Stiff Person Syndrome
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Direct answer
Stiff person syndrome is a rare autoimmune disorder of progressive axial rigidity with painful, stimulus-sensitive spasms, usually caused by antibodies against glutamic acid decarboxylase (anti-GAD65) that impair GABA-mediated inhibition. Continuous motor unit activity in the paraspinal muscles on EMG supports the diagnosis. Benzodiazepines are the first symptomatic treatment, with immunotherapy for flares.
What you must remember
- Antibodies: anti-GAD65 antibodies in most patients, which impair GABA-mediated inhibition, while anti-amphiphysin antibodies suggest a paraneoplastic form, often linked with breast cancer.
- Distribution: progressive rigidity of the trunk and axial muscles, lumbar hyperlordosis and a stiff, short-stepped gait, with the limbs involved later.
- Spasms: painful, stimulus-sensitive spasms triggered by emotion, startle, noise or touch, which can disturb sleep and cause falls.
- EMG: continuous motor unit activity in paraspinal and abdominal muscles, present even at rest, is the key electrophysiological finding.
- Associations: type 1 diabetes, thyroid autoimmunity, vitiligo, pernicious anaemia and epilepsy occur more often than in the general population.
- Mimics: tetanus, which causes trismus and risus sardonicus after a wound, and hyperekplexia, which has exaggerated startle without axial rigidity.
- First-line symptomatic therapy: diazepam or another benzodiazepine, with baclofen as an alternative or add-on.
- Immunotherapy: intravenous immunoglobulin or plasma exchange for flares, with rituximab used in refractory disease.
A pathway from stiffness to treatment
The pathway moves from confirming the clinical picture to proving the immune basis, then to treatment. Each step is needed because seronegative patients do exist.
- Confirm the rigidity: Examine for axial rigidity, lumbar hyperlordosis and spasms triggered by stimulus, rather than rigidity that is task-related or functional.
- Test the antibodies: Serum anti-GAD65 antibodies are measured, and a negative result does not exclude the diagnosis in seronegative patients.
- Record the EMG: Continuous paraspinal activity at rest supports the diagnosis, and it is the finding most helpful when serology is negative.
- Screen for associations: Check thyroid function, blood glucose and vitamin B12, and look for breast cancer when anti-amphiphysin antibodies are present.
- Start symptomatic treatment: Benzodiazepines are used first for spasms, and baclofen is added where sedation limits the dose.
- Add immunotherapy: Intravenous immunoglobulin or plasma exchange is used for flares and selected long-term cases, with physiotherapy to protect function.
Worked example: a 42-year-old woman with type 1 diabetes has two years of worsening stiffness of the back and legs, with painful spasms when startled. Anti-GAD65 antibodies are high and EMG shows continuous paraspinal activity, so the diagnosis is confirmed and diazepam is started.
Where the examiner tests the syndrome
Questions often describe a stiff, spasming patient and ask for the antibody, the EMG finding or the treatment.
- Trap: Diagnosing stiff person syndrome from negative antibodies alone. Correct: Some patients are seronegative, so the clinical picture and the EMG findings still matter.
- Trap: Labelling the spasms as functional without EMG. Correct: Continuous paraspinal activity on EMG shows an organic process, so a functional label should not be applied.
- Trap: Stopping diazepam abruptly. Correct: Sudden withdrawal can precipitate severe spasms, so the dose is tapered.
- Trap: Confusing it with tetanus. Correct: Tetanus is an acute emergency with trismus and a wound history, whereas stiff person syndrome runs a slow course with characteristic antibodies.
Frequently asked questions
Which antibody is associated with stiff person syndrome?
Anti-glutamic acid decarboxylase (anti-GAD65) antibodies are the antibody most often associated with stiff person syndrome. They impair GABA-mediated inhibition in the spinal cord and brain. Some patients are seronegative, so the clinical and EMG features remain important.
What EMG finding is characteristic of stiff person syndrome?
Continuous motor unit activity in paraspinal and abdominal muscles, present even at rest, is the characteristic EMG finding in stiff person syndrome. This activity reflects failure of inhibitory control in the spinal cord. Its presence supports the diagnosis when the clinical features are consistent.
Which drugs are used first to treat stiff person syndrome?
Benzodiazepines such as diazepam are used first to treat the spasms and rigidity of stiff person syndrome. Baclofen is an alternative or add-on, and intravenous immunoglobulin or plasma exchange treats flares. Abrupt withdrawal of diazepam must be avoided, because it can precipitate severe spasms.
How does stiff person syndrome differ from tetanus?
Stiff person syndrome differs from tetanus by its slow, progressive course and characteristic autoantibodies. Tetanus presents acutely with trismus, risus sardonicus and a history of a wound, and it is a medical emergency. A careful history and urgent assessment separate the two conditions.