Stiff person syndrome

Abstract

Stiff person syndrome (SPS), stiff limb syndrome, jerking SPS and progressive encephalomyelitis with rigidity and myoclonus (PERM) are a family of rare, insidiously progressive diseases of the central nervous system. They all share the core clinical features of appendicular and axial rigidity caused by continuous involuntary motor unit activity, and superimposed stimulus-sensitive spasms. There is good evidence for a primary auto-immune aetiology. Anti-glutamic acid decarboxylase (anti-GAD) antibodies, specifically to the GAD65 isoform, are present in serum or cerebrospinal fluid of 60-80% of patients with SPS and its variants. A paraneoplastic form of SPS is recognized in about 5%, associated with a different profile of auto-antibodies. Repeated intravenous immunoglobulin is the mainstay of disease-modifying therapy in SPS. Rigidity and spasms may be treated symptomatically with benzodiazepines, baclofen, tiagabine and levetiracetam. After an initial progressive phase, patients with SPS generally stabilize over a period of months to years. However, 10% will require prolongedadmission to intensive care at some stage during the disease. Sudden death has been reported in asmany as 10% of patients because of unexplained metabolic acidosis or autonomic crises. The prognosis in paraneoplastic SPS, jerking SPS and PERM, in terms of mortality, is generally worse than in primary SPS.