Stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease

Abstract

Background: Stiff-person syndrome (SPS), formerly Stiff-man syndrome, is a rare autoimmune disease usually exhibiting severe spasms and thoracolumbar stiffness, with very elevated glutamic acid decarboxylase antibodies (GAD Ab). A paraneoplastic variant, less well characterized, is associated with amphiphysin antibodies (amphiphysin Ab). The objective of this study was to identify distinctive clinical features of amphiphysin Ab-associated SPS.

Methods: Records associated with 845 sera tested in the Yale SPS project were examined, and 621 patients with clinically suspected SPS were included in the study. Clinical characteristics were assessed with correction for multiple comparisons.

Results: In all, 116 patients had GAD antibodies and 11 patients had amphiphysin Ab; some clinical information was available for 112 and 11 of these patients, respectively. Patients with amphiphysin Ab-associated SPS were exclusively female; mean age was 60. All except one had breast cancer; none had diabetes. Compared to patients with GAD Ab-associated SPS, those with amphiphysin Ab were older (p = 0.02) and showed a dramatically different stiffness pattern (p < 0.0000001) with cervical involvement more likely, p < or = 0.001. Electromyography showed continuous motor unit activity or was reported positive in eight. Benzodiazepines at high dose (average 50 mg/day diazepam) were partially effective. Four patients were steroid responsive and tumor excision with chemotherapy produced marked clinical improvement in three of five patients.

Conclusions: Amphiphysin Ab-associated stiff-person syndrome is strongly associated with cervical region stiffness, female sex, breast cancer, advanced age, EMG abnormalities, and benzodiazepine responsiveness. The condition may respond to steroids and can dramatically improve with cancer treatment.

Figure 1 Age distribution of patients with stiff-person syndrome with antineuronal antibodies

Figure 2 Regions of the body affected by stiff-person syndrome (SPS) (A) GAD Ab-associated SPS shows a distinct pattern of stiffness with a rostral to caudal gradient of involvement. (B) Percent of patients with amphiphysin Ab-associated stiffness in various body regions. The regional pattern of stiffness is different from that of GAD Ab-associated SPS, p < 0.001. The arms exhibit more stiffness in amphiphysin Ab-associated SPS, p = 0.01.