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Myasthenia gravis
Classification and external resources

Detailed view of a neuromuscular junction:
1. Presynaptic terminal
2. Sarcolemma
3. Synaptic vesicle
4. Nicotinic acetylcholine receptor
5. Mitochondrion
ICD-10 G70.0
ICD-9 358.0
OMIM 254200
DiseasesDB 8460
MedlinePlus 000712
eMedicine neuro/232
emerg/325 (emergency), med/3260 (pregnancy), oph/263 (eye)
MeSH D009157
.Myasthenia gravis (from Greek μύς "muscle", ἀσθένεια "weakness", and Latin gravis "serious"; abbreviated MG) is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability.^ Myasthenia gravis is a neuromuscular disorder primarily characterized by muscle weakness and muscle fatigue.
  • Myasthenia Gravis - Caring4Cancer 16 January 2010 20:27 UTC www.caring4cancer.com [Source type: Academic]

^ Myasthenia gravis has been shown to be an autoimmune disease.

^ Myasthenia Gravis comes from the Greek and Latin words meaning "grave muscular weakness."
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

.It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction,[1] inhibiting the stimulative effect of the neurotransmitter acetylcholine.^ Review Autoimmune disorders of neuromuscular transmission.

^ Mechanisms of acetylcholine receptor loss from the neuromuscular junction.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ 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 .
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

.Myasthenia is treated medically with cholinesterase inhibitors or immunosuppressants, and, in selected cases, thymectomy.^ Myasthenia is treated medically with cholinesterase inhibitors or immunosuppressants , and, in selected cases, thymectomy .
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Myasthenia is treated with immunosuppressants, cholinesterase inhibitors and, in selected cases, thymectomy.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

^ In that case, immunosuppressive medications would not be advisable.
  • Myathenia Gravis in Dogs 16 January 2010 20:27 UTC www.vetinfo.com [Source type: FILTERED WITH BAYES]

.At 200–400 cases per million it is one of the less common autoimmune disorders [1].^ Acquired myasthenia gravis (MG) is an uncommon disorder (200–400 cases per million; ref.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ At 200–400 cases per million it is one of the less common autoimmune disorders .
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ RESULTS: One hundred cases were identified in a population of 684000 (prevalence 15 per 100000 population, 95% confidence intervals (95% CIs) 12-18).

.MG must be distinguished from congenital myasthenic syndromes that can present similar symptomatology but offer no response to immunosuppressive interventions.^ Engle A. Congenital myasthenic syndromes.
  • Ocular Aspects of Myasthenia Gravis: Abstract and Introduction 16 January 2010 20:27 UTC www.medscape.com [Source type: Academic]
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ No response to immunosuppressant therapy.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Congenital (genetic) myasthenic syndromes .
  • Ocular Aspects of Myasthenia Gravis: Abstract and Introduction 16 January 2010 20:27 UTC www.medscape.com [Source type: Academic]

Contents

Classification

The most widely accepted classification of myasthenia gravis is the Myasthenia Gravis Foundation of America Clinical Classification:[2]
  • Class I: Any eye muscle weakness, possible ptosis, no other evidence of muscle weakness elsewhere
  • Class II: Eye muscle weakness of any severity, mild weakness of other muscles
    • Class IIa: Predominantly limb or axial muscles
    • Class IIb: Predominantly bulbar and/or respiratory muscles
  • Class III: Eye muscle weakness of any severity, moderate weakness of other muscles
    • Class IIIa: Predominantly limb or axial muscles
    • Class IIIb: Predominantly bulbar and/or respiratory muscles
  • Class IV: Eye muscle weakness of any severity, severe weakness of other muscles
    • Class IVa: Predominantly limb or axial muscles
    • Class IVb: Predominantly bulbar and/or respiratory muscles (Can also include feeding tube without intubation)
  • Class V: Intubation needed to maintain airway

Signs and symptoms

Blepharoptosis of the left eye.
.The hallmark of myasthenia gravis is fatiguability.^ Fatigue and its impact on patients with myasthenia gravis.
  • Myasthenia Gravis - Caring4Cancer 16 January 2010 20:27 UTC www.caring4cancer.com [Source type: Academic]

^ The hallmark of myasthenia gravis is fatiguability.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Myasthenia gravis is a neuromuscular disorder primarily characterized by muscle weakness and muscle fatigue.
  • Myasthenia Gravis - Caring4Cancer 16 January 2010 20:27 UTC www.caring4cancer.com [Source type: Academic]

.Muscles become progressively weaker during periods of activity and improve after periods of rest.^ Muscles become progressively weaker during periods of activity and improve after periods of rest.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ The hallmark of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]
  • Diagnose-Me: Condition: Myasthenia Gravis 16 January 2010 20:27 UTC www.diagnose-me.com [Source type: Academic]

^ The muscle weakness of MG increases with continued activity and improves after periods of rest.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

.Muscles that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are especially susceptible.^ Certain muscles are more frequently involved and these include the ones that control eye movements, eyelids, chewing, swallowing, coughing and facial expression.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

^ Muscles that control eye and eyelid movement, facial expression, chewing , talking , and swallowing are especially susceptible.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Weakness may be limited to the muscles controlling eye movements and the eyelids.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

.The muscles that control breathing and neck and limb movements can also be affected.^ The muscles that control breathing and neck and limb movements can also be affected.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

^ The muscles that that control breathing and neck and limb movements may also be affected.
  • Diagnose-Me: Condition: Myasthenia Gravis 16 January 2010 20:27 UTC www.diagnose-me.com [Source type: Academic]

^ Muscles that control breathing and movements of the arms and legs may also be affected.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

.Often the physical examination is within normal limits.^ Often the physical examination is within normal limits.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

^ Moreover, blood chemistry values remained within normal limits for the duration of the 15-wk study.
  • Myasthenia Gravis - Abstracts : Online Reference for Health Concerns 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

[3]
.The onset of the disorder can be sudden.^ The onset of the disorder may be sudden or rapid.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

Often symptoms are intermittent. .The diagnosis of myasthenia gravis may be delayed if the symptoms are subtle or variable.^ What are the symptoms of myasthenia gravis?
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.sharp.com [Source type: Academic]

^ The symptoms of myasthenia gravis may resemble other conditions.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.sharp.com [Source type: Academic]

^ Tonography in the diagnosis of Myasthenia Gravis.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

.In most cases, the first noticeable symptom is weakness of the eye muscles.^ In most cases, the first noticeable symptom is weakness of the eye muscles.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

^ The disease most commonly affects muscles that control eye and eyelid movement, so the first symptoms you notice may be eyelid drooping and/or blurred or doubled vision.
  • GHI Your Health: Myasthenia Gravis Basics 16 January 2010 20:27 UTC www.ghi.com [Source type: Academic]

^ Eye muscles In more than half the people who develop myasthenia gravis, their first signs and symptoms involve eye problems, such as: .
  • OhioHealth - Myasthenia gravis 16 January 2010 20:27 UTC www.ohiohealth.com [Source type: General]
  • Myasthenia gravis - Valley Health System 16 January 2010 20:27 UTC www.valleyhealth.com [Source type: General]

.In others, difficulty in swallowing and slurred speech may be the first signs.^ In others, difficulty in swallowing and slurred speech may be the first signs.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

^ The speech may be slurred and the vision blurred.

^ Some common symptoms of MG are drooping eyelid (ptsosis), blurred or double vision, slurred speech, difficulty chewing and/or swallowing, weakness in the arms and legs, chronic muscle fatigue and difficulty breathing.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

.The degree of muscle weakness involved in MG varies greatly among patients, 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 breathing - are affected.^ Most patients with ocular myasthenia affecting the extra-ocular muscles also have ptosis, [6] but exceptions are not infrequent.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ The muscles involved may vary greatly from one patient to the next.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

^ The degree of muscle weakness involved in myasthenia gravis varies greatly among patients, 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 breathing - are affected.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

.Symptoms, which vary in type and severity, may include asymmetrical ptosis (a drooping of one or both eyelids), diplopia (double vision) due to weakness of the muscles that control eye movements, unstable or waddling gait, weakness in arms, hands, fingers, legs, and neck, a change in facial expression, dysphagia (difficulty in swallowing), shortness of breath and dysarthria (impaired speech, often nasal due to weakness of the velar muscles).^ Frequently double vision (diplopia) develops as the disease progresses, also difficulty chewing or swallowing or even breathing.

^ The muscles that that control breathing and neck and limb movements may also be affected.
  • Diagnose-Me: Condition: Myasthenia Gravis 16 January 2010 20:27 UTC www.diagnose-me.com [Source type: Academic]

^ A case of diplopia and arm weakness.
  • NEJM -- Myasthenia Gravis 16 January 2010 20:27 UTC content.nejm.org [Source type: Academic]

.In myasthenic crisis a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life.^ Treatment of myasthenic crisis in late life.

^ Weakness of the muscles of ventilation can cause acute respiratory failure.
  • Myasthenia Gravis | Doctor | Patient UK 16 January 2010 20:27 UTC www.patient.co.uk [Source type: FILTERED WITH BAYES]

^ Complications include respiratory failure due to myasthenic crisis in 6%, infection in 11%, and recurrent laryngeal or phrenic nerve injury in 2% [ 88 ].
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.In patients whose respiratory muscles are already weak, crises may be triggered by infection, fever, an adverse reaction to medication, or emotional stress.^ Myasthenia crisis may be caused by a lack of MG medication or by other factors, such as a respiratory infection, emotional stress, surgery, or some other type of stressor.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.sharp.com [Source type: Academic]

^ If you begin to have difficulty breathing due to weakness of the respiratory muscles, you may need to be admitted to the hospital intensive care unit and placed temporarily on a respirator.
  • GHI Your Health: Myasthenia Gravis Detection & Treatment 16 January 2010 20:27 UTC www.ghi.com [Source type: Academic]

^ The major problem is that changes in alignment may not only reflect increased strength but also increased weakness after edrophonium, [91] which can occur in normal muscles and nonmyasthenic weakness.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

[4] Since the heart muscle is stimulated differently, it is never affected by MG.

Pathophysiology

A juvenile thymus. It shrinks with age.
.Myasthenia gravis is an autoimmune channelopathy: it features antibodies directed against the body's own proteins.^ Myasthenia gravis has been shown to be an autoimmune disease.

^ Myasthenia gravis, Autoimmune myasthenia gravis .
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Myasthenia Gravis is an autoimmune disease.
  • myasthenia gravis links 16 January 2010 20:27 UTC www.berner.org [Source type: Academic]

.While in various similar diseases the disease has been linked to a cross-reaction with an infective agent, there is no known causative pathogen that could account for myasthenia.^ There are no known means of preventing myasthenia gravis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ There are no known ways to prevent myasthenia gravis.
  • GHI Your Health: Myasthenia Gravis Detection & Treatment 16 January 2010 20:27 UTC www.ghi.com [Source type: Academic]

^ In myasthenia gravis caused by antibodies to the acetylcholine receptor, there is blockade of the binding site for acetylcholine, cross-linking of the acetylcholine receptor with subsequent internalisation and reduction in its surface expression, and initiation of complement and cellular inflammatory cascades with damage to the post- and presynaptic structures.
  • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

.There is a slight genetic predisposition: particular HLA types seem to predispose for MG (B8 and DR3 with DR1 more specific for ocular myasthenia).^ Myasthenia crisis may be caused by a lack of MG medication or by other factors, such as a respiratory infection, emotional stress, surgery, or some other type of stressor.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.sharp.com [Source type: Academic]

^ Other immunosuppressant drugs such as cyclosporine [130] are more toxic and there is even less data on their use for ocular myasthenia.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ More specific techniques to remove pathogenic anti-AChR Abs utilizing immunoadsorption have been developed recently, which offer a more targeted approach to MG treatment ( 105 ).
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.Up to 75% of patients have an abnormality of the thymus; 25% have a thymoma, a tumor (either benign or malignant) of the thymus, and other abnormalities are frequently found.^ About 15% of all myasthenia gravis patients are found to have a thymoma, a tumor of the thymus.
  • GHI Your Health: Myasthenia Gravis Basics 16 January 2010 20:27 UTC www.ghi.com [Source type: Academic]

^ The myasthenic thymus demonstrates frequent abnormalities.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Although most thymomas are benign, the thymus is usually removed (thymectomy) to prevent the potential spread of cancer.
  • GHI Your Health: Myasthenia Gravis Basics 16 January 2010 20:27 UTC www.ghi.com [Source type: Academic]

.The disease process generally remains stationary after thymectomy (removal of the thymus).^ Although most thymomas are benign, the thymus is usually removed (thymectomy) to prevent the potential spread of cancer.
  • GHI Your Health: Myasthenia Gravis Basics 16 January 2010 20:27 UTC www.ghi.com [Source type: Academic]

^ We recommend thymectomy for generalized disease in childhood, except in very young children on account of possible long-term effects on immunological development.

^ In patients with disease onset after the age of 60, treatment mainly relies on medical therapy because thymectomy is generally not performed unless a thymoma is present.

The acetylcholine receptor.
.In MG, the autoantibodies are directed most commonly against the nicotinic acetylcholine receptor (nAChR)[5] , the receptor in the motor end plate for the neurotransmitter acetylcholine that stimulates muscular contraction.^ Acetylcholine receptor autoantibody secretion by thymocytes.
  • Myasthenia Gravis - Caring4Cancer 16 January 2010 20:27 UTC www.caring4cancer.com [Source type: Academic]

^ Autoantibodies to acetylcholine receptors in myasthenia gravis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Muscle and neuronal nicotinic acetylcholine receptors.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.Some forms of the antibody impair the ability of acetylcholine to bind to receptors.^ The disorder is characterized by a decrease of the number of acetylcholine receptors in the neuromuscular plates, due to an autoimmune process mediated by antibodies directed against the alpha-subunit of the nicotine receptor of the acetylcholine [ 1 ].
  • BioMed Central | Full text | Myasthenia gravis and pregnancy: clinical implications and neonatal outcome 16 January 2010 20:27 UTC www.biomedcentral.com [Source type: Academic]

^ Weakness is typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine.
  • Myasthenia Gravis Support Group - DailyStrength 16 January 2010 20:27 UTC www.dailystrength.org [Source type: General]

^ Anti-acetylcholine receptor antibodies directed against the alpha-bungarotoxin binding site induce a unique form of experimental myasthenia.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.Others lead to the destruction of receptors, either by complement fixation or by inducing the muscle cell to eliminate the receptors through endocytosis.^ However, in individuals with myasthenia gravis, antibodies are inappropriately directed against sites (receptors) on the surface of certain muscle cells that bind with the neurotransmitter acetylcholine (acetylcholine receptors).
  • Myasthenia Gravis - Caring4Cancer 16 January 2010 20:27 UTC www.caring4cancer.com [Source type: Academic]

^ Vitamin E is important to protect cell membranes from damage through oxidation and peroxidation, while a deficiency causes changes in muscle protein with swelling and fragmentation of individual muscle fibres, leading to muscle weakness, dystrophy and paralysis.

^ This, then, leads to the formation of antibodies that attack healthy muscle receptors as an unintended side effect.

.The antibodies are produced by plasma cells, derived from B cells.^ As discussed previously, recent work demonstrates that the AChR epitopes stimulating B-cell antibody production are also heterogenous, producing a variety of potentially pathogenic antibodies.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

B-cells convert into plasma cells by T-helper cell stimulation. .In order to carry out this activation T-helpers must first be activated themselves, which is done by binding of the T-cell receptor (TCR) to the acetylcholine receptor antigenic peptide fragment (epitope) resting within the major histocompatibility complex of an antigen presenting cells.^ Anti-acetylcholine receptor antibodies directed against the alpha-bungarotoxin binding site induce a unique form of experimental myasthenia.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Almon RR, Andrew CG, Appel SH. Serum globulin in myasthenia gravis: inhibition of a-bungarotoxin binding to acetylcholine receptors.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Vitamin B1 also helps acetylcholine to bind to receptors.

.Since the thymus plays an important role in the development of T-cells and the selection of the TCR myasthenia gravis is closely associated with thymoma.^ Titin, thymoma, and myasthenia gravis.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ The role of thymectomy in the treatment of myasthenia gravis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Management of Myasthenia Gravis: Immunomodulating Therapies 16 January 2010 20:27 UTC www.medscape.com [Source type: Academic]

^ Steroid treatment for myasthenia gravis: steroids have an important role.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.The exact mechanisms are however not convincingly clarified although resection of the thymus (thymectomy) in MG patients without a thymus neoplasm often have positive results.^ Although most thymomas are benign, the thymus is usually removed (thymectomy) to prevent the potential spread of cancer.
  • GHI Your Health: Myasthenia Gravis Basics 16 January 2010 20:27 UTC www.ghi.com [Source type: Academic]

^ However, the efficacy of thymectomy in these patients is difficult to gauge because of the small numbers of patients reported thus far.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ A recent multivariate analysis involving a total of 756 MG patients found thymectomy to be significantly associated with remission; however, the odds ratio was only 1.6.
  • Management of Myasthenia Gravis: Immunomodulating Therapies 16 January 2010 20:27 UTC www.medscape.com [Source type: Academic]

.In normal muscle contraction, cumulative activation of the nAChR leads to influx of sodium ions which in turn causes depolarization of muscle cell and subsequent opening of voltage gated sodium channels.^ In the normal neuromuscular junction, acetylcholine released from the nerve terminal following a nerve action potential, binds to the acetylcholine receptor on the postsynaptic muscle, triggering a muscle action potential propagated by the voltage gated sodium channel.
  • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

^ When a nerve action potential depolarizes the presynaptic terminal, voltage-dependent calcium channels are activated, allowing an influx of calcium that results in a release of acetylcholine from the presynaptic terminal.
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

^ The resulting endplate potential (EPP) activates voltage-gated Na + channels, leading to further influx of Na + and spreading of the action potential along the muscle fiber.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.This ion influx then travels down the cell membrane via T-tubules and, via calcium channel complexes leads to the release of calcium from the sarcoplasmic reticulum.^ The resulting endplate potential (EPP) activates voltage-gated Na + channels, leading to further influx of Na + and spreading of the action potential along the muscle fiber.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ This allows entry of sodium ions into the interior of the muscle cell, which results in partial depolarization of the postsynaptic membrane and generation of an excitatory postsynaptic potential (EPSP).
  • Myasthenia Gravis: eMedicine Neurology 16 January 2010 20:27 UTC emedicine.medscape.com [Source type: Academic]

^ The resulting EPP activates voltage-gated Na + channels at the bottom of the folds, leading to further Na + influx and spreading of the action potential along the muscle fiber.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.Only when the levels of calcium inside the muscle cell are high enough will it contract.^ If enough receptors are blocked by autoantibodies, then the muscle contraction will be weak, causing the principal symptoms of myasthenia gravis.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

^ The muscle contracts when enough of the receptor sites have been activated by the acetylcholine.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

^ In myasthenia gravis many or most of the receptors are already occupied by antibodies, therefore, not enough acetylcholine molecules find receptors to trigger this discharge and subsequent muscle contraction.

.Decreased numbers of functioning nAChRs therefore impairs muscular contraction by limiting depolarization.^ It is essential for the development and functioning of nerves and muscles, specifically it is involved with muscular contraction.

.In fact, MG causes the motor neuron action potential to muscular twitch ratio to vary from the non-pathological one to one ratio.^ Myasthenia can sometimes present with dysarthria , dysphagia , and minimal diplopia with or without extremity weakness, causing confusion with motor neuron disease .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Abnormal fatigue or variability on these electrophysiological tests may also be seen with polymyositis, muscular dystrophy, chronic progressive external ophthalmoplegia, neuropathy, radiculopathy, motor neuron disease, and even brain stem disorders.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Neuromuscular blocking is the failure of transmission of one of the potentials, when one of the muscle fibers fails to transmit an action potential because the EPP does not reach the necessary threshold.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.It has recently been realized that a second category of gravis is due to auto-antibodies against the MuSK protein (muscle specific kinase), a tyrosine kinase receptor which is required for the formation of the neuromuscular junction.^ A more recently available commercial test is the muscle-specific receptor tyrosine kinase (MuSK).
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

^ MuSK -- Muscle Specific Kinasen -- is a protein that can be identified by a blood test.
  • Myasthenia Gravis Community - myMDA Group - Strength in Community 16 January 2010 20:27 UTC mymda.mda.org [Source type: General]
  • Myasthenia Gravis Community - myMDA Group - Strength in Community 16 January 2010 20:27 UTC mymda.mda.org [Source type: General]

^ The molecular physiology of myasthenia gravis mediated by antibodies to muscle specific tyrosine kinase has not been established.
  • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

.Antibodies against MuSK inhibit the signaling of MuSK normally induced by its nerve-derived ligand, agrin.^ Anti-MuSK antibodies do not appear in normal controls.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ The agrin/MuSK signaling pathway likely maintains the structural and functional integrity of the postsynaptic NMJ apparatus also in adult muscle.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ An altered peptide ligand inhibits the activities of matrix metalloproteinase-9 and phospholipase C, and inhibits T cell interactions with VCAM-1 induced in vivo by a myasthenogenic T cell epitope.
  • NEJM -- Myasthenia Gravis 16 January 2010 20:27 UTC content.nejm.org [Source type: Academic]

The result is a decrease in patency of the neuromuscular junction, and the consequent symptoms of MG.
.People treated with penicillamine can develop MG symptoms.^ The result is a decrease in patency of the neuromuscular junction, and the consequent symptoms of MG. People treated with penicillamine can develop MG symptoms.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ A major step forward occurred in 1934 when Mary Walker realized that MG symptoms were similar to those of curare poisoning, which was treated with physostigmine, a cholinesterase inhibitor.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Some people develop only localized weakness, especially in the muscles around the eyes ( ocular MG ).

.Their antibody titer is usually similar to that of MG, but both the symptoms and the titer disappear when drug administration is discontinued.^ A major step forward occurred in 1934 when Mary Walker realized that MG symptoms were similar to those of curare poisoning, which was treated with physostigmine, a cholinesterase inhibitor.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Administration of high doses of manganese reportedly causes the thymus to shrink to its normal size in a very short time and thymomas and symptoms of MG to disappear.

^ Within one week her muscle strength was better than at any time during previous treatments and all symptoms of MG disappeared.

.MG is more common in families with other autoimmune diseases.^ As with other autoimmune diseases, the reason for development of MG remains unclear.
  • Myasthenia Gravis - North American Neuro-Ophthalmology Society 16 January 2010 20:27 UTC www.nanosweb.org [Source type: FILTERED WITH BAYES]

^ What other diseases can be mistaken for MG? .

^ MG is more common in families with other autoimmune diseases.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

A familial predisposition is found in 5% of the cases. .This is associated with certain genetic variations such as an increased frequency of HLA-B8 and DR3. People with MG suffer from co-existing autoimmune diseases at a higher frequency than members of the general population.^ MG patients, like patients with other autoimmune diseases, express some MHC (HLA) alleles with higher frequency than expected in the general population.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ There is an increased frequency of other autoimmune conditions with myasthenia.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ If this expectation is fulfilled, MG, which has been a benchmark to understanding autoimmunity in humans, will become a reference point for the design of specific immunosuppressive treatments of other autoimmune Ab-mediated diseases.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.Of particular mention is co-existing thyroid disease where episodes of hypothyroidism may precipitate a severe exacerbation.^ They include thyroid diseases, rheumatoid arthritis , pernicious anaemia and SLE as well as thymoma or hyperplasia of thymus (as mentioned above).
  • Myasthenia Gravis | Doctor | Patient UK 16 January 2010 20:27 UTC www.patient.co.uk [Source type: FILTERED WITH BAYES]

^ Some initially SN patients may seroconvert within the first several months of disease.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Intercurrent illness, medications, pregnancy, emotions and hypokalaemia can all exacerbate weakness and may swiftly precipitate a myasthenic crisis and respiratory inadequacy.
  • Myasthenia Gravis | Doctor | Patient UK 16 January 2010 20:27 UTC www.patient.co.uk [Source type: FILTERED WITH BAYES]

.The acetylcholine receptor is clustered and anchored by the Rapsyn protein, research in which might eventually lead to new treatment options.^ Nelson S, Conti-Tronconi BM. Adult thymus expresses an embryonic nicotinic acetylcholine receptor-like protein.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Research plays an important role in finding new answers and treatments for MG. .
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.squidoo.com [Source type: General]

^ Acetylcholine receptor epitope in proteins of myasthenia gravis-associated thymomas and non-thymic tissues.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

[6]

Diagnosis

.Myasthenia can be a difficult diagnosis, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders.^ Patients with myasthenia gravis will have a therapeutic response to various immunomodulating therapies including plasmapheresis, corticosteroids, intravenous immunoglobulin (IVIg), other immunosuppressants, and thymectomy.
  • Myasthenia Gravis: eMedicine Neurology 16 January 2010 20:27 UTC emedicine.medscape.com [Source type: Academic]

^ Other disorders People who have myasthenia gravis are also more likely to have the following problems: .
  • Myasthenia gravis - Valley Health System 16 January 2010 20:27 UTC www.valleyhealth.com [Source type: General]

^ J Child Neurol 2000 Nov;15(11):767-9 Abstract quote Myasthenia gravis has been associated with other autoimmune disorders.

[3] .A thorough physical examination can reveal easy fatiguability, with the weakness improving after rest and worsening again on repeat of the exertion testing.^ This leads to muscular weakness with easy fatiguability, which is worse on exercise and improves with rest.
  • Myasthenia Gravis | Doctor | Patient UK 16 January 2010 20:27 UTC www.patient.co.uk [Source type: FILTERED WITH BAYES]

^ With generalized disease, extremity weakness, usually involving the proximal upper and lower extremities and the extensor muscles, is common and typically worsens with exertion.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ To diagnose myasthenia gravis, the nerve will be tested many times to see if its ability to send signals worsens with fatigue.
  • Myasthenia gravis - Valley Health System 16 January 2010 20:27 UTC www.valleyhealth.com [Source type: General]

.Applying ice to weak muscle groups characteristically leads to improvement in strength of those muscles.^ Edrophonium test Injection of the chemical edrophonium (Tensilon) may result in a sudden, although temporary, improvement in your muscle strength — an indication that you may have myasthenia gravis.
  • Myasthenia gravis - Valley Health System 16 January 2010 20:27 UTC www.valleyhealth.com [Source type: General]

^ In 1672, the English physician Thomas Willis described a patient with the “fatiguable weakness” of limbs and bulbar muscles characteristic of MG ( 3 ).
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Dogs usually show an immediate improvement in muscle strength that is of short duration.
  • Myathenia Gravis in Dogs 16 January 2010 20:27 UTC www.vetinfo.com [Source type: FILTERED WITH BAYES]

.Additional tests are often performed, as mentioned below.^ Additional tests are often performed, as mentioned below.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Additional testing, including blood tests or other imaging tests, often is suggested to exclude other possible explanations for a person's symptoms.

^ In addition, a blood test known as an antibody titer can often detect the antibodies that attack the muscles.
  • Myasthenia Gravis Information - Health Articles From ActiveForever.com 16 January 2010 20:27 UTC www.activeforever.com [Source type: FILTERED WITH BAYES]

.Furthermore, a good response to medication can also be considered a sign of autoimmune pathology.^ If patients do not show a good response or cannot be decreased to a small dose of medication, then thymectomy is considered.
  • Management of Myasthenia Gravis: Immunomodulating Therapies 16 January 2010 20:27 UTC www.medscape.com [Source type: Academic]

^ Age, length of symptoms, thymic pathology, and medications appear to be predictors of response to thymectomy for MG. .

Physical examination

.Muscle fatigability can be tested for many muscles.^ Muscle fatigability can be tested for many muscles.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

[7] A thorough investigation includes:
  • looking upward and sidewards for 30 seconds: ptosis and diplopia.
  • looking at the feet while lying on the back for 60 seconds
  • keeping the arms stretched forward for 60 seconds
  • 10 deep knee bends
  • walking 30 steps on both the toes and the heels
  • 5 situps, lying down and sitting up completely
  • "Peek sign": after complete initial apposition of the lid margins, they quickly (within 30 seconds) start to separate and the sclera starts to show[3]

Blood tests

If the diagnosis is suspected, serology can be performed in a blood test to identify certain antibodies:
.
  • One test is for antibodies against the acetylcholine receptor.^ Conversely, 8% of patients with Graves' disease have antibodies against the acetylcholine receptor.
    • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

    ^ Diagnostic testing with the drug edrophonium chloride (Tensilon), and a blood test to look for antibodies against certain muscle components will aid in achieving the diagnosis.
    • Myasthenia Gravis in Puppies 16 January 2010 20:27 UTC www.peteducation.com [Source type: Academic]

    ^ Tests to confirm the diagnosis include edrophonium challenge, repetitive nerve stimulation, single-fiber electromyography (EMG) of the frontalis, and assays for antibody directed against the acetylcholine receptor: all are less sensitive for ocular myasthenia than for generalized myasthenia.
    • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

    [3] .The test has a reasonable sensitivity of 80–96%, but in MG limited to the eye muscles (ocular myasthenia) the test may be negative in up to 50% of the cases.
  • A proportion of the patients without antibodies against the acetylcholine receptor have antibodies against the MuSK protein.^ Anti-acetylcholine receptor antibodies were found in 94% of the patients with generalized MG and in 29% of the ocular patients.

    ^ Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis.
    • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

    ^ Acetylcholine receptor antibody characteristics in myasthenia gravis.
    • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

    [8]
  • In specific situations (decreased reflexes which increase on facilitation, co-existing autonomic features, suspected presence of neoplasm, especially of the lung, presence of increment or facilitation on repetitive EMG testing) testing is performed for Lambert-Eaton syndrome, in which other antibodies (against a voltage-gated calcium channel) can be found.

Neurophysiology

.Muscle fibers of patients with MG are easily fatigued, and thus do not respond as well as muscles in healthy individuals to repeated stimulation.^ Although reports of patient responses to treatment are based on small numbers, almost all patients appear to respond to immunomodulatory therapy and many appear to respond particularly well to plasmapheresis .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ MG patients may also synthesize Abs against non–muscle-specific proteins, such as myofibrillar proteins ( 82 ).
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ In 1672, the English physician Thomas Willis described a patient with the “fatiguable weakness” of limbs and bulbar muscles characteristic of MG ( 3 ).
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.By repeatedly stimulating a muscle with electrical impulses, the fatiguability of the muscle can be measured.^ These include dynamic tests for measuring muscle weakness (for example, response to edrophonium or ice pack), electrical tests such as repetitive stimulation or single fibre electromyography, and measurement of antibodies to acetylcholine receptor and to muscle-specific tyrosine kinase.
  • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

^ During repetitive nerve stimulation (RNS), all measurements are made on the compound muscle fiber–action potential, the sum of the individual muscle fiber–action potentials generated in a muscle.
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

^ Single-fiber electromyography (EMG) Electromyography (EMG) measures the electrical activity traveling between your brain and your muscle.
  • Myasthenia gravis - Valley Health System 16 January 2010 20:27 UTC www.valleyhealth.com [Source type: General]

.This is called the repetitive nerve stimulation test.^ This is a test of specific muscle fatigue by repetitive nerve stimulation.
  • Myasthenia Gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: FILTERED WITH BAYES]

^ This is called the repetitive nerve stimulation test.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Repetitive nerve stimulation: Decrement .

.In single fiber electromyography, which is considered to be the most sensitive (although not the most specific) test for MG,[3] a thin needle electrode is inserted into a muscle to record the electric potentials of individual muscle fibers.^ The sensitivity and specificity of repetitive nerve stimulation and single fiber electromyography differ considerably.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ In most normal muscles, this arrangement facilitates recordings from two individual muscle fiber action potentials.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ In single-fiber EMGs, a single muscle fiber is tested.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.cnn.com [Source type: General]

By finding two muscle fibers belonging to the same motor unit and measuring the temporal variability in their firing patterns (i.e. their 'jitter'), the diagnosis can be made.

Edrophonium test

.
Photograph of a patient showing right partial ptosis (left picture).
^ Note the greater degree of scatter of individual saccades around the curve in the myasthenic patient (left), compared to the patient with VI nerve palsy (right).
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

.The left lid shows compensatory pseudo lid retraction because of equal innervation of the levator palpabrae superioris (Hering's law of equal innervation).^ In response to unilateral or asymmetric ptosis, the system increases innervation to both lids (Hering's law): the resulting lid retraction on the less affected side may appear more prominent than the ptosis on the weaker side.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ This second-eye ptosis had been masked because the central compensatory increase in innervation directed at overcoming the more severe ptosis in the first eye is distributed to both eyes by Hering's law.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Equally clearly, combined patterns of weakness of the extra-ocular muscles, levator palpebrae superioris, and orbicularis oculi are highly indicative of myasthenia.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

Right picture: after an edrophonium test, note the improvement in ptosis.
.The "edrophonium test" is infrequently performed to identify MG; its application is limited to the situation when other investigations do not yield a conclusive diagnosis.^ If in doubt perform an edrophonium test .
  • Myasthenia Gravis | Doctor | Patient UK 16 January 2010 20:27 UTC www.patient.co.uk [Source type: FILTERED WITH BAYES]

^ The edrophonium is administered next with an initial dose of 2 mg (0.2 mL), with observation and strength testing over 1 minute.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ The primary limitation of edrophonium testing relates to selection of an objective muscle strength parameter for assessment.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.This test requires the intravenous administration of edrophonium chloride (Tensilon, Reversol) or neostigmine (Prostigmin), drugs that block the breakdown of acetylcholine by cholinesterase (cholinesterase inhibitors) and temporarily increases the levels of acetylcholine at the neuromuscular junction.^ Pharmacologic Studies Edrophonium chloride (Tensilon) is a short-acting acetylcholine esterase inhibitor.
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

^ Edrophonium is a fast-acting acetylcholinesterase inhibitor that, when administered intravenously, will produce immediate and temporary relief of muscle weakness in myasthenia gravis patients by sparing existing acetylcholine.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

^ Edrophonium chloride temporarily improves the safety factor of neuromuscular transmission and may elicit improved strength in patients with abnormal neuromuscular transmission.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness.^ Saccadic eye movements in myasthenia gravis.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Myasthenia gravis patients reported increased muscle weakness after smoking.

^ Myasthenia gravis is an autoimmune disorder characterized by muscle weakness.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

[9]

Imaging

A chest CT-scan showing a thymoma (red circle).
.A chest X-ray is frequently performed; it may point towards alternative diagnoses (e.g.^ An alternative or additional model of MG may be based on the observation that MG frequently starts during or following a prolonged period of intense stress.

^ Any improvement may point toward a myasthenia gravis diagnosis.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

Lambert-Eaton due to a lung tumor) and comorbidity. .It may also identify widening of the mediastinum suggestive of thymoma, but computed tomography (CT) or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas, and are generally done for this reason.^ The enlarged muscles may be demonstrated by orbital magnetic resonance imaging (MRI).

^ All newly diagnosed MG patients should have a computed tomography scan or magnetic resonance imaging of the chest to look for a thymoma.
  • Management of Myasthenia Gravis: Immunomodulating Therapies 16 January 2010 20:27 UTC www.medscape.com [Source type: Academic]

^ These include a computed tomography chest scan to reveal a thymoma or enlarged thymus gland and thyroid function tests to detect hyperthyroidism.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

[10]

Pulmonary function test

.Spirometry (lung function testing) may be performed to assess respiratory function if there are concerns about a patient's ability to breathe adequately.^ Consequently, pulmonary function must be carefully assessed and closely followed in newly diagnosed patients or in confirmed myasthenics experiencing a symptomatic exacerbation.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Antibodies to MuSK have been demonstrated recently in about one third of patients with generalized SN MG. Patients with MuSK MG are predominantly female and may exhibit prominent bulbar, neck, shoulder girdle, and respiratory weakness [ 1 , 2 , 4 ].
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Asthma and cardiac disease are relative contraindications: the sleep test [78] may be a useful substitute in patients with these.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

.The forced vital capacity may be monitored at intervals in order not to miss a gradual worsening of muscular weakness.^ The patient was discharged after completion of 6 plasma exchanges, with near-normal strength, mild dysarthria and diplopia, and a forced vital capacity of 90% of predicted.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Forced vital capacity on admission was 40% of predicted.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Hospitalization for observation and serial vital capacity measurements is often required, and intubation and mechanical ventilation may ultimately be needed in severe cases.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

.Severe myasthenia may cause respiratory failure due to exhaustion of the respiratory muscles.^ Respiratory muscle weakness Such weakness may produce acute respiratory failure.
  • Myasthenia Gravis: eMedicine Neurology 16 January 2010 20:27 UTC emedicine.medscape.com [Source type: Academic]

^ Edrophonium test Injection of the chemical edrophonium (Tensilon) may result in a sudden, although temporary, improvement in your muscle strength — an indication that you may have myasthenia gravis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.cnn.com [Source type: General]

^ More severe myasthenia gravis affects multiple muscular regions and may be sufficiently severe to cause respiratory failure and death if untreated.
  • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

[11]

Pathological findings

Muscle biopsy is only performed if the diagnosis is in doubt and a muscular condition is suspected. .Immunofluorescence shows IgG antibodies on the neuromuscular junction.^ Autoimmune MG results from antibody-mediated, T cell-dependent immunologic attack on the postsynaptic membrane of the neuromuscular junction.
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.(Note that it is not the antibody which causes myasthenia gravis that fluoresces, but rather a secondary antibody directed against it.^ Anti-acetylcholine receptor antibodies directed against the alpha-bungarotoxin binding site induce a unique form of experimental myasthenia.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ PubMed ] Mygland A, Aarli JA, Matre R, Gilhus NE. Ryanodine receptor antibodies related to severity of thymoma associated myasthenia gravis.

^ PubMed ] Sanders DB, Massey JM. The diagnostic utility of anti-striational antibodies in myasthenia gravis [abstract].

) .Muscle electron microscopy shows receptor infolding and loss of the tips of the folds, together with widening of the synaptic clefts.^ Physiology of Neuromuscular Transmission The NMJ is composed of the nerve terminal, the synaptic cleft, and the highly organized postjunctional folds on the muscle membrane.
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

^ The acetylcholine diffuses across the synaptic cleft and binds to acetylcholine receptors (AchR) on the postsynaptic membrane, resulting in an end-plate potential (EPP).
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

^ By inhibiting acetylcholinesterase in the synaptic cleft, the life span of acetylcholine transmitter released from the presynaptic terminal is prolonged, increasing the probability of interaction with the postsynaptic receptor.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

.Both these techniques are currently used for research rather than diagnostically.^ Occasionally, the diagnostic impression with a myasthenic patient is led astray because of apparent lid retraction rather than ptosis.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

[6]

Associations

Myasthenia Gravis is associated with various autoimmune diseases[12], including:
.Seropositive and "double-seronegative" patients often have thymoma or thymic hyperplasia.^ Thymic hyperplasia, characterized by infiltration of the thymus with lymphocytes and plasma cells, is found in as many as 65-70% of myasthenic patients.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Whether it should be routinely used in other patients with pure ocular myasthenia, with or without suspected thymic hyperplasia, is more controversial.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Radiographic Studies Approximately 20% of patients with MG have a thymoma present, whereas about 70% have thymic hyperplasia.
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

.However, anti-MuSK positive patients do not have evidence of thymus pathology.^ Thymus changes in anti-MuSK-positive and negative myasthenia gravis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ The available studies suggest that between 40% and 70% of patients who are seronegative for anti-AChR antibodies are anti-MuSK positive; it now appears to be more common in females than in males.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ To determine differences in presentation and outcome, thymoma patients were compared with patients with atrophic (n = 49) or hyperplastic (n = 36) thymus gland on final pathology.

In pregnancy

.In the long term, pregnancy does not affect myasthenia gravis.^ Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis.

^ Johns TR. Long term corticosteroid treatment of myasthenia gravis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Long-term corticosteroid treatment of myasthenia gravis.

.Up to 10% of infants with parents affected by the condition are born with transient (periodic) neonatal myasthenia (TNM) which generally produces feeding and respiratory difficulties.^ The obstetrician must also be aware of possible compromise of the newborn, including possible arthrogryposis or transient neonatal myasthenia.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ In general, anti-MuSK associated myasthenia gravis appears at an earlier age than other varieties and disproportionately affects the neck, shoulder, and respiratory muscles, with less limb weakness and rare ocular symptoms.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Of this group with ocular myasthenia, about 30% did not generalize over a mean of 17 years of follow-up; among the 70% who progressed, 94% did so within the first 3 years.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

[13] .TNM usually presents as poor sucking and generalized hypotonia (low muscle tone).^ With generalized disease, extremity weakness, usually involving the proximal upper and lower extremities and the extensor muscles, is common and typically worsens with exertion.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ The symptoms usually progress to the other bulbar muscles and limb muscles, resulting in generalized MG (gMG).
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ In MG, patients present with fluctuating and fatigable weakness of specific muscle groups rather than with generalized fatigue or pain.
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.Other reported symptoms include a weak cry, facial diplegia (paralysis of one part of the body) or paresis (impaired or lack of movement) and mild respiratory distress.^ Patients with mild lower facial weakness develop a transverse pucker when they attempt to hold air within inflated cheeks.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Symptoms may appear within hours after birth or may be delayed for several days; they can include poor suck and swallow, generalized hypotonia, and respiratory depression.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ In general, anti-MuSK associated myasthenia gravis appears at an earlier age than other varieties and disproportionately affects the neck, shoulder, and respiratory muscles, with less limb weakness and rare ocular symptoms.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

A child with TNM typically responds very well to acetylcholinesterase inhibitors. .The mothers themselves suffer from exacerbated myasthenia in a third of cases and for those who it does worsen, it usually occurs in the first trimester of pregnancy.^ Rheumatoid arthritis is the second most prevalent associated disorder, with a frequency ranging from 0% to 10.3% (excluding those cases in which myasthenia was induced by d-Penicillamine).
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Approximately one third of myasthenic women will experience worsening symptoms with pregnancy (most commonly in the first trimester, usually followed by improvement in the third trimester), whereas another third will remain stable, and a final third will improve.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Myasthenic crisis, or respiratory failure due to myasthenic weakness occurs in about 20% of patients, usually within the first year of illness [ 90 , 91 ].
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.Signs and symptoms in pregnant mothers tend to improve during the second and third trimester.^ Approximately one third of myasthenic women will experience worsening symptoms with pregnancy (most commonly in the first trimester, usually followed by improvement in the third trimester), whereas another third will remain stable, and a final third will improve.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males.

Complete remission can occur in some mothers.[14] .Immunosuppressive therapy should be maintained throughout pregnancy as this reduces the chance of neonatal muscle weakness, as well as controlling the mother's myasthenia.^ At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%.

^ The principal manifestations of myasthenia gravis are weakness and premature fatigue, variably affecting the ocular, bulbar, and peripheral muscles.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ See more articles cited in this paragraph Development of a thymectomy trial in nonthymomatous myasthenia gravis patients receiving immunosuppressive therapy.

[13]
.Very rarely, an infant can be born with arthrogryposis multiplex congenita, secondary to profound intrauterine weakness.^ In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. .

^ Moreover, we were able to clone high-affinity combinatorial Fab antibodies from thymic cells of two mothers with MG who had babies with arthrogryposis multiplex congenita.

.This is due to maternal antibodies that target an infant's acetylcholine receptors.^ Anti-acetylcholine receptor antibodies directed against the alpha-bungarotoxin binding site induce a unique form of experimental myasthenia.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Monoclonal antibodies as probes of acetylcholine receptor structure.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

In some cases, the mother remains asymptomatic.[13]

Treatment

Treatment is by medication and/or surgery. .Medication consists mainly of cholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process.^ BACKGROUND: Medical treatment for myasthenia gravis (MG) involves the use of anticholinesterase agents, immunosuppressive drugs, plasmapheresis, and gamma-globulin.

^ Treatment consists of symptomatic use of acetylcholinesterase inhibitors and immunosuppression with steroids or azathioprine.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

.Thymectomy is a surgical method to treat MG. For emergency treatment, plasmapheresis or IVIG can be used as a temporary measure to remove antibodies from the blood circulation.^ Ryanodine antibodies are also associated with late-onset MG. Patients with ryanodine antibodies may exhibit severe, treatment-resistant MG associated with malignant thymomas [ 34 ].
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ The patients were evaluated clinically using a quantified MG clinical score (QMGS) before and at follow-up visits after each treatment.

^ METHODS: Acute treatment of MG by IVIG therapy has been well established in the literature.

Medication

.
Neostigmine, chemical structure.
  • Acetylcholinesterase inhibitors: neostigmine and pyridostigmine can improve muscle function by slowing the natural enzyme cholinesterase that degrades acetylcholine in the motor end plate; the neurotransmitter is therefore around longer to stimulate its receptor.^ The mainstays are acetylcholinesterase inhibitors such as pyridostigmine and neostigmine.
    • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

    ^ It is a reversible inhibitor of acetylcholinesterase so increases acetylcholine stimulation of the remaining acetylcholine receptors.
    • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

    ^ These include dynamic tests for measuring muscle weakness (for example, response to edrophonium or ice pack), electrical tests such as repetitive stimulation or single fibre electromyography, and measurement of antibodies to acetylcholine receptor and to muscle-specific tyrosine kinase.
    • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

    .Usually doctors will start with a low dose, eg 3x20mg pyridostigmine, and increase until the desired result is achieved.^ Increasing weakness after an increase in the pyridostigmine dose (when high doses are already being given) suggests deteriorating disease and/or a depolarising crisis.
    • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

    ^ The drug is usually started at 5 mg daily and may be increased by 5 mg every 4 to 7 days until a clinical benefit is achieved or 1 mg per kilogram of body weight is reached.
    • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

    ^ An alternative dosing strategy of starting corticosteroids at a low initial dose with gradual dose increases has been advocated to reduce the risk for corticosteroid-related MG exacerbations [ 44 ].
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    .If taken 30 minutes before a meal, symptoms will be mild during eating.^ For example, patients with prominent dysphagia may benefit by taking pyridostigmine 30 minutes before meals and those with more symptoms in the afternoon and evening may shift their dosing to later in the day to better target symptoms.
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    .Side effects, like perspiration and diarrhea can be countered by adding atropine.^ Because of the potential for serious muscarinic side effects including bronchospasm and bradycardia, atropine should be readily available.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    ^ Their main side effects are dose-related and due to muscarinic excess, such as hypotension, bradycardia, excess salivation, abdominal cramps, and diarrhea.
    • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

    ^ These dose dependent and self-limited side effects may be treated with glycopyrrolate, and the gastrointestinal side effects may be treated with diphenoxylate hydrochloride with atropine or loperamide hydrochloride.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    Pyridostigmine is a short-lived drug with a half-life of about 4 hours.
.
Azathioprine, chemical structure.
  • Immunosuppressive drugs: prednisone, cyclosporine, mycophenolate mofetil and azathioprine may be used.^ Azathioprine is used as a steroid sparing drug and additional immunosuppressant with prednisone.
    • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

    ^ If not using azathioprine, other steroid-sparing drugs used include mycophenolate mofetil, cyclosporin, methotrexate and cyclophosphamide.
    • Treatment of myasthenia gravis 16 January 2010 20:27 UTC www.cidpusa.org [Source type: Academic]

    ^ Treatment must be individualized, and may include symptomatic treatment with cholinesterase inhibitors and immune modulation with corticosteroids, azathioprine, cyclosporine, and mycophenolate mofetil.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    .It is common for patients to be treated with a combination of these drugs with a cholinesterase inhibitor.^ No thymectomy was done in 14 patients, and immunosuppressive treatment and AChE inhibitors were given in 9 of these cases.

    ^ Because most of these patients were treated with anticholinesterases only, the evolution of their clinical state represents the natural course of MG. .

    ^ Azathioprine —The most commonly used drug to treat patients with MG is now azathioprine.
    • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

    .Treatments with some immunosuppressives take weeks to months before effects are noticed.^ Twelve patients with generalized moderate to severe MG on immunosuppressive treatment for at least 12 months were included.

    ^ The increased weakness develops within 7–10 days after treatment begins and may last for up to one week before strength improves [ 40 , 43 ].
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    ^ Clinical recurrence may be delayed weeks to months after a dosage change and may require reinstitution of higher-dose therapy before control is again achieved.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

    Other immunomodulating substances, like drugs preventing acetylcholine receptor modulation by the immune system are currently being researched[15]

Plasmapheresis and IVIG

.If the myasthenia is serious (myasthenic crisis), plasmapheresis can be used to remove the putative antibody from the circulation.^ Determination of anti-acetylcholine receptor antibodies in myasthenic patients by use of time-resolved fluorescence.

^ Circulating antibodies against the nicotinic acetylcholine receptor are the immunopathogenic hallmark in acquired myasthenia gravis.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Dozens of studies support the use of thymectomy, or surgical removal of the thymus gland, to treat myasthenia gravis patients (Roberts PF et al 2001).
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

.Also, Intravenous immunoglobulins (IVIG) can be used to bind the circulating antibodies.^ In the binding antibody assay, immunoglobulin is coprecipitated from the patient's serum with solubilized human AChR labeled with I125-radiolabeled alpha-bungarotoxin (Lennon 1994) .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ The AChR modulating and blocking antibody assays are probably useful only when the AChR binding antibody assay is negative, since they increase diagnostic sensitivity only slightly.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ High-dose intravenous human immunoglobulin (IVIg) has emerged as a therapy for various neurologic diseases, including myasthenia gravis.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

.Both of these treatments have relatively short-lived benefits, typically measured in weeks.^ Both treatments have a clinically significant effect 4 weeks out in patients with chronic MG, but the improvement has a more rapid onset after plasma exchange than after IVIG. .

^ Prednisone treatment produced significant improvement in strength within two to three weeks in retrospective studies of MG [ 40 , 41 ], and a Cochrane review cites significant short term benefit in MG with corticosteroids [ 42 ].
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Patients should be warned of these potential adverse effects at the initial stages of therapy and reassured that they will have benefits in 6 to 8 weeks after therapy is initiated.
  • Myasthenia Gravis -- Kothari 104 (9): 377 -- Journal of the American Osteopathic Association 16 January 2010 20:27 UTC www.jaoa.org [Source type: Academic]

[16]

Surgery

.Thymectomy, the surgical removal of the thymus, is essential in cases of thymoma in view of the potential neoplastic effects of the tumor.^ This treatment improves symptoms temporarily and is especially valuable in preparation for surgical removal of the thymus.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

^ Myasthenia gravis and tumors of the thymic region: report of a case in which the tumor was removed.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%).

.However, the procedure is more controversial in patients who do not show thymic abnormalities.^ MG patients with thymoma have more severe and generalized weakness, higher AChR antibody titers, and more severe electrophysiologic abnormalities.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Whether it should be routinely used in other patients with pure ocular myasthenia, with or without suspected thymic hyperplasia, is more controversial.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Younger patients showed a more favorable outcome as well as patients with a shorter duration of symptoms before the operation; patients with lower classes of myasthenia showed a higher rate of remission.

.Although some of these patients improve following thymectomy, some patients experience severe exacerbations and the highly controversial concept of "therapeutic thymectomy" for patients with thymus hyperplasia is disputed by many experts and efforts are underway to unequivocally answer this important question.^ Some patients with ocular myasthenia and normal antibody titres will develop low positive titres after several months.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ However, the efficacy of thymectomy in these patients is difficult to gauge because of the small numbers of patients reported thus far.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Although reports of patient responses to treatment are based on small numbers, almost all patients appear to respond to immunomodulatory therapy and many appear to respond particularly well to plasmapheresis .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

.There are a number of surgical approaches to the removal of the thymus gland: transsternal (through the sternum, or breast bone), transcervical (through a small neck incision), and transthoracic (through one or both sides of the chest).^ Since the late 1960s a variety of surgical methods have been devised for thymic resection, including Blalock's classic transsternal approach (splitting of the sternum with removal of the well-defined mediastinal lobes and partial extraction of the cervical extensions of the thymus from below), the extended transsternal thymectomy (splitting of the sternum with wider exploration of the extrapleural and cervical regions), maximal transcervical and transsternal thymectomy (extensive exploration of the neck and mediastinum with direct visual inspection and removal of all suspected thymic tissue; care must be taken to avoid injury to the phrenic and vagus nerves), and in recent years, the focused transcervical approach (a more limited resection through a cervical incision instead of a sternotomy, with or without mediastinoscopy).
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Though more invasive than other approaches, a combined transsternal-transcervical technique is considered to be optimal as it provides the widest exposure for complete removal of thymic tissue that may be widely distributed in mediastinum and neck [ 85 ].
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ These include a computed tomography chest scan to reveal a thymoma or enlarged thymus gland and thyroid function tests to detect hyperthyroidism.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

.The transsternal approach is most common and uses the same length-wise incision through the sternum (breast bone)used for most open-heart surgery.^ This open, retrospective analysis suggests that juvenile-onset myasthenia gravis can be treated satisfactorily in most patients by the use of thymectomy and/or immunosupressive medication.

.The transcervical approach is a less invasive procedure that allows for removal of the entire thymus gland through a small neck incision.^ Though more invasive than other approaches, a combined transsternal-transcervical technique is considered to be optimal as it provides the widest exposure for complete removal of thymic tissue that may be widely distributed in mediastinum and neck [ 85 ].
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Removal of the thymus gland is recommended for most patients with myasthenia, as well as when thymoma is present.

^ For the last half-century, removal of the thymus gland has been considered a standard therapy for myasthenia gravis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

.There has been no difference in success in symptom improvement between the transsternal approach and the minimally invasive transcervical approach.^ There was no statistical difference between these 2 groups.

^ Though more invasive than other approaches, a combined transsternal-transcervical technique is considered to be optimal as it provides the widest exposure for complete removal of thymic tissue that may be widely distributed in mediastinum and neck [ 85 ].
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ CONCLUSION: There was no statistical difference between the conservative treatment and thymectomy groups, regarding remission or improvement.

[17] .However for patients with a thymoma it is important that all the tissue is removed as thymic tissue can regrow.^ Thymoma will be found in 10% to 15% of all myasthenic patients, whereas 40% of patients with thymoma will develop myasthenia (Aarli 1994) .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Of thymomas, 90% are benign and easily treatable with resection, whereas 10% are malignant and will spread beyond the thymic capsule to local tissue, the lymphatic system, or the blood.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Comparative analyses of these techniques, however, suggest steady improvements in remission rates with greater removal of thymic tissue.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

.Thymomas can be malignant and are thought to be the onset of other diseases as well.^ Ryanodine antibodies are also associated with late-onset MG. Patients with ryanodine antibodies may exhibit severe, treatment-resistant MG associated with malignant thymomas [ 34 ].
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ High titers may be found in early onset disease as well as in patients with thymoma; decreased titers following therapy correlate with symptomatic improvement in some patients (Limburg et al 1981) .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ In patients with disease onset after the age of 60, treatment mainly relies on medical therapy because thymectomy is generally not performed unless a thymoma is present.

For this reason, many surgeons will only recommend the full sternotomy approach to a thymectomy.
.Thymoma is relatively rare in younger (<40) patients, but paradoxically especially younger patients with generalized MG without thymoma benefit from thymectomy.^ Thymectomy also improved the prognosis but only for those patients without thymoma.

^ Thymoma will be found in 10% to 15% of all myasthenic patients, whereas 40% of patients with thymoma will develop myasthenia (Aarli 1994) .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Ryanodine antibodies are also associated with late-onset MG. Patients with ryanodine antibodies may exhibit severe, treatment-resistant MG associated with malignant thymomas [ 34 ].
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.Of course, resection is also indicated for those with a thymoma, but it is less likely to improve the MG symptoms.^ Accordingly, patients with SN and ocular MG are less likely to have thymomas.
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ A major step forward occurred in 1934 when Mary Walker realized that MG symptoms were similar to those of curare poisoning, which was treated with physostigmine, a cholinesterase inhibitor.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ A delay in diagnosis indicates that early signs and symptoms of MG are still not well known by all doctors.

Prognosis

.With treatment, patients have a normal life expectancy, except for those with a malignant thymoma (whose lesser life expectancy is on account of the thymoma itself and is otherwise unrelated to the myasthenia).^ Some patients with ocular myasthenia and normal antibody titres will develop low positive titres after several months.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ Ryanodine antibodies are also associated with late-onset MG. Patients with ryanodine antibodies may exhibit severe, treatment-resistant MG associated with malignant thymomas [ 34 ].
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Paletto AE, Maggi G. Thymectomy in the treatment of myasthenia gravis: results in 320 patients.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

Quality of life can vary depending on the severity and the cause. .The drugs used to control MG either diminish in effectiveness over time (cholinesterase inhibitors) or cause severe side effects of their own (immunosuppressants).^ Excessive use of antiacetylcholinesterase drugs can have fatal side effects.
  • Myasthenia Gravis - Autoimmune, Myasthenia Gravis Patients, Thymus Gland - Life Extension Health Concern 16 January 2010 20:27 UTC www.lef.org [Source type: Academic]

^ A major step forward occurred in 1934 when Mary Walker realized that MG symptoms were similar to those of curare poisoning, which was treated with physostigmine, a cholinesterase inhibitor.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Side effects of excess muscarinic activity are common, including tearing, salivation, sweating, abdominal cramps and nausea, and provide useful confirmation that the patient has received an active systemic dose of the drug.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

.A small percentage (around 10%) of MG patients are found to have tumors in their thymus glands, in which case a thymectomy is a very effective treatment with long-term remission.^ Generalized MG was found in 79% of patients, and 10% had severe symptoms.

^ Long-term treatment with steroids.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ We recommend thymectomy for generalized disease in childhood, except in very young children on account of possible long-term effects on immunological development.

.However, most patients need treatment for the remainder of their lives, and their abilities vary greatly.^ The course is variable, and most patients with initial ocular weakness develop bulbar or limb weakness within three years of initial symptom onset.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.It should be noted that MG is not usually a progressive disease.^ The symptoms usually progress to the other bulbar muscles and limb muscles, resulting in generalized MG (gMG).
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

.The symptoms may come and go, but the symptoms do not always get worse as the patient ages.^ Seroconversion may be identified in these patients by repeating the AChR binding antibody studies after six months of symptoms [ 28 ].
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

^ Frequently, the deltoid or an upper extremity extensor is chosen, or alternatively, in the case of clinically obvious ptosis, the patient may be observed for improvement in ptosis symptoms.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Intravenous administration of edrophonium, an acetylcholinesterase inhibitor, to a suspected myasthenia gravis patient may transiently improve certain symptoms, providing supporting evidence for the diagnosis.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

For some, the symptoms decrease after a span of 3–5 years.

Epidemiology & MG in children

.Myasthenia gravis occurs in all ethnic groups and both genders.^ Myasthenia gravis occurs in all ethnic groups and both genders.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Myasthenia gravis occurs can affect both males and females.
  • Myasthenia Gravis, Causes of Myasthenia Gravis, Symptoms of Myasthenia Gravis, Diagnoses of Myasthenia Gravis, Treatment of myasthenia Gravis 16 January 2010 20:27 UTC www.herbalcureindia.com [Source type: FILTERED WITH BAYES]

^ See myasthenia gravis - support group .
  • Wilmington/Newark - Myasthenia gravis is a neuromuscular disorder characterized... 16 January 2010 20:27 UTC www.christianacare.org [Source type: Academic]

.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.^ Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG. .

^ Cosegregation of an additional autoimmune disease occurred in 27 patients and in 24/49 (49%) women with onset <50 years of age.

^ The mean age of thymoma patients is 50 years, with a 1:1 male to female ratio.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

.Younger patients rarely have thymoma.^ Younger patients rarely have thymoma.
  • Myasthenia gravis encyclopedia topics | Reference.com 16 January 2010 20:27 UTC www.reference.com [Source type: Academic]

^ Anti-MuSK myasthenia gravis patients are less likely to have thymic hyperplasia and rarely have thymoma (Lauriola et al 2005) .
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ These antibodies may be useful as a serological marker for thymoma in younger patients.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

.The prevalence in the United States is estimated at 20 cases per 100,000.[18] Risk factors are the female gender with ages 20 – 40, familial myasthenia gravis, D-penicillamine ingestion (drug induced myasthenia), and having other autoimmune diseases.^ The first American case of myasthenia gravis.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ Clinical characteristics and prognosis of myasthenia gravis with other autoimmune disease.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ The prevalence of acquired myasthenia gravis ranges from 0.5 to 14.2 per 100,000.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

Three types of myasthenic symptoms in children can be distinguished:[7]
.
  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 root cause of myasthenia gravis is unknown.

    ^ Neonatal myasthenia gravis: clinical and immunological study of seven mothers and their newborn infants.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

    ^ In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. .

    .The symptoms will start in the first two days and disappear within a few weeks after birth.^ Symptoms may appear within hours after birth or may be delayed for several days; they can include poor suck and swallow, generalized hypotonia, and respiratory depression.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

    ^ Improvement appears in approximately 70% of patients within 5 days of initiation, with maximal effects at 8 to 9 days and a duration of 8 to 12 weeks (Arsura 1989) .
    • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

    ^ About 60% of patients were diagnosed within the first year after initial symptoms.

    .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.^ We recommend thymectomy for generalized disease in childhood, except in very young children on account of possible long-term effects on immunological development.

    ^ In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. .

    ^ Iodinated contrast agents have rarely precipitated significant worsening of myasthenic weakness [ 35 , 36 ].
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    .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.^ Myasthenia gravis and myasthenic disorders.

    ^ Clinical characteristics and prognosis of myasthenia gravis with other autoimmune disease.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

    ^ Congenital myasthenic syndromes stem from genetic mutations that result in abnormal neuromuscular transmission.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    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.^ About 60% of patients were diagnosed within the first year after initial symptoms.

^ Its symptoms are caused by a characteristic muscle weakness that worsens after use of affected muscles.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

^ A major step forward occurred in 1934 when Mary Walker realized that MG symptoms were similar to those of curare poisoning, which was treated with physostigmine, a cholinesterase inhibitor.
  • Journal of Clinical Investigation -- Myasthenia gravis: past, present, and future 16 January 2010 20:27 UTC www.jci.org [Source type: Academic]

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.^ Because of its proximal distribution, such weakness may result in a misdiagnosis of myopathy if extremity symptoms are the presenting feature.
  • Myasthenia gravis 16 January 2010 20:27 UTC www.medlink.com [Source type: Academic]

^ Ninety percent of patients have some benefit from such drugs, although this may be relatively mild in half.
  • Ocular Aspects of Myasthenia Gravis 16 January 2010 20:27 UTC www.eyeplastics.com [Source type: Academic]

^ In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001).

Only rarely do symptoms of CMS become worse with time.

Notable patients

  • Amitabh Bachchan, Bollywood superstar, voted Star of Millennium on BBC.
  • Brandon Cox, starting Auburn Quarterback from 2005-2007. Finished with a record of 29-9.
  • Howard Hughes
  • Henrique Mecking, Brazilian chess grandmaster.
  • Christopher Robin Milne, 1920-1996, of Winnie-the-Pooh fame and son of author A.A. Milne.
  • Aristotle Onassis, Greek shipbuilder and husband of Jacqueline Kennedy Onassis.
  • Augustus Pablo, reggae musician. .Died May 18, 1999 due to a collapsed lung and had suffered from the disease for some time.
  • Suzanne Rogers, Emmy award winning daytime television actress; plays Maggie Horton on Days of our Lives.^ Some initially SN patients may seroconvert within the first several months of disease.
    • Myasthenia gravis 16 January 2010 20:27 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
    • Orphanet Journal of Rare Diseases | Full text | Myasthenia gravis 16 January 2010 20:27 UTC www.ojrd.com [Source type: Academic]

    Diagnosed in 1984, but currently in remission; her condition was dramatized on the series as her character was shown to be suffering from it as well.
  • Roger Smith, semi-retired actor/talent manager, husband of Ann-Margret.
  • John Spencer, World professional snooker champion 1969, 1971 and 1977. Double vision, associated with the disease, effectively ended his career in the mid 1980s.
  • Vijay Tendulkar, a renowned Indian playwright; died May 19, 2008 due to complications arising out of Myasthenia gravis.
  • Mary Broadfoot Walker, British physician who first discovered the effectiveness of physostigmine in the treatment of myasthenia gravis.
  • Madame Web, a fictional character from the Spider-Man comics and other media.

References

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  2. ^ Jaretzki A, Barohn RJ, Ernstoff RM, et al. (2000). "Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America". Neurology 55 (1): 16–23. PMID 10891897. http://www.neurology.org/cgi/content/full/55/1/16.  
  3. ^ a b c d e Scherer K, Bedlack RS, Simel DL. (2005). "Does this patient have myasthenia gravis?". JAMA 293 (15): 1906–14. doi:10.1001/jama.293.15.1906. PMID 15840866.  
  4. ^ Bedlack RS, Sanders DB. (2000). "How to handle myasthenic crisis. Essential steps in patient care.". Postgrad Med 107 (4): 211–4, 220–2. PMID 10778421. http://www.postgradmed.com/issues/2000/04_00/bedlack.htm.  
  5. ^ Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science (1973) 180:871–2.
  6. ^ a b Losen M, Stassen MH, Martínez-Martínez P, et al. (2005). "Increased expression of rapsyn in muscles prevents acetylcholine receptor loss in experimental autoimmune myasthenia gravis". Brain 128 (Pt 10): 2327–37. doi:10.1093/brain/awh612. PMID 16150851.  
  7. ^ a b Baets, M.H.; H.J.G.H. Oosterhuis (1993). Myasthenia gravis. DRD Press. pp. 158. ISBN 3805547366.  
  8. ^ Leite MI, Jacob S, Viegas S, et al. (July 2008). "IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis". Brain 131 (Pt 7): 1940–52. doi:10.1093/brain/awn092. PMID 18515870. PMC 2442426. http://brain.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18515870.  
  9. ^ Seybold ME (1986). "The office Tensilon test for ocular myasthenia gravis". Arch Neurol 43 (8): 842–3. PMID 3729766.  
  10. ^ de Kraker M, Kluin J, Renken N, Maat AP, Bogers AJ (2005). "CT and myasthenia gravis: correlation between mediastinal imaging and histopathological findings". Interact Cardiovasc Thorac Surg 4 (3): 267–71. doi:10.1510/icvts.2004.097246. PMID 17670406.  
  11. ^ Thieben MJ, Blacker DJ, Liu PY, Harper CM Jr, Wijdicks EF (2005). "Pulmonary function tests and blood gases in worsening myasthenia gravis". Muscle Nerve 32 (5): 664–667. doi:10.1002/mus.20403. PMID 16025526.  
  12. ^ S. Thorlacius et al., “Associated disorders in myasthenia gravis: autoimmune diseases and their relation to thymectomy,” Acta Neurologica Scandinavica 80, no. 4 (1989): 290-295.
  13. ^ a b c Warrell, David A; Timothy M Cox, et al. (2003). Oxford Texbook of Medicine — Fourth Edition — Volume 3. Oxford. pp. 1170. ISBN 0-19852787-X.  
  14. ^ Téllez-Zenteno JF, Hernández-Ronquillo L, Salinas V, Estanol B, da Silva O (2004). "Myasthenia gravis and pregnancy: clinical implications and neonatal outcome". BMC Musculoskeletal Disorders 5: 42. doi:10.1186/1471-2474-5-42. PMID 15546494. PMC 534111. http://www.biomedcentral.com/1471-2474/5/42. Retrieved 2008-07-10.  
  15. ^ Losen M, Martínez-Martínez P, Phernambucq M, Schuurman J, Parren PW, DE Baets MH (2008). "Treatment of myasthenia gravis by preventing acetylcholine receptor modulation". Ann N Y Acad Sci 1132: 174–9. doi:10.1196/annals.1405.034. PMID 18567867.  
  16. ^ Juel VC. (2004). "Myasthenia gravis: management of myasthenic crisis and perioperative care.". Semin Neurol 24 (1): 75–81. doi:10.1055/s-2004-829595. PMID 15229794.  
  17. ^ Calhoun R, et al. (1999). "Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients.". Annals of Surgery 230 (4): 555–561. doi:10.1097/00000658-199910000-00011. PMID 10522725.  
  18. ^ "What is Myasthenia Gravis (MG)?". Myasthenia Gravis Foundation of America. http://www.myasthenia.org/amg_whatismg.cfm.  

External links


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