SPS was first described by Moersch and Woltman in 1956. Their description of the disease was based on 14 cases that they had observed over 32 years. Using electromyography, they noted that motor-unit firing suggested that voluntary muscle contractions were occurring in their patients. Previously, cases of SPS had been dismissed as psychogenic problems. Moersch and Woltman initially called the condition "stiff-man syndrome", but the first female patient was confirmed in 1958 and a young boy was confirmed to have it in 1960. Clinical diagnostic criteria were developed by Gordon et al. in 1967. They observed "persistent tonic contraction reflected in constant firing, even at rest" after providing patients with muscle relaxants and examining them with electromyography. In 1989, criteria for an SPS diagnosis were adopted that included episodic axial stiffness, progression of stiffness, lordosis, and triggered spasms. The name of the disease was shifted from "stiff-man syndrome" to the gender-neutral "stiff-person syndrome" in 1991.
SPS was first described in 1956. Diagnostic criteria were proposed in the 1960s and refined two decades later. In the 1990s and 2000s, the roles of antibodies in the condition became clearer. SPS patients generally have glutamic acid decarboxylase (GAD) antibodies, which seldom occur in the general population. In addition to blood tests for GAD, electromyography tests can help confirm the condition's presence.
In 1963, diazepam was determined to help alleviate symptoms of SPS. Corticosteroids were first used to treat the condition in 1988, and plasma exchange was first applied the following year. The first use of intravenous immunoglobulin to treat the condition came in 1994.
In 1988, Solimena et al. discovered that autoantibodies against GAD played a key role in SPS. Two years later, Solimena found the antibodies in 20 out of 33 patients examined. In the late 1980s, the serum of SPS patients was also found to bind to GABAergic neurons. In 2006, the role of GABARAP in SPS was discovered. The first case of paraneoplastic SPS was found in 1975. In 1993, antiamphiphysin was shown to play a role in paraneoplastic SPS, and seven years later, antigephyrin was also found to be involved in the condition.
Tacrolimus belongs to the same class of medication as cyclosporine (calcineurin inhibitor), but is more potent. Tacrolimus inhibits the activity of T cells by decreasing the levels of IL-2. leading to a reduction of activation of B cells to produce antibodies. A small (n=2) study in 2013 showed that patients treated with tacrolimus and additional immunotherapies, after four weeks, reported improvement in their symptoms and a reduction of antibody titers. T helper cells. If the T helper cells can conduct their function, there will be less activation of B cells to produce antibodies.
In December 2022, singer Céline Dion announced that she is suffering from this syndrome, resulting in cancelled performances.