Clinical Vignette

A 53-year-old woman with myeloid metaplasia reported a 6-month history of severe back pain, difficulty walking, and occasional falls. No lumbosacral disc disorder could be identified. During the past month, these spasmodic muscle pains of her legs, back, and abdomen were induced by attempting to sit up, stand, or walk. Occasionally, these spasms led to stiffening of her entire body; at their extreme these induced urinary incontinence. At times, the severity of the pain led her to cry out to such a degree that it caused one observer to liken her distress to that of a “bellowing cow”! These outbursts led to her being referred to a psychiatrist.

Neurologic examination demonstrated an anxious and alert middle-aged woman. The primary finding was her spontaneous reaction to the slightest sensory stimuli wherein she totally stiffened, reminding this neurologist (HRJ) of a tetanus patient. Other than hyperlordosis, marked hyperreflexia at her knees and a right Babinski sign, her basic neurologic examination was normal. However, on a neurosurgeon’s brusque attempt to get her out of bed to stand, she developed severe painful body spasm and fell into the hospital room wall as if a chain saw had cut her legs off.

Head and cervicothoracic spine magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) study were normal, as was serum B₁₂ level. Nerve conduction studies were normal. Her needle electromyography (EMG) study demonstrated prolonged motor unit activity in contracting muscles during episodes of stiffness and spasm but was otherwise normal. Double-antibody radioimmunoassay demonstrated a high level of serum glutamic acid decarboxylase 65 (GAD-65) antibodies (138 nmol/L; reference range: ≤0.02 nmol/L). The patient was diagnosed with stiff person syndrome (SPS).

Increasing doses of diazepam alleviated symptoms at a dose of 60 mg daily. A course of plasmapheresis treatments followed by prednisone (80 mg daily) led to gradual symptomatic improvement. She was successfully tapered off corticosteroids during a 2-year period and diazepam over 5 years.

Etiology

The findings that support an autoimmune basis for SPS are the following: (1) SPS is associated with autoantibodies, both the classic GAD-65 antibodies and a paraneoplastic variant, amphiphysin antibodies; (2) SPS is frequently accompanied by other autoimmune disorders such as type 1 diabetes, thyroiditis, vitiligo, and pernicious anemia; and (3) intravenous immunoglobulin (IVIg) and plasma exchange provide effective treatments for some patients.

The precise pathophysiologic role for the specific antibodies is unclear, although it is speculated that the autoimmune lesions are directed at a site on the inhibitory spinal interneurons (Fig. 69-1). Although a direct relation is inferred, this is not fully substantiated. Factors supporting a direct role for antibodies are (1) the finding of elevated intrathecal GAD antibodies; (2) the antibody concentration correlates with the degree of motor excitability; (3) GAD antibodies, obtained from serum of stiff person patients, inhibit both GAD and GABA synthesis in vitro.

Figure 69-1 Renshaw Cell Bias.

Clinical Presentation