Mr. A appeared very uncomfortable as he sat on the examination table. A vigorous 86-year-old, he always kept his regular appointments for the monitoring of hypertension that was well-controlled with amlodipine (Norvasc) and lisinopril (Prinivil). He was also taking tamsulosin (Flomax) for benign prostatic hyperplasia. But this time he was here for an emergency visit.
It was the week before Christmas, and Mr. A was concerned about an extremely painful vesicular rash that started on the left side of his neck and involved his left upper back, arm, and forearm. We diagnosed acute herpes zoster and started treatment with an antiviral and steroids. Although he required narcotics to control the pain, Mr. A was able to spend the holidays with his family. It was three weeks until the pain subsided. After resolution of the eruption, he returned, frustrated by a persistent discomfort in the distribution of the rash.
Gabapentin (Neurontin) 300 mg was started for the postherpetic neuralgia. Pain control was obtained after the dose was up-titrated to 2,400 mg. Four weeks later, Mr. A was pleased with the dramatic decrease in pain but said he felt “tired.” He expressed concern about “weakness” in his neck muscles.
Laboratory tests, including hemoglobin as well as thyroid, kidney, and liver function tests, were normal. We recommended physical therapy, reduced the dose of gabapentin to 1,200 mg, and asked him to return in one week.
PUT IT IN WRITING
Just before his next appointment, Mr. A sent us a letter in which he reported on the state of his health:
“I would like to alert you to the following symptoms:
Tiredness. This symptom continues to be very debilitating and seems to be much greater than one would expect from the drowsiness caused by medications. It is very difficult to hold my head up. In addition, my vision, at times, is reduced.
I am taking Neurontin three times per day, 400 mg per capsule, for a total of 1,200 mg. I have been going to physical therapy. I am sure it is helping me generally, but it is not doing anything for the tiredness debility. I have also had difficulty with swallowing. I am wondering if the symptoms described above are to be expected after having had shingles.”
We immediately called Mr. A and asked him to come in for reevaluation.
THE DEFINITIVE TEST
Mr. A’s continued weakness and letter documenting his symptoms made us suspect myasthenia gravis. Patients often use words like “tiredness” and “fatigue” to describe a multitude of symptoms, including weakness. Other differential diagnoses to be considered were Lambert-Eaton myasthenic syndrome, amyotrophic lateral sclerosis (ALS), botulism, and myopathy on an autoimmune or drug-induced basis (e.g., statins).
ALS causes progressive upper and lower motor-neuron disease. Upper motor signs, such as hyperreflexia and Babinski’s sign, as well as lower motor findings, such as muscle atrophy and fasciculations, are diagnostic. An electromyogram can confirm the diagnosis.
Patients with Lambert-Eaton myasthenic syndrome most often present with proximal leg weakness. The pathophysiology involves an autoimmune process often secondary to a malignancy. Symptoms of Lambert-Eaton syndrome frequently occur in the morning and improve with activity, differentiating it from myasthenia gravis, which is worsened by activity.
Botulism has a rapid progression associated with food contaminated by Clostridium botulinum. Myopathy often affects proximal muscles in the legs and shoulders. Muscle enzymes may be elevated, and an EMG or muscle biopsy can confirm the diagnosis.
REACHING A DIAGNOSIS
When Mr. A arrived at the office, we immediately drew blood for an acetylcholine receptor (AChR) antibody level. Results showed marked elevation to 26.70 nmol/L (normal 0.0-0.40), confirming a diagnosis of myasthenia gravis.
An autoimmune disease, myasthenia gravis is the result of antibodies that interfere with the muscle AChRs of the neuromuscular junction. The annual incidence in the United States is 10 new cases per million people. There are 15-20 new cases per million diagnosed in Spain and Cyprus. An estimated 10% of patients with myasthenia gravis have a thymoma. (Mr. A did not.)
In approximately 15% of myasthenia gravis patients, AChR antibodies are absent. Some will have antibodies to muscle-specific kinase, another neuromuscular junction protein.
The characteristic clinical feature of myasthenia gravis is fatigue and weakness. Symptoms appear or worsen with continued use of affected muscles.The muscle groups involved vary. Frequent symptoms include ptosis and diplopia. Speech, chewing, and swallowing may be compromised. Limb weakness is most evident in proximal muscle groups. Neck weakness may cause difficulty with holding up the head unless it is supported (a prominent symptom in our patient). Respiratory weakness should be monitored with pulmonary function tests.
A HAPPY ENDING
Treatment of myasthenia gravis consists of anticholinesterase and immunosuppressive drugs. Young patients with a thymus may improve after thymectomy.
Our patient responded to cholinesterase inhibitors, oral steroids, and IV immune globulin.
Mr. A knew something was wrong, and his letter eloquently described many of the classic symptoms of myasthenia gravis, leading us to the proper diagnosis.