There is a dearth of literature surrounding the neuropathological findings of the spinal cord in Glutamate Decarboxylase-65 (GAD-65) antibody associated Stiff Person Syndrome (SPS). We present the autopsy findings in a 51-year-old female with this disorder. 

A 51-year-old female presented with chronic low back pain associated with severe muscle spasms, intermittent leg stiffness, progressive fatigue and memory disturbances for the last 18 months. Examination was pertinent for reduced motor strength (4/5) in left hemi-body; reflexes were brisk in bilateral upper extremities with positive Hoffman’s sign and crossed adductors.  Basic laboratory workup was unrevealing; however, serum GAD-65 antibody titers were high (>250, normal range 0-5) along with positive oligoclonal bands. Imaging of the lumbar spine showed multilevel degenerative changes of the spine with grade 4 anterolisthesis at L5- S1 level that was later fixated. She was diagnosed with SPS in 2020 and treated with regular IVIg infusions alongside various immunosuppressive treatments. Despite our best efforts, her condition continued to deteriorate, and she was bedbound in mid 2024, with severe contractions in her feet and uncontrollable pain. She eventually transitioned to hospice care and passed away in early 2025.  Postmortem autopsy revealed significant findings within her spinal cord with vacuolations and degenerative changes of anterior horn cells, degeneration of posterior columns, and mild inflammatory changes. Other findings included mild arteriosclerotic changes in the brain, a 0.2 cm pituitary adenoma, and neurogenic atrophy in the skeletal muscle.  

The neuropathological findings described above have rarely been reported. The spinal cord degenerative findings are especially indicative of a cytotoxic cell mediated response being an important driver of this inflammation. This may have significant therapeutic implications as it supports the possibility that the inflammation is pathogenic, potentially warranting early and aggressive immunosuppressive therapy in addition to therapies targeting humoral immunity