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Myasthenia Gravis Clinical Presentation

  • Author: Aashit K Shah, MD, FAAN, FANA; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
 
Updated: Mar 23, 2016
 

History

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.

In a surveillance study of 57 cases of pediatric myasthenia, including 34 generalized and 18 ocular cases of juvenile myasthenia gravis (JMG) and 5 cases of congenital myasthenic syndrome, ptosis was the most common symptom, occurring in all patients with ocular JMG and 82% of those with generalized JMG. Tests for acetylcholine receptor antibodies were positive in 67% of the patients with generalized JMG and 44% of those with ocular.[19, 20] All 33 patients with JMG who were treated with pyridostigmine showed improvement, and the majority of patients treated with steroids or intravenous immunoglobulin also improved. Of the 17 patients with ocular JMG treated with pyridostigmine, 88% improved.[20]

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.[21] 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.

Anti-MuSK-positive MG has several clinical characterisitics that differ from more common anti-ACh-R-positive myasthenia gravis. It occurs predominately in women with onset typically occurring in the fourth decade of life. Patients with anti-MuSK antibodies rarely have isolated occular presentation but may have significant oculobulbar involvelment and respiratory muscle weakness and may have facial and tongue muscle atrophy.[22] Myasthenic crisis is also more common.[23]

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.[3] 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
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Physical Examination

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.[24]

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.

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Contributor Information and Disclosures
Author

Aashit K Shah, MD, FAAN, FANA Professor and Associate Chair of Neurology, Director, Comprehensive Epilepsy Program, Program Director, Clinical Neurophysiology Fellowship, Detroit Medical Center, Wayne State University School of Medicine

Aashit K Shah, MD, FAAN, FANA is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Received consulting fee from UCB pharma for speaking and teaching; Received grant/research funds from UCB Pharma for other; Received consulting fee from Sunovion for speaking and teaching; Received consulting fee from Lundbeck for speaking and teaching.

Coauthor(s)

William D Goldenberg, MD Assistant Professor, Department of Emergency Medicine, Uniformed Services University of Health Sciences; Staff Emergency Physician, Naval Hospital San Diego

William D Goldenberg, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Society for Academic Emergency Medicine, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, MHA, CPE Founding Editor-in-Chief, eMedicine Neurology; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, MHA, CPE is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American Academy of Neurology

Disclosure: Nothing to disclose.

Acknowledgements

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa

Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Normal neuromuscular junction showing a presynaptic terminal with a motor nerve ending in an enlargement (bouton terminale): Synaptic cleft and postsynaptic membrane with multiple folds and embedded with several acetylcholine receptors.
Acetylcholine receptor. Note 5 subunits, each with 4 membrane-spanning domains forming a rosette with a central opening. The central opening acts as an ion channel.
CT scan of chest showing an anterior mediastinal mass (thymoma) in a patient with myasthenia gravis.
Increasing left ptosis developing upon sustained upward gaze in patient with myasthenia gravis (A through F). Note limited elevation of left eye, denoting superior rectus palsy (A). A initially, C after around 20 seconds, F after 1 minute.
Cogan sign. Patient changes gaze from downward position (A) to primary position (B). Both lids are seen to overshoot in twitch (B) before gaining their initial ptotic position (D). In this case, Cogan sign is seen more obviously on right, whereas left lid is more ptotic.
CT scan of chest and mediastinum showing thymoma in patient with myasthenia gravis.
Repetitive nerve stimulation at frequency of 2 Hz showing increasing decrement in amplitude of compound muscle action potential up to fourth response (42% amplitude loss), after which it stabilizes.
Single-fiber electromyography showing so-called jitter phenomenon (second action potential wave group).
Table. Prevalence and Titers of Antibody to Acetylcholine Receptor in Patients with Myasthenia Gravis
Osserman MG Class* Mean Anti-AChR Titer (× 10–9 M) Positive Results, %
R 0.79 24
I 2.17 55
IIA 49.8 80
IIB 57.9 100
III 78.5 100
IV 205.3 89
AChR = acetylcholine receptor; MG = myasthenia gravis.



*Osserman classification: R = remission, I = ocular only, IIA = mild generalized, IIB = moderate generalized, III = acute severe, IV = chronic severe.



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