Many medications are known to interfere with neuromuscular transmission and exacerbate weakness, particularly in patients with myasthenia gravis. Little is known about the effect of such medications on patients with LambertEaton myasthenic syndrome (LEMS). Case reports have described exacerbation or unmasking of weakness in LEMS patients in association with the use of drugs including diltiazem, 5,8,10 verapamil, 6 anesthetics, 2,7 ofloxacin, 9 botulinum toxin, 3 and magnesium. 4 We describe a 61-yearold woman with LEMS, whose symptoms started after she began using varenicline (Chantix). The drug was started for smoking cessation after she developed sudden dysarthria and unsteadiness. Stroke risk factors were limited to a 40-pack-year smoking history. Symptoms resolved within 24 hours, and investigations, including brain magnetic resonance imaging, transthoracic echocardiogram, and carotid duplex, were unrevealing. A few days after starting varenicline, she felt tired and weak, especially in the legs. She reported difficulty with standing from a chair or from squatting, combing her hair, mouth dryness, and urinary urgency without orthostatic dizziness. Symptoms quickly improved but did not resolve after she quit varenicline 3 weeks later. She sought medical attention 2 months after symptom onset.Neurologic examination revealed normal muscle bulk and tone. Strength was normal except for mild symmetric weakness in deltoids (5 Ϫ /5) and iliopsoas and hip adductors (4 ϩ /5). The degree of weakness did not change following activation of these muscles. Muscle stretch reflexes were absent throughout; however, after sustained activation of the quadriceps, trace patellar reflexes were elicited. Gait, cerebellar, and sensory examinations were unremarkable.Blood serology revealed a high titer (Ͼ23,000 pmol/L) of P/Q-type voltage-gated calcium channel (VGCC) antibodies, normal acetylcholine (ACh) receptor antibody levels, and undetectable muscle-specific tyrosine kinase antibodies. Electrophysiologic studies showed decreased compound muscle action potential (CMAP) amplitude of the radial nerve (0.8 mV) with a dramatic increase to 3.3 mV (393%) after 10 seconds of exercise and to 309% with repetitive stimulation at 20 Hz. Transbronchial fine needle aspirate of a hilar lymph node indicated small-cell lung cancer.Varenicline partially stimulates nicotinic receptors in the ventral tegmental area. This allows release of dopamine, but to a lesser degree than nicotine, thus reducing nicotine craving and withdrawal. In addition, it acts as an antagonist to block the binding and reinforcing effects of nicotine. Varenicline is highly specific for the ␣4/2 nicotinic receptor in the central nervous system. The nicotinic receptor found at the neuromuscular junction has a different subunit composition that makes varenicline 20,000 times less likely to bind to it. 1 Our patient developed weakness after taking varenicline. She had no prior symptoms, and her strength improved after she discontinued the medication. Although a causal relation...
