Myasthenia gravis: Clinical sciences

Myasthenia gravis is a progressive autoimmune neuromuscular junction disorder characterized by fatigable weakness in skeletal muscles. In myasthenia gravis, antibodies can bind to postsynaptic acetylcholine receptors, as well as to muscle-specific kinase and low-density lipoprotein receptor-related protein 4. Once bound, antibodies activate the classical complement pathway, which triggers local inflammation, eventually reducing the number of functioning acetylcholine receptors and flattening the postsynaptic folds.

Ultimately, this impairs neuromuscular transmission and results in progressive weakness that worsens with repeated activity.

Myasthenia gravis can be limited to the ocular muscles, or generalized, affecting the bulbar, axial, limb, and respiratory muscles as well. In severe cases, a person can present with respiratory failure, which is also known as a myasthenic crisis.

Now, if your patient presents with chief concerns suggestive of myasthenia gravis, perform an ABCDE assessment to determine if they are unstable or stable. If unstable, stabilize their airway, breathing, and circulation. At this point, you might need to provide noninvasive positive pressure ventilation or mechanical ventilation. Next, obtain IV access, and don’t forget to put your patient on continuous vital signs monitoring, including heart rate, blood pressure, and pulse oximetry.

Next, obtain a focused history and physical exam, order arterial blood gas analysis, and assess your patient’s respiratory status by obtaining bedside pulmonary function tests, which include vital capacity, maximum inspiratory pressure, and maximum expiratory pressure.

Your patient will report rapidly worsening painless weakness, shortness of breath, and difficulty swallowing or choking when eating. Most patients will have a known history of myasthenia gravis, but some individuals might present for the first time in a crisis. Additionally, history might reveal conditions associated with a weakened immune system, including active infections as well as recent surgical operations and postpartum state.

The patient might also report tapering of their immunosuppressants. Another possible trigger of myasthenic crisis is the use of medications known to exacerbate myasthenic symptoms, such as magnesium, botulinum toxin injections, paralytics, beta-blockers, and certain antibiotics, including aminoglycosides, fluoroquinolones, and macrolides.

Next, the physical exam will show shallow breathing and increased respiratory rate. With time, your patient will tire out, so their respiratory rate can subsequently drop. The patient might have hypophonia, which is a weak voice, as well as drooling and dysarthria because of bulbar weakness. They may also be using accessory muscles for respiration. However, in severe cases, the generalized weakness is too severe for the patient to recruit accessory muscles, so the absence of it should not reassure you!

Additionally, there may be paradoxical breathing, which occurs as a result of diaphragm weakness and results in inward abdominal movement on inspiration instead of outward.

Next, arterial blood gas analysis will usually be normal, but there might be hypercarbia and hypoxemia. Keep in mind that hypercarbia and hypoxemia are “late” clues, so, if there are signs of severe respiratory and bulbar weakness, you should not wait for these findings to intubate the patient.

Finally, bedside pulmonary function tests will show a reduced vital capacity, which is the amount of air exhaled after a maximum inhalation. There will also be reduced maximal inspiratory pressure, which is known as negative inspiratory force, and maximal expiratory pressure. If vital capacity is less than 20 milliliters per kilogram, maximal inspiratory pressure is less than 30 centimeters of water, and maximal expiratory pressure is less than 40 centimeters of water, you should probably intubate the patient. This is known as the 20, 30, 40 rule to guide intubation timing in a patient with neuromuscular weakness.

With these findings, diagnose myasthenic crisis and begin treatment immediately with plasmapheresis or intravenous immunoglobulin. Corticosteroids should be started carefully, because of the potential to transiently worsen weakness. Finally, don’t forget to address the provoking condition, such as treating an underlying infection.

Now, here’s a clinical pearl to keep in mind! Cholinergic crisis presents similarly to myasthenic crisis and can be tricky to diagnose, because it can be due to overdose with acetylcholinesterase inhibitors, which are medications commonly used to treat myasthenia gravis! It can also occur as a result of organophosphate poisoning, such as pesticides. You can use the mnemonic SLUDGE for the symptoms of a cholinergic crisis, which stands for Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress, and Emesis. Another sign that would point to a cholinergic crisis as opposed to a myasthenic crisis is pupillary constriction.

Okay, now, let’s go back to the ABCDE assessment. If your patient is stable, first obtain a focused history and physical exam, which is going to help you differentiate ocular from generalized myasthenia gravis!

First, let’s focus on the ocular type! These individuals typically report intermittent double vision or eyelid drooping that worsens with sustained and repeated muscle activity, such as reading or looking up. Also, these symptoms will worsen at the end of the day and improve with rest.

The exam will show worsening ptosis with sustained upgaze, worsening double vision with a fixed gaze, and weak eye closure. Finally, if there is ptosis, perform an ice pack test by applying a bag of ice to the eyelid for 2 minutes because cold temperature can improve neuromuscular transmission. If the symptoms improve, the ice pack test is positive. With these findings, you should suspect ocular myasthenia gravis!