Stiff Person Syndrome

Stiff Person Syndrome is an autoimmune disorder of the central nervous system involving antibodies against glutamate decarboxylase (GAD), the enzyme producing GABA from glutamate. Reduced GABA results in loss of inhibitory control over motor neuron firing, leading to unopposed motor neuron activation and muscle rigidity. Two main antibody types are identified: anti-GAD65 antibodies (most common, 50-80% of patients) and anti-amphiphysin antibodies (present in ~30% of cases, particularly paraneoplastic SCLC-associated SPS). Seronegative patients (lacking both antibodies) also exist, possibly with other undiscovered antigenic targets. The disease progresses from mild stiffness and muscle tension to severe rigidity, potentially involving respiratory muscles and requiring mechanical ventilation in extreme cases. Patients develop characteristic hyperlordotic posture and distinctive gait abnormalities. Muscle spasms are often extremely painful and can be triggered by emotional stress, sudden movements, or auditory stimuli. Symptoms may stabilize or continue progressing slowly over years. The condition significantly impacts quality of life, with many patients requiring mobility aids and experiencing psychological distress from anxiety and social isolation. Paraneoplastic SPS, particularly associated with SCLC, may have more aggressive progression.