signs and symptoms:-
  • Ocular involvement produce ptosis and muscle paresis.
  • Weakness of jaw muscles allows the mouth to hang open.
  • Weakness of facial muscles results in expressionless appearance.
  • On smiling , buccinator weakness produce a characteristic smile (myasthenic snare).
• Bulbar involvement may result in:-
  • Dysarthric dysphonic speech and dysphagia.
  • Nasal regurgitation of fluids-nasal quality to speech.
• Limb and trunk signs and symptoms:-
  • Weakness of neck muscles may result in lolling of the head.
  • Fatigue may be demonstrated by movement against a constant resistance.
  • Limb reflexes are often hyperactive and fatigue on repeated testing.
  • Muscle wasting occur in 15% of cases.
  • Stress, infection and pregnancy and drug that alter neuromuscular transmission all exacerbate the weakness.

CLASSIFICATION

When diagnosed with MG, a person is assessed for his or her neurological status and the level of illness is established.

This is usually done using the accepted Myasthenia Gravis Foundation of America Clinical Classification scale, which is:

INVESTIGATION:-

A) Pharmacological:-

• Anticholinesterase drugs are used to confirm diagnosis
• Tensilon test (endrophonium) short action 2-4 min., give I.V. 2-10 mg slowly.This is positive when clear improvement in weakness occurs on objective testing.

B) SEROLOGICAL:-

Acetylcholine receptor antibodies (anti-ACHR) are detected in 90% of patient.

C) ELECTROPHYSIOLOGICAL:-

Reduction of the amplitude of the compound muscle action potential evoked by repetitive supra maximal nerve stimulation- the decrementing response.

Additional:-

• Chest x-ray will show a large mediastinal mass but will not exclude a small Thyoma.
• CT of chest should be performed in all newly diagnosed cases.

TREATMENT

In severely ill patient, the first priority is to protect respiration by intubation and if necessary, ventilation.

ANTICHOLINESTERASE DRUG:-

• Inhibit cholinesterase ( the enzyme responsible for the breakdown of acetylcholine) ⇒ Allowing enhanced receptor stimulation ⇒ As a more acetylcholine is available to effect neuromuscular transmission.

• A muscuranic inhibitor, atropine may be required to side effect.( nausea, vomiting, diarrhea, muscle fasciculation and increase weakness.)

STEROIDS:-

Because these disorder is immune- mediated, steroids are logical choice.prednisone inhibit the immune system, limiting antibody production.

IMMUNOSUPPRESSANTS

Medications that alter your immune system, such as

• azathioprine (Imuran),
• mycophenolate mofetil (CellCept),
• cyclosporine (Sandimmune, Neoral),
• methotrexate (Trexall) or
• tacrolimus (Prograf).

THYMECTOMY –

Two indications⇒

• When thymoma is present.
• When myasthenia is generalized and benefits of surgery out weigh risks.

A thymectomy may be performed as an open surgery or as a minimally invasive surgery.

In an open surgery, your surgeon splits the central breast bone (sternum) to open your chest and remove your thymus gland.

Minimally invasive thymectomy may include:

• Video-assisted thymectomy.
  • In one form of this surgery, surgeons make a small incision in your neck and use a long thin camera (video endoscope) and small instruments to visualize and remove the thymus gland through your neck.
  • Alternatively, surgeons may make a few small incisions in the side of your chest.
• Robot-assisted thymectomy.
  • In a robot-assisted thymectomy, surgeons make several small incisions in the side of your chest.
  • Surgeons conduct the procedure to remove the thymus gland using a robotic system, which includes a camera arm and mechanical arms.

Benefits of these procedures may include less blood loss, less pain, lower mortality rates and shorter hospital stays compared with open surgery.

PLASMAPHERESIS

Plasma Filtration remove antibodies and other circulating factor and has short term benefit (4-6 weeks).

INTRAVENOUS IMMUNOGLOBULIN

• This therapy provides your body with normal antibodies, which alters your immune system response.
• IVIg (intravenous immunoglobulin) has a lower risk of side effects than do plasmapheresis and immune-suppressing therapy.
• Mechanism-blocking ACH  receptors.
• Positive response (75% of patient lasts for 2-3 months.
• Treatment is expensive and long term effect and complication unknown.

COMPLICATIONS

Complications of myasthenia gravis are treatable, but some can be life-threatening.

 Myasthenic crisis

• Myasthenic crisis is a life-threatening condition that occurs when the muscles that control breathing become too weak to do their jobs.
• Emergency treatment is needed to provide mechanical assistance with breathing.
• Medications and blood-filtering therapies help people to again breathe on their own.

Other disorders

People with myasthenia gravis are more likely to have the following conditions:

• Underactive or overactive thyroid.
  • The thyroid gland, which is in the neck, secretes hormones that regulate your metabolism.
  • If your thyroid is underactive, you may have difficulties dealing with cold, weight gain and other issues.
  • An overactive thyroid can cause difficulties dealing with heat, weight loss and other issues.
• Autoimmune conditions.
  • People with myasthenia gravis may be more likely to have autoimmune conditions, such as rheumatoid arthritis or lupus.

PHYSIOTHERAPY TREATMENT

• Physical therapist will design a program of exercises that focus on myasthenia gravis.
• Squats to strengthening the quadriceps and hamstring muscle.
• SLR to promote strength in your abdominal and hip muscles.
• If your muscles are extremely weak,
  • PROM
  • Assisted ROM
  • ROM
  • Resisted ROM
  • Or strengthening exercises such as weight lifting.

BREATHING EXERCISE:-

• To improve lung function and breathing pattern.
• To strengthen lung muscles.
  • Pursed lip breathing
  • Diaphragmatic breathing
  • Abdominal breathing.