Myasthenia%20gravis Diagnosis

• Weakness and fatigability of muscles as described in signs and symptoms
• Previous treatments and their effects

Stages of the Disease

• Active phase: Symptoms typically fluctuate and then become more severe; myasthenic crisis occur in this phase
• Stable/Inactive phase: Symptoms are stable but still persist; worsening symptoms usually attributable to infection, fatigue, tapering of medications, or other identifiable factors
• Burnt-out phase: Remission may occur wherein patients are on immunotherapy and symptom-free, or may even be off medications
  • In 15-20 years, if the symptoms left untreated, patient's weakness becomes fixed wherein the most severely affected muscles become atrophic

Factors that Exacerbate Symptoms

• Infection
• Emotional stress
• Thyroid disorder (eg hypothyroidism or hyperthyroidism)
• Hormonal changes particularly menstrual cycle, pregnancy
• Drugs that affect neuromuscular transmission (eg aminoglycosides, beta-blockers, fluoroquinolones, Penicillamine, Magnesium sulfate, Deferoxamine, macrolides, and IV local anesthetics)

• Patients often have associated disorders and should be evaluated for these

Thymic Abnormalities

• Thymoma, hyperplasia

Autoimmune disorders

• Rheumatoid arthritis, lupus erythematosus, Graves’ disease, family history of autoimmune disorder, skin disorders

Disease States That May Exacerbate Myasthenia Gravis

• Hyper- or hypothyroidism, infection, medical treatment for other condition (eg antiarrhythmic agents, aminoglycosides, Quinine, etc)

Disease States That May Interfere with Therapy

• Asthma, osteoporosis, diabetes mellitus (DM), tuberculosis (TB), peptic ulcer, renal disease, hypertension

• Ptosis, diplopia
  • Ptosis improved after rest, sleep (sleep test) or applying ice on lid (ice test)

• Repeated testing of muscle strength with periods of rest in between
  • Muscle strength is reduced and worsens with repetition but improves after rest

• Quantitative testing of muscle strength (eg motor power survey)
• Forward arm abduction (usually 5 minutes)
• Forced vital capacity (FVC)
• Lack of other neurologic signs

• Most of the patients with generalized myasthenia gravis patients are positive for acetylcholine receptor (AChR) antibodies on radioimmunoassay
  • Presence of antibodies results in a definitive diagnosis
  • 50-60% of patients with ocular myasthenia gravis are positive for anti-acetylcholine receptor
  • Negative anti-acetylcholine receptor radioimmunoassay does not exclude myasthenia gravis
  • 66% of seronegative myasthenic patients have low-affinity antibodies to acetylcholine receptor that cannot be detected by common assays

• In 50% of myasthenia gravis patients who are negative for acetylcholine receptor antibodies, they are positive for antibodies to muscle-specific tyrosine kinase (Anti-MuSK antibodies)
  • Patients with muscle-specific tyrosine kinase myasthenia gravis are predominantly female and may exhibit prominent bulbar, neck, shoulder girdle, and respiratory weakness

•  In approximately 10% of patients who are seronegative for both acetylcholine receptor and muscle specific tyrosine kinase antibodies, there is the demonstrable antibodies to the low-density LRP4
• Edrophonium Cl administration at 2-mg and 8-mg IV doses gives probable diagnosis if positive
  • Positive response is improvement of weakness within 30 seconds
  • If no response, administer 8 mg IV, for a total of 10 mg
  • Has high sensitivity for ocular myasthenia gravis and generalized myasthenia gravis

• Repetitive nerve stimulation test
  • Positive when the amplitude of the 4th compound muscle action potential (CMAP) is reduced >10% from the baseline value

• Single-fiber electromyography (SFEMG)
  • Sensitive test to detect neuromuscular transmission defect
  • Abnormal single-fiber electromyography findings may be seen in motor neuropathic and in myopathic disorders
  • Normal single-fiber electromyography findings in a clinically weak muscle exclude a diagnosis of myasthenia gravis

• Computed tomography (CT) or magnetic resonance imaging (MRI) of chest to diagnose associated thymic tumors
• MRI of the brain if brainstem lesion is possible

Ocular Myasthenia Gravis

• Disease is confined to weakness of the ocular muscles

Generalized Myasthenia Gravis

• Weakness affects muscles other than the ocular muscles; may have ocular weakness
• May be mild, moderate, or severe (with respiratory involvement)

Autoimmune Myasthenia Gravis

• Anti-acetylcholine receptor antibodies (AChR-MG) - Most common form
• Anti-muscle specific tyrosine kinase antibodies (MuSK-MG) - Usually presents as generalized myasthenia gravis with prominent bulbar involvement

• Patients tend to be younger, more often are female, and have milder disease
• There appears to be no association with thymic pathology, particularly thymoma

Myasthenic Crisis/Relapse

• Relapse occurs when a patient with previously controlled disease deteriorates
• A crisis if severe and requiring respiratory assistance
• May be caused by reduction or withdrawal of previous therapy
• May be elicited by stress (eg infection, surgery, hormonal factors) or by the introduction of a new drug (eg beta-blocker)