International Delphi Survey of Clinical Practice in Stiff Person Syndrome and Related Disorders: Terminology and Diagnosis

ObjectiveTo establish expert consensus and identify practice variation in terminology and diagnostic approaches for stiff person syndrome (SPS) and related disorders. BackgroundSPS is a rare and clinically heterogeneous condition. Although expert-proposed diagnostic criteria exist, international consensus guidance is lacking, and approaches to terminology and diagnosis vary across centers, countries, and resource settings. Design/MethodsForty international experts in SPS were identified based on peer-reviewed authorship. A modified Delphi survey was designed to evaluate agreement on terminology and diagnosis. Consensus was predefined as greater than 80% agreement. ResultsOf 40 invited expert clinicians, 33 (83%) from 15 countries participated. Consensus was achieved for the terminology of classic SPS; partial SPS; SPS-plus; progressive encephalomyelitis with rigidity and myoclonus (PERM); and glutamic acid decarboxylase 65 (GAD65)-associated cerebellar ataxia. Consensus was also reached for key diagnostic elements, including core clinical symptoms and signs of classic/partial SPS; supportive features (exaggerated startle responses and coexisting autoimmune comorbidities in GAD65-positive cases); the importance of serologic testing; clinically relevant high-titer GAD65 antibody thresholds according to assay methodology; the diagnostic utility of glycine receptor alpha1 antibody in suspected PERM and GAD65 antibody negative SPS cases; the role of electrophysiology, especially in seronegative cases; definite diagnostic criteria for classic/partial SPS and SPS-plus; diagnostic frameworks for PERM and GAD65-associated cerebellar ataxia; and major exclusion criteria and diagnostic pitfalls. Consensus was not reached after Round 1 for the use of stiff person spectrum disorder as an umbrella term including PERM, epilepsy and cerebellar ataxia phenotypes; probable and possible SPS diagnostic criteria; and the terminology and diagnostic approach for GAD65-associated epilepsy. ConclusionsThis international Delphi survey helps identify areas of expert agreement and variation in the diagnosis of SPS and related disorders across diverse clinical settings. These findings, supplemented by the round 2 data, may help inform future consensus recommendations.