To report the clinical features of stiff-person spectrum disorder (SPSD).

SPSD is a collective term encompassing classic stiff-person syndrome (SPS), stiff-limb syndrome (SLS), SPS-plus including progressive encephalomyelitis with rigidity and myoclonus (PERM), and overlapping syndromes. A large cohort study reported that 66.9% of patients with SPSD had neuronal antibodies (GAD65 [43.0%], glycine receptor (GlyR) [19.8%], and others [4.1%]), and patients with GAD65-antibodies had worse outcome than those with GlyR-antibodies or those without neuronal antibodies.

We reviewed the clinical information of 20 patients with clinical feaures of SPSD (median age 48 years [15-80 years], 10 female), who underwent testing for antibodies against neuronal cell-surface antigens (NSAs) in serum and CSF as well as GAD65 and amphiphysin in serum between July 2008 and August 2018.

The median long-term follow-up was 28.5 months (3.9 to 150 months). Clinical phenotypes included SPS-plus (n=11), SLS (n=5), overlapping syndrome (n=2), and classic SPS (n=2). Only 7 patients (35%) had neuronal antibodies: 5 GlyR (2 with GAD65), 1 AMPAR, GABA(B)R and CV2 associated with thymoma, and 1 GAD65. Three patients had an associated tumor (thymoma, follicular lymphoma, renal cancer), and 1 had a past history of breast cancer. GlyR-antibodies were detected in 3 of 11 patients (27.2%) with SPS-plus, and 2 of 5 patients (40.0%) with SLS. Compared with antibody-negative cases, antibody-positive cases had more frequently CSF oligoclonal bands (3/7 vs 0/11, p=0.0429), but no difference in age of onset, gender, CSF pleocytosis, IgG index, or tumor association. All patients received immunotherapy, but the long-term outcome (defined as modified Rankin Scale ≤ 2) was better in patients with NSA-antibodies than those without (6/6 vs 4/14, p=0.0108).

Patients with SPSD and NSA antibodies have better prognosis than those without antibodies.