What is Stiff-Person Syndrome?

Stiff-Person Syndrome (SPS) is an autoimmune disease that affects the nervous system, specifically the brain and spinal cord. Symptoms may include muscle stiffness in the trunk and limbs and heightened sensitivity to noise, touch, and emotional distress, which can set off muscle spasms. People with SPS may also have abnormal postures, such as being hunched over. The syndrome affects twice as many women as men. It is frequently associated with other autoimmune diseases such as diabetes, thyroiditis, vitiligo, and pernicious anemia. SPS may be diagnosed by a blood test for glutamic acid decarboxylase (GAD) antibodies because people with SPS usually have elevated levels of GAD antibodies. Treatment may involve high-dose diazepam, anti-convulsants, or intravenous immunoglobulin (IVIG).

Symptoms

Stiff person syndrome (SPS) is characterized by episodes of muscle stiffness in the trunk and limbs. This muscle rigidity may cause abnormal postures such as being stiffened and hunched over. During episodes of muscle stiffness, affected individuals may also have muscle spasms. The spasms and muscle rigidity may cause people to fall when they are walking or standing. These spasms are especially likely during times of emotional distress or startle.

Age of onset of SPS can vary, but most people start experiencing symptoms between ages 30 and 60. Some people with this syndrome may have other clinical findings such as cerebral palsy or epilepsy.

Many people with stiff person syndrome suffer from anxiety and depression. This is caused in part by the symptoms of the syndrome affecting a person’s daily life, but also because the cause of the syndrome is having low levels of neurotransmitters. Neurotransmitters help to maintain a person’s mood

Cause

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.

Inheritance

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.

Diagnosis

A diagnosis of stiff person syndrome (SPS) is typically made based on the presence of the characteristic symptoms, a detailed medical history and clinical exam, and various tests. Specific tests are used to support or confirm the diagnosis, and to rule out conditions with overlapping symptoms. One commonly used diagnostic tool is a blood test to detect the presence of glutamic acid decarboxylase (GAD) antibodies. About 60-80% of affected people have antibodies against GAD that can be detected on a blood test. Therefore, the absence of GAD antibodies does not rule out SPS, but the presence of high levels of GAD antibodies in people with symptoms of SPS strongly supports the diagnosis.

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 laboratory testing may also be used to determine if a person with SPS has other diseases that may be associated with the syndrome. This testing includes hemoglobin A1C levels to rule out diabetes mellitus, a complete blood count to rule out pernicious anemia, and thyroid-stimulating hormone (TSH) test to rule out thyroiditis. A lumbar puncture to analyze cerebral spinal fluid may also be obtained to rule out other causes of the symptoms associated with SPS. Proteins called oligoclonal bands indicate that the central nervous system is inflamed, and these bands can be seen in about two thirds of affected people who have GAD antibodies. Because the underlying genetic cause of stiff person syndrome has not been established, genetic testing is not available.

Treatment

Treatment of stiff person syndrome (SPS) focuses on the specific symptoms present in each person. Benzodiazepines, diazepam, or baclofen may be used to treat muscle stiffness and spasms. Anti-seizure medications and pain medications may also be effective for some people.

Recently, studies have shown that intravenous immunoglobulin (IVIG) or plasmapheresis may be effective in improving some of the symptoms of SPS. For some people, autologous stem cell transplants have been shown to successfully treat SPS. Clinical trials are being completed to confirm if this may be an effective treatment. Physical and occupational therapy may help to slow the progression of stiff person syndrome, but should be completed by someone who is familiar with the condition so as not to make symptoms worse.

Prognosis

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.