Stiff-person syndrome

Abstract

Stiff-person syndrome (SPS) is an autoimmune disease associated mainly with antibodies to glutamic acid decarboxylase (GAD) or to glycine, characterised by intermittent painful spasms, stiffness and rigidity of the proximal and truncal muscles. Neuro-ophthalmological and gastrointestinal symptoms also occur. The symptoms are caused by neuronal excitability due to impaired inhibitory (gamma amino butyric acid [GABA] and glycine) neurotransmission. SPS is part of a larger spectrum of GAD antibody-spectrum disorders, which overlaps with autoimmune epilepsy, cerebellar ataxia, myoclonus, progressive encephalomyelitis, rigidity and myoclonus (PERM) and limbic encephalitis. PERM is often caused by antibodies against the glycine receptor. Some SPS cases are paraneoplastic. Diagnostic delay is often associated with irreversible disability, and therefore, clinicians need a high degree of clinical suspicion to make an earlier diagnosis. This review updates the various clinical presentations that should raise suspicion of SPS and its related conditions and includes a diagnostic algorithm and various treatment strategies including immunotherapy and GABA-ergic drugs.