Stiff person spectrum disorder is a neurological autoimmune condition characterised by muscle stiffness, painful spasms (involuntary contraction) and hypersensitivity to stimulus such as noise, touch, or emotional stress.¹ Stiff person spectrum disorder have a wide range of symptoms and severity. It can range from, but is not limited to the following:^2,3

• Classic stiff person syndrome (ORPHA:443192) – affects the whole body
• Focal stiff limb syndrome (ORPHA:443804) – affects only one area of the body
• Progressive encephalomyelitis with rigidity and myoclonus/PERM (ORPHA:438266) – a more severe and progressive form that affects the whole body and the central nervous system (brain and spinal cord)

Stiff person spectrum disorder most commonly develops between the age of 30 – 60, but in rare cases, it can occur in children.^3,4 More females are affected compared to males.

Synonyms: Stiff man syndrome, SMS, stiff person syndrome, SPS, gamma neuron overactivity syndrome, Moersch-Woltman syndrome.^2,3

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:3198 Stiff person spectrum disorder

ICD-11 8E4A.0 Paraneoplastic or autoimmune disorders of the central nervous system, brain or spinal cord

Symptoms of Stiff person spectrum disorder usually appear randomly and gradually progress over months. Symptoms may remain stable for a long period of time or slowly worsen.^1,3

Some common symptoms may include:^1-4

• rigidity and stiffness in the legs, torso and arms
• muscle spasms (involuntary contractions) which can last minutes or hours
• difficulty walking, stiff and unstable gait. Individuals may require use of a walker or wheelchair or may become bedridden.
• unexplained falls
• exaggerated startle responses (responses that are greater in intensity than normal) to sudden stimulus such as sound, touch, or conditions that trigger anxiety and emotional stress. This can cause temporary muscle stiffness.
• lumbar lordosis (exaggerated inward curve of the lower spine that can make the stomach and buttocks appear protrude)

Individuals often develop depression, anxiety, fear of open spaces, phobias to certain tasks such as fear of walking and crossing a street due to triggered spasms.^4,7 These symptoms may contribute to individuals being misdiagnosed with other conditions such as a primary psychiatric condition or functional neurological disorder.

PERM is a more severe and progressive form, which affects the central nervous system leading to additional neurological symptoms. This may include poor muscle control, incoordination, difficulty speaking and swallowing, paralysis of certain eye movements, confusion, seizures, changes in blood pressure and heart rate (autonomic disturbance).^2-4

Stiff person spectrum disorder has been associated with other autoimmune conditions and cancers such as thyroid autoimmune disease, type 1 diabetes mellitus, coeliac, breast cancer, lung cancer, lymphoma and thymoma.^1,5

Please speak to your medical team to learn more about the symptoms and health implications of Stiff person spectrum disorder.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Stiff person spectrum disorder is an autoimmune condition, where the body’s immune system produce antibodies that mistakenly attack its own body (autoantibodies). In Stiff person spectrum disorder, the autoantibodies attack proteins involved in regulating nerve signals that control muscle movement.⁴ Among the common proteins targeted are glutamic acid decarboxylase/GAD (most common), glycine receptor, amphiphysin, gephyrin, and dipeptidyl peptidase-like protein 6.^1,6

Most of these proteins are involved in the production and signaling of GABA. GABA is a chemical messenger in the brain that stops nerve cell’s activity, and prevent hyperexcitability within the nervous system.^3,4,7 As GABA signaling is impaired, overactive nerves signaling lead to uncontrollable muscle contraction, resulting in stiffness and spasms.⁷

Some individuals with Stiff person spectrum disorder have not been detected to have any autoantibodies so far, and the cause of their condition is yet to be well understood.³

Diagnosis of Stiff person syndrome may be made based on:^1,3,4

• physical examination
• neurological tests to check the function of the brain, nervous system and muscles
• antibody tests to measure the level of auto-antibodies
• imaging scan of the brain and spinal cord to rule out other causes of rigidity and stiffness
• family history and medical history of autoimmunity

As part of the diagnostic process, doctors may do a differential diagnosis, where they rule out other conditions that have similar symptoms, such as tetanus, chronic pain syndrome and/or functional neurologic disease, hyperekplexia, multiple sclerosis, transverse myelitis, occult vascular malformations, Isaac’s syndrome, Schwartz-Jampel syndrome, muscular dystrophy, and metabolic myopathies.^1,3

Please speak to your medical team to learn more about the available diagnostic pathways for Stiff person spectrum disorder.

There is currently no curative treatment for Stiff person spectrum disorder. Treatment is targeted at managing symptoms (symptomatic management) and involves a multidisciplinary care team. This may include:^1,3,4

• medications to reduce muscle stiffness, rigidity and spasms
• immunotherapy such as intravenous immunoglobulin (IVIg) In Australia, IVIg is available under the national blood arrangements for eligible patients with specific conditions. National Blood Authority Ig Governance: Stiff person syndrome has information about the criteria for the clinical use of immunoglobulin for people with Stiff person syndrome in Australia.
• physiotherapy
• occupational therapy
• other therapies such as osteopathy, chiropractic treatment, acupuncture may be helpful as complementary therapies ^3,5

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of people with Stiff person spectrum disorder may include general practitioners (GP), neurologists, immunologists, physiotherapists, occupational therapists, orthopaedic surgeons, psychiatrists and others.⁴ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. Palliative care is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. For more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any clinical care guidelines for Stiff person spectrum disorder in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following guidance is available from international experts outside Australia. However, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

Stiff person spectrum disorder diagnosis, misdiagnosis, and suggested diagnostic criteria includes recommendations for diagnostic criteria based on evaluation of patients at the Autoimmune Neurology Clinic (Mayo Clinic Rochester), published in 2023.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Australia Organisation:
We are not aware of any rare disease organisations for Stiff person spectrum disorder in Australia. If you are aware of any relevant Australian organisations, please let us know via the Contribute page.

International Organisation:
The Stiff Person Syndrome Research Foundation (United States of America)
Website: https://www.stiffperson.org/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Stiff person spectrum disorder varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on Stiff person spectrum disorder can be found at:

• The Stiff person Syndrome Research Foundation: Patient Resources
• National Organization for Rare Disorders (NORD): Stiff Person Syndrome
• Genetic and Rare Diseases (GARD) Information Center: Stiff-Person syndrome

StatPearls: Stiff Person Syndrome

Online Mendelian Inheritance in Man, OMIM^®: %184850 Stiff-Person syndrome; SPS

Orphanet: Stiff person spectrum disorder

Human Phenotype Ontology (HPO): Stiff-Person syndrome

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.