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Symptomatic treatment of stiff-person syndrome (SPS) might be challenging and a significant improvement of stiffness and rigidity is generally reached with high doses of benzodiazepines or baclofen causing side effects. A 71-year old woman diagnosed with SPS complained of marked stiffness of trunk and lower limb muscles with sudden painful spasms. She was unable to walk and she could not lean on her right leg. Cortical silent period (CSP) duration evaluated from right abductor pollicis brevis (APB) with transcranial magnetic stimulation was shortened. Polygraphic electromyographic (EMG) evaluation from paraspinal and leg muscles disclosed continuous motor unit activity at rest with interference muscular pattern. Symptomatic treatment with diazepam was withdrawn because of excessive sedation. In order to relieve the intense lumbar pain, she was prescribed pregabalin; since the day after, rigidity and painful spasms dramatically improved and she could walk without assistance. The clinical benefit persisted at 3 months follow-up and was paralleled by almost complete disappearance of EMG activity at rest and prolongation of CSP. The clinical and electrophysiological data in this SPS patient suggest the possible efficacy of pregabalin as symptomatic treatment without any significant side effects, which needs to be replicated in larger case series., (Copyright © 2011 Elsevier B.V. All rights reserved.)