Background Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. Methods To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. Results GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum, but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). Conclusions GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. Classification of evidence This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.
Bibliographical noteFunding Information:
This study was supported by the Mayo Clinic Center for Individualized Medicine.
S.R. Hinson and A.J. Lopez-Chiriboga report no disclosures. J.H. Bower received research support from AbbVie and the Parkinson Disease Foundation. J.Y. Matsumoto reports no disclosures. A. Hassan serves on the editorial board of Parkinsonism and Related Disorders and consulted for Bioblast Pharma. E. Basal reports no disclosures. V.A. Lennon holds a patent for and receives royalties from RSR/Kronus for sale of aquaporin-4 antibody testing kits and for commercial aquaporin-4 autoantibody testing performed outside Mayo Clinic; receives research support from the NIH and has a potential financial interest in “Aquaporin-4 as an aid for cancer diagnosis.” S.J. Pittock and Mayo Clinic have a financial interest in patents that relate to functional AQP4/NMO-IgG assays and NMO IgG as a cancer marker. S.J. Pittock consulted for Alexion and MedImmune (compensation paid directly to Mayo Clinic) and received research support form Grifols, MedImmune, Alexion, and the NIH. A. McKeon has patents pending for GFAB and MAP1B as markers of neurologic autoimmunity and paraneoplastic disorders; consulted for Grifols, MedImmune, and EUROIMMUM; and received research support from MedImmune and EUROIMMUM. Go to Neurology.org/NN for full disclosure forms.
Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.