Exploring if Longitudinal Changes on PET Imaging Can Serve as a Biomarker for Stiff Person Syndrome Spectrum Disorders.

Objective: To identify metabolic patterns in the brain and musculoskeletal system of stiff person syndrome spectrum disorders (SPSD) patients over time using PET imaging and evaluate the impact of immune therapy on metabolic activity as a surrogate for treatment response.

Methods: This observational study at the Johns Hopkins SPS Center of Excellence included adults (≥ 18 years) diagnosed with classic SPS, partial SPS, SPS plus, or PERM, who were treated from 2009 to 2023. Participants underwent at least two whole-body and/or dedicated brain PET scans. Brain PET analysis utilized NeuroQ v3.8 software to generate standardized Z-scores for 47 distinct brain regions, assessed by expert nuclear medicine radiologists. Patient demographics, antibody types, immune therapies, and symptomatic treatments were assessed.

Results: Eighteen patients met inclusion criteria (10 SPS plus, 6 classic SPS, 2 PERM), with a mean age of 50.7 (SD 8.5) years; 77.8% were female and 50.0% were Black/African American. Hypermetabolic activity and hypometabolism were both seen over time in the brain and the musculoskeletal system. Two patients starting immune therapy in between PET scans demonstrated improvement in brain but not body PET findings.

Interpretation: The study findings indicate that PET imaging abnormalities are present over time and appear to have regional patterns that are common among phenotypes. Additionally, starting immune therapy between scans appears to correlate with stabilization or improvement in brain PET abnormalities, though this was less clear in body PET scans. PET scans have the potential to be an imaging biomarker in SPSD, but future studies are needed to validate this.