Myasthenia Gravis Disease

BASICS

DESCRIPTION

A disorder of the neuromuscular junction resulting in a pure motor syndrome characterized by weakness and fatigue particularly of the extraocular, pharyngeal, facial, cervical, proximal limb and respiratory musculature. Typical and neonatal forms are immunologically mediated. A number of congenital forms of obscure pathogenesis exist. Onset may be sudden and severe (myasthenic crisis) but, more typically, is mild and intermittent over many years.

System(s) affected: Musculoskeletal, Hemic/Lymphatic/Immunologic
Genetics:
- 15% of infants born to myasthenic mothers have neonatal myasthenia gravis, due to the transplacental passage of acetylcholine receptor antibodies. The condition completely resolves in weeks to months. Neonatal myasthenia gravis is not a genetic disorder.
- Infants with congenital myasthenia gravis syndromes are born to normal mothers. The onset is at birth or in early childhood. Inheritance is typically autosomal recessive. The condition is persistent.
- Typical adult and juvenile myasthenia gravis do have a familial predisposition (5% of cases) and an increased frequency of HLA-B8 and DR3.
Incidence/Prevalence in USA: 2-5/year/million; 3/100,000
Predominant age: Ages 20-40, but occurs at any age. Incidence in females peaks in the 3rd decade, in males in the 5th and 6th decades.
Predominant sex:
- Adults - Female > Male (3:2)
- Children - Female > Male (3:2)
- Children with myasthenia plus associated disease - Female > Male (5:1)

SIGNS AND SYMPTOMS

Ptosis
Diplopia
Facial weakness
Fatigue on chewing
Dysphagia
Dysarthria
Dysphonia
Neck weakness
Proximal limb weakness
Respiratory weakness
Generalized weakness

CAUSES

Humoral immune-mediated injury of the post-synaptic neuromuscular junction acetylcholine receptors

RISK FACTORS

Female
Age 20–40
Familial myasthenia gravis
D-penicillamine ingestion
Other autoimmune diseases

DIAGNOSIS

LABORATORY

Acetylcholine receptor antibody - generalized myasthenia 80% positive; ocular myasthenia 50% positive; myasthenia + thymoma 100% positive; congenital myasthenia 0% positive; no clear correlation between antibody titer and disease severity
Check thyroid function tests

Drugs that may alter lab results: N/A
Disorders that may alter lab results: N/A

PATHOLOGICAL FINDINGS

Muscle electron microscopy - receptor infolding and the tips of the folds are lost, synaptic clefts are widened
Immunofluorescence - IgG antibodies and complement on receptor membranes

SPECIAL TESTS

Motor nerve conduction velocity – normal
Sensory nerve conduction velocity – normal
Concentric needle (conventional) electromyography – normal in mild cases; low amplitude, short duration, polyphasic motor unit potentials with a varying morphology (may be called "myopathic")
Repetitive nerve stimulation – shows a decremental response at 3Hz which is seen more frequently in the proximal, cervical, or facial muscles. The decrement is less pronounced 30 seconds after a 30-second maximal voluntary contraction (post-tetanic facilitation) and most pronounced 120 seconds after the contraction (post-tetanic depression)
Single fiber EMG (SFEMG) – highly sensitive but less specific, technically difficult to perform, limited availability. SFEMG assesses the temporal variability between two muscle fibers within the same motor unit (jitter). Myasthenia is one condition that increases jitter
Edrophonium (Tensilon) test – initial dose is 2 mg IV, followed in 30 seconds by 3 mg, followed in 30 seconds by 5 mg to a maximum dose of 10 mg. A positive test is characterized by improvement of strength (of striated muscle) within 30 seconds of administration. False positives make a saline placebo control desirable. Atropine 0.4 mg IV may rarely be required as an antidote for severe bradycardia, but should always be available. Perform in a suitable setting with monitoring of EKG and vital signs and resuscitation capability

IMAGING

Chest CT scan - thymoma

DIAGNOSTIC PROCEDURES

History and physical
Electrodiagnostic studies; repetitive nerve stimulation (RNS)
Edrophonium (Tensilon) test

TREATMENT

APPROPRIATE HEALTH CARE

Typically outpatient
Inpatient care for plasmapheresis, intravenous gamma globulin, management of pulmonary infections, myasthenic or cholinergic crises

GENERAL MEASURES

Management of myasthenia gravis is difficult and should be carried out by a neurologist with experience in the field
Three basic approaches to treatment, 1) Symptomatic, 2) Immunosuppressive, 3) Supportive. No or few patients should receive a single therapeutic modality
Symptomatic therapy consists of reversal of weakness with an acetylcholinesterase inhibitor (e.g., pyridostigmine bromide; also available as slow-release oral preparation), or neostigmine methylsulfate which can be administered parenterally. Symptomatic therapy does not stop ongoing immunologically mediated damage to the muscle receptor. An overdose may induce severe weakness known as a cholinergic crisis. Suspect cholinergic crisis if there are other signs of cholinergic overactivity (excessive secretions, diarrhea, bradycardia)
Immunosuppressive or immunomodulatory therapy in some form is necessary. This includes thymectomy, corticosteroids, plasmapheresis, immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporine), and/or intravenous human gamma globulin
Supportive therapy may be intermittently, occasionally, or eventually continually required; may include intubation, tracheostomy, artificial ventilation, respiratory therapy, administration of antibiotics, nasogastric tube, and/or gastrostomy

SURGICAL MEASURES

Thymectomy

ACTIVITY

As tolerated. Heat and exercise both temporarily exacerbate symptoms.

DIET

As tolerated

PATIENT EDUCATION

Printed materials, reference lists and other forms of patient and family support available from:

Myasthenia Gravis Foundation, 2225 Riverside Plaza, #1540, Chicago, IL 60606, (800) 541-5454; www.myasthenia.org
Muscular Dystrophy Association, 3300 E. Sunrise Drive, Tucson, AZ 85718-3208, (800) 572-1717, (520) 529-2000; www.mdausa.org

FOLLOW UP

PREVENTION/AVOIDANCE

Not possible

POSSIBLE COMPLICATIONS

Acute respiratory arrest
Chronic respiratory insufficiency
Atelectasis, aspiration, pneumonia

EXPECTED COURSE AND PROGNOSIS

Highly variable, ranging from remission to death. Mortality is probably less than 10%.

MISCELLANEOUS

ASSOCIATED CONDITIONS

Thymoma
Thymic hyperplasia
Thyrotoxicosis
Other autoimmune diseases

AGE-RELATED FACTORS

Pediatric: N/A
Geriatric: N/A
Others: Occurs in patients of all ages

PREGNANCY

N/A

OTHER NOTES

N/A

ABBREVIATIONS

MG = myasthenia gravis

Clinical Investigations

ROLE OF HOMOEOPATHY

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