The patient was lying placidly on the stretcher with her eyes closed when I introduced myself. “I’m Paul Austin, one of the ER doctors. Can you open your eyes and talk with me?”
She raised her eyebrows a few millimeters, not even enough to wrinkle her forehead. Her right eye remained shut, and her left eye opened just enough to expose a narrow sliver of white. She turned her face toward me, her eyes still closed.
I looked at her paperwork. She was a 63-year-old woman who said she couldn’t keep her eyes open, had difficulty swallowing, and had fallen four times the day before. She also had complaints of general weakness for about two years. That bothered me. The possible causes of overall weakness could fill a textbook. Yet in cases that have gone on for two years without a diagnosis, doctors often find no physical cause.
Her chart noted that she had recently been hospitalized for schizo-affective disorder, which causes symptoms of both schizophrenia and a mood disorder, and had recently been discharged. That concerned me as well. When a psychiatric diagnosis is present, it can distract doctors from looking for an organic cause of symptoms.
“Can you open your eyes for me?” I asked again. Her eyebrows moved a millimeter up.
“Open them all the way.”
Using her index fingers she raised both her upper eyelids. She stared at me, holding her eyelids up with her fingers, her elbows sticking out at her sides.
“Can you see me?” I asked.
“Yeah,” she said, “but you’re blurry. Like there’s two of you.” She removed her hands, and her eyelids slipped shut.
Was she experiencing side effects from her medications? She said she was taking the same drugs she had always taken. When I asked about recent injuries, infections, or exposures, she said she hadn’t been exposed to any toxins and hadn’t had recent fever, tick bites, trauma, or sudden increase in weakness. She had no chest pain or breathing problems. Occasionally she felt as if she were choking when she swallowed.
When I checked her cognitive status, she was alert and knew her name, the day’s date, and where she was. I looked for subtle signs of a stroke, but her smile wasn’t crooked, and her speech wasn’t slurred. Despite her complaints of weakness, the strength in her arms and legs was nearly normal.
“Let’s get some blood work,” I said. “I’ll be back to talk with you when the results return.”
She smiled pleasantly and nodded.
Although the patient’s weakness wasn’t pronounced, her difficulty keeping her eyes opened worried me.
When emergency room doctors encounter a patient with a neuromuscular disorder, usually the diagnosis has already been made. What I did recall is that double vision and problems opening the eyes are typical early symptoms of myasthenia gravis. Patients can also have difficulty swallowing.
For more detail, I pulled out a textbook. Myasthenia gravis is among the most common neuromuscular diseases, affecting 140 people per million in the United States. In 10 to 20 percent of patients, myasthenia gravis affects only the muscles controlling eye movement. Other people develop general muscle weakness. In most cases, the disease progresses over the first few years and then stabilizes, although the degree of muscle weakness fluctuates from day to day.
Control over muscles—including the tiny muscles in the eyelid—depends on the smooth transmission of signals between the muscles and the nerve endings, called axons. As the axon reaches its designated muscle, it branches out, and each tip extends to an individual muscle fiber. When a nerve signal travels down the axon, packets of the neurotransmitter acetylcholine are released, diffuse across the gap, and bind to receptors on the muscle-cell side. When enough receptors on the muscle cell have been activated, the muscle fiber contracts. The muscle doesn’t contract indefinitely, because an enzyme, acetylcholinesterase, continually breaks down acetylcholine for reuse.
In patients with myasthenia gravis, an autoimmune reaction interrupts this chemical signaling. For unknown reasons, the immune system produces antibodies that stick to the acetylcholine receptors, not only blocking the receptors but also marking them for destruction by the immune cells.
I’d seen a diagnostic test for myasthenia done once while I was in medical school. The test involves injecting Tensilon, a drug (edrophonium chloride) that inhibits acetylcholinesterase, the enzyme that degrades acetylcholine. The injection briefly allows enough acetylcholine to accumulate and bind to unblocked receptors, thus improving muscle strength.
The textbook mentioned that a test dose is recommended because “some patients have a severe reaction.” Another source listed slow heart rate and problems breathing as some of the serious adverse reactions.
I contacted the neurologist at the university hospital across town to discuss the testing protocol. I explained that the blood tests had showed no signs of disturbed metabolism, such as low potassium. He agreed the Tensilon test was the next step.
“And I should just do it here? I mean, the whole ‘respiratory failure’ thing has me a little worried.”
“If it’s going to happen, what better place than in the ER? And if you’re going to have a problem you’ll see it immediately; there aren’t any delayed complications.”
“OK.”
“If it’s positive,” he said, “call me back.”
I pulled the crash cart into the patient’s room. The patient’s nurse joined me.
The textbook suggested monitoring a specific physical finding, such as the position of the eyelid relative to the iris and the pupil, before and after giving the drug. A thin sliver was all that was visible of the patient’s left eye. Her right eye was completely shut. We began with a one-milligram test dose. I glanced from her face to the cardiac monitor and back to her face.
No change. A minute passed.
“OK,” I told the nurse. “Give her three milligrams.”
He slowly pushed the plunger of the syringe. Within 60 seconds, the patient’s eyelids lifted.
“I can see you,” she said. “You aren’t even blurry.”
I monitored her pulse for problems. None. I looked at her eyes closely. On both sides, the entire irises were visible.
“How are you feeling?”
“Strong.” She grinned and made a muscle, like Popeye.
When she showed no sign of complications after a few minutes, I called the neurologist.
“Sounds like she’s got it,” he said. “Send her over.”
I went back to talk with the patient. “I don’t think the signals are getting from your nerves to your muscles. We need to send you to the university hospital for more tests.”
A few weeks later, I called the neurologist to see how she was doing.
“She did well,” he said. “We confirmed it with single-fiber EMG.”
“Single-fiber EMG?” I asked.
“Single-fiber electromyography, the most sensitive test for the diagnosis of MG,” he said. “We measure the electrical impulses from single muscle fibers. Her EMG confirmed myasthenia gravis. We gave her six rounds of plasmapheresis and a course of prednisone.”
During plasmapheresis, plasma, the portion of the blood that contains antibodies, is removed and replaced with a substitute fluid. Giving prednisone, an immune-system-suppressing steroid, is a more long-term strategy. Damping the overall immune response decreases the number of circulating antibodies, thus reducing the attack on the acetylcholine receptors.
As long as their condition is managed well, most patients with myasthenia gravis can expect to have a normal life span. In about 5 to 10 percent of cases, patients must alter their lifestyle and arrange activities to coincide with the times they have maximal strength.
You can’t work in an emergency room without seeing people whose lives are changed forever. Someone’s grandmother is having a stroke, someone’s child is having a seizure, someone else has a sliver of bone poking up through the skin. Over time, these can become ordinary events. Giving the Tensilon test was new for me, and I was relieved that the test and diagnosis had gone smoothly. I felt lucky to have helped my patient open her eyes to a world that was suddenly clear. With good care, she should do well.
Paul Austin is an emergency room physician in Durham, North Carolina. The cases described in Vital Signs are true stories, but the authors have changed some details about the patients to protect their privacy.
