Stiff person syndrome

Información en español Title

Other Names:

Stiff man syndrome; Morsch Woltman syndrome; SPS; Stiff man syndrome; Morsch Woltman syndrome; SPS; Moersch-Woltman syndrome; SMS; Stiff person syndrome and related disorders See More

Categories:

Congenital and Genetic Diseases; Endocrine Diseases; Musculoskeletal Diseases; Congenital and Genetic Diseases; Endocrine Diseases; Musculoskeletal Diseases; Nervous System Diseases See More

Subtypes:

Progressive encephalomyelitis with rigidity and myoclonus

Summary Summary

Stiff person syndrome (SPS) is a rare, progressive syndrome that affects the nervous system, specifically the brain and spinal cord. Symptoms may include extreme muscle stiffness, rigidity and painful spasms in the trunk and limbs, severely impairing mobility. Spasms can generate enough force to fracture bone. People with SPS often have heightened sensitivity to noise, sudden movements, and emotional distress, which can set off muscle spasms. Persistent symptoms can lead to abnormal posturing of the spine, such as being hunched over. The syndrome affects twice as many women as men.^[1]^[2]

SPS is caused by increased muscle activity due to decreased inhibition of the central nervous system. It is thought to have an autoimmune component and is often associated with diabetes, as well as other autoimmune diseases such as thyroiditis, vitiligo, and pernicious anemia.^[1]^[2] It may be diagnosed after having various tests including blood tests (including a test showing elevated glutamic acid decarboxylase (GAD) antibodies), a lumbar puncture, and electromyography. Treatment aims to control symptoms and improve mobility, and may involve benzodiazepines, muscle relaxants, and/or intravenous immunoglobulin (IVIG).^[1]^[2] While some people with SPS may maintain reasonable levels of activity with treatment, the majority become disabled over time.^[2]

Last updated: 3/12/2018

Symptoms Symptoms

Stiff person syndrome (SPS) is a progressive syndrome characterized by recurrent episodes of severe muscle stiffness, rigidity, and painful spasms in the trunk and limbs. The age that symptoms begin can vary, but most people start experiencing symptoms between ages 30 and 60. Spasms can be prolonged and extremely forceful, with the ability to generate enough force to fracture bone. They may cause a person to fall when walking or standing. Spasms are especially likely or may worsen during times of emotional distress, when being touched, when there is sudden movement, or with noise.^[2]^[3]

Over time, persistent symptoms can lead to abnormal posturing of the spine, such as being stiffened and hunched over.^[1] Daily activities such as getting into or out of bed, getting up from a chair, or dressing may become increasingly difficult.^[2] People with SPS also may become fearful and anxious about navigating daily life, which in turn may trigger additional spasms. Many people with SPS develop depression as the syndrome progresses and quality of life becomes severely impaired.^[2]^[3]

Last updated: 3/13/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Anxiety	Excessive, persistent worry and fear	0000739
EMG abnormality		0003457
Falls		0002527
Hyperhidrosis	Excessive sweating Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ]	0000975
Intermittent painful muscle spasms		0011964
30%-79% of people have these symptoms
Agoraphobia	Fear of open spaces	0000756
Autoimmune antibody positivity		0030057
Difficulty walking	Difficulty in walking	0002355
Emotional lability	Emotional instability	0000712
Exaggerated startle response		0002267
Paraspinal muscle hypertrophy		0012894
Rigidity	Muscle rigidity	0002063
5%-29% of people have these symptoms
Diabetes mellitus		0000819
Hypothyroidism	Underactive thyroid	0000821
Lumbar hyperlordosis	Excessive inward curvature of lower spine	0002938
Percent of people who have these symptoms is not available through HPO
Adult onset	Symptoms begin in adulthood	0003581
Anemia	Low number of red blood cells or hemoglobin	0001903
Asymmetric limb muscle stiffness		0007156
Autoimmunity	Autoimmune disease Autoimmune disorder [ more ]	0002960
Axial muscle stiffness		0006921
Depressivity	Depression	0000716
Fever		0001945
Frequent falls		0002359
Hyperreflexia	Increased reflexes	0001347
Hypertension		0000822
Myoclonic spasms		0003739
Opisthotonus		0002179
Proximal limb muscle stiffness		0007066
Sporadic	No previous family history	0003745
Tachycardia	Fast heart rate Heart racing Racing heart [ more ]	0001649
Vitiligo	Blotchy loss of skin color	0001045

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 3/1/2019

Do you have updated information on this disease? We want to hear from you.

Cause 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.^[1] 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.^[3]

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.^[3]^[4]^[5]^[6]

Last updated: 7/23/2017

Inheritance 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.^[7] 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.^[3]

Last updated: 7/23/2017

Diagnosis Diagnosis

A diagnosis of stiff person syndrome (SPS) is typically made based on symptoms, a detailed medical history, and various tests used to support the diagnosis or rule out other diseases with overlapping symptoms.^[4]^[8] One commonly used test is a blood test to detect the presence of glutamic acid decarboxylase (GAD) antibodies. About 60-80% of people with SPS have antibodies against GAD that can be detected on a blood test.^[8] The absence of GAD antibodies does not rule out SPS, but the presence of high levels of GAD antibodies strongly supports the diagnosis.^[5] GAD antibodies may also be measured in the cerebral spinal fluid from a lumbar puncture.^[9]

Additionally, a doctor may recommend electromyography (EMG), which records electrical activity in skeletal muscles.^[4]^[8] The EMG of a person with SPS typically shows continuous motor activity in the skeletal muscles.^[4]^[8]

Other testing that may be used to confirm or rule out the diagnosis includes:

A hemoglobin A1C test to rule out diabetes mellitus.
A complete blood count to rule out pernicious anemia.
A thyroid-stimulating hormone (TSH) test to rule out thyroiditis.
A lumbar puncture to look for oligoclonal bands which indicate that the central nervous system is inflamed (these bands can be seen in about two thirds of people who have GAD antibodies).^[3]

Genetic testing currently is not available because the underlying genetic cause of stiff person syndrome has not been established.^[5]

Last updated: 3/13/2018

Treatment Treatment

Treatment aims to control symptoms and improve mobility and function. While some people on treatment for SPS may maintain reasonable levels of activity, the majority become increasingly disabled over time. Treatment options depend on the symptoms and severity in each person and may include:^[2]^[3]

Benzodiazepines - these are drugs that slow down the nervous system and may relieve muscle spasms and anxiety. They are generally considered the best initial therapy for SPS. Examples include diazepam and clonazepam.
Baclofen - this is a muscle relaxant that may be used for people in whom benzodiazepines are not effective or not well-tolerated. Some people benefit from using baclofen in addition to benzodiazepines.
Immune modulating therapies - these may be considered in people with severe symptoms who do not experience relief with benzodiazepines and baclofen. Options may include intravenous immune globulin (IVIG) therapy, plasmapheresis (also called plasma exchange), and rituximab. However studies supporting the effectiveness and safety of these therapies for SPS are limited.

Physical therapy and occupational therapy are also an important part of management for SPS and may help with side effects of medications (such as weakness) in addition to symptoms of the disease.^[3]

Last updated: 3/14/2018

Management Guidelines

Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Prognosis 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.^[3]^[4]

Treatment may be helpful for some people with SPS, but for others current treatment options do not relieve the symptoms of the disorder.^[1]^[3] For these people, daily living can become very difficult due to symptoms of muscle rigidity, anxiety, and depression.^[3]

Last updated: 7/23/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes an atypical manifestation of a spinal cord disease (e.g. multiple sclerosis; tumours), axial dystonia, neuromyotonia, acquired hyperekplexia (startle disease), and psychogenic movement disorders (see these terms). Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.
ClinicalTrials.gov lists trials that are related to Stiff person syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

European Alliance of Neuromuscular Disorders Associations
MDG Malta 4
Gzira Road
Gzira, Intl GAR 04
Malta
Telephone: 003-56 -21 346688
E-mail: eamda@hotmail.com
Website: http://www.eamda.eu/
International Parkinson and Movement Disorder Society
555 East Wells Street, Suite 1100
Milwaukee, WI 53202-3823
Telephone: +1-414-276-2145
Fax: +1-414-276-3349
E-mail: info@movementdisorders.org
Website: https://www.movementdisorders.org/

Organizations Providing General Support

American Autoimmune Related Diseases Association (AARDA)
22100 Gratiot Avenue
Eastpointe, MI 48021
Toll-free: 800-598-4668
Telephone: 586-776-3900
Fax: 586-776-3903
E-mail: aarda@aarda.org
Website: https://www.aarda.org/

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Stiff person syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

NORD Announces Research Grants Available for Study of Rare Diseases
August 24, 2016

GARD Answers GARD Answers

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Have a question? Contact a GARD Information Specialist.

References References

NINDS Stiff-Person Syndrome Information Page. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Stiff-Person-Syndrome-Information-Page#disorders-r1. Accessed 7/12/2017.
Helfgott SM. Stiff-person syndrome. UpToDate. Waltham, MA: UpToDate; December 28, 2016; https://www.uptodate.com/contents/stiff-person-syndrome.
Rodgers-Neame NT. Stiff Person Syndrome. Medscape Reference. May 30, 2017; http://emedicine.medscape.com/article/1172135-overview.
Murinson BB. Stiff Person Syndrome. National Organization for Rare Disorders (NORD). 2010; http://rarediseases.org/rare-diseases/stiff-person-syndrome/.
Stiff Person Syndrome. Johns Hopkins Medicine: Neurology & Neurosurgery. http://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/neuroimmunology_and_neurological_infections/conditions/stiff_person_syndrome.html.
Meinck HM. Stiff person syndrome and related disorders. Orphanet. August 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=3198.
Stiff-Person Syndrome; SPS. Online Mendelian Inheritance in Man (OMIM). August 31, 2016; http://www.ncbi.nlm.nih.gov/omim/184850.
Sanders S, Bredeson C, Pringle CE, et. al. Autologous stem cell transplantation for stiff person syndrome: two cases from the Ottawa blood and marrow transplant program. JAMA Neurology. October, 2014; 71(10):1296-9. http://jamanetwork.com/journals/jamaneurology/fullarticle/1897093.
Rakocevic G, Raju R, Dalakas MC. Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: correlation with clinical severity. Arch Neurol. June, 2004; 61(6):902-904. https://www.ncbi.nlm.nih.gov/pubmed/15210528.