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Case Reports
. 2013 Jan;70(1):44-50.
doi: 10.1001/jamaneurol.2013.574.

Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype

Andrew McKeon  1 , Eugenia Martinez-Hernandez, Eric Lancaster, Joseph Y Matsumoto, Robert J Harvey, Kathleen M McEvoy, Sean J Pittock, Vanda A Lennon, Josep Dalmau
Affiliations
Case Reports

Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype

Andrew McKeon et al. JAMA Neurol. 2013 Jan.

Abstract

Objectives: To determine whether glycine receptor α1 subunit-specific autoantibodies (GlyRα1-IgG) occur in a broader spectrum of brainstem and spinal hyperexcitability disorders than the progressive encephalomyelitis with rigidity and myoclonus phenotype recognized to date, and to ascertain disease specificity.

Design: Retrospective, case-control study.

Settings: Mayo Clinic, Rochester, Minnesota, and University of Barcelona, Spain.

Patients: Eighty-one patients with stiff-man syndrome phenotype, 80 neurologic control subjects, and 20 healthy control subjects.

Intervention: Glycine receptor α1-transfected cells to test serum or cerebrospinal fluid from cases and control subjects.

Main outcome measures: Frequency of GlyRα1-IgG positivity among stiff-man syndrome phenotype cases and control subjects. Comparison of GlyRα1-IgG seropositive and seronegative cases.

Results: Seropositive cases (12% of cases) included 9 with stiff-man syndrome (4 classic; 5 variant; 66% were glutamic acid decarboxylase 65-IgG positive) and 1 with progressive encephalomyelitis with rigidity and myoclonus. Immunotherapy responses were noted more frequently in GlyRα1-IgG-positive cases (6 of 7 improved) than in seronegative cases (7 of 25 improved; P= .02). The single seropositive control patient had steroid-responsive vision loss and optic atrophy with inflammatory cerebrospinal fluid.

Conclusions: Glycine receptor α1-IgG aids identification of autoimmune brainstem/spinal cord hyperexcitability disorders and may extend to the glycinergic visual system.

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Figures

Figure 1
Figure 1
Graph showing that 81 patients with stiff-man syndrome (SMS) phenotype (classic, variant, progressive encephalomyelitis with rigidity and myoclonus [PERM], and hyperekplexia) were tested for glycine receptor α1 (GlyRα1)-IgG.
Figure 2
Figure 2
Glycine receptor α1 (GlyRα1)–IgG demonstrated in HEK293 cells expressing the human GlyRα1 subunit. The reactivity of serum from 2 representative patients with HEK293 cells expressing the human GlyRα1 subunit is shown in panels A and D. G, Serum from a control patient lacks reactivity with transfected cells. Panels B, E, and H show the reactivity with a commercial GlyRα1 monoclonal antibody. The immunostaining colocalizes with that of patient antibodies (C and F, but not I). Scale bar=20 μm.
See this image and copyright information in PMC

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References

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