MG is a relatively uncommon neurological disorder affecting about 1 in 5,000 individuals in the United States with a variable prevalence in different countries. MG has a bimodal distribution. It typically peaks in females younger than forty and males older than fifty. MG is one of several neuromuscular junction disorders, that is disorders affecting the point of communication between nerves and muscles.
What happens in MG:
To understand how MG takes place, understanding normal nerve signaling is important. A nerve cell can trigger a muscle contraction using an electrical-chemical signal. This signal originates in the body of the nerve cell then travels the length of the neuron (nerve cell) through influx and efflux of various electrolytes. When the signal arrives to the end of the neuron, by way of calcium, the nerve cell releases a chemical referred to as Acetylcholine which is stored in sacks (or vesicles). This chemical then diffuses across a space between the nerve and muscle referred to as the synaptic cleft. Once across the cleft, it binds to Acetylcholine receptors on the muscle membrane which again using various movement of electrolytes results in a muscle contraction.
MG occurs when our immune system (the part of us fighting infections and foreign bodies) attacks the neuromuscular junction. Specifically, this inappropriate immune insult results in internalization of the Acetylcholine receptors on the muscle membrane and their destruction. As such, with loss of Acetylcholine receptors, activation of the muscle is lacking and the symptoms of MG occur.
Diagnosis of MG:
The diagnosis of MG is mainly a clinical diagnosis. It is made when a patient of the right age group presents with typical symptoms of MG which include but are not limited to drooping eyelid, double vision, nasal voice, trouble swallowing, trouble chewing, slurred speech, weakness in the proximal arms/legs, and shortness of breath.
MG is classified based on presentation and or antibody status. If a patient presents with isolated symptoms affecting the eye, they are said to have ocular MG. And patients presenting with involvement of the eyes and limbs are referred to as having generalized MG. While measurable in the blood, antibodies are not always detected. In fact, up to 50% of ocular cases and 20% of generalized cases lack detectable MG specific antibodies (Acetylcholine receptor antibodies). In select cases, the diagnosis is supported by an abnormal electromyography and nerve conduction test showing fatigability of the muscles with repetitive stimulation.
In approximately 15% of patients, MG can result in respiratory failure, a phenomenon referred as myasthenic crisis, which is a neurological emergency that requires treatment in the intensive care unit. If not treated, death can ensue, hence the Gravis in MG.
Treatment of MG:
The treatment of MG is often individualized based on the patient’s clinical status and tolerability of side effects. Obviously, in patients with crisis, the treatment is mainly aimed at resolving the crisis first. This may involve ventilator support, plasmaphoresis (plasma wash out of the harmful antibodies), and other support measures. Outside of crisis, there are two types of medications prescribed to MG patients. Medications that reduce the severity of symptoms such as Pyridostigmine, this is referred to symptomatic management. And there are medications that modulate the immune system to prevent further immunologic damage of the neuromuscular junction. These are referred to as disease modifying treatment (DMT). These medications come in various modes of administration including oral pills, subcutaneous injections, and intravenous infusions.
One emerging treatment of MG is a surgical procedure called thymectomy. The thymus gland housed in the chest is the source of our immune T cells which are thought to play a role in the pathogenesis of MG. Removal of this gland, especially when a tumor in the gland called a thymoma is present, can not only reduce the need for medications for MG, but also induce remission of the illness.
While it is not possible to always avoid the immune insult on the neuromuscular junction if one is genetically predisposed, there are certain medications that can precipitate MG symptoms and should be avoided if possible. One emerging and cutting-edge class of cancer treatments is now well recognized as not only a cause of symptoms in a patient with MG, but also a cause of developing new onset MG. These medications are collectively referred to as immune checkpoint inhibitors (ICI) such as Pembrolizumab. Various other oral medications can exacerbate MG symptoms and include certain antibiotics, magnesium, Botox injections, arrhythmia treatment, anesthetics, and neuromuscular blockers. If you suffer with MG, always check with your Neurologist before starting new medications.
Oliver Achi, MD, Medical Director, Neurology Services
Iberia Medical Center
2312 East Main Street
New Iberia, LA 70560