No One Single Test for SPS

A diagnosis of Stiff Person Syndrome (SPS) depends on multiple factors. There is no one single lab test or study that determines the diagnosis. A detailed medical history, physical exam, blood tests, and other lab tests can support the diagnosis. Importantly, these tests and their interpretation should be done by a physician who has expertise in the evaluation of SPS. The history should be consistent with one of the forms of SPS described in Types of SPS, most commonly including muscle stiffness of the legs or trunk, usually worsening over months or years.

Since SPS symptoms may overlap with other disorders, an evaluation for SPS would include multiple other blood tests and possibly a spinal tap to examine cerebral spinal fluid (CSF).

70-80% of People with SPS have GAD Antibodies

One useful blood test can detect the presence of antibodies to glutamic acid decarboxylase (GAD). The antibodies are abnormal while the GAD is a normal enzyme. About 70 – 80% of people with SPS have antibodies against GAD. These antibodies can be detected by a blood test.

The absence of GAD antibodies does not rule out SPS.

The presence of extremely high levels of GAD antibodies strongly supports the diagnosis of SPS in the context of the appropriate medical history and physical exam findings. GAD antibodies may also be measured in the cerebrospinal fluid obtained by a spinal tap. However, GAD antibodies can also be found in other autoimmune neurological disorders and in other autoimmune disorders that are not neurologic, including type 1 diabetes mellitus, thyroiditis, pernicious anemia, celiac disease, and very rarely in certain cancers.

It is worth emphasizing that having elevated GAD antibodies does not by itself determine a diagnosis of SPS. The medical history, exam and lab findings must also be consistent. Extremely high levels of GAD antibodies are most suggestive of an SPS diagnosis. This highlights the importance of being evaluated by an appropriate medical expert who has the experience to correctly assess these different factors.

Other Antibodies Could Indicate SPS

Glycine receptor antibodies are the second most common SPS antibodies, found in about 10% of SPS patients, followed by amphiphysin antibodies and DPPX (dipeptidyl peptidase-like protein 6) antibodies.

Some neurologists also recommend an electromyogram (EMG), which records electrical activity in affected skeletal muscles, including the legs. The EMG findings can support the diagnosis of SPS by demonstrating abnormal continuous muscle activity in the tested muscles. An EMG may also help distinguish SPS from other neuromuscular disorders. EMG testing can be uncomfortable, though not to the extent that it requires sedation or pain medication. In fact, it is important that patients avoid sedation and refrain from using muscle relaxants or pain medication in advance of an EMG, as use of these drugs can interfere with accurate EMG results.

Imaging Not As Useful In Diagnosis

Imaging studies such as x-rays, CT scans, MRIs, and ultrasounds do not have findings that are unique to SPS, though may be ordered by your doctor to evaluate for other possible disorders.

Antibodies Associated with Stiff Person Syndrome

GAD 65 Antibodies

GAD is the abbreviation for an enzyme called either glutamate decarboxylase or glutamic acid decarboxylase. The “65” is a measure of the size of GAD. As an enzyme, GAD speeds up specific chemical reactions. In the brain, GAD facilitates the formation of GABA, (gamma-aminobutyric acid) which is a neurotransmitter that helps to reduce nerve and muscle excitation. Antibodies to GAD would be expected to interfere with the function of GAD and therefore lower GABA and reduce the inhibitory signals to muscles, resulting in more muscle contractions. However, it is important to emphasize that while GAD antibodies are usually present in SPS, the antibodies have not yet been shown to be the definitive cause of SPS. GAD 65 antibodies are currently only considered a “marker” of SPS. About 70 – 80% of people with SPS have GAD antibodies.

GAD antibodies may also be seen in other neuro autoimmune disorders and in many people who have type 1 diabetes. About 40% of people with GAD-antibody-positive SPS will also have type 1 diabetes.

The presence of GAD antibodies does not mean that someone has SPS or type 1 diabetes. In fact, a small portion of the general population have GAD antibodies and are completely healthy. GAD antibody levels do not correlate with the severity of symptoms.

Glycine receptor α1 (alpha 1) antibodies

About 10% of people with SPS have glycine receptor alpha-1 (GlyRα1) antibodies. The glycine receptor is found in the brain and spinal cord and produces inhibitory signals to the nerves in response to the neurotransmitter glycine. Glycine receptor antibodies reduce the number of functioning glycine receptors. Therefore, transmission of inhibitory signals is reduced allowing for excessive excitatory neurotransmitter signals, or otherwise stated, decreasing normal inhibition results in excessive stimulation. This may cause seizures, muscle stiffness and spasms.

Amphiphysin antibodies

Antibodies to amphiphysin are a much less frequent (about 5%) finding in SPS. Amphiphysin is found in the brain and in nerve terminals. The abnormal antibody to amphiphysin is usually triggered by cancer, therefore described as a “paraneoplastic” variant of SPS. Treatment of the cancer usually improves SPS symptoms.

Other Antibodies in Stiff Person Syndrome

Other rare antibodies which have been found in SPS include gephyrin (extremely rare), and dipeptidyl peptidase-like protein 6 (DPPX). There are some people diagnosed with SPS who have no detectable known antibodies. There may be other SPS antibodies which have not yet been discovered.