Stiff person syndrome (SPS) is a rare autoimmune neurologic disorder characterized by fluctuating muscle rigidity and painful spasms, most often affecting axial muscles and leading to postural abnormalities such as hyperlordosis. Symptoms are typically stimulus-sensitive, worsening with sudden movement, emotional stress, or unexpected noise. Although classically presenting with progressive stiffness of the trunk and proximal limbs, variants include stiff limb syndrome and severe progressive encephalomyelitis with rigidity and myoclonus (PERM). [1, 2] SPS is strongly associated with anti-GAD65 antibodies, although cases linked to amphiphysin and glycine receptor antibodies are seen, particularly in paraneoplastic and PERM presentations. A subset of patients remains seronegative, supporting a broader SPS-spectrum immunopathogenesis.

Several autoantibodies have been implicated in the pathogenesis of stiff person syndrome (SPS) and its related spectrum disorders: Anti–glutamic acid decarboxylase 65 (GAD65) antibodies: The most frequently identified and best-characterized antibody in SPS. High-titer anti-GAD65 antibodies are found in the majority of patients with the classic form and are considered highly specific for the disorder Anti–amphiphysin antibodies: Typically associated with paraneoplastic variants of SPS, most notably those linked to breast carcinoma and other malignancies [7] Anti–glycine receptor (GlyR) antibodies: Often encountered in SPS-spectrum presentations such as progressive encephalomyelitis with rigidity and myoclonus (PERM), but can occasionally occur in classic or SPS-plus phenotypes Anti–DPPX (dipeptidyl-peptidase–like protein 6) antibodies: Rarely detected, yet reported in certain SPS-spectrum cases Anti–GABA(A) receptor–associated protein antibodies: Occasionally identified in SPS and related autoimmune neurologic disorders [8] Anti–gephyrin antibodies: Very uncommon, but have been described in isolated SPS-spectrum cases [1]