Stiff Person Syndrome

Specialty Area: Neuroimmunology & Neurological Infections

 

What is Stiff Person Syndrome?
Stiff Person Syndrome (SPS) is a rare disease of the nervous system. Progressively severe muscle stiffness typically develops in the spine and lower extremities; often beginning very subtly during a period of emotional stress. Most patients experience painful episodic muscle spasms that are triggered by sudden stimuli. An auto-immune component is typical and patients often have other auto-immune disorders. Symptoms usually begin in the mid-forties. The severe muscle stiff-ness of SPS responds to benzodiazepines. Testing with an EMG (electro-myogram) needle will assist the diagnosis and testing the blood for anti-GAD (glutamic acid decarboxylase) antibodies (if present at very high levels) will confirm the diagnosis in the majority of people with SPS.

SPS is extremely rare. Although it is not possible to determine the exact prevalence, it may occur in fewer that 1 per million. The disease is more common in women (the ratio is 2 women for every man effected). There is no predilection for any race or ethnic group. There is an association with diabetes and perhaps over half of patients with SPS have or will develop diabetes. Other autoimmune diseases have been found in association with SPS, for example: thyroid disease and vitiligo. There is an increased incidence of epilepsy. An important but especially rare variant of SPS is associated with breast or lung cancer. Characterized by the production of antibodies to amphiphysin, this variant of SPS has certain features that distinguish it from the more typical SPS with GAD antibodies.

How is SPS Disagnosed?

• Physical exam
  A neurological history and exam are required for the diagnosis of SPS. Laboratory results in isolation do not establish the diagnosis. Working together, the patient and physician identify the symptoms and signs of disease. For SPS, the symptoms include stiffness, rigidity or increased tone and painful spasms involving most typically the legs or lumbar spine but also effecting the face, neck, abdomen or arms. It is important to exclude other causes of stiffness for example dystonia, transverse myelitis, vascular malformation or Parkinson's disease.
  
• Antibody testing
  Although the absence of GAD antibodies in the serum does not rule out SPS, the presence of high levels GAD antibodies in appropriate patients strongly supports that diagnosis (99% specific by immunocytochemistry). In the general population, GAD antibodies are most commonly associated with diabetes, i.e. most people with GAD antibodies have low positive values that are typical of diabetes (the distinction between high and low levels is important). Very high GAD antibodies levels make SPS more likely.
  
• Electromyography
  Electromyography (EMG) remains an important and standard diagnostic tool in evaluating SPS. The usual finding is continuous (low frequency) motor unit activity (CMUA) simultaneously occurring in agonist and antagonist muscles. This test should be performed by a physician familiar with the findings of SPS.
  
• Genetics
  Genetic testing is not used for SPS. Although there is an association with HLA (Human Leukocyte Antigen) type, there is no tendency of SPS to run in families.

Treatment of SPS
Multi-modality treatment for SPS is our approach at Johns Hopkins. Treatments include immune-modulating therapies such as IVIg (intravenous immune-globulin) and plasmapheresis; pharmacological therapy, patient and staff education, behavioral and physical therapy.

Benzodiazepines and other GABA-acting medications remain essential to managing the stiffness and spasms of SPS. If these medications are withdrawn from SPS patients, the muscle rigidity can be over-whelming and fatal respiratory compromise occur. Benzodiazepines are the treatment of choice for rapid control of SPS.

Although SPS is a serious potentially life-threatening disease, and some of the treatments have serious potential side effects; the course of SPS is variable. There are patients who, with proper treatment, are able to return to activities they enjoy.

CAUTIONS ABOUT SPS