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Myasthenia Gravis
Myasthenia Gravis
Epidemiology
Bimodal Age of Onset
- Females predominate at younger age (peak incidence at ~ 25 y.o.).
- Males predominate at older ages (peak incidence at ~ 65 y.o).
Myasthenia Gravis Variants
- Neonatal MG: maternal to neonatal transmission of Ach antibodies
- Juvenile MG: < 18 y.o.
- Early-onset MG: 18- 50 y.o. (higher likelihood of thymic hyperplasia)
- Late-onset MG: > 50 y.o. (higher likelihood of thymoma)
Clinical Features
Fatigable Weakness
Fatigue that is worsened with activity and diminished with rest.
Ocular Weakness
MG most often presents with ocular symptoms (~ 75%), most often asymmetric ptosis, which manifests with diplopia or blurred vision (worsened with reading or driving). Fatigable ptosis can be brought-out on physical exam with prolonged upgaze.
- We use the term ocular myasthenia for the ~ 20% of patients who never develop additional symptoms.
- Cogan’s twitch sign demonstrates subtle weakness of the superior rectus and inferior oblique muscles.
Bulbar Weakness
Bulbar weakness, which manifests with dysarthria and dysphagia, trouble swallowing with choking or regurgitating food when eating, and fatigable weakness with chewing.
Respiratory Failure
Bulbar weakness can lead to respiratory failure. We follow breath count, forced vital capacity, and negative inspiratory force to determine need for endotracheal intubation, which can be life-saving.
Limb/Girdle Weakness
Generalized weakness presents in the majority of MG patients (even ~50% of the patients who present with isolate ocular involvement will still progress to limb weakness).
- Proximal leg weakness typically presents with trouble getting up (ilopsoas) and down stairs (quadriceps), and getting out of a low chair (however, wrist drop or foot drop would not be expected in MG).
Deep tendon reflexes
Deep tendon reflexes will not be affected, which helps distinguish MG from neuropathy (decreased reflexes), myopathies (decreased reflexes) and, notably, Lambert-Eaton myasthenic syndrome (decreased reflexes).
Thymoma/Thymic Hyperplasia
In MG there can sometimes be either a thymoma or thymic hyperplasia.
- Early-onset MG patients have a higher likelihood of demonstrating thymic hyperplasia, thus in these patients, thymectomy is often performed as a potential management strategy for the disorder, although response to thymectomy is variable.
- Late-onset MG patients have a higher likelihood of having thymoma, thus it is critical to get a chest CT to look for an associated thymoma.
Exacerbating Medications
Numerous medications that can worsen MG but pay attention for aminoglycosides (eg, gentamicin), fluroquinolones (eg, ciprofloxacin), macrolides (eg, azithromycin), beta-blockers (eg, metoprolol), magnesium, succinylcholine.
Laboratory Testing
Edrophonium & Ice-pack
Improvement of ptosis with the application of edrophonium or an ice-pack are helpful diagnostic tools in the evaluation for MG but serologies and electrophysiologic studies (EMG/NCS) are more often relied upon.
EMG/NCS
Repetitive nerve conduction studies demonstrate decreased compound muscle action potential (CMAP) response following low frequency (3 Hz) repetitive nerve stimulation and following prolonged exercise.
Single fiber EMG can be used to evaluate for increased jitter but this is a technically difficult study to perform.
Acetylcholine receptor antibodies
Acetylcholine receptor antibodies (binding (most frequently), and also blocking and modulating (less frequently)) are positive in ~ 85% of patients with generalized MG (~ 50% of those with ocular myasthenia).
Other Serologies
Of the potential tests, indicate that MuSK (muscle-specific tyrosine kinase) antibody has the highest sensitivity; it will be positive in ~ 40% of the AchR antibody negative MG patients.
Additional potential serologic tests include striational antibodies (antibodies to titin and ryanodine) and, more recently discovered, LPR4 antibody testing.
Treatments
Pyridostigmine
Pyridostigmine, an acetylcholinesterase inhibitor, is a symptomatic treatment in MG. Gastrointestinal upset is a key side effect because of its pro-cholinergic effect.
Immune Suppression
Steroids and other steroid-sparing immune suppressants (eg, azathioprine) reduce the production of acetylcholine antibodies.
Steroid-sparing immune suppressant medications as follows:
- Long-standing MG treatments (azathioprine, mycophenolate, cyclosporine, tacrolimus)
- Newer, biological therapies that target specific antibodies (efgartigimod alfa, ravulizumab, rozanolixizumab, zilucoplan).
- See Current Treatment of Myasthenia Gravis (2022) and Novel Immunotherapies in Myasthenia Gravis (2023) for more details.
Rescue therapy
Intravenous Immunoglobulin (IVIG) and plasmapharesis reduces the load of acetylcholine antibodies.
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