Myasthenia Gravis
An autoimmune neuromuscular disorder causing fluctuating weakness of skeletal muscles, often starting with drooping eyelids and double vision.
Emergency Management: Myasthenic crisis presents with respiratory failure (FVC < 15 mL/kg, NIF < -20 cmH2O). Requires ICU admission, intubation or BiPAP, and rapid rescue therapy with IVIG (2g/kg over 2-5 days) or Plasmapheresis (5 exchanges over 7-10 days). Hold pyridostigmine to reduce airway secretions.
Myasthenia gravis is an acquired autoimmune disorder of the neuromuscular junction. It is characterized by fluctuating, fatigable weakness of skeletal muscles. The disease is caused by autoantibodies directed against the postsynaptic acetylcholine receptors (AChR) or related proteins.
Detailed Overview
The hallmark of MG is muscle weakness that worsens with exertion and improves with rest. It commonly affects ocular, bulbar, respiratory, and limb muscles. The thymus gland plays a central role in the pathogenesis of AChR-antibody positive MG, with thymic hyperplasia or thymomas frequently present. Without treatment, MG can lead to life-threatening respiratory failure.
Epidemiology & Demographics
Prevalence is approximately 15 to 20 per 100,000. It shows a bimodal distribution: an early peak in the 2nd-3rd decades (female predominant) and a late peak in the 6th-8th decades (male predominant).
Etiological Mechanism
Caused by pathogenic autoantibodies. 85% of generalized MG patients have anti-AChR antibodies. The thymus is abnormal in 75% of AChR-positive patients (65% hyperplasia, 10% thymoma).
Primary Causes
Antibody-mediated blockade, cross-linking/internalization, and complement-mediated destruction of postsynaptic acetylcholine receptors at the neuromuscular junction.
In normal neuromuscular transmission, acetylcholine is released from the presynaptic nerve terminal and binds to AChRs on the muscle endplate, generating an endplate potential (EPP). In MG, autoantibodies bind to the AChR. This activates the classical complement pathway resulting in destruction of the junctional folds (MAC complex formation). It also increases AChR turnover and blocks the binding site. The reduced number of functional receptors decreases the EPP. During repeated muscle contraction, the normal physiologic decline in ACh release leads to a failure to reach the threshold for an action potential, resulting in clinical fatigue.
Diagnostic Criteria & Guidelines
Clinical presentation combined with positive serology (AChR or MuSK antibodies). If seronegative, diagnosis requires electrodiagnostic confirmation with Repetitive Nerve Stimulation (RNS) showing a >10% decremental response, or Single-Fiber EMG showing increased 'jitter'.
Symptomatic treatment with Pyridostigmine 60 mg PO TID or QID. For chronic immunosuppression: Oral Glucocorticoids (Prednisone 20 mg/day titrated up) often combined with an immunomodulator like Azathioprine (2-3 mg/kg/day).
Second-Line & Adjunctive Therapy
Mycophenolate mofetil (1000 mg PO BID) or Tacrolimus. For refractory disease: Eculizumab (complement inhibitor) or Efgartigimod (FcRn antagonist).
Surgical & Procedural Management
Thymectomy via VATS or sternotomy is recommended for all patients with thymoma, and for AChR-positive, non-thymomatous patients aged 18-50 to improve clinical outcomes and reduce medication requirements.
Patient Counseling & Advice
Provide a list of contraindicated medications (e.g., ciprofloxacin, magnesium supplements, certain anesthetics). Emphasize going to the ER for shortness of breath or difficulty clearing secretions.
Follow-Up & Monitoring Schedule
Monitor forced vital capacity (FVC) and negative inspiratory force (NIF) during clinic visits if the patient has respiratory symptoms. Assess MG-ADL (Activities of Daily Living) score at every visit.
Preventive Strategies
Infection prevention (pneumococcal and influenza vaccines) is crucial, as infections are the most common trigger for myasthenic crisis.
With modern treatment, mortality is <5%. The life expectancy is typically normal. Maximum weakness usually occurs within the first 2-3 years of onset.