These cancers are associated with the synaptic proteins amphiphysin and gephyrin. Paraneoplastic SPS with amphiphysin antibodies and breast adenocarcinoma tend to occur together. These patients tend not to have GAD antibodies. Passive transfer of the disease by plasma injection has been shown in paraneoplastic SPS but not classical SPS.There is evidence of genetic risk of SPS. The HLA class II locus makes patients susceptible to the condition. Most SPS patients have the DQB1* 0201 allele. This allele is also associated with type 1 diabetes. Diagnosis
SPS is diagnosed by evaluating clinical findings and excluding other conditions. There is no specific laboratory test that confirms its presence. Underdiagnosis and misdiagnosis are common.The presence of antibodies against GAD is the best indication of the condition that can be detected by blood and cerebrospinal fluid (CSF) testing. Anti-GAD65 is found in about 80 percent of SPS patients. Anti-thyroid, anti-intrinsic factor, anti-nuclear, anti-RNP, and anti-gliadin are also often present in blood tests. Electromyography (EMG) demonstrates involuntary motor unit firing in SPS patients. EMG can confirm the diagnosis by noting spasms in distant muscles as a result of subnoxious stimulation of cutaneous or mixed nerves. Responsiveness to diazepam helps confirm that the patient has SPS, as this decreases stiffness and motor unit potential firing.The same general criteria are used to diagnose paraneoplastic SPS as the normal form of the condition. Once SPS is diagnosed, poor response to conventional therapies and the presence of cancer indicate that it may be paraneoplastic.
Intrathecal baclofen administration may not have long-term benefits though, and there are potential serious side effects.Treatments that target the autoimmune response are also used. 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. Steroids, rituximab, and plasma exchange have been used to suppress the immune system in SPS patients, but the efficacy of these treatments is unclear. 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 for the condition to be contained. Opiates are sometimes used to treat severe pain, but in some cases they 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.