Myasthenia Gravis

• Females predominate at younger age (peak incidence at ~ 25 y.o.).
• Males predominate at older ages (peak incidence at ~ 65 y.o).

• 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)

Fatigue that is worsened with activity and diminished with rest. 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, which manifests with dysarthria and dysphagia, trouble swallowing with choking or regurgitating food when eating, and fatigable weakness with chewing. 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. 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 will not be affected, which helps distinguish MG from neuropathy (decreased reflexes), myopathies (decreased reflexes) and, notably, Lambert-Eaton myasthenic syndrome (decreased reflexes). 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.

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. 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. 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 (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). 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. Pyridostigmine, an acetylcholinesterase inhibitor, is a symptomatic treatment in MG. Gastrointestinal upset is a key side effect because of its pro-cholinergic effect. 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.

IVIG is also used as regular infusions (typically every 3 weeks) in the chronic management of MG and plasmapheresis is sometimes scheduled at regular intervals, as well, to prevent worsening. Intravenous Immunoglobulin (IVIG) and plasmapharesis reduces the load of acetylcholine antibodies. Getting ready for boards? Review these concise, bulleted high yield reviews for your exam. USMLE Step 1 / COMLEX-USA Level 1 USMLE Step 2 / COMLEX-USA Level 2 USMLE Step 3 / COMLEX-USA Level 3 Nurse Practitioner Licensing Exam Physician Assistant Licensing Exam American Board of Psychiatry & Neurology (ABPN) Exam American Board of Internal Medicine (ABIM) Exam