myasthenia%20gravis
MYASTHENIA GRAVIS
Myasthenia gravis is an autoimmune neurological disorder caused by autoantibodies against the acetylcholine receptor or against a receptor-associated protein, muscle-specific tyrosine kinase (MuSK-Ab).
The autoimmune attack at the muscle endplate leads to failure of neuromuscular transmission and eventually muscle weakness.
In the active phase of the disease, symptoms typically fluctuates and then become severe; myasthenic crisis occur in this phase.
In the stable/inactive phase, symptoms are stable but still persist; it usually worsen attributable to infection, fatigue, tapering of medications or other identifiable factors.
In the 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.

Myasthenia%20gravis Diagnosis

History

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

Stages of the Disease

  • Active phase: Symptoms typically fluctuate & 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 & 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

Associated Conditions

  • Patients often have associated disorders & 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

Physical Examination

  • 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 & 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

Laboratory Tests

  • 85% of 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-AChR
    • Negative anti-AChR radioimmunoassay does not exclude myasthenia gravis
    • 66% of seronegative myasthenic patients have low-affinity antibodies to AChR that cannot be detected by common assays
  • In 50% of myasthenia gravis patients who are negative for AChR 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 & may exhibit prominent bulbar, neck, shoulder girdle, & respiratory weakness
  •  In approximately 10% of patients who are seronegative for both AChR & MuSK antibodies there is the demonstrable antibodies to the low-density LRP4
  • Edrophonium Cl administration at 2-mg & 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 & 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 & 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

Evaluation

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 MG with prominent bulbar involvement
Anti-Lipoprotein Receptor Protein 4 (LRP4) Myasthenia Gravis
  • Patients tend to be younger, more often are female, & 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 & 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)
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