Miastenia gravis (MG)

Clinical Patterns and Subtypes

The hallmark of Myasthenia Gravis is a characteristic pattern of muscle weakness that varies by subtype:

Cardinal Symptoms:

• Muscle Fatigability: Worsening with repeated physical activity and temperature variations (extreme heat/cold); improvement with rest; daily fluctuations with typical worsening in the evening.

• Ptosis (Drooping Eyelid): Present in 90% of patients; can be unilateral or asymmetric bilateral; characteristically fluctuating.

• Diplopia (Double Vision): Present in 85% of patients; variable across all directions of gaze; worsens after prolonged fixation.

• Fluctuating Weakness: A pathognomonic feature; pupillary sparing is a key diagnostic sign.

Specific Muscle Distribution:

• Ocular muscles: Ptosis, diplopia (pupils spared).

• Bulbar muscles: Dysphagia, dysarthria, dysphonia, “myasthenic facies” (expressionless face/snarling smile).

• Respiratory muscles: Dyspnea, respiratory failure.

• Limb muscles: Symmetric proximal weakness.

• Neck muscles: “Dropped head syndrome.”

Clinical Classes (MGFA):

• Class I (Ocular): Exclusive involvement of ocular muscles. Most frequent onset; 85% of cases progress to generalized form within 2 years.

• Class II (Mild Generalized): Mild symptoms; IIa predominantly affects limb and axial muscles; IIb predominantly affects oropharyngeal and respiratory muscles.

• Classes III-IV: Moderate and severe symptoms, respectively.

• Class V (Myasthenic Crisis): Respiratory failure requiring assisted ventilation.

Antibody Subtypes

• AChR-MG: The most frequent serotype; generally shows a good response to standard therapies; typically starts with ocular symptoms before generalizing.

• MuSK-MG: Predominant bulbar muscle involvement; often shows a poor response to standard therapies (e.g., pyridostigmine).

• LRP4-MG: Phenotype similar to AChR-MG.

• Seronegative MG: Negative for known antibodies; diagnosis is based on clinical and electrophysiological findings.

Myasthenic Crisis

• Frequency: Occurs in 15–20% of patients; mortality is now <5% with modern care.

• Triggers: Infections, certain medications (e.g., specific antibiotics, beta-blockers), and surgical procedures.

• Management: Requires mechanical ventilation and rapid immunomodulation (IVIG or Plasma Exchange).

Diagnostic Evaluation

• Clinical Assessment: Detailed medical history (fatigability, fluctuations), neurological examination (muscle endurance and fatigability testing), identification of characteristic weakness patterns, and recognition of precipitating factors.

• Bedside Clinical Tests: * Ice Pack Test: (Sensitivity 80–90%, specificity >95%).

  • Edrophonium Test: (Transient improvement for 2–5 minutes).

  • Fatigability Assessment: Physical maneuvers to elicit muscle exhaustion.

• Gold Standard Electrophysiology:

  • Repetitive Nerve Stimulation (RNS): (3 Hz, >10% decrement; sensitivity 60–80%).

  • Single-Fiber EMG (SFEMG): (Assesses neuromuscular jitter; sensitivity 95–99%).

• Serological Testing:

  • Anti-AChR antibodies: (Sensitivity 85–90% in generalized MG).

  • Anti-MuSK: (Found in 5–10% of AChR-seronegative cases).

  • Anti-LRP4: (1–2% of cases).

  • Anti-titin/RyR antibodies: (Associated with thymoma).

  • Approximately 5% of patients remain seronegative.

• Specialized Imaging: Contrast-enhanced Chest CT (to identify thymic mass); annual follow-up if initially negative.

• Assessment Scales: * MG-ADL: (Activities of Daily Living, 0–24 points).

  • QMG: (Quantitative Myasthenia Gravis score, 0–39 points).

  • SPRS: (Specific Pulmonary Respiratory Scale).

• Diagnostic Strategy: Clinical suspicion $\rightarrow$ Electrophysiology $\rightarrow$ Serology $\rightarrow$ Chest Imaging $\rightarrow$ MGFA Classification.