Myasthenia Gravis

Submitted to:
Jammaella Vernice Tevez-Gomez, PTRP Prime Rose Lanete, PTRP

Submitted by:
Agcaoili, Kalenina Nathalia C. Cuenca, Charisse M. Jabal, Jan Evan C. Navarro, Randolf N. Sevilla, Myrtz Melody R.

Definition of Terms

Myasthenia Gravis - a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Endocytosis process in which a cell takes in a particular substance. HLA or Human Leukocyte Antigen - the name of the major histocompatibility complex (MHC) in humans. B Cell lymphocyte that can develop into a clone of antibody-producing plasma cells or memory cells when properly stimulated by a specific antigen. T Cell lymphocyte that becomes immunocompetent in the thymus and can differentiate into a helper T cell or a cytotoxic T cell; both of which function in cell mediated immunity. Pathogen a specific substance that cause illness to the host it invades. Thymus - organ located in the upper anterior portion of the chest cavity just behind the sternum; provides an area for T cell maturity and is vital in protecting against autoimmunity. Ptosis drooping of eyelid Diplopia double vision Dysarthria difficulty speaking Dysphagia difficulty swallowing Myasthenic Crisis - a medical emergency that develops when muscles that control breathing become severely weakened.

Brief History

It was first described in 1672 by Thomas Willis, an English physician, and fully described in 1890 by three German physicians, Samuel Goldflam, Wilhelm Erb, and Friedrich Jolly. Even though the disease was then well recognized, it was still rare and often times fatal.

Epidemiology

Myasthenia gravis occurs in all ethnic groups and both genders. It most commonly affects women under 40 - and people from 50 to 70 years old of either sex, but it has been known to occur at any age. Younger patients rarely have thymoma. The prevalence in the United States is estimated at 20 cases per 100,000 Risk factors are the female gender with ages 20 40, familial myasthenia gravis, D-penicillamine ingestion (drug induced myasthenia), and having other autoimmune diseases.

Three types of myasthenic symptoms in children can be distinguished: 1. Neonatal: In 12% of the pregnancies with a mother with MG, she passes the antibodies to the infant through the placenta causing neonatal myasthenia gravis. The symptoms will start in the first two days and disappear within a few weeks after birth. With the mother it is not uncommon for the symptoms to even improve during pregnancy, but they might worsen after labor. 2. Congenital: Children of a healthy mother can, very rarely, develop myasthenic symptoms beginning at birth. This is called congenital myasthenic syndrome or CMS. Other than Myasthenia gravis, CMS is not caused by an autoimmune process, but due to synaptic malformation, which in turn is caused by genetic mutations. Thus, CMS is a hereditary disease. More than 11 different mutations have been identified and the inheritance pattern is typically autosomal recessive. 3. Juvenile myasthenia gravis: myasthenia occurring in childhood but after the peripartum period. The congenital myasthenias cause muscle weakness and fatigability similar to those of MG. The symptoms of CMS usually begin within the first two years of life, although in a few forms patients can develop their first symptoms as late as the seventh decade of life. A diagnosis of CMS is suggested by the following:

Onset of symptoms in infancy or childhood. Weakness which increases as muscles tire. A decremental EMG response, on low frequency, of the compound muscle action potential (CMAP).

No anti-AChR or MuSK antibodies. No response to immunosuppressant therapy. Family history of symptoms which resemble CMS.

The symptoms of CMS can vary from mild to severe. It is also common for patients with the same form, even members of the same family, to be affected to differing degrees. In most forms of CMS weakness does not progress, and in some forms, the symptoms may diminish as the patient gets older. Only rarely do symptoms of CMS become worse with time.

Pathophysiology
Antibodies directed against nicotinic acetylcholine receptor

Impair acetylcholines ability to bind with the receptor or others lead to the destruction of receptors

Post synaptic muscle membrane is distorted

Concentration of AcH is reduced

Post junctional membrane is less sensitive to applied AcH

Nerve impulse that cause muscle action potential is reduced

Explanation:

Myasthenia Gravis is an autoimmune disease which means that it is caused by the bodys own immune system. The antibodies are somehow directed against the bodys own proteins. Specifically, there is no known causative pathogen for this disease. The antibodies are produced by plasma cells which are derived from B cells. B cells become plasma cells by T cell stimulation. The antibodies are directed towards a specific receptor called the nicotinic acetylcholine receptor. This receptor is found at the motor end plate for the neurotransmitter acetylcholine to stimulate muscle contraction. The antibody impairs the ability of acetylcholine to bind with the receptor or in some cases, it destroys the receptor itself either by complement fixation or by endocytosis. With the decreasing number of receptors, the post synaptic membrane then loses its folded shape and eventually becomes distorted causing the concentration of acquired acetylcholine (AcH) to be reduced. Since the membrane is less sensitive to AcH, nerve impulse that cause muscle action potential is also reduced.

Clinical Manifestations
A person with MG often encounters dysarthria, dysphagia, ptosis, and diplopia. Patients often have nasal-sounding speech and weak neck muscles that give the head a tendency to fall forward or backward. These symptoms occur in about 90% of MG cases and are usually intermittent. In myasthenic crisis a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life. In patients whose respiratory muscles are already weak, crises may be triggered by infection, fever, an adverse reaction to medication, or emotional stress. Since the heart muscle is stimulated differently, it is never affected by MG. Factors that can trigger complications in patients with myasthenia gravis include illness (e.g., viral respiratory infection), surgery, corticosteroid use that is tapered too quickly, overexertion (especially in hot weather), pregnancy, and emotional stress.

Treatment and PT Management

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, cyclosporine, and azathioprine may also be used. These medications improve muscle strength by suppressing the production of abnormal antibodies. They must be used with careful medical follow up because they may cause major side effects. Thymectomy, the surgical removal of the thymus gland (which often is abnormal in myasthenia gravis patients), reduces symptoms in more than 70

percent of patients without thymoma and may cure some individuals, possibly by re-balancing the immune system. Other therapies used to treat myasthenia gravis include plasmapheresis, a procedure in which abnormal antibodies are removed from the blood, and high-dose intravenous immune globulin, which temporarily modifies the immune system and provides the body with normal 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. Since a patient with MG has weak muscles because of weak impulses, a PT may introduce other physical exercises to help tone the muscles affected.

References:
Colliers Encyclopedia Fishbeins Illustrated Medical and Health Encyclopedia Principles of Anatomy and Physiology by Tortora and Grabowski Textbook of Medical Physiology by Guyton Pathophysiology, Concepts of Altered Health States by Carol Matson Porth Myasthenia Gravis, A Manual for the Health Care Provider by James F. Howard http://wikipedia.com/