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Stiff-man syndrome is a rare disorder of the CNS, characterised by painful spasms and progressive symmetric rigidity of the axial and proximal muscles. 1 Three different aetiological subtypes of stiff-man syndrome have been described: an autosomal dominant disorder with early onset in childhood called stiff-baby syndrome, 2 stiff-man syndrome associated with breast cancer and characterised by autoantibodies to the 128 kDa synaptic vesicle associated protein amphiphysin, 3 4 and the most common autoimmune stiff-man syndrome (60%) often associated with additional autoimmune diseases such as insulin dependent diabetes mellitus. 5 6 The association of stiff-man syndrome and insulin dependent diabetes mellitus is, from an immunological point of view, extremely interesting, because the two diseases share a major autoantigen, the enzyme glutamic acid decarboxylase (GAD). GAD is located in the [beta] cells of the pancreas and in the GABA producing neurons of the peripheral nervous system and CNS. 7 In stiff-man syndrome, high GAD antibody (GADA) titres are characteristic and, although controversial, these have been suggested to cause functional impairment of the GABA mediated physiological process, thereby explaining the neurological symptoms. In accordance with this, treatment of patients by plasmapheresis and/or immunosuppressive agents such as prednisolone result in an improvement of neurological symptoms. 8 However, no studies so far exist on the course of humoral and cellular immune markers during immune intervention therapy.
GADA recognises several epitopes within the GAD65 molecule, including two relatively stiff-man syndrome specific epitopes contained within the carboxy and amino terminal regions. 9 Antibodies to other pancreatic islet proteins including insulin and the protein tyrosine phosphatase-like molecule IA-2 are also found in patients with insulin dependent diabetes mellitus. IA-2 antibodies (IA-2A) can be detected in a minority of patients with stiff-man syndrome, most, 10 but not all 11 having insulin dependent diabetes mellitus. [beta] Cell death and decline of insulin release in insulin dependent diabetes mellitus are not considered to be causally related to antibodies, including GADA, but are more likely to be T cell mediated. T Cell proliferative responses to GAD65 and other islet autoantigens can be found in patients with insulin dependent diabetes mellitus, 12 but as yet there have been no reports of cellular immunity to GAD in stiff-man syndrome.
To determine whether neurological symptoms in stiff-man syndrome are directly...