SPS is exceedingly rare, with an estimated prevalence of 1-2 cases per million. It is twice as common in women than in men, often presenting in middle age (30-60 years). Cases of stiff person syndrome occur more often in people with existing autoimmune diseases, such as type 1 diabetes, autoimmune thyroid disease, vitiligo, pernicious anemia, and celiac disease.

The exact cause is unknown, but SPS is thought to be an autoimmune disorder,where the immune system produces antibodies that attack nerve cells that produce the enzyme glutamic acid decarboxylase (GAD). This enzyme produces a neurotransmitter called gamma-aminobutyric acid (GABA) that is responsible for sending messages to the body’s muscles to relax. Antibodies that attack the GAD enzyme lead to a deficiency of the neurotransmitter GABA that inhibits muscle activity, resulting in an overstimulation of muscles. There are other antibody targets responsible for muscle movement that have been implicated in cases of SPS, such as the glycine receptor, amphiphysin, and DPPX. Research is ongoing to determine which antibodies cause certain symptoms of stiff person syndrome.

The symptom complex of SPS suggests a derangement of physiology mediated by spinal cord reflexes, however, the specific mechanism of disease has not been defined. Stiffness, spasms, pain, trigger response and falls could all result from failed modulation of spinal cord reflexes. The neurons controlling these functions use gamma-aminobutyric acid (GABA) as a neurotransmitter and are called GABAergic neurons. GAD (glutamic acid decarboxylase) is an enzyme which produces GABA and is localized to the synaptic nerve terminal. GAD is the protein antigen that is specifically bound by the anti-GAD auto-antibodies found in approximately half of SPS patients. First described by Solimena and coworkers in 1988, at high titer anti-GAD autoantibodies are almost exclusively associated with SMS. Sporadic reports of association with cerebellar ataxia, type I (autoimmune) diabetes and autoimmune polyendocrine syndrome have been made. At low titer anti-GAD antibodies are found in type I diabetes; pancreatic beta cells, like GABAergic neurons, express GAD. Although the presence of high titer anti-GAD antibodies is highly specific for SMS, the role that the humoral immune system plays in pathogenesis of this disease is unclear. It is not known whether the antibodies have a causative role or are the consequence of a process that leads to impairment of neurotransmission. 

The main symptoms of SPS include:

• Progressive muscle stiffness and rigidity, especially in the trunk and limbs.

• Painful muscle spasms that can be prolonged and forceful.

• Difficulty walking and unsteady gait.

• Hunched posture.

• Falls due to muscle stiffness.

• Anxiety and depression from chronic pain and disability.

Spasms can be triggered by stimuli like noise, touch, cold temperatures, sudden movement, or emotional stress. Symptoms typically begin between ages 30-60.

The diagnosis is challenging and involves a combination of clinical evaluation and diagnostic tests:

1. Clinical Presentation: Observing hallmark symptoms like stiffness and spasms.

2. Blood Tests: Detecting anti-GAD antibodies or other associated autoantibodies.

3. Electromyography (EMG): Revealing continuous motor unit activity in affected muscles.

4. MRI or CT: To exclude structural lesions or other neurological causes.

5. Lumbar Puncture: Occasionally performed to assess cerebrospinal fluid for markers of inflammation or autoimmunity.

There is no cure for SPS, but treatments can focus on managing symptoms and modulating the immune response:

• Muscle relaxants (like diazepam or baclofen) and anti-anxiety medications.

• Immunotherapy treatments:

  • Corticosteroids: To suppress the immune system.

  • Intravenous Immunoglobulin (IVIG): To neutralize harmful antibodies.

  • Plasmapheresis: To remove circulating autoantibodies.

  • Rituximab: A monoclonal antibody targeting immune cells.

• Physical therapies like stretching, heat therapy, and massage.

• Psychological support to address anxiety and phobias.

• Occupational therapy to assist with daily living activities and adaptive equipment.

The course of SPS varies and can worsen over time without proper treatment. With appropriate management, patients can experience significant symptomatic improvement and maintain their quality of life and daily functioning, though some may have residual stiffness, spasms or  increasing disability.

1. Dalakas, M. C. (2009). "Stiff Person Syndrome: advances in pathogenesis and therapeutic interventions.” Curr Treat Options Neurol, 11(2), 102-110. doi: 10.1007/s11940-009-0013-9. PMID: 19210912.

2. Solimena, M., & De Camilli, P. (1991). "Autoimmunity to glutamic acid decarboxylase (GAD) in Stiff-Man syndrome and insulin-dependent diabetes mellitus." Trends in Neurosciences, 14(10), 452-457. doi: 10.1016/0166-2236(91)90044-u. PMID: 1722364.

3. Bose S, & Jacob S. (2025). “Stiff-person syndrome.” Practical Neurology, 25, 6-17. doi: 10.1136/pn-2023-003974.

4. The Stiff Person Syndrome Research Foundation:  https://www.stiffperson.org.

Cleveland Clinic:  Stiff Person Syndrome.