Anti‐Amphiphysin Stiff‐Person Spectrum Disorders: A Systematic Review and Case Series Featuring an Unusual Isolated Upper‐Limb Presentation
Andrew Leslie Lee, Divyani Garg, Jie Ping Schee, Alfand Marl F. Dy Closas, Jeffrey Wei Yang Tee, Emilie Sing Yee Wong, Khean Jin Goh, Mee Hoong See, Mei‐Ling Sharon Tai, Ai Huey Tan, Shen‐Yang LimAbstract
Background
Anti‐amphiphysin stiff‐person spectrum disorders (SPSD) are paraneoplastic syndromes with few Asian reports and limited clinico‐demographic data. We present two Asian cases alongside the largest pooled cohort analysis to date ( n = 64).
Cases
Two breast adenocarcinoma‐associated cases are presented. Case 1 (Chinese Malaysian) describes an unusual upper‐limb stiff‐limb syndrome (SLS) resolving fully following early tumor resection and intravenous immunoglobulin (IVIG). Case 2 (India) describes stiff‐person syndrome (SPS) with relief from IVIG, but died from cancer progression.
Literature Review
Analysis of 64 cases of anti‐amphiphysin SPSD revealed a stiffness hierarchy: lower limbs (37/45 = 82.2%) were most frequently affected, followed by upper limbs (57.8%), paraspinal muscles (55.6%), neck (28.9%), abdomen (26.7%), thorax (8.9%), and face (2.2%). Malignancy occurred in 93.8% ( n = 60/64), the majority involving breast (73.4%, n = 47/64) or lung (14.1%, n = 9/64). SPSD symptoms preceded cancer detection in 80.0% ( n = 32/40) by a median of 8 (range:1–60) months. Overall, the majority of cases (25/44 = 56.8%) had good functional outcomes (modified Rankin Scale ≤2). Good outcomes were documented in most (19/29 = 65.5%) patients receiving “triple” (symptomatic, immunomodulatory, oncological) therapy and those with oncological remission reported (10/13 = 76.9%).
Conclusions
Properly managed, anti‐amphiphysin SPSD has good outcomes in the majority of patients, particularly when the underlying cancer is successfully treated. Atypical presentations, including upper‐limb SLS, warrant high diagnostic suspicion.