To evaluate long-term outcomes of patients GAD65-IgG-positive with stiff person syndrome spectrum disorder (SPSD).

Long-term outcome data for GAD65-IgG-positive SPSD patients remain limited, and sustained response to treatment varies.

We assessed patients meeting diagnostic criteria for probable or definite SPSD who were evaluated at Mayo Clinic (12/1995-07/2024), were seropositive for GAD65-IgG (high-titer in serum [≥20 nmol/L] or any titer in CSF), and had a follow-up ≥5 years from diagnosis. The modified Rankin scale (mRS) and use of gait assistive devices were used as outcome measures.

Forty-three patients were included, predominantly female (34 [79%]), with a median age at onset of 45 years (range: 16-78). Four patients had a stiff-limb variant (9%). Co-existent autoimmune disorders were present in 33 (77%). The median interval from onset to diagnosis was 2 years (range: 0-34), and the median interval from diagnosis to last visit, 9 years (range: 5-26). Most (36 [84%]) received immunosuppressive/modulating therapy. 

All patients had significant impairment (mRS≥2) at nadir, with half losing functional independence (mRS≥3; 22 [51%]) and 74% requiring bilateral gait assistance. The median time from onset to nadir was 6 years (range: 0-39). At last follow-up, most were functionally independent (mRS<3; 29 [67%]), with 11 (26%) having minimal restrictions (mRS≤1). Bilateral gait assistance was needed in 18 (42%). The most common symptoms at last follow-up were spasms (37 [86%]), gait instability (32 [74%]), pain (27 [63%]), anxiety (16 [37%]), fatigue (16 [37%], and falls (14 [33%]). The most common signs were persistent hypertonia (28 [65%]), and hyperlordosis (18 [42%]).