1/16. GAD65-Reactive T cells in a non-diabetic stiff-man syndrome patient.GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. Still, only 30% of SMS patients also have type 1 diabetes. To study regulation of T cell responsiveness to GAD65, we investigated a non-diabetic SMS patient with HLA-DR3/7 (predisposing to type 1 diabetes) and high levels of type 1 diabetes-associated autoantibodies against GAD65 and islet cells, and compared the results with those of her diabetic son and two other SMS patients. T cell responses to GAD65 were repeatedly absent in primary stimulation, whereas IA-2, islet antigen and tetanus toxoid induced significant T cell proliferation. However, after in vitro restimulation, GAD65 reactive T cell lines and clones were obtained that were HLA-DR3 restricted, and cross-reactive with a homogenate of purified human pancreatic islets. These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0). The dominant T cell epitope was mapped to the central region of GAD65. Although no primary response to whole GAD65 was detectable, the naturally processed GAD65 peptide epitope was recognized vigorously in the primary stimulation assay. The lack of detectable primary T cell responses to GAD65, together with the GAD65-specific cytokine production of restimulated T cells, suggest that GAD65-specific cellular autoimmunity in this patient is suppressed and may be related to the absence of diabetes despite humoral autoreactivity and genetic predisposition.- - - - - - - - - - ranking = 1keywords = diabetes mellitus, insulin-dependent, diabetes, mellitus (Clic here for more details about this article) |
2/16. stiff-person syndrome associated with cerebellar ataxia and high glutamic acid decarboxylase antibody titer.glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in patients with insulin-dependent diabetes mellitus (IDDM) and stiff-person syndrome. We reviewed the case of a 46-year-old woman who had cerebellar ataxia before getting stiff-person syndrome and IDDM with high anti-GAD autoantibody titers. This was a rare case in which there were both the clinical symptoms of stiff-person syndrome and cerebellar ataxia. In western blot analysis her serum reacted with 65-kDa proteins from rat cerebellum, cerebral cortex, and spinal cord. autoantibodies to GAD may cause functional impairment of gamma-aminobutyric acid (GABA) neurons in the spinal cord as well as in the cerebellum.- - - - - - - - - - ranking = 0.56673222492795keywords = diabetes mellitus, insulin-dependent, diabetes, mellitus (Clic here for more details about this article) |
3/16. Stiff leg syndrome: case report.We report on a 28-year-old woman with insulin-resistant diabetes mellitus with a 5-year history of progressive stiffness and painful spasms of the right leg, exaggerated by sudden auditory and tactile stimuli or by emotional stress. There were no signs of truncal rigidity or exaggerated lumbar lordosis. Anti-glutamic acid decarboxylase antibodies were positive in her serum. She improved substantially with clonazepam 4 mg/day. She presented with electrophysiological findings not previously reported in stiff leg syndrome, which may suggest increased inhibition in the uninvolved upper extremities.- - - - - - - - - - ranking = 0.44437155346121keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
4/16. T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity.Antibodies to glutamic acid decarboxilase (GAD-Abs) are present in the serum of 60-80% of newly diagnosed type 1 diabetes (DM1) patients and patients with autoimmune polyendocrine syndrome (APS) associated with DM1. Higher titre of GAD-Abs are also present in the serum of 60% of patients with stiff-man syndrome (SMS) and all reported patients with cerebellar ataxia associated with polyendocrine autoimmunity (CAPA). Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. GAD-65-specific cellular proliferation was significantly higher in SMS than in CAPA, DM1, APS or controls. In contrast, only T cells from CAPA patients showed a significantly high production of interferon-gamma after GAD stimulation, compared to all other patients and controls. No differences were found for IL-4 production. These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases.- - - - - - - - - - ranking = 0.10831694376801keywords = diabetes (Clic here for more details about this article) |
5/16. stiff-person syndrome.The stiff-person syndrome is a disorder of persistent, painful muscle contractions predominately affecting the axial musculature. We describe a patient with this disorder and review its pathophysiology. Molecular biologic and immunologic techniques have recently added to the understanding of the mechanism of this disorder. association with diseases such as diabetes, vitiligo and hypothyroidism have strengthened the auto-immune nature of this syndrome. Auto-antibodies against glutamic acid decarboxylase (GAD), an intraneuronal enzyme, have been implicated in the etiology of this unique disease. Therapeutic intervention with agents such as benzodiazepines that modify central GABAergic activity have demonstrated significant benefit in patients with stiff-person syndrome.- - - - - - - - - - ranking = 0.10831694376801keywords = diabetes (Clic here for more details about this article) |
6/16. Stiff child syndrome with mutation of DYT1 gene.The authors report a Chinese boy with a DYT1 gene mutation having muscle stiffness, severe painful muscle spasm, myoclonus, and dystonia compatible with stiff child syndrome. autoantibodies to glutamic acid decarboxylase (anti-GAD) were absent. His asymptomatic mother had a DYT1 mutation. His asymptomatic sister has diabetes mellitus and antibodies to glutamic acid decarboxylase but no DYT1 mutation.- - - - - - - - - - ranking = 0.44437155346121keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
7/16. Stiff-man syndrome: case report.Stiff-man syndrome is a rare neurologic disorder characterized by progressive, fluctuating muscle rigidity with painful muscle contractions affecting predominantly the back and proximal extremities. In the ED, the diagnosis can be easily overlooked and misdiagnosed as acute or chronic low back pain and muscle spasm. This syndrome is often associated with diabetes, autoimmune diseases, and cancer. This report describes an illustrative case of a 39-year-old woman who presented to the ED with a two-year history of right leg spasms and low back pain that had become so severe in the preceding two days that she was unable to ambulate. Clues to the patient's proper diagnosis coincide with the diagnostic criteria for stiff-man syndrome: the presence of a slowly progressive stiffness of the axial muscles and proximal limb muscles, making ambulation difficult; hyperlordosis of the lumbar spine; episodic spasms precipitated by jarring or sudden movement; a normal intellectual, sensory, and motor examination when not in spasm; and a marked amelioration of symptoms with the IV administration of diazepam. High-dose oral diazepam is the maintenance drug of choice.- - - - - - - - - - ranking = 0.10831694376801keywords = diabetes (Clic here for more details about this article) |
8/16. Stiff-man syndrome. Report of a case.Stiff-man syndrome is a well-described, but rare and often overlooked, neuromuscular syndrome of rigidity, spasm, and gait abnormality that is associated with several endocrinologic and autoimmune disorders. A patient exhibiting many typical features of stiff-man syndrome had intermittent symptoms for 22 years before the correct diagnosis was made. Similar to many described patients, she was diabetic, hyperthyroid, and had elevated islet cell, antithyroid, and glutamic acid decarboxylase antibody levels. The high frequency of diabetes mellitus among patients with stiff-man syndrome is emphasized, as is increasing evidence to suggest that elaboration of anti-glutamic acid decarboxylase and anti-islet cell antibodies may play a role in the pathophysiologic state of the disorder.- - - - - - - - - - ranking = 0.44437155346121keywords = diabetes mellitus, diabetes, mellitus (Clic here for more details about this article) |
9/16. autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer.BACKGROUND. The stiff-man syndrome is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. autoantibodies directed against glutamic acid decarboxylase are present in about 60 percent of patients with the syndrome. In this group, there is a striking association of the stiff-man syndrome with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus. methods. We studied three women with the stiff-man syndrome and breast cancer, seeking autoantibodies directed against nervous system antigens in serum and cerebrospinal fluid by immunocytochemical techniques, Western blotting, and immunoprecipitation. RESULTS. autoantibodies directed against a 128-kd brain protein were found in two of the women with the stiff-man syndrome and breast cancer. These results led to a search for breast cancer in the third patient with the stiff-man syndrome, who also had autoantibodies. A small invasive ductal carcinoma was detected by ultrasonography and removed. serum samples from all three patients were negative for autoantibodies directed against glutamic acid decarboxylase. autoantibodies against the 128-kd antigen were not detected in control patients with the stiff-man syndrome without breast cancer or in patients with cancer who did not have the syndrome. Within the nervous system, the 128-kd autoantigen was localized in neurons and concentrated at synapses. CONCLUSIONS. In a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.- - - - - - - - - - ranking = 0.56673222492795keywords = diabetes mellitus, insulin-dependent, diabetes, mellitus (Clic here for more details about this article) |
10/16. stiff-person syndrome with anti-glutamic acid decarboxylase autoantibodies: complete remission of symptoms after intrathecal baclofen administration.A female patient, aged 61 years, who developed a severe immobilizing stiff-person syndrome in conjunction with insulin-dependent diabetes mellitus, is described. In addition to the typical clinical symptoms, diagnosis was proven by the presence of autoantibodies against glutamic acid decarboxylase in serum and cerebrospinal fluid. Symptomatic treatment with continuous intrathecal application of baclofen administered by a subcutaneous pump resulted in rapid clinical improvement so that the patient became ambulatory. Intermittent withdrawal from intrathecal baclofen therapy led to complete remanifestation of stiff-person syndrome within 18 h; after re-introduction of intrathecal therapy stiffness disappeared completely within 48 h. The clinical course has been stable now for over 24 months and stiffness has completely disappeared. The effect of baclofen in this patient is discussed in the light of the suggested pathophysiological mechanisms in stiff-person syndromes.- - - - - - - - - - ranking = 0.56673222492795keywords = diabetes mellitus, insulin-dependent, diabetes, mellitus (Clic here for more details about this article) |
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