Definition
Stiff person syndrome (SPS) is an extremely rare progressive neurological disorder characterized by persistent rigidity and spasms of certain voluntary muscles, especially those of legs and feet. In some cases, muscles of the neck, trunk, and shoulders may also be involved. SPS may begin as recurring (intermittent) episodes of stiffness and spasms, often precipitated by surprise or minor physical contact.
Description
SPS is a rare progressive neurological disorder characterized by constant painful contractions and spasms of voluntary muscles, particularly the muscles of the back and upper legs. In 1956, scientists at the Mayo Clinic also coined the term stiff man syndrome, and clearly described the stiff person syndrome as a neurological disorder. The rigidity, which is characterized by tightness and stiffness, begins slowly over several months at the axial muscles, especially the thoracic and lumbar spine, and spreads to the legs. The stiffness may worsen when the affected individual is anxious or exposed to sudden motion or noise. Affected muscles may become twisted and contracted, resulting in bone fractures in the most severe cases.
Another abnormality in SPS is called co-contraction: when the person attempts to contract a muscle to move in one direction, muscles that pull in the opposite direction are involuntarily activated. Individuals with SPS may have difficulty making sudden movements and may have a stiff-legged unsteady gait (manner of walking). The muscle contractions are usually reduced with extra rest.
Eventually, persons with stiff person syndrome may develop a hunched posture (kyphosis) or a swayback (lordosis).
Demographics
The frequency of SPS worldwide or in the United States is unknown, but the syndrome is rare. Unlike many autoimmune diseases, which have a higher incidence in women, SPS is found more frequently in men, occurring in men in approximately 70% of all cases. The syndrome also occurs in children younger than three years, most commonly in infants. Onset in adults is most frequent in the third to fifth decades of life.
Causes and symptoms
The cause of stiff person syndrome is unknown, however, researchers theorize that SPS may be an autoimmune disorder. An autoimmune disorder involves a malfunction of the immune system, where the body produces antibodies against its own tissues. Antibodies are proteins produced by the body as part of its defense against foreign bacteria, viruses, or other harmful substances. Other autoimmune disorders such as diabetes, pernicious anemia (a chronic, progressive blood disorder), and thyroiditis (inflammation of the thyroid gland) may occur more frequently in patients with SPS.
Often SPS, antibodies are produced against glutamic acid decarboxylase (GAD), an enzyme largely found in the central nervous system. However, GAD antibodies alone appear to be insufficient to cause SPS, as some persons with stiff person disease do not have the GAD antibodies, and GAD antibodies are associated with a number of diseases.
Symptoms may occur gradually, spreading from the back and legs to involve the arms and neck. Initially, the patient has an exaggerated upright posture and may experience back discomfort, stiffness or pain in the entire back, which worsens with tension or stress. Some persons with SPS, in the early stages, show brief episodes of rather dramatic severe worsening that resolve spontaneously within hours or days. Later in the disease, upper limb muscles also begin to be involved, particularly when the person is stimulated, surprised, angered, upset, or frightened. This sort of stimulation may evoke painful severe spasms in the upper arm and leg muscles that resolve slowly. The person with SPS begins to move very slowly because rapid movement induces severe spasms. Even the lower extremities may become involved when moved rapidly. In the end stages of the disease, few muscles in the body are spared. However, facial and pharyngeal muscles may be especially affected.
Babies and young children are less rigid between attacks. Involvement of lower arm and leg muscles is often more evident, particularly during muscle spasms.
Diagnosis
During physical examination, the physician who suspects SPS looks for stiffness, rigidity or increased tone, spasm, or pain. The areas of involvement may include the face, neck, abdomen, or arms, but more typically the legs or lumbar spine are involved. Evaluation may include tests to rule out other causes of stiffness such as multiple sclerosis. When overwhelming anxiety and fear overshadow the stiffness, it may be difficult to distinguish SPS from an emotional disorder.
Laboratory procedures assess the presence of specific autoantibodies called anti-GAD, which are found at high levels in the blood of a person with SPS. These examinations include immunocytochemistry, Western blotting, ELISA (enzyme-linked immunosorbent assay), and radioimmunoassay (RIA). The last two procedures have the advantage of quantitatively assessing the amount of anti-GAD antibody a patient produces.
Electromyography (EMG) is an important diagnostic tool to determine an abnormal firing pattern in the muscles sometimes seen in persons with SPS. The EMG findings of SPS may be subtle in patients who are fully treated for symptoms of SPS. Except for global muscle stiffness, results of a neurological examination are usually normal. Results of conventional computed tomography and magnetic resonance imaging of the brain are also normal.
Treatment team
The treatment team for a person with SPS is often composed of physical and occupational therapists, nutritionists, neurosurgeons, and neurologists.
Treatment
SPS is clinically elusive, but potentially treatable. Traditional treatment for SPS starts with medications such as baclofen or a benzodiazepine. Commonly used benzodiazepines are diazepam (Valium) or lorazepam (Ativan). Both benzodiazepine and baclofen act increasing the activity of the central inhibitory systems. Although no studies have been performed, tizanidine (Zanaflex) may be a less sedating alternative, and prednisone is also a commonly prescribed drug for treatment of SPS.
In some patients, plasmapheresis, a process of filtering the blood to remove excess antibodies, has been demonstrated to be useful in removing anti-GAD antibodies from the bloodstream. In the hospital setting, intravenous immunoglobulin (IVIG) has also been used in the treatment of SPS.
Recovery and rehabilitation
Physical therapy and occupational therapy are critical to the recovery of patients under treatment. Medical treatment can make the patient feel weak, a feeling that may be alleviated by therapy. The person with SPS may also have problems with voluntary movements and fine motor skills. Occupational and physical therapists devise strategies to compensate for these weaknesses during the common daily activities of living.
Clinical trials
In 2004 there were two open clinical trials recruiting patients entitled "Cause, Development, and Progression of Stiff-Person Syndrome" and "Diagnostic Evaluation of Patients with Neuromuscular Disease," sponsored by National Institute of Neurological Disorders and Stroke (NINDS). For further and updated information, visit the website
Prognosis
There is no cure for SPS and the long-term prognosis is variable. Many patients have a slow course of the disorder that is mostly without symptoms, punctuated by occasional episodes of stiffness. Other patients may have a much more aggressive course, rapidly progressing to the late stages of disease. Other forms of the disease have been described that are accompanied by brain disorders and other central nervous system abnormalities, but whether they are separate diseases or different manifestations of the same disease is unclear. Management of the disorder with drug therapy usually provides significant improvement and relief of symptoms.
Special concerns
Many of the medications prescribed for SPS are not indicated during pregnancy. Elderly persons with SPS may have increased chances of falling and injury because of concurrent disability from other causes. As with all autoimmune disorders, dietary changes are sometimes helpful. For best results, dietary changes should be made under the supervision of a physician experienced in nutritional medicine.
Resources
BOOKS
Icon Health Publications. The Official Patient's Sourcebook on Stiff-Person Syndrome: A Revised and Updated Directory for the Internet Age. San Diego: Icon Group International, 2002.
Larsen, Povl K., J. Egeberg, and A. Schousboe. Glutamate and GABA Receptors and Transporters. Taylor & Francis, 2001.
PERIODICALS
Gerschlager, W. et al. "Quality of life in stiff person syndrome." Movement Disorders 17 (2002): 1064–1067.
OTHER
"NINDS Stiff-Person Syndrome Information Page." National Institute of Neurological Disorders and Stroke. (March 11, 2004). http://www.ninds.nih.gov/health_and_medical/disorders/stiffperson_doc.htm.
ORGANIZATIONS
National Rehabilitation Information Center (NARIC). 4200 Forbes Boulevard; Suite 202, Lanham, Maryland 20706-4829. (301) 562-2400 or (800) 346-2742; (301) 562-2401. naricinfo@heitechservices.com. http://www.naric.com.
National Organization for Rare Disorders (NORD). 55 Kenosia Avenue, Danbury, Connecticut 06813-1968. (203) 744-0100; Fax: (203) 798-2291. orphan@rarediseases.org. http://www.rarediseases.org.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Bldg. 31, Rm. 4C05, Bethesda, Maryland 20892-2350. (301) 496-8188. NIAMSInfo@mail.nih.gov. http://www.nih.gov/niams.
Bruno Verbeno Azevedo
Iuri Drumond Louro, MD, PhD
