What to know about Stiff Person Syndrome, a rare autoimmune condition

There are over 7,000 rare diseases that affect very small numbers of patients around the world. Due to the rarity of these conditions, it can be difficult to conduct the research needed to better understand them and to develop effective treatments. One rare disease that has recently come into the spotlight is called Stiff Person Syndrome (SPS). In 2022, global superstar Celine Dion revealed that she had been diagnosed with SPS, which had caused her to stop performing. This year, she released a documentary shedding light on her struggles with SPS symptoms and raising awareness. The Celine Dion foundation donated $2 million to the University of Colorado Anschutz Medical Campus to advance research in SPS and other rare autoimmune disorders.

At Private Health Management (PHM), our experts have deep expertise in a variety of serious and complex diseases. Here’s what you need to know about SPS.

Stiff Person Syndrome
SPS is a rare autoimmune neurological disease that affects the brain and spinal cord of the central nervous system. Autoimmune diseases occur when a person’s immune system is overactive and attacks their own body tissue. SPS causes spasms and progressive stiffness in the muscles of the trunk, including the belly, chest, back, shoulders, and hips. This can cause difficulty walking, coordinating movement, and sometimes breathing. The spasms occur in episodes that can be worsened by external stimuli, such as sudden movements, cold temperatures, and emotional stress.

First described in 1956, SPS has an estimated prevalence of 1–2 cases per million people, and occurs more often in women than men.^1–3 Most patients develop symptoms between 20 and 60 years of age, and only 5% of cases of SPS have been reported in children.⁴ SPS may occur alongside other autoimmune disorders such as type 1 diabetes, autoimmune thyroid disease, pernicious anemia, celiac disease, and vitiligo.⁵

Classic SPS is the most common form, present in 70–80% of SPS patients. It is associated with elevated levels of anti-GAD antibodies, which recognize an enzyme called anti-glutamic acid decarboxylase.^3,6 SPS is believed to be caused by low levels of GABA, a neurotransmitter that is responsible for inhibiting signaling across synapses, which are junctions between two neurons. Low levels of GABA result in failure to inhibit this signaling, which leads to increased muscle activity.^7,8 Classic SPS begins subtly, gradually worsening over time, and often results in permanent disability or, in some cases, death.

There are other, even rarer forms of SPS, including jerky-stiff person syndrome (JSPS), SPS-Plus, and progressive encephalomyelitis with rigidity and myoclonus (PERM).^6,8–10 The symptoms, underlying causes, and course of disease progression of these forms of SPS are somewhat different from classic SPS, and proper diagnosis of the variant is important to guide management strategies. There is also a form of SPS associated with cancer (paraneoplastic SPS), which is more common in patients with breast, colorectal, lung, thyroid and thymus cancers, as well as Hodgkin’s lymphoma.⁵

Symptoms of SPS
Common symptoms of SPS include severe muscle stiffness, hunched posture, overactive reflexes, and spontaneous painful spasms that primarily impact the limbs and torso, which can lead to difficulty walking as well as falls.^1,2 Less typical symptoms include eye movement problems that cause double vision, speech issues, urinary retention, constipation, abdominal cramps, and bowel urgency.¹¹

SPS-related spasms can be triggered by anxiety, task-specific phobias, and excessive startles from unexpected stimuli. For example, loud noises and throbbing lights can induce spasms and falls, hindering individuals from performing their everyday activities, and leading to depression, anxiety and avoidance of stressful situations.^12,13 As the disease progresses, some people may experience rigidity of facial muscles, severe and lasting muscle spasms, and in rare cases, difficulty breathing.

Diagnosis of SPS
Stiff person syndrome is very complex, and its many symptoms can be caused by other, more common conditions. Proper diagnosis may take time and include several tests, such as:

• Assessment of symptoms by a specialist.
• Antibody blood tests to identify the presence of anti-GAD or other relevant antibodies and help rule out other diseases.
• Electromyography (EMG) to measure electrical activity in the muscles, which can help exclude other causes of the patient’s symptoms. Monitoring trunk muscles for overactivity is a key diagnostic component used to identify SPS.
• Lumbar puncture (spinal tap), a procedure that uses a needle to draw fluid from the spinal canal, to check for GAD antibodies and other indicators that might confirm the diagnosis or rule out other conditions.
• Diagnosis of cancer-related, paraneoplastic SPS includes testing for antibodies against other proteins (amphiphysin and gephyrin).

Management of Stiff Person Syndrome
There is no cure for SPS, but there are some medications and lifestyle modifications that are used to help manage the disease. The first-line treatment often prescribed for symptom management is diazepam, a benzodiazepine that is used for anxiety, seizures, and insomnia. Muscle relaxants (baclofen) may reduce muscle spasms and stiffness, and neuropathic pain medications such as gabapentin and pregabalin can help to alleviate symptoms.

Immunotherapy to address the underlying cause of the disease involves immune-modulating treatments designed to reduce the body’s autoimmune response. Intravenous immunoglobulin (IVIG) is the most effective immunotherapy for SPS, providing clinical improvement for up to one year after a standard course of five sessions. Some evidence suggests that rituximab, a monoclonal antibody, can provide a long-lasting benefit.¹⁴

In addition to medication, other interventions are often helpful for coping with and managing symptoms. These include physical therapy or occupational therapy, massage, hydrotherapy, heat therapy, and acupuncture.

Prognosis
The outlook for SPS patients depends on factors like clinical presentation, duration of symptoms, co-existing cancers, and treatment response. Getting patients started on a treatment early in the disease is crucial to prevent or slow disease progression and avoid long-term complications. Although most patients improve with medication, they can still experience symptom fluctuations due to physical and emotional stress. Despite available treatments, some patients still deteriorate over time, resulting in permanent orthopedic problems, walking difficulties, and disability.

At PHM, we provide comprehensive care for patients with serious and complex diseases. We support patients with complex symptoms by coordinating testing, arranging consultations with experts to obtain accurate diagnoses, and developing strategies for disease treatment and symptom management. Our team of clinicians and researchers stays up to date on the latest developments related to rare diseases, including autoimmune disorders, and continuously monitors the treatment landscape for clinical trials and emerging therapies.

References

1. Moersch, F. P. & Woltman, H. W. Progressive fluctuating muscular rigidity and spasm (‘stiff-man’ syndrome); report of a case and some observations in 13 other cases. Proc Staff Meet Mayo Clin 31, 421–427 (1956).
2. Hadavi, S., Noyce, A. J., Leslie, R. D. & Giovannoni, G. Stiff person syndrome. Practical Neurology 11, 272–282 (2011).
3. Blum, P. & Jankovic, J. Stiff-person syndrome: An autoimmune disease. Movement Disorders 6, 12–20 (1991).
4. Clardy, S. L. et al. Childhood Onset of Stiff-Man Syndrome. JAMA Neurol 70, 1531 (2013).
5. Baizabal-Carvallo, J. F. & Jankovic, J. Stiff-person syndrome: insights into a complex autoimmune disorder. J Neurol Neurosurg Psychiatry 86, 840–848 (2015).
6. Rakocevic, G. & Floeter, M. K. AUTOIMMUNE STIFF PERSON SYNDROME AND RELATED MYELOPATHIES: UNDERSTANDING OF ELECTROPHYSIOLOGICAL AND IMMUNOLOGICAL PROCESSES. Muscle Nerve 45, 623–634 (2012).
7. Identification of a dominant epitope of glutamic acid decarboxylase (GAD-65) recognized by autoantibodies in stiff-man syndrome. J Exp Med 178, 2097–2106 (1993).
8. Rakocevic, G., Raju, R., Semino-Mora, C. & Dalakas, M. C. Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology 67, 1068–1070 (2006).
9. Whiteley, A. M., Swash, M. & Urich, H. Progressive encephalomyelitis with rigidity. Brain 99, 27–42 (1976).
10. Meinck, H.-M. & Thompson, P. D. Stiff man syndrome and related conditions. Mov Disord 17, 853–866 (2002).
11. Dumitrascu, O. M., Tsimerinov, E. I. & Lewis, R. A. Gastrointestinal and Urologic Sphincter Dysfunction in Stiff Person Syndrome. J Clin Neuromuscul Dis 18, 92–95 (2016).
12. Ameli, R., Snow, J., Rakocevic, G. & Dalakas, M. C. A neuropsychological assessment of phobias in patients with stiff person syndrome. Neurology 64, 1961–1963 (2005).
13. Nasri, A. et al. Psychiatric Symptoms in Stiff-Person Syndrome: A Systematic Review and a Report of Two Cases. Journal of the Academy of Consultation-Liaison Psychiatry 64, 183–191 (2023).
14. Dalakas, M. C. Therapies in Stiff-Person Syndrome. Neurology Neuroimmunology & Neuroinflammation 10, e200109 (2023).