(Image: Perea Clinic)
Writers: Somil Bhushan, MPH; Karishma Pilla; Whitney Elaine
Editor: Nadia Hall
Stiff person syndrome (SPS) is a rare and debilitating neurological disorder characterized by progressive muscle stiffness and painful spasms (Johns Hopkins Medicine, n.d.). Imagine your body slowly turning rigid, with every movement becoming a potential trigger for excruciating muscle contractions. This is the reality for SPS patients. While the exact number of people affected remains unknown, estimates suggest a prevalence of 1-2 cases per million individuals (Cleveland Clinic, n.d.).
Risk factors for SPS are still being unraveled, but research points towards an autoimmune component. Women are twice as likely as men to develop SPS, and it often appears in middle age (Cleveland Clinic, n.d.). The presence of other autoimmune conditions, such as diabetes and thyroid disease, also seems to be linked to SPS (Johns Hopkins Medicine, n.d.). Understanding the risk factors and improving diagnostic accuracy are crucial steps towards effective management and treatment strategies for this life-altering condition.
While the exact cause remains elusive, research points towards an autoimmune attack. The body's own immune system mistakenly targets glutamic acid decarboxylase (GAD), an enzyme crucial for producing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) (Graus et al., 2020). This disrupts the delicate balance between excitatory and inhibitory signals in the nervous system, leading to uncontrolled muscle firing and rigidity.
Figure 1: GAD Antibodies in Neurological Disorders (Graus et al., 2020)
The precise structural changes within the brain associated with SPS are still under investigation. However, brain imaging techniques might reveal subtle differences in regions responsible for movement control and sensory processing compared to healthy individuals (Graus et al., 2020). SPS significantly disrupts the body's metabolic and movement processes. The constant muscle tension increases energy expenditure, while the reduced GABA function disrupts smooth, coordinated movements (Graus et al., 2020). This can lead to tremors, difficulty walking, and a heightened startle response. Understanding the complex interplay between the immune system, neurotransmitters, and brain function is vital for developing effective treatments for this challenging condition.
Muscle rigidity and spasms are the hallmarks of Stiff Person Syndrome. As there is no known cure for SPS, treatment approaches concentrate on symptom management and quality of life enhancement. Usually, a mix of drugs, immunotherapies, and physical treatments are used in the treatment (Johns Hopkins Medicine, n.d.).
Medications:
Muscular relaxants: Drugs that lessen muscular rigidity and spasms include diazepam, clonazepam, baclofen, and tizanidine (Johns Hopkins Medicine, n.d.).
Medications for neuropathic pain: By altering the GABA neurotransmitter pathway, gabapentin and pregabalin can help control symptoms (Graus et al., 2020).
Botulinum toxin: This is occasionally used to treat stiffness and isolated muscular spasms (Johns Hopkins Medicine, n.d.).
Immunotherapies:
Intravenous immunoglobulin (IVIG): IVIG may be employed in the event that traditional pharmacological therapy is insufficient. For certain individuals, it has improved mobility and quality of life while lowering stiffness. Trials are still in progress to optimize the administration and dosage (Nolan & Nicholas, 2020).
Plasma exchange (PLEX): Although it is less frequently used and often in conjunction with other therapy, this procedure can be helpful for refractory patients of SPS (Graus et al., 2020).
Occupational and Physical Therapy:
Physical therapy: Consistent physical treatment that emphasizes mobility, balance, and stretching exercises can help preserve function and lessen stiffness (Johns Hopkins Medicine, n.d.).
Occupational therapy: It assists patients in adjusting to their everyday routines and enhances their capability to function (Cleveland Clinic, n.d.).
Aquatic therapy: This kind of treatment uses warm water to ease tense muscles and enhance mobility (Johns Hopkins Medicine, n.d.).
Alternative Medical Interventions:
Cannabinoids: New research indicates that cannabinoids may lessen muscle spasms and spasticity in SPS patients (Nolan & Nicholas, 2020).
Osteopathic manipulative therapy (OMT): When combined with pharmaceutical therapies, this manual therapy can help reduce muscle tension and increase mobility (Nolan & Nicholas, 2020).
Psychological Support:
Cognitive behavioral therapy and other psychological support can be helpful in treating mental health symptoms, given the anxiety and tension associated with SPS due to its unpredictable nature (Johns Hopkins Medicine, n.d.).
In general, effective management of SPS requires a multidisciplinary approach comprising neurologists, physical therapists, and mental health specialists. Personalized treatment strategies and routine follow-up are essential for managing the condition's complicated and variable symptoms (Graus et al., 2020).
The goals of current SPS research are to comprehend the biology of the condition, find efficient therapies, and investigate novel therapeutic modalities. Here are a few recent findings and current trends in SPS research:
Drugs and Clinical Trials:
Rituximab: A recent investigation examined the use of this monoclonal antibody, which targets B cells involved in the autoimmune response, as a treatment for SPS. The outcomes have demonstrated potential in lowering patients' muscular rigidity and spasms (Graus et al., 2020).
Spinal cord stimulation (SCS): In preliminary research, the use of SCS to treat patients' painful spasms and stiffness symptoms is being investigated. Positive preliminary findings suggest that it might be a good choice for symptom management (Patel et al., 2024).
Innovations and Realizations:
Autoantibody research: New research has broadened our knowledge of autoantibodies linked to SPS, including those that target glycine receptors, amphiphysin, and glutamic acid decarboxylase. For more precise diagnosis and individualized treatments, these insights are essential (Graus et al., 2020).
Pathophysiological mechanisms: Knowledge of the mechanisms behind the disease has progressed, notably with regard to the central nervous system's inhibitory pathways. New therapeutic targets and tactics have resulted from this (Graus et al., 2020).
Emerging Therapies:
Stem cell therapy: Hematopoietic stem cell transplantation (HSCT) has been investigated in preliminary trials for SPS, and results have indicated potential for immune system resetting and long-term symptom alleviation. Although this method is still in the experimental stage, it presents hope for a longer-term fix (Vlad et al., 2023).
Small molecule inhibitors: Studies into small molecule inhibitors, which can alter particular immune pathways implicated in SPS, are being conducted with the goal of offering more specialized and less immunosuppressive therapeutic options (Vlad et al., 2023).
These trials have the potential to enhance the quality of life for people living with this difficult condition and represent a major advancement in the understanding and treatment of SPS (Graus et al., 2020).
Celine Dion
Celine Dion, an internationally renowned singer, revealed her diagnosis of Stiff Person Syndrome in December 2022, sparking significant media attention regarding this rare and debilitating condition (McNeal, 2022). Dion, who had planned to go on tour in 2023 after cancellations due to the COVID-19 pandemic, had to cancel the tour (Olson, 2022). Dion spoke out in an emotional video on social media, describing how the spasms not only affected her ability to walk at times, but also affected her vocal cords, limiting her singing abilities (McNeal, 2022). More recently, in May 2024, Dion revealed even more about her struggles with Stiff Person Syndrome in a trailer for her upcoming documentary I Am: Celine Dion (Tarkazikis, 2024). In the teary trailer, Dion recounts how she almost died from the disease, but continues to stay positive, work with her physical therapy team, and strive to get better each and every day (Tarkazikis, 2024).
(Image: Business Insider)
The journey of individuals like Celine Dion brings vital attention to Stiff Person Syndrome, a rare and often misunderstood neurological disorder. By highlighting not only the epidemiology, neurological basis, treatment, and current research in SPS treatment, but also Celine Dion’s diagnosis and the media coverage surrounding it, the need for increased awareness and dedicated research becomes evident. Enhancing public knowledge and scientific understanding of SPS is crucial for improving the lives of those affected and for fostering advancements in treatment options.
References
Cleveland Clinic. (n.d.) Stiff person syndrome. https://my.clevelandclinic.org/health/diseases/6076-stiff-person-syndrome
Johns Hopkins Medicine. (n.d.). Stiff person syndrome (SPS). https://www.hopkinsmedicine.org/health/conditions-and-diseases/stiff-person-syndrome-sps
Graus, F., Saiz, A., & Dalmau, J. (2020). GAD antibodies in neurological disorders—Insights and challenges. Nature Reviews Neurology, 16(7), 353–365. https://doi.org/10.1038/s41582-020-0359-x
Guenot, M. (2023, December 19). What is Stiff Person Syndrome? Céline Dion was diagnosed with the rare condition affecting her voice and ability to walk. Business Insider. https://www.businessinsider.com/cline-dion-stiff-person-syndrome-symptoms-causes-of-rare-disease-2022-12
McNeal, B. (2022, December 8). Céline Dion Shares Diagnosis of Rare, Incurable Stiff Person Syndrome. Esquire. https://www.esquire.com/entertainment/music/a42188201/celine-dion-stiff-person-syndrome-diagnosis/
Nolan, J. D., & Nicholas, J. A. (2020, September). Stiff-Person Syndrome. Practical Neurology. https://practicalneurology.com/articles/2020-sept/stiff-person-syndrome
Olson, E. (2022, December 8). Céline Dion was diagnosed with stiff-person syndrome. Here’s how it affects people. NPR. https://www.npr.org/2022/12/08/1141538144/celine-dion-stiff-person-syndrome-canceled-shows
Patel, J., Deschler, E., & Galang, E. (2024). Spinal cord stimulation for the symptomatic treatment of rigidity and painful spasm in a case of stiff person syndrome. Pain Practice: The Official Journal of World Institute of Pain. https://doi.org/10.1111/papr.13340
Perea, Y. (2022, December 12). What is Stiff-person syndrome (SPS)?: How to relieve symptoms. Perea Clinic. https://pereaclinic.com/what-is-stiff-person-syndrome-sps-how-to-relieve-symptoms/
Tarkazikis, E. (2024, May 24). Celine Dion reveals she almost died amid battle with stiff person syndrome. Scripps News. https://www.scrippsnews.com/entertainment/celebrity/celine-dion-reveals-she-almost-died-amid-battle-with-stiff-person-syndrome
Vlad, B., Wang, Y., Newsome, S. D., & Balint, B. (2023). Stiff person spectrum disorders—An update and outlook on clinical, pathophysiological and treatment perspectives. Biomedicines, 11(9), 2500. https://doi.org/10.3390/biomedicines11092500
Yale Medicine. (n.d.). Stiff-person syndrome. https://www.yalemedicine.org/conditions/stiff-person-syndrome
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