Acetylcholine Receptor-Antibody-Positive Myasthenia Gravis Presenting with Early Atrophy and Nonfluctuating Weakness of Proximal Limb Muscles

Abstract

Dear Editor, Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission caused by antibodies targeting postsynaptic muscle end plates at the neuromuscular junction. 1 The cardinal symptom of MG is fluctuating weakness of voluntary muscles. 1 An 82-year-old male presented with an 8-month history of slowly progressive dysphagia and weakness predominantly involving the proximal muscles of the upper limbs. No fatigability, myalgia, cramps, fasciculation, dysarthria, shortness of breath, or sensory symptoms were present. His past and family histories were unremarkable. A neurological examination revealed that the patient could lift his arms only up to 90° (Fig. 1A). There was mild symmetric muscle weakness of the shoulder abductors, elbow extensors and flexors, hip flexors, and knee flexors, which did not worsen with repeated or sustained exertion. The neck extensors and orbicularis oculi muscles also exhibited mild weakness. Eyelid ptosis or weakness of extraocular muscles was not noticed even after provocative tests, and there was no evidence of tongue atrophy. The patient had mild-to-moderate wasting of the periscapular muscles, especially the deltoid, with scapular winging, of the pectoralis major, biceps brachii, and quadriceps muscles (Fig. 1A, B, and C, Supplementary Fig. 1 in the online-only Data Supplement). Deep tendon reflexes, sensation, and the findings of a cerebellar examination were normal. Laboratory investigations including serum creatine kinase (CK) and tumor markers produced findings that were all within the normal ranges. A workup for dysphagia that included a videofluoroscopic swallowing study and esophagogastroduodenoscopy did not reveal any structural abnormalities. The findings of nerve conduction studies were normal, and needle electromyography (EMG) recorded normal motor-unit potentials with a full interference pattern and no spontaneous activity in the deltoid, vastus lateralis, and gastrocnemius muscles. Repetitive nerve stimulation of the deltoid muscle at 2-5 Hz induced a 30% decrease in the amplitude of compound muscle action potentials, and increased jitter in the single-fiber EMG of the extensor digitorum communis muscle with a mean consecutive difference of 75.9 μsec (range 45.7-133 μsec; normal value <55 μsec). MG was suspected based on the neurophysiological findings. Serum testing for acetylcholine receptor (AChR)-binding antibody was positive, with a titer of 95 pmol/mL (normal <0.25 pmol/mL) confirming the diagnosis, while a radioimmunoprecipitation assay showed negativity for anti-musclespecific tyrosine kinase (MuSK) antibodies. A whole-body computed tomography scan showed no evidence of thymoma or other tumors, and cervical spine imaging was unremarkable. The patient was started on pyridostigmine at 90 mg per day, which was gradually increased to 300 mg per day to produce a partial response that was not sustained. However, adding prednisone at up to 12.5 mg per day led to long-lasting clinical improvement. At 4