Stiff-person syndrome

Jose Fidel Baizabal-Carvallo MD (Dr. Baizabal-Carvallo of Baylor College of Medicine has no relevant financial relationships to disclose.)
Joseph Jankovic MD, editor. (Dr. Jankovic, Director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine, received research funding from Allergan, Allon, Ceregene, Chelsea, EMD Serono, Impax, Ipsen, Lundbeck, Medtronic, Merz, and Teva, and compensation for his services as a consultant or an advisory committee member by Allergan, Auspex, EMD Serono, Lundbeck, Merz, Neurocrine Biosciences, and Teva.)
Originally released September 2, 1994; last updated July 22, 2016; expires July 22, 2019

This article includes discussion of stiff-person syndrome, stiff-man syndrome, Moersch and Woltman syndrome, congenital stiff-man syndrome, and jerking stiff-man syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

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 (GLRA), 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.

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" (Moersch and Woltman 1956). 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 (Gordon et al 1967). In 1991, McEvoy summarized clinical, immunologic, and presumed pathogenesis of the disorder in 98 cases seen at the Mayo Clinic, or reported in other literature between 1956 and 1991 (McEvoy 1991a). 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.

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.