Myasthenia Gravis
About the disease
Myasthenia gravis is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles.
This is caused by an antibody-mediated autoimmune progress that results in a decreased number of available acetylcholine receptors (AChRs).
These changes lead to reduced efficiency of neuromuscular transmission. Failure of transmission at many neuromuscular junctions results in weakness of muscle contraction¹.
The initiation and maintenance of the autoimmune response is myasthenia is not entirely understood, but the thymus appears to play a role in this process¹.
Peaks of incidence occur in women in their twenties and thirties and in men in their fifties and sixties¹.
Symptoms
The hallmark of the disorder is a fluctuating degree and variable combination of weakness in the ocular, bulbar, limb, and respiratory muscles².
Muscle weakness
The weakness may fluctuate throughout the day, but it is most commonly worse later in the day or evening, or after exercise².
Fatigability of muscles
The fatigue is manifest by worsening contractile force of the muscle, not a sensation of tiredness².
As these conditions can affect different regions of the body, symptoms may be as follows:
Ocular symptoms — common initial complaints
- Ptosis
- Diplopia
- Blurred vision
Bulbar symptoms — especially prominent in MuSK antibody–positive MG.
- Dysarthria
- Dysphagia
- Fatigable chewing
Facial muscle weakness
Involvement of facial muscles makes the patient appear expressionless.
When attempting to smile, the patient may produce the “myasthenic sneer”, where the mid-lip rises but the outer corners of the mouth fail to move².
Limb weakness
Myasthenia produces predominantly proximal weakness similar to other muscle diseases. The arms tend to be more often affected than the legs².
Respiratory muscle weakness
This can lead to respiratory insufficiency.
If the deficiency of respiration becomes so severe as to require respiratory assistance, the patient is said to be in ‘myasthenic crisis’¹.
Clinical progress
The symptoms are often transient at the early stages of the disease².
The severity of myasthenia gravis peaks within a few years of disease onset².
Ocular vs. generalized
In ocular myasthenia, the weakness is limited to the eyelids and extraocular muscles².
In generalized disease, along with the affection of ocular muscle, it also involves a variable combination of bulbar, limb, and respiratory muscles².
In the majority of patients, the weakness becomes generalized. If weakness remains restricted to the extraocular muscles for 3 years, it is likely that it will not become generalized¹.
Diagnostic pathway — Important aspects
First, establish that the symptoms and signs are consistent with myasthenia gravis. Pay particular attention to the following:
History taking
Eyes history — for ocular symptoms
Throat history — for bulbar symptoms
Musculoskeletal history — limb weakness
Neurological history — for other related or unrelated symptoms
Physical examination
Eyes physical exam— for ocular symptoms
Neurological examination
- Despite the muscle weakness, deep tendon reflexes are preserved¹.
- The sensory system is commonly not affected.
- Patterns do not conform to the anatomy of one specific nerve or muscle
Musculoskeletal examination— for limb weakness
Vital signs, respiratory examination— to evaluate the respiratory status
Confirm the suspicion of clinical diagnosis by immunologic and/or electro-physiologic testing³:
Laboratory
Serology — AChR-AB, MuSK-AB
Patients with positive AChR-Ab or MuSK-Ab assays have seropositive myasthenia gravis (SPMG).
Check AChR-Ab
- The level of anti-AChR antibody does not correspond well with the severity of MG in different patients¹.
- The presence of anti-AChR antibodies is virtually diagnostic of MG, but a negative test does not exclude the disease¹.
Check MuSK-Ab
- An immune response to muscle-specific kinase (MuSK) — a protein involved in AChR clustering at neuromuscular junctions can also result in myasthenia gravis¹.
- Anti-MuSK antibody occurs in about 40% of patients without AChR antibody¹.
Those lacking both AChR and MuSK antibodies on standard assays are considered to have seronegative myasthenia².
Thyroid panel
As some endocrine disorders can mimic myasthenia, blood tests should include thyroid function tests, see differential diagnosis below³.
Electrodiagnostic Tests
Electrodiagnostic studies can provide confirmation of the diagnosis of myasthenia. These tests usually allow verification of the diagnosis in patients who have seronegative myasthenia gravis³.
Anticholinesterase Test
Edrophonium (a drug that inhibit the enzyme AChE) was widely used for diagnostic testing because of its short duration and rapid onset³.
Since August 2018, this test is no longer commercially available in North America and many other areas³.
Drugs — use with caution
Many medications can increase weakness in myasthenia and should be avoided or used with great caution².
- Beta-blockers (e.g., atenolol, propranolol)
- Clindamycin
Differential diagnosis¹⋅²
- Generalized fatigue (“tiredness”)
- Hyperthyroidism (Graves’ disease),
- Motor neuron disease (amyotrophic lateral sclerosis [ALS])
- Botulism
- Drug-induced myasthenia
- Intracranial mass lesions,
- Lambert-Eaton myasthenic syndrome (LEMS),
- Non-autoimmune CMS(Congenital myasthenic syndromes),
- variants of Guillain-Barré syndrome
- Oculopharyngeal muscular dystrophy,
- Neurasthenia,
- Kearns-Sayre syndrome (KSS)
Treatment
The most useful treatments for MG include anticholinesterase medications, immunosuppressive agents, thymectomy, and plasmapheresis or intravenous immunoglobulin (IVIg)¹.
Nearly all myasthenic patients can be returned to fully productive lives with proper therapy¹.
Practice
Now it’s time for some practice. Download the InSimu Patient app and solve the Myasthenia Gravis Challenge.
iOS: https://apple.co/2Spz5Nl
Android: http://bit.ly/2VlnRvb
References:
- Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L. 1., Jameson, J. L., & Loscalzo, J. (2015). Harrison’s principles of internal medicine (19th edition.). New York: McGraw Hill Education, chapter 461, page 2701–2706
- Shawn J Bird, MD. Clinical manifestations of myasthenia gravis, ed. UpToDate, 2018.https://www.uptodate.com/contents/clinical-manifestations-of-myasthenia-gravis
- Shawn J Bird, MD. Diagnosis of myasthenia gravis, ed. UpToDate, 2018. https://www.uptodate.com/contents/diagnosis-of-myasthenia-gravis
