Objective:

To identify key features that are critical for helping aid in the diagnosis  of Stiff Person Syndrome Spectrum Disorders (SPSD)  and highlight characteristics associated with misdiagnosis.

Background:

SPSD are rare neuroimmunological disorders that can be difficult to diagnose due to the lack of validated diagnostic criteria and awareness of non-classical symptoms or atypical presentations.

Design/Methods:

We conducted a retrospective review of patients seen at a large academic center from 1997 to 2021. Clinical characteristics, examination findings, and diagnostic studies were analyzed to compare patients with SPSD to those receiving alternative diagnoses (controls). Sensitivity, specificity, and diagnostic odds ratios were calculated for key clinical features. Logistic regression helped define key diagnostic features for classic SPS and SPS-plus phenotypes.

Results:

We included 154 classic SPS cases, 45 SPS-plus cases, and 66 controls. The most sensitive findings (>80%) for classic SPS were torso and lower extremity involvement, stress and noise as symptom triggers, paravertebral stiffness, and gait dysfunction. The most specific findings included characteristic EMG results, high GAD65 antibody titers (>1000 IU/mL via ELISA or >20 nmol/L via RIA), GAD65 positivity in cerebrospinal fluid, agoraphobia, and hyperlordosis. For SPS-plus, cerebellar and brainstem involvement were highly specific (>95%). In univariate analysis, high GAD65 antibody titers, stress as a trigger, and paravertebral stiffness were most associated with SPSD. In multivariate analysis, the presence of high-titer GAD65 antibodies was  the strongest independent  feature for diagnosis. Misdiagnosis was more likely with upper extremity or brainstem/cerebellar involvement.

Conclusions:

This study highlights important clinical and paraclinical features in SPSD that can help clinicians make accurate and timely diagnoses. Further studies are needed to validate these findings.