Information on the following diseases can be found in the Related Disorders section of this report:

• Torsion dystonia (dystonia musculorum deformans, DMD)

Stiff person syndrome is characterized by progressive muscular rigidity. Muscle stiffness generally starts in the back or neck muscles. Early on, stiffness may be present only intermittently, but it gradually becomes fixed. As the disease progresses, stiffness of the leg muscles develops, and it is often more pronounced on one side than the other (asymmetrical). This leads to a slow, stiff way of walking. In some individuals, stiffness may progress to involve the arms or face.

The most disabling problem is episodic spasms, which are often very painful. They may involve the entire body or only a localized region, and often lead to falls. Spasms are precipitated by unexpected noises or minor physical contact, as well as by anxiety-producing situations. In some cases, no precipitant is evident. Spasms involving the chest and respiratory muscles can be serious. Spasms may last several minutes, but occasionally last for hours, requiring emergency medical treatment with ventilatory support.
Profuse sweating and a rapid heartbeat (tachycardia) may accompany the muscle spasms.

Sleep usually suppresses frequency of contractions. Stiff person syndrome may be progressive and may gradually involve additional muscles of the back and abdomen. Stiffness may increase, and patients may develop a hunched posture (kyphosis) or a swayback (lordosis).

The exact cause of stiff person syndrome is not understood. However, some studies in the medical literature indicate that it may be an autoimmune disorder. Autoimmune disorders are caused when the body's natural defenses against "foreign" or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons.

Two-thirds of those affected have antibodies to GAD-65, a protein in inhibitory nerve cells involved in the synthesis of a substance that helps to control muscle movement. The symptoms of stiff person syndrome may develop when the immune system mistakenly attacks certain nerve cells (neurons) that produce GAD-65.

Sometimes, muscle spasms appear to be triggered by external or environmental factors such as sudden noises and emotional stimuli. Also, people who have stiff person syndrome often have other autoimmune diseases such as diabetes, hyperthyroidism, and hypothyroidism. In rare cases, stiff person syndrome appears in association with cancers, including lung or breast cancer.

Stiff-person syndrome is a very rare disorder. Although the prevalence has not been well established, this disease may affect about one in a million people, according to one estimate. Many affected individuals also have diabetes, and some also have breast cancer or lung cancer. There is no clear racial or ethnic predisposition.

Symptoms of the following disorders can be similar to those of stiff-person syndrome. Comparisons may be useful for a differential diagnosis:

Torsion dystonia (dystonia musculorum deformans, DMD) is an incapacitating neurological disorder that causes affected individuals to develop repetitive twisting and writhing movements. The movements may affect a single muscle, a group of muscles such as those in the arms, legs, or neck, or the entire body. Experts have lately been referring to this disorder as "the dystonias," indicating a group of related movement disorders rather than a single disorder. (For more information choose "Torsion Dystonia" as your search term in the Rare Disease Database.)

The diagnosis of stiff person syndrome is based upon a thorough clinical evaluation, a detailed patient history, and characteristic physical findings. Treatment of stiff person syndrome is symptomatic and supportive. Drugs known as benzodiazepines, such as diazepam and clonazepam, are used to treat muscle stiffness and episodic spasms.

Many patients also benefit from baclofen, usually given in addition to benzodiazepines. Other medications reported to have benefit in a small number of patients include vigabatrin, valproate, and gabapentin

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:184850; Last Update:10/22/01.

TEXTBOOKS
Adams, RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:1492.

Magalini SI, et al., eds. Dictionary of Medical Syndromes. 4th ed. New York, NY: Lippincott-Raven Publishers; 1997:763.

JOURNAL ARTICLES
Dalakas MC. Intravenous immunoglobulin in autoimmune diseases. JAMA. 2004;291:2367-75.

Szczepanska-Szerej A, et al. Botulinum toxin A in the treatment of stiff man syndrome. Neurol Neurochir Pol. 2003;37:175-8.

Dalakas MC, et al. High-Dose Intravenous Immune Globuline for Stiff-Person Syndrome. New Engl J Med. 2001;345:1870-76.

Souza-Lima CFL, et al. Marked improvement in a stiff-limb patient treated with intravenous immunoglobulin. Movement Disorders. 2000;15:358-9.

Khanlou H, et al. Long term remission of refractory stiff man syndrome after treatment with intravenous immunoglobulin. Mayo Clin Proc. 1999;74:1231-2.

Brown P, et al. The stiff man and stiff man plus syndromes. J Neurol. 1999;246:648-52.

Hao W, et al. Plasmapheresis and immunosuppression in stiff-man syndrome with type 1 diabetes: a 2-year study. J Neurol. 1999;246:731-5.

Levy LM, et al. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999;131:522-30.

Rosin L, et al. Stiff-man syndrome in a woman with breast cancer: an uncommon central nervous system paraneoplastic syndrome. Neurology. 1998;50:94-8.

Kissel JT, et al. Stiff-person syndrome: stiff opposition to a simple explanation. Neurology. 1998;51:11-4.

Liguori R, et al., Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome. Mov Disord. 1997;12:1060-3.

Stayer C, et al. Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus. Neurology. 1997;49:1591-7.

Amato A, et al. Treatment of stiff-man syndrome with intravenous innumoglobulin. Neurology. 1994;44:1652-4.

Solimena M, et al. Autoantibodies to gaba-ergic neurons and pancreatic beta cells in stiff man syndrome. Michele Solimena et al.; New Engl J Med. 1990;322:1555-60.