Myasthenia Gravis Clinical Presentation

The presentation and progression of myasthenia gravis (MG) vary. The usual initial complaint is a specific muscle weakness rather than generalized muscle weakness. The severity of the weakness typically fluctuates over hours being least severe in the morning and worse as the day progresses; it is increased by exertion and alleviated by rest. The degree of weakness also varies over the course of weeks or months, with exacerbations and remissions.

Extraocular muscle weakness or ptosis is present initially in 50% of patients and occurs during the course of illness in 90%. Bulbar muscle weakness is also common, along with weakness of head extension and flexion. Weakness may involve limb musculature with a myopathylike proximal weakness that is greater than the distal muscle weakness. Isolated limb muscle weakness as the presenting symptom is rare and occurs in fewer than 10% of patients.

Patients progress from mild to more severe disease over weeks to months. Weakness tends to spread from the ocular to facial to bulbar muscles and then to truncal and limb muscles.^[11] On the other hand, symptoms may remain limited to the extraocular and eyelid muscles for years. Rarely, patients with severe, generalized weakness may not have associated ocular muscle weakness.

The disease remains exclusively ocular in only 16% of patients. About 87% of patients have generalized disease within 13 months after onset. In patients with generalized disease, the interval from onset to maximal weakness is less than 36 months in 83% of patients.

Exposure to bright sunlight, surgery, immunization, emotional stress, menstruation, and physical factors might trigger or worsen exacerbations. Intercurrent illness (eg, viral infection) or medication can exacerbate weakness, quickly precipitating a myasthenic crisis and rapid respiratory compromise.

Spontaneous remissions are rare. Long and complete remissions are even less common. Most remissions with treatment occur during the first 3 years of disease.

MGFA classification of myasthenia gravis

In May 1997, the Medical Scientific Advisory Board (MSAB) of the Myasthenia Gravis Foundation of America (MGFA) formed a task force to address the need for universally accepted classifications, grading systems, and analytic methods for management of patients undergoing therapy and for use in therapeutic research trials. As a result, the MGFA Clinical Classification was created.^[12] This classification divides MG into 5 main classes and several subclasses, as follows.

Class I MG is characterized by the following:

• Any ocular muscle weakness
• May have weakness of eye closure
• All other muscle strength is normal

Class II MG is characterized by the following:

• Mild weakness affecting other than ocular muscles
• May also have ocular muscle weakness of any severity

Class IIa MG is characterized by the following:

• Predominantly affecting limb, axial muscles, or both
• May also have lesser involvement of oropharyngeal muscles

Class IIb MG is characterized by the following:

• Predominantly affecting oropharyngeal, respiratory muscles, or both
• May also have lesser or equal involvement of limb, axial muscles, or both

Class III MG is characterized by the following:

• Moderate weakness affecting other than ocular muscles
• May also have ocular muscle weakness of any severity

Class IIIa MG is characterized by the following:

• Predominantly affecting limb, axial muscles, or both
• May also have lesser involvement of oropharyngeal muscles

Class IIIb MG is characterized by the following:

• Predominantly affecting oropharyngeal, respiratory muscles, or both
• May also have lesser or equal involvement of limb, axial muscles, or both

Class IV MG is characterized by the following:

• Severe weakness affecting other than ocular muscles
• May also have ocular muscle weakness of any severity

Class IVa MG is characterized by the following:

• Predominantly affecting limb, axial muscles, or both
• May also have lesser involvement of oropharyngeal muscles

Class IVb MG is characterized by the following:

• Predominantly affecting oropharyngeal, respiratory muscles, or both
• May also have lesser or equal involvement of limb, axial muscles, or both

Class V MG is characterized by the following:

• Defined by intubation, with or without mechanical ventilation, except when used during routine postoperative management
• Use of a feeding tube without intubation places the patient in class IVb

Patients with MG can present with a wide range of signs and symptoms, depending on the severity of the disease.

Mild presentations may be associated with only subtle findings, such as ptosis, that are limited to bulbar muscles. Findings may not be apparent unless muscle weakness is provoked by repetitive or sustained use of the muscles involved. Recovery of strength is seen after a period of rest or with application of ice to the affected muscle. Conversely, increased ambient or core temperature may worsen muscle weakness.

Variability in weakness can be significant, and clearly demonstrable findings may be absent during examination. This may result in misdiagnosis (eg, functional disorder). The physician must determine strength carefully in various muscles and muscle groups to document severity and extent of the disease and to monitor the benefit of treatment.

Another important aspect of the physical examination is to recognize a patient in whom imminent respiratory failure is imminent. Difficulty breathing necessitates urgent or emergent evaluation and treatment.

Weakness can be present in a variety of different muscles and is usually proximal and symmetric. Sensory examination and deep tendon reflexes are normal.

Weakness of the facial muscles is almost always present. Bilateral facial muscle weakness produces a masklike face with ptosis and a horizontal smile. The eyebrows are furrowed to compensate for ptosis, and the sclerae below the limbi may be exposed secondary to weak lower lids. Mild proptosis attributable to extraocular muscle weakness also may be present.

Weakness of palatal muscles can result in a nasal twang to the voice and nasal regurgitation of food (especially liquids). Chewing may become difficult. Severe jaw weakness may cause the jaw to hang open (the patient may sit with a hand on the chin for support). Swallowing may become difficult, and aspiration may occur with fluids, giving rise to coughing or choking while drinking. Weakness of neck muscles is common, and neck flexors are usually affected more severely than neck extensors are.

Certain limb muscles are involved more commonly than others (eg, upper limb muscles are more likely to be involved than lower limb muscles). In the upper limbs, deltoids and extensors of the wrist and fingers are affected most. The triceps is more likely to be affected than the biceps. In the lower extremities, commonly involved muscles include hip flexors, quadriceps, and hamstrings, with involvement of foot dorsiflexors or plantar flexors less common.

Respiratory muscle weakness that produces acute respiratory failure is a true neuromuscular emergency, and immediate intubation may be necessary. Weakness of the intercostal muscles and the diaphragm may result in carbon dioxide retention as a result of hypoventilation. Respiratory failure usually occurs around the time of surgery (eg, after thymectomy) or during later stages of the disease. However, it can be a presenting feature in about 14-18% of patients with MG.^[13]

Weak pharyngeal muscles may collapse the upper airway. Careful monitoring of respiratory status is necessary in the acute phase of MG. Negative inspiratory force, vital capacity, and tidal volume must be monitored carefully. Relying on pulse oximetry to monitor respiratory status can be dangerous. During the initial phase of neuromuscular hypoventilation, carbon dioxide is retained but arterial blood oxygenation is maintained. This can lull the physician into a false sense of security regarding a patient’s respiratory status.

Typically, extraocular muscle weakness is asymmetric. The weakness usually affects more than 1 extraocular muscle and is not limited to muscles innervated by a single cranial nerve; this is an important diagnostic clue. The weakness of lateral and medial recti may produce a pseudointernuclear ophthalmoplegia, described as limited adduction of 1 eye, with nystagmus of the abducting eye on attempted lateral gaze. The nystagmus becomes coarser on sustained lateral gaze as the medial rectus of the abducting eye fatigues.

Eyelid weakness results in ptosis. Patients may furrow their foreheads, using the frontalis muscle to compensate for this weakness. A sustained upward gaze exacerbates the ptosis; closing the eyes for a short period alleviates it.

Evidence of coexisting autoimmune diseases

MG is an autoimmune disorder, and other autoimmune diseases are known to occur more frequently in patients with MG than in the general population. Some autoimmune diseases that occur at higher frequency in MG patients are hyperthyroidism, rheumatoid arthritis, scleroderma, and lupus.

A thorough skin and joint examination may help diagnose any of these coexisting diseases. Tachycardia or exophthalmos point to possible hyperthyroidism, which may be present in up to 10-15% of patients with MG. This is important because in patients with hyperthyroidism, weakness may not improve if only the MG is treated.

Systemically, myasthenic crisis is the most dreadful complication. Aspiration pneumonia also may occur as a consequence of poor oropharyngeal muscle function. Cholinergic crisis may follow excessive treatment with cholinesterase inhibitors.

The most common severe complication of MG is respiratory failure, which often presents with the rapid deterioration of respiratory effort that ultimately results in apnea.

Pneumonia is a common complication in patients with MG and often is the cause of death in fatal cases. Community-acquired pneumonia often is more severe in patients with MG because of their marginal respiratory function, inability to cough effectively, and inability to maintain tachypnea for long periods.

Other types of pneumonia are more common in patients with MG because these patients have a higher risk of aspiration. MG patients are also in a relatively immunocompromised state because of immunosuppressive medications. Consequently, they are at risk for aspiration pneumonia with mixed aerobic and anaerobic organisms, as well as organisms associated with immunocompromise (eg, Pseudomonas, other gram-negative organisms, and fungi).

Hypoxemia and respiratory acidosis often render the patient somnolent or unresponsive, in which case a clear history may be difficult to obtain.