To characterize the “invisible”/non-physical symptoms in a cohort of patients with Stiff Person Spectrum Disorders (SPSD) and identify potential associations with clinical outcome.

SPSD are a group of rare and disabling disorders with the main manifestations being physical symptoms of stiffness and episodic spasms. The burden of “invisible” symptoms (agoraphobia, hypersensitivity triggers, mood disorders, and others), has not been as well characterized as the physical symptoms. Moreover, the overall impact of “invisible” symptoms on clinical outcomes is unknown.

A single-site, longitudinal observational database, containing clinical characteristics of patients with SPSD, was queried from 1997 to 4/2024. In 2018, a “Review of Symptoms” survey was implemented with the goal of better capturing the varied symptoms more systematically. Using univariate analysis, we assessed the frequency of “invisible” symptoms prior to the survey implementation (“pre-survey”) as well as after (“post-survey”). Multivariable logistic regression was used to assess for association with the main clinical outcome measures of modified Rankin Scale (mRS) score.

216 individuals were included, majority being classic SPS phenotype; mean age was 59 years old (SD 14.81), 72.8% were female, 71.8% were White-American, and 19.4% were Black-American. Comparing the pre-survey to the post-survey group, respectively, the percentage that reported the following were: agoraphobia 18.1% versus 41.6%, hypersensitivity triggers 39.8% versus 70.3%, pain 60% versus 56.5%, cognitive symptoms 20.8% versus 39.2%, fatigue 24.5% versus 53.1%, depression 19.4% versus 34.4%, anxiety 23.1% versus 57.4%, photosensitivity 8.3% versus 23.4%. In preliminary analyses, the presence of depression and agoraphobia appeared to be associated with worse clinical outcomes (higher mRS score).

“Invisible” symptoms are less appreciated than the typical physical manifestations of SPSD; however, the burden of these symptoms appears to be high. Further studies are needed to assess how these symptoms may impact SPSD and its clinical course and disease outcomes.