Search Results (7)

SPS is characterized by progressive spasmodic muscular rigidity. SPS is thought to be an autoimmune disease with a prominent feature of antibodies against glutamic acid decarboxylase (GAD). GAD is responsible for the enzymatic conversion of glutamic acid (glutamate) into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Reduced GABA activity leads to increased excitability in the central nervous system, resulting in muscle rigidity and spasms characteristic of SPS. While SPS is rare, anti-GAD antibodies seen in SPS are also seen in the much more common autoimmune disease, type 1 diabetes (T1D). There is evolving research showing that the anti-GAD antibodies of T1D are produced in response to the presence of mycobacterial heat shock protein 65 (mHSP65), and the mHSP65 is produced in response to an occult infection by a bacterium, Mycobacterium avium subspecies Paratuberculosis (MAP). Humans are broadly exposed to MAP in food, water, and air. There are linear and conformational similarities between the epitopes of GAD and mHSP65. This article proposes that MAP is also an infectious trigger for SPS. Dehydroepiandrosterone (DHEA) is a principal component of the steroid metabolome; it plateaus in young adults and then steadily declines. Bromo-epi-androsterone (BEA) is a potent synthetic analog of DHEA; unlike DHEA, it is non-androgenic, non-anabolic, and an effective modulator of immune dysregulation. BEA is also an anti-infective agent and has been shown to benefit mycobacterial infections, including tuberculosis and leprosy. With the immune stabilizing capacity of BEA as well as its anti-mycobacterial properties, there is reason to believe that a randomized clinical trial with BEA may be beneficial for SPS. Full article

Antibodies to glutamic acid decarboxylase (GAD) have been predominantly associated with stiff-person syndrome (SPS), which is often accompanied by organ-specific autoimmune diseases, such as late-onset type 1 diabetes. Autoimmune retinal pathology in SPS has recently been suggested to coexist in patients suffering from this disease; however, evidence reporting potential treatment options for the neurological and visual symptoms these patients experience remains scarce. We provide a review of the relevant literature, presenting a rare case of a middle-aged woman with autoimmune retinopathy (AIR) followed by stiff-leg syndrome who responded to intravenous immune globulin treatment (IVIg). Our report adds to previously reported data supporting the efficacy of IVIg in SPS spectrum disorders while also proposing the potential effect of IVIg in treating SPS spectrum patients with coexisting AIR. Full article

Glutamic acid decarboxylase (GAD) antibody-related encephalitis is an autoimmune disease associated with intracellular neuronal antigens. We report on a rare case of GAD antibody-associated encephalitis complicated with focal segmental stiffness-person syndrome (SPS) in a middle-aged woman. The disease course lasted for >10 years, initially presenting with drug-resistant epilepsy, followed by stiffness of the right lower limb, and right upper limb involvement. The patient experienced anxiety and depression symptoms due to long-term illness. During hospitalization, serum and cerebrospinal fluid GAD antibodies were positive and no tumor was found. The symptoms were significantly relieved after corticosteroid therapy and intravenous immunoglobulin immunomodulation therapy. To the best of our knowledge, this case is the first to discuss the early recognition and treatment of chronic epilepsy and focal segmental SPS caused by anti-GAD antibody-related encephalitis. Full article

Two isoforms of the glutamate decarboxylase (GAD) enzyme exist, GAD65 and GAD67, which are associated with type 1 diabetes (T1D) and stiff-person syndrome (SPS), respectively. Interestingly, it has been reported that T1D patients seldom develop SPS, whereas patients with SPS occasionally develop T1D. In addition, coxsackievirus B4 (CVB4) has previously been proposed to be involved in the onset of T1D through molecular mimicry. On this basis, we aimed to examine antibody cross-reactivity between a specific region of GAD65 and GAD67, which has high sequence homology to the nonstructural P2C protein of CVB4 to determine potential correlations at antibody level. Monoclonal peptide antibodies generated in mice specific for a region with high similarity in all three proteins were screened for reactivity along with human sera in immunoassays. In total, six antibodies were generated. Two of the antibodies reacted to both GAD isoforms. However, none of the antibodies were cross-reactive to CVB, suggesting that antibody cross-reactivity between GAD65 and CVB, and GAD67 and CVB may not contribute to the onset of T1D and SPS, respectively. Full article

Anti-GAD ataxia is one of the most common forms of immune-mediated cerebellar ataxias. Many neurological syndromes have been reported in association with anti-GAD. Ophthalmoparesis has been described in stiff person syndrome. We report a case of anti-GAD ataxia presenting initially with isolated ophthalmoplegia and showing complete resolution after immunotherapy. A 26-year-old male patient presented with ophthalmoparesis characterized by tonic upwards deviation of the right eye. In the following month, he developed progressive ataxia with anti-GAD titers of 1972 UI/mL. After treatment with methylprednisolone and immunoglobulin, there was complete resolution of symptoms and anti-GAD titers decreased. This is the first report of isolated ophthalmoparesis due to tonic eye deviation associated with anti-GAD antibodies without stiff-person syndrome. Tonic eye deviation has been reported in SPS, possibly secondary to continuous discharge in gaze holding neurons in the brainstem (similar to what occurs in spinal motor neurons). With growing evidence for ocular abnormalitites in SPS, anti-GAD associated neurological syndromes should be included in the differential diagnosis of isolated ophthalmoplegia. Full article

Stiff person syndrome (SPS) is a rare autoimmune disease characterised by axial stiffness and episodic painful spasms. It is associated with additional autoimmune diseases and cerebellar ataxia. Most patients with SPS have high levels of glutamic acid decarboxylase (GAD) antibodies. The aetiology of SPS remains unclear but autoimmunity is thought to play a major part. We have previously demonstrated overlap between anti-GAD ataxia and gluten sensitivity. We have also demonstrated the beneficial effect of a gluten-free diet (GFD) in patients with anti-GAD ataxia. Here, we describe our experience in the management of 20 patients with SPS. The mean age at symptom onset was 52 years. Additional autoimmune diseases were seen in 15/20. Nineteen of the 20 patients had serological evidence of gluten sensitivity and 6 had coeliac disease. Fourteen of the 15 patients who had brain imaging had evidence of cerebellar involvement. Twelve patients improved on GFD and in seven GFD alone was the only treatment required long term. Twelve patients had immunosuppression but only three remained on such medication. Gluten sensitivity plays an important part in the pathogenesis of SPS and GFD is an effective therapeutic intervention. Full article

Stiff-person syndrome (SPS) is a rare neurologic disorder characterized by waxing and waning muscular rigidity, stiffness and spasms. Three subtypes have been described: paraneoplastic, autoimmune and idiopathic. Rhabdomyolysis has been described in the paraneoplastic variant, but to our knowledge no case has been reported involving the autoimmune variant. We report a case report of a 50-year-old man with history of SPS who presented with recurrent episodes of severe limb and back spasms. He was hospitalized on two separate occasions for uncontrollable spasms associated with renal failure and creatinine phosphokinase elevations of 55,000 and 22,000 U/L respectively. Laboratory tests were otherwise unremarkable. The acute renal failure resolved during both admissions with supportive management. Rhabdomyolysis has the potential to be fatal and early diagnosis is essential. It should be considered in patients who have SPS and are experiencing an exacerbation of their neurologic condition. Full article