Antibody–phenotype correlation in stiff-person syndrome

Abstract

Stiff-person syndrome (SPS) is a neurologic disease characterized by progressive muscle stiffness predominant in axial and proximal limb muscles. EMG reveals continuous motor unit activity of agonist and antagonist muscles at rest. Increased lumbar lordosis and gait abnormality with frequent falls caused by rigidity of leg and paraspinal muscles are the most common clinical findings in these patients.1 Superimposed are muscle spasms triggered by sensory stimuli, movements, and emotional stress. Clinical variants of this classic SPS include a focal disease, the stiff-limb syndrome, and a progressive encephalomyelitis with rigidity and myoclonus (PERM).1 The clinical response to γ-aminobutyric acid (GABA) agonists such as benzodiazepines and baclofen suggests that the sustained muscle contraction in SPS is due to an impairment of central inhibitory circuits with increased excitation of spinal motoneurons. A major breakthrough in the understanding of the disease pathogenesis came with the finding of its association with antibodies against glutamic acid decarboxylase (GAD-Ab), the rate-limiting enzyme in GABA synthesis.2 Later on, antibodies against …