Stiff person syndrome is a rare autoimmune or paraneoplastic disorder characterized by progressive muscle stiffness and spasms. It can be associated with significantly elevated levels of anti-glutamic acid decarboxylase (anti-GAD) antibodies. Average age of onset is between 20 and 50 years old. Onset in childhood is rare. Women are affected 2-3 times more often than men.

Patients present with nonspecific back pain or axial stiffness with or without episodes of severe spasms that resolve over hours to days. Some patients may only present with stiffness in the extremities or facial muscles. Spasms can be precipitated by stress, anxiety, other emotional upset, startle responses, physical touch, sudden voluntary movement, or cold temperature. There can be abdominal contractions as well as significant lumbar lordosis. Contractions of agonist and antagonist muscles can limit range of motion and lead to falls. More than one-half of patients have a history of other autoimmune conditions, often diabetes mellitus type 1 or thyroid disease; it rarely occurs as a paraneoplastic syndrome. Prognosis is variable.