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  • Updated 08.16.2020
  • Released 09.02.1994
  • Expires For CME 08.16.2023

Stiff-person syndrome

Introduction

Overview

Stiff-person syndrome is a progressive neurologic disorder characterized by rigidity, superimposed spasm, and abnormal postures and gait. In this article, the author discusses the clinical and immunological features of this autoimmune disorder. Stiff-person syndrome has been associated with a growing number of antibodies, particularly directed against glutamic acid decarboxylase 65 (GAD65), glycine receptor α1 (GlyR), and amphiphysin. Other antibodies associated with stiff-person syndrome include anti-GAD67, gephyrin, GABA-A and GABA-B receptor-associated protein, DPPX, glycine receptor β subunit, glycine transporter 2/SLCA5 (GlyT2), and anti-Ri antibodies. Animal models have demonstrated the potential pathogenic role of some of these antibodies. Therapies directed at increasing GABAergic tone and immunotherapy can provide benefit in these patients, although the level of evidence is low for these therapies.

Key points

• Stiff-person syndrome is a rare disorder that causes continuous muscle contractions with spasms, abnormal postures, and progressive disability.

• Stiff-person syndrome is often associated with other autoimmune signs and symptoms as well as nonspecific and organ-specific autoantibodies.

• There has been a long association between stiff-person syndrome and the presence of various autoantibodies, mainly those directed against the glutamic acid decarboxylase (GAD) of 65 and 67 kD, gamma-aminobutyric acid A receptor-associated protein, various paraneoplastic antibodies (especially amphiphysin), and, more recently, to glycine α1 receptor.

• The symptoms of stiff-person syndrome likely relate to cortical and spinal cord hyperexcitability secondary to reduction of GABA.

• Symptomatic therapy with GABA-ergic drugs is often effective but frequently related to side effects, and progressively higher doses are usually required.

• The response to immunosuppressants is variable, but small trials of intravenous immunoglobulins and rituximab have shown benefit in patients with stiff-person syndrome.

Historical note and terminology

In 1956, Moersch and Woltman described 14 patients who had a progressive syndrome comprised of fluctuating muscle rigidity and spasm. They named this symptom complex "stiff-man syndrome" (124). Gordon later summarized additional cases from the literature, adding a case of his own, and suggested diagnostic criteria that, with minimal revision, remain valid to this day (74). In 1991, McEvoy summarized clinical, immunologic, and presumed pathogenesis of the disorder in 98 cases seen at the Mayo Clinic, reported in medical literature between 1956 and 1991 (115). Although the name "stiff-person syndrome" is more accurate in both the epidemiologic and political senses as the disorder is more frequent in women, the moniker "stiff-man syndrome" is sometimes used.

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