sps. rituximab rituximab is a genetically engineered monoclonal antibody directed against cd20, which causes a sustained depletion of b cells and has demonstrated promising results in several autoimmune neurological diseases. tacrolimus 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. intravenous immunoglobulin (ivig)therapy intravenous immune globulin has been found to be a "well-tolerated and effective" therapy. intravenous immunoglobin is the best second-line treatment for sps. it often decreases stiffness and improves quality of life and startle reflex. it is generally safe, but there are possible serious side effects, and it is expensive. the european federation of neurological societies suggests it be used when disabled patients do not respond well to diazepam and baclofen. plasma exchange (plasmapheresis) therapy plasma exchange, or plasmapheresis, has been shown to benefit patients who do not respond to first-line therapy, specifically beneficial for patients with anti-gad65 positive sps. other therapies botulinum toxin has been used to treat sps, but it does not appear to have long-term benefits and has potential serious side effects. in paraneoplastic cases, tumors must be managed in order for the condition to be contained. opiates are sometimes used to treat severe pain, but they may exacerbate symptoms. hematopoietic stem cell transplantation (hsct) with high intensity conditioning protocol has been performed in a few cases with severe anti-gad positive sps, resulting in clinical remission. in carefully selected cases of severe, treatment refractory sps, hsct may be an effective therapeutic option. prognosis the progression of sps depends on whether it is a typical or abnormal form of the condition and the presence of comorbidities. early recognition and neurological treatment can limit its progression. sps is generally responsive to treatment, but the condition usually progresses and stabilizes periodically. even with treatment, quality of life generally declines as stiffness precludes many activities. some patients require mobility aids due to the risk of falls. about 65 percent of sps patients are unable to function independently. about ten percent of sps patients require intensive care at some point; sudden death occurs in about the same number of patients. these deaths are usually caused by metabolic acidosis or an autonomic crisis. epidemiology sps is estimated to have a prevalence of about one or two per million people. it affects women up to three times as frequently as men. in the united kingdom, 119 cases were identified between 2000 and 2005. it does not predominantly occur in any racial or ethnic group. sps can start at any age, though it most frequently occurs in people in their 40s. about 35 percent of sps patients have type i diabetes. history 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. in 1963, it was determined that diazepam helped 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, it was also demonstrated that the serum of sps patients would 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. in december 2022, singer céline dion announced that she is suffering from this syndrome, resulting in cancelled performances.