What is the definition of Stiff Person Syndrome?

Stiff person syndrome (SPS) is a rare, progressive syndrome that affects the nervous system, specifically the brain and spinal cord. Symptoms may include extreme muscle stiffness, rigidity and painful spasms in the trunk and limbs, severely impairing mobility. Spasms can generate enough force to fracture bone. People with SPS often have heightened sensitivity to noise, sudden movements, and emotional distress, which can set off muscle spasms. Persistent symptoms can lead to abnormal posturing of the spine, such as being hunched over. The syndrome affects twice as many women as men. SPS is caused by increased muscle activity due to decreased inhibition of the central nervous system. It is thought to have an autoimmune component and is often associated with diabetes, as well as other autoimmune diseases such as thyroiditis, vitiligo, and pernicious anemia. It may be diagnosed after having various tests including blood tests (such as for glutamic acid decarboxylase (GAD) antibodies which is elevated in about 2 in 3 people with SPS), a lumbar puncture, and electromyography. Treatment aims to control symptoms and improve mobility. Examples of treatments that have been used for SPS, include benzodiazepines, muscle relaxants, intravenous immune globulin (IVIG) therapy, plasmapheresis (also called plasma exchange), and rituximab. While some people with SPS may maintain reasonable levels of activity with treatment, the majority become disabled over time.

What are the alternative names for Stiff Person Syndrome?

  • Stiff man syndrome
  • Morsch Woltman syndrome
  • SPS
  • Moersch-Woltman syndrome
  • SMS
  • Stiff person syndrome and related disorders

What are the causes for Stiff Person Syndrome?

Scientists don’t yet understand the complete picture of what causes stiff person syndrome, but research indicates that it is the result of an abnormal autoimmune response in the brain and spinal cord. Autoimmune responses occur when the immune system mistakenly attacks the body. Most people with stiff person syndrome have antibodies that are made to attack glutamic acid decarboxylase (GAD). GAD is a protein in some neurons that are involved in making a substance called gamma-aminobutyric acid (GABA), which is responsible for controlling muscle movement. The symptoms of stiff person syndrome may develop when the immune system mistakenly attacks the neurons that produce GAD. When GAD is not working properly, there is not enough GABA to help control muscle movement. The exact role that deficiency of GAD plays in the development of stiff person syndrome is not fully understood. Some individuals with stiff person syndrome will have antibodies to amphiphysin, a protein involved in the transmission of signals from one neuron to another. Individuals with these antibodies have a higher risk for developing breast, lung, or colon cancer.

What are the symptoms for Stiff Person Syndrome?

Stiff person syndrome (SPS) is a progressive syndrome characterized by recurrent episodes of severe muscle stiffness, rigidity, and painful spasms in the trunk and limbs. The age that symptoms begin can vary, but most people start experiencing symptoms between ages 30 and 60. Spasms can be prolonged and extremely forceful, with the ability to generate enough force to fracture bone. They may cause a person to fall when walking or standing. Spasms are especially likely or may worsen during times of emotional distress, when being touched, when there is sudden movement, or with noise. Over time, persistent symptoms can lead to abnormal posturing of the spine, such as being stiffened and hunched over. Daily activities such as getting into or out of bed, getting up from a chair, or dressing may become increasingly difficult. People with SPS also may become fearful and anxious about navigating daily life, which in turn may trigger additional spasms. Many people with SPS develop depression as the syndrome progresses and quality of life becomes severely impaired.

What is the outlook (prognosis) for Stiff Person Syndrome?

The long-term outlook for people affected by stiff person syndrome (SPS) can vary widely depending on the symptoms of each person. For some people with this syndrome, symptoms resolve with treatment, or symptoms only affect a particular area of the body. For other people, symptoms may progress to include the muscles of the face, and some of the muscles in the body may be constantly rigid. Progression of the symptoms related to SPS can lead to frequent falls, which can become dangerous. Treatment may be helpful for some people with SPS, but for others current treatment options do not relieve the symptoms of the disorder. For these people, daily living can become very difficult due to symptoms of muscle rigidity, anxiety, and depression.  

How is Stiff Person Syndrome diagnosed?

A diagnosis of stiff person syndrome (SPS) is typically made based on symptoms, a detailed medical history, and various tests used to support the diagnosis or rule out other diseases with overlapping symptoms. One commonly used test is a blood test to detect the presence of glutamic acid decarboxylase (GAD) antibodies. About 60-80% of people with SPS have antibodies against GAD that can be detected on a blood test. The absence of GAD antibodies does not rule out SPS, but the presence of high levels of GAD antibodies strongly supports the diagnosis. GAD antibodies may also be measured in the cerebral spinal fluid from a lumbar puncture. Additionally, a doctor may recommend electromyography (EMG), which records electrical activity in skeletal muscles. The EMG of a person with SPS typically shows continuous motor activity in the skeletal muscles. Other testing that may be used to confirm or rule out the diagnosis includes:
  • A hemoglobin A1C test to rule out diabetes mellitus.
  • A complete blood count to rule out pernicious anemia.
  • A thyroid-stimulating hormone (TSH) test to rule out thyroiditis.
  • A lumbar puncture to look for oligoclonal bands which indicate that the central nervous system is inflamed (these bands can be seen in about two thirds of people who have GAD antibodies).

Genetic testing currently is not available because the underlying genetic cause of stiff person syndrome has not been established.

Is Stiff Person Syndrome an inherited disorder?

As is the case with most autoimmune diseases, genetic factors involved in causing stiff person syndrome have not been established. While most cases appear to occur in an isolated manner, there have been reported cases of multiple people in the same family being affected by SPS. Although one specific genetic change (mutation) is not known to cause stiff person syndrome, it is thought that genetics in combination with other factors may play a role in causing SPS.