Stiff-Man-Syndrome (SMS) is a complex neuroimmunological disease of the Central Nervous System (CNS) with endocrinological, motoric, vegetative symptoms and is associated with autoantibodies to glutamate decarboxylase (GAD). SMS and its variants, stiff limb syndrome (SLS) and progressive encephalomyelitis with rigidity and myoclonus (PERM), appear to occur more frequently than hitherto thought. The cause of SMS is unknown. In a retrospective assessment of 92 patients (1989 –2005 ) we investigated the correlation between SMS/SLS/PERM, associated autoimmune disorders, organ -specific antibodies and immungenetic HLA- association to find out the immunological differences between SMS, its variants and GAD-Ab positive- and negative patients. In total 54 of 92 patients with SMS and its variants were associated with 96 autoimmune diseases included autoimmune-endocrinopathies, e.g. Diabetes mellitus Typ I n=40, Hashimoto Thyroiditis n=13, Vitamine B12 Hypovitaminosis n=11, Pernicious anemia n=4 and Atrophic gastritis n=4. Associated immunopathies are most presented in patients with GAD-Ab: in 65 patients with GAD-Ab appeared 83 immunopathies , 26 patients without GAD-Ab only 13. In total 70% of autoimmune-endocrinopathies were diagnosed after the manifestation of this neurological disorder . Organ-specific antibodies are more frequent in patients with GAD-Ab than in patients without GAD-Ab, e.g. beta cell antibodies were found in 23 of 40 patients with GAD-Ab, but no antibodies were found in 13 patients without GAD-Ab. Two different groups can be distinguished pathogenetic. GAD-Ab as a Master-Ab is leading the way in the diagnostics of SMS. We have observed a noticeable association of this autoimmune-encephalomyelitis between GAD-Ab and HLA- haplotypes DQB1*03, DRB1*04, DQB1*02 and DQA1*0102 . This show a similarity with diabetes mellitus Type I and may represent a genetic disposition . These results show interactions between neuroimmunology, endocrinology, immungenetics. Diagnostic, therapy and treatment of these patients indicate integrative and complementary proceedings. We hope that , e .g. natural medicine, ayurveda , TCM will help to find the cause of this disease and extend the therapeutical options in the treatment of Stiff- Man -Syndrome and many other neuroimmunological diseases.